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Drug overview for LINEZOLID (linezolid):
Generic name: LINEZOLID (lin-AYZ-oh-lid)
Drug class: Oxazolidinediones
Therapeutic class: Anti-Infective Agents
Linezolid is an oxazolidinone anti-infective agent.
Linezolid is used for the treatment of community-acquired pneumonia, nosocomial pneumonia, and uncomplicated or complicated skin and skin structure infections caused by certain susceptible staphylococci or streptococci. Linezolid also is used for the treatment of infections caused by vancomycin-resistant Enterococcus faecium. Linezolid is not indicated for the treatment of infections caused by gram-negative bacteria. It is critical that an anti-infective active against gram-negative bacteria be used concomitantly if documented or presumed pathogens include gram-negative bacteria.
Generic name: LINEZOLID (lin-AYZ-oh-lid)
Drug class: Oxazolidinediones
Therapeutic class: Anti-Infective Agents
Linezolid is an oxazolidinone anti-infective agent.
Linezolid is used for the treatment of community-acquired pneumonia, nosocomial pneumonia, and uncomplicated or complicated skin and skin structure infections caused by certain susceptible staphylococci or streptococci. Linezolid also is used for the treatment of infections caused by vancomycin-resistant Enterococcus faecium. Linezolid is not indicated for the treatment of infections caused by gram-negative bacteria. It is critical that an anti-infective active against gram-negative bacteria be used concomitantly if documented or presumed pathogens include gram-negative bacteria.
DRUG IMAGES
LINEZOLID 100 MG/5 ML SUSP
The following indications for LINEZOLID (linezolid) have been approved by the FDA:
Indications:
Complicated skin and skin structure Staphylococcus aureus infection
Complicated skin and skin structure Streptococcus agalactiae infection
Complicated skin and skin structure Streptococcus pyogenes infection
Diabetic foot infection due to gram-positive bacteria
Nosocomial pneumonia due to Streptococcus pneumoniae
Skin and skin structure Streptococcus pyogenes infection
Staphylococcal pneumonia
Staphylococcus aureus skin and skin structure infection
Staphylococcus nosocomial pneumonia
Streptococcal pneumonia
Vancomycin resistant Enterococcus faecium bacteremia
Vancomycin-resistant Enterococcus faecium infection
Professional Synonyms:
Bacteremia due to VREF
Complicated skin and skin soft tissue infection due to Streptococcus pyogenes
Complicated Staphylococcus aureus skin and skin soft tissue infection
Complicated Streptococcus pyogenes skin and skin structure infection
Nosocomial Pneumococcal pneumonia
Nosocomial pneumonia due to Staphylococcus species
Pneumonia due to Staphylococcus species
Pneumonia due to Staphylococcus spp.
Pneumonia due to Streptococcus species
Pneumonia due to Streptococcus spp.
Skin & skin soft tissue Streptococcus pyogenes infection
Skin and skin soft tissue Staphylococcus aureus infection
Vancomycin-resistant Enterococcus faecium bacteremia
Vancomycin-resistant Streptococcus faecium bacteremia
VREF infection
Indications:
Complicated skin and skin structure Staphylococcus aureus infection
Complicated skin and skin structure Streptococcus agalactiae infection
Complicated skin and skin structure Streptococcus pyogenes infection
Diabetic foot infection due to gram-positive bacteria
Nosocomial pneumonia due to Streptococcus pneumoniae
Skin and skin structure Streptococcus pyogenes infection
Staphylococcal pneumonia
Staphylococcus aureus skin and skin structure infection
Staphylococcus nosocomial pneumonia
Streptococcal pneumonia
Vancomycin resistant Enterococcus faecium bacteremia
Vancomycin-resistant Enterococcus faecium infection
Professional Synonyms:
Bacteremia due to VREF
Complicated skin and skin soft tissue infection due to Streptococcus pyogenes
Complicated Staphylococcus aureus skin and skin soft tissue infection
Complicated Streptococcus pyogenes skin and skin structure infection
Nosocomial Pneumococcal pneumonia
Nosocomial pneumonia due to Staphylococcus species
Pneumonia due to Staphylococcus species
Pneumonia due to Staphylococcus spp.
Pneumonia due to Streptococcus species
Pneumonia due to Streptococcus spp.
Skin & skin soft tissue Streptococcus pyogenes infection
Skin and skin soft tissue Staphylococcus aureus infection
Vancomycin-resistant Enterococcus faecium bacteremia
Vancomycin-resistant Streptococcus faecium bacteremia
VREF infection
The following dosing information is available for LINEZOLID (linezolid):
When clinically appropriate, patients treated initially with IV linezolid may be switched to oral linezolid without dosage adjustment.
The manufacturer states that safety and efficacy of more than 28 days of linezolid treatment have not been evaluated in controlled clinical trials. Linezolid is administered for longer durations when used in multiple-drug regimens for the treatment of multidrug-resistant (MDR) tuberculosis.
In premature neonates younger than 7 days of age, the manufacturer recommends an initial linezolid dosage of 10 mg/kg every 12 hours; a dosage of 10 mg/kg every 8 hours may be considered in those with an inadequate response to the lower dosage. The manufacturer recommends that all neonates 7 days of age or older receive a linezolid dosage of 10 mg/kg every 8 hours.
When linezolid is used in neonates 7 days of age or younger, the American Academy of Pediatrics (AAP) recommends an IV dosage of 10 mg/kg every 12 hours in those with gestational age less than 34 weeks and 10 mg/kg every 8 hours in those with gestational age of 24 weeks or more. For neonates 8-28 days of age, AAP recommends an IV dosage of 10 mg/kg every 8 hours, regardless of gestational age.
The manufacturer states that safety and efficacy of more than 28 days of linezolid treatment have not been evaluated in controlled clinical trials. Linezolid is administered for longer durations when used in multiple-drug regimens for the treatment of multidrug-resistant (MDR) tuberculosis.
In premature neonates younger than 7 days of age, the manufacturer recommends an initial linezolid dosage of 10 mg/kg every 12 hours; a dosage of 10 mg/kg every 8 hours may be considered in those with an inadequate response to the lower dosage. The manufacturer recommends that all neonates 7 days of age or older receive a linezolid dosage of 10 mg/kg every 8 hours.
When linezolid is used in neonates 7 days of age or younger, the American Academy of Pediatrics (AAP) recommends an IV dosage of 10 mg/kg every 12 hours in those with gestational age less than 34 weeks and 10 mg/kg every 8 hours in those with gestational age of 24 weeks or more. For neonates 8-28 days of age, AAP recommends an IV dosage of 10 mg/kg every 8 hours, regardless of gestational age.
No enhanced Administration information available for this drug.
| DRUG LABEL | DOSING TYPE | DOSING INSTRUCTIONS |
|---|---|---|
| LINEZOLID 100 MG/5 ML SUSP | Maintenance | Adults take 30 milliliters (600 mg) by oral route every 12 hours |
| DRUG LABEL | DOSING TYPE | DOSING INSTRUCTIONS |
|---|---|---|
| LINEZOLID 100 MG/5 ML SUSP | Maintenance | Adults take 30 milliliters (600 mg) by oral route every 12 hours |
The following drug interaction information is available for LINEZOLID (linezolid):
There are 9 contraindications.
These drug combinations generally should not be dispensed or administered to the same patient. A manufacturer label warning that indicates the contraindication warrants inclusion of a drug combination in this category, regardless of clinical evidence or lack of clinical evidence to support the contraindication.
| Drug Interaction | Drug Names |
|---|---|
| Live Typhoid Vaccine/Antimicrobials SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: The antimicrobial may be active against the organism in the live-vaccine. Antimicrobial therapy may prevent the vaccine organism from replicating enough to trigger an immune response.(1) CLINICAL EFFECTS: Vaccination may be ineffective. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Do not give oral typhoid vaccine until 72 hours after the last dose of antimicrobial. If possible, to optimize vaccine effectiveness, do not start antibacterial drugs for 72 hours after the last dose of oral typhoid vaccine. A longer interval should be considered for long-acting antimicrobials, such as azithromycin.(3) DISCUSSION: Because antimicrobial therapy may prevent sufficient vaccine-organism replication to generate an immune response, the manufacturer of live-attenuated typhoid vaccine and the Centers for Disease Control (CDC) state that the vaccine should not be administered to patients receiving antimicrobial therapy.(1-3) |
VIVOTIF |
| Apraclonidine/MAOIs SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Apraclonidine is an alpha-2-adrenergic agonist used to decrease intraocular pressure. The use of apraclonidine ophthalmic solution leads to systemic absorption.(1) As apraclonidine does not cross the blood brain barrier, peripheral alpha-2-adrenergic effects could potentially result in vasoconstriction.(1) CLINICAL EFFECTS: Not described.(1) PREDISPOSING FACTORS: Unknown. PATIENT MANAGEMENT: The manufacturer of apraclonidine states that concurrent administration of apraclonidine to patients on monoamine oxidase inhibitors (MAOI's) is contraindicated.(1) DISCUSSION: There is no clinical documentation to support this interaction. The manufacturer of apraclonidine states that concurrent administration of apraclonidine to patients on MAOI's is contraindicated.(1) Methylene blue, when administered intravenously, has been shown to reach sufficient concentrations to be a potent inhibitor of MAO-A. Metaxalone is a weak inhibitor of MAO. |
APRACLONIDINE HCL, IOPIDINE |
| COMT Inhibitors/Selected MAOIs SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Since MAOI's and COMT are the two major enzymes responsible for the metabolism of catecholamines, the combination of entacapone, tolcapone, or opicapone and a non-selective MAOI may inhibit the majority of catecholamine metabolism pathways.(1-3) CLINICAL EFFECTS: Concurrent administration of entacapone, tolcapone, or opicapone with a non-selective MAOI may result in elevated levels of catecholamines, which may result in elevated heart rate and blood pressure. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The Canadian(4) and UK(1) manufacturers of entacapone state that concomitant use of either a non-selective MAOI or a selective MAO-A inhibitor with a selective MAO-B inhibitor with entacapone is contraindicated. Nonselective MAOI should be discontinued at least 2 weeks prior to initiating entacapone therapy.(4) The UK manufacturer of tolcapone states that tolcapone should not be coadministered with either a non-selective MAOI or a selective MAO-A inhibitor with a selective MAO-B inhibitor. (5) The US manufacturer of tolcapone states that patients should not ordinarily be treated concomitantly with tolcapone and a non-selective MAOI. Tolcapone may be concurrently administered with a selective MAO-B inhibitor.(2) The Middle East and US manufacturers of opicapone state that concomitant use of opicapone with MAO inhibitors other than those for the treatment of Parkinson's disease is contraindicated.(10,11) DISCUSSION: Monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT) are the two major enzymes systems involved in the metabolism of catecholamines. Therefore, theoretically, the combination of either entacapone, tolcapone, or opicapone with a non-selective MAO inhibitor will result in inhibition of the majority of catecholamine metabolism pathways.(1,2) At daily oral doses of 10 mg, selegiline is primarily a selective MAO-B inhibitor; however, at higher doses, selegiline is capable of inhibiting MAO-A.(6) At dosages administered transdermally for the treatment of depression, selegiline is not selective for MAO-B.(7) Methylene blue, when administered intravenously, has been shown to reach sufficient concentrations to be a potent inhibitor of MAO-A.(8,9) Metaxalone is a weak inhibitor of MAO.(12,13) |
ENTACAPONE, ONGENTYS, TASMAR, TOLCAPONE |
| Atomoxetine; Reboxetine; Viloxazine/Monoamine Oxidase Inhib SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Monoamine oxidase Inhibitors (MAOIs) block the enzymes that degrade monoamine neurotransmitters-norepinephrine and serotonin. Atomoxetine, reboxetine, and viloxazine inhibit the pre-synaptic norepinephrine transporter. Concomitant use of atomoxetine, reboxetine, or viloxazine with MAOIs may potentiate the release of norepinephrine and other monoamines from adrenergic nerve endings.(1-3) CLINICAL EFFECTS: Concurrent use may result in serious and sometimes fatal reactions including hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations of vital signs, and mental status changes that include extreme agitation progressing to delirium and coma.(1-3) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturers of atomoxetine and viloxazine state that the concurrent use of atomoxetine or viloxazine with a monoamine oxidase inhibitor (MAOI) is contraindicated. At least a two-week washout period should occur between switching a patient from a MAOI to atomoxetine or viloxazine, or from atomoxetine to a MAOI.(1,3) The Australian manufacturer of reboxetine states that concurrent use with an MAOI is contraindicated.(2) DISCUSSION: Because the use of other drugs that affect brain monoamine concentrations with monoamine oxidase inhibitors has resulted in serious and sometimes fatal reactions, the manufacturer of atomoxetine states that the concurrent use of atomoxetine with a MAOI is contraindicated. At least a two-week washout period should occur between switching a patient from a MAOI to atomoxetine or from atomoxetine to a MAOI.(1) The Australian manufacturer of reboxetine and the US manufacturer of viloxazine state that concurrent use with an MAOI is contraindicated.(2-3) Methylene blue, when administered intravenously, has been shown to reach sufficient concentrations to be a potent inhibitor of MAO-A.(4-5) Metaxalone is a weak inhibitor of MAO.(8,9) One or more of the drug pairs linked to this monograph have been included in a list of interactions that should be considered "high-priority" for inclusion and should not be inactivated in EHR systems. This DDI subset was vetted by an expert panel commissioned by the U.S. Office of the National Coordinator (ONC) for Health Information Technology. |
ATOMOXETINE HCL, QELBREE, STRATTERA |
| Deutetrabenazine; Tetrabenazine/MAOIs SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: The exact mechanism is unknown. CLINICAL EFFECTS: Concurrent use of deutetrabenazine or tetrabenazine with an MAOI may result in restlessness, disorientation, and confusion.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Concurrent use of deutetrabenazine or tetrabenazine with a MAOI is contraindicated.(1-3) A two-week washout period should elapse between discontinuing a MAOI and the initiation of deutetrabenazine or tetrabenazine.(1-3) DISCUSSION: Because concurrent use of deutetrabenazine or tetrabenazine with an MAOI may result in restlessness, disorientation, and confusion, tetrabenazine should not be given after a course of any of the MAOI's.(1-3) Methylene blue, when administered intravenously, has been shown to reach sufficient concentrations to be a potent inhibitor of MAO-A.(4,5) Metaxalone is a weak inhibitor of MAO.(6,7) |
AUSTEDO, AUSTEDO XR, AUSTEDO XR TITRATION KT(WK1-4), TETRABENAZINE, XENAZINE |
| Methyldopa/MAOIs SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Monoamine oxidase inhibitors (MAOI's) may inhibit the antihypertensive effects of methyldopa.(1) CLINICAL EFFECTS: Concurrent use of MAOI's and methyldopa may result in hypertensive crisis(2) and/or hallucinations.(3) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The Australian,(4) UK,(1) and US(5,6) manufacturers of methyldopa state that concurrent use of MAOI's is contraindicated. The US manufacturer of phenelzine states that concurrent use of methyldopa is contraindicated.(2) DISCUSSION: In a case report, a patient maintained on pargyline developed hallucinations following the increase of her methyldopa from 250 mg daily to 250 mg twice daily.(2) Methylene blue, when administered intravenously, has been shown to reach sufficient concentrations to be a potent inhibitor of MAO-A.(7,8) Metaxalone is a weak inhibitor of MAO.(9,10) |
METHYLDOPA, METHYLDOPA-HYDROCHLOROTHIAZIDE, METHYLDOPATE HCL |
| Guanethidine/MAOIs SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: In patients treated with MAOIs, guanethidine may result in the release of a large quantity of catecholamines.(1,2) CLINICAL EFFECTS: Use of guanethidine in patients treated with a MAOI may result in hypertensive crisis.(1,2) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: At least 2 weeks should elapse between the discontinuation of an MAOI and the use of guanethidine.(1,2) DISCUSSION: In patients treated with MAOIs, guanethidine may result in the release of a large quantity of catecholamines, which may result in hypertensive crisis.(1,2) Methylene blue, when administered intravenously, has been shown to reach sufficient concentrations to be a potent inhibitor of MAO-A.(3,4) Metaxalone is a weak inhibitor of MAO.(5,6) |
GUANETHIDINE HEMISULFATE |
| Linezolid/MAOIs SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Linezolid is a reversible, nonselective inhibitor of monoamine oxidase (MAO).(1,2) CLINICAL EFFECTS: Concurrent use of linezolid and other MAO inhibitors may result in additive effects and toxicity.(1,2) Symptoms of serotonin syndrome may include tremor, agitation, diaphoresis, hyperreflexia, clonus, tachycardia, hyperthermia, and muscle rigidity. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US and UK manufacturer of linezolid state that it should not be used within 2 weeks of another product which inhibits monoamine oxidase A or B.(1,2) In emergency situations in patients maintained on linezolid, weigh the availability and safety of alternatives to linezolid against the risk of serotonin syndrome. If therapy with linezolid is required, discontinue the MAOI immediately. Patients should be monitored for serotonin syndrome for 2 weeks or until 24 hours after the last dose of linezolid, whichever comes first.(3,4) In non-emergency situations in patients maintained on MAOIs when linezolid therapy is planned, discontinue the patient's MAOI at least 2 weeks in advance of linezolid therapy. The patient's MAOI therapy may be resumed 24 hours after the last dose of linezolid.(3) Do not initiate MAOI therapy in patients receiving linezolid until 24 hours after the last dose of the linezolid.(3,4) If concurrent therapy is warranted, patients should be monitored for signs and symptoms of serotonin syndrome. Instruct patients to report muscle twitching, tremors, shivering and stiffness, fever, heavy sweating, heart palpitations, restlessness, confusion, agitation, trouble with coordination, or severe diarrhea. DISCUSSION: Linezolid is a reversible, nonselective inhibitor MAO. Concurrent use of linezolid and other MAO inhibitors may result in additive effects and toxicity. The US and UK manufacturer of linezolid state that it should not be used within 2 weeks of another product which inhibits monoamine oxidase A or B.(1,2) Methylene blue, when administered intravenously, has been shown to reach sufficient concentrations to be a potent inhibitor of MAO-A.(5,6) Metaxalone is a weak inhibitor of MAO.(7.8) The FDA AERS contains reports of serotonin syndrome with the concurrent use of linezolid and citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, and venlafaxine as well as reports of serotonin syndrome with concurrent injectable methylene blue and citalopram, clomipramine, escitalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, and venlafaxine. The risk of serotonin syndrome with other psychiatric drugs is unclear.(9,10) |
AZILECT, EMSAM, FURAZOLIDONE, MARPLAN, MATULANE, METAXALONE, METHYLENE BLUE, NARDIL, PARNATE, PHENELZINE SULFATE, PROCARBAZINE HCL, PROVAYBLUE, RASAGILINE MESYLATE, SELEGILINE HCL, TRANYLCYPROMINE SULFATE, XADAGO, ZELAPAR |
| Ozanimod/MAOIs SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Ozanimod is metabolized by CYP3A4 to RP101075 (a minor active metabolite), which is further metabolized by monoamine oxidase-B (MAO-B) to major active metabolites that make up the predominant circulating active species in the plasma. The major and minor active metabolites have similar activity as ozanimod. Inhibition of MAO-B may alter exposure to ozanimod and its metabolites.(1) CLINICAL EFFECTS: Concurrent use of ozanimod and MAO inhibitors may result in altered exposure to ozanimod and its active metabolites and may result in decreased efficacy.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The concurrent use of ozanimod with MAO inhibitors is contraindicated. At least 14 days should elapse between discontinuation of ozanimod and initiation of MAO inhibitors.(1) DISCUSSION: The combination of ozanimod with MAO inhibitors has not been studied. The combination of steady state ozanimod 0.92 mg or 1.84 mg with tyramine, an MAO substrate, did not have an effect on tyramine plasma concentrations or tyramine-induced pressor response. However, MAO inhibitors may alter the exposure to ozanimod and its metabolites.(1) Metaxalone is a weak inhibitor of MAO.(2,3) |
ZEPOSIA |
There are 23 severe interactions.
These drug interactions can produce serious consequences in most patients. Actions required for severe interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration scheduling, and providing additional patient monitoring. Review the full interaction monograph for more information.
| Drug Interaction | Drug Names |
|---|---|
| Selected Opioids/MAOIs SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Selected opioids inhibit neuronal reuptake of serotonin. Non-selective MAOIs increase neuronal serotonin concentration via inhibition of MAO-A. CLINICAL EFFECTS: The concurrent use of some opioids with MAOIs has resulted in serotonin syndrome. Symptoms of serotonin syndrome may include tremor, agitation, diaphoresis, hyperreflexia, clonus, tachycardia, hyperthermia, and muscle rigidity.(1) PREDISPOSING FACTORS: Treatment with multiple medications which increase serotonin levels or inhibit the metabolism of serotonin are risk factors for serotonin syndrome. Higher opioid concentrations, as may occur due to inhibition of opioid clearance, patient specific genomic factors (e.g. poor metabolizer status for a P450 enzyme), or high opioid dosage may increase the risk for an interaction. PATIENT MANAGEMENT: Use an alternative analgesic when possible. If concurrent therapy is warranted, patients should be monitored for signs and symptoms of serotonin syndrome. Instruct patients to report muscle twitching, tremors, shivering and stiffness, fever, heavy sweating, heart palpitations, restlessness, confusion, agitation, trouble with coordination, or severe diarrhea. DISCUSSION: Although documentation is lacking for some opioids, the FDA recommends health professionals monitor and advise patients to report symptoms of serotonin syndrome in patients receiving analgesic opioids and serotonergic agents.(2) The interaction between meperidine and MAOIs has been well documented. There are two reports of potential interactions between MAOIs and dextromethorphan.(3,4) In another case report, the concurrent use of propoxyphene and phenylzine resulted in sedation and somnolence. The patient had previously taken both agents alone with no adverse effects.(5) Although some studies have shown that morphine does not interact with MAOIs,(6,7) other data indicates that MAOIs markedly potentiate the effect of morphine.(8) One study indicates that methadone does not interact with MAOIs;(7) however, the UK manufacturer of methadone states that concurrent use is contraindicated.(9) US manufacturers recommend sensitivity tests with small, incremental doses of methadone in patients maintained on MAOIs with careful observation of vital signs.(11) Selected opioids linked to this monograph include: alfentanil, anileridine (not available in US/CA), diphenoxin, meptazinol (not available in US/CA), pentazocine, phenoperidine (not available in US/CA), propoxyphene (not available in US/CA), remifentanil, and sufentanil. Furazolidone and linezolid are known to be monoamine oxidase inhibitors. Methylene blue, when administered intravenously, has been shown to reach sufficient concentrations to be a potent inhibitor of MAO-A.(12,13) |
DSUVIA, MOTOFEN, PENTAZOCINE-NALOXONE HCL, REMIFENTANIL HCL, SUFENTANIL CITRATE, ULTIVA |
| Serotonin Reuptake Inhibitors/Linezolid SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Serotonin reuptake inhibitors and linezolid, which inhibits MAO, may act synergistically to increase central nervous system (CNS) serotonin concentrations, leading to toxicity. CLINICAL EFFECTS: Concurrent use or switching between agents without a sufficient washout period may result in serotonin syndrome. Symptoms of serotonin syndrome may include tremor, agitation, diaphoresis, hyperreflexia, clonus, tachycardia, hyperthermia, and muscle rigidity.(2) Serotonin syndrome may result in death. PREDISPOSING FACTORS: High doses of serotonin reuptake inhibitors or concurrent use of multiple drugs which increase CNS serotonin levels may increase risk for serotonin syndrome. PATIENT MANAGEMENT: If linezolid is required for urgent or life threatening treatment, the FDA states the interacting serotonergic drug should be stopped. Although discontinued, serotonin toxicity due to the interaction is still possible. Patients should be monitored for CNS serotonin toxicity for two weeks (five weeks if fluoxetine, 3 weeks if vortioxetine, 7 days if desvenlafaxine or venlafaxine, or 5 days if duloxetine was taken) or until 24 hours after the last linezolid dose, whichever comes first. Therapy with the SSRI may be resumed 24 hours after the last dose of linezolid.(1,3-13) DISCUSSION: Serotonin syndrome has been reported in four patients receiving concurrent citalopram and linezolid, in a patient in whom linezolid was initiated 18 days after fluoxetine discontinuation, in a patient receiving concurrent linezolid and fluoxetine, in a patient in whom linezolid was initiated three days after the discontinuation of paroxetine, in three patients receiving concurrent linezolid and sertraline, and in a patient receiving concurrent linezolid and venlafaxine. Many authors state that linezolid is a weak MAOI and rarely causes serotonin toxicity. Cases of serotonin toxicity were rapidly reversible with discontinuation of the offending agent(s) and supportive care. Some authors suggest that use of serotonergic medications should not preclude the use of linezolid but that the clinical situation should be assessed. If concurrent use or use of linezolid without a washout is warranted, the patient should be closely monitored.(24-29) |
CELEXA, CITALOPRAM HBR, CYMBALTA, DESVENLAFAXINE ER, DESVENLAFAXINE SUCCINATE ER, DRIZALMA SPRINKLE, DULOXETINE HCL, DULOXICAINE, EFFEXOR XR, ESCITALOPRAM OXALATE, FLUOXETINE DR, FLUOXETINE HCL, FLUVOXAMINE MALEATE, FLUVOXAMINE MALEATE ER, GEODON, LEXAPRO, NEFAZODONE HCL, OLANZAPINE-FLUOXETINE HCL, PAROXETINE CR, PAROXETINE ER, PAROXETINE HCL, PAROXETINE MESYLATE, PAXIL, PAXIL CR, PRISTIQ, PROZAC, SERTRALINE HCL, TRINTELLIX, VENLAFAXINE BESYLATE ER, VENLAFAXINE HCL, VENLAFAXINE HCL ER, VIIBRYD, VILAZODONE HCL, ZIPRASIDONE HCL, ZIPRASIDONE MESYLATE, ZOLOFT |
| Milnacipran/Linezolid SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Serotonin reuptake inhibitors and MAOIs may act synergistically to increase blood pressure and evoke behavioral excitation. CLINICAL EFFECTS: Concurrent use or switching between agents without a sufficient washout period may result in serotonin syndrome.(1,2) Symptoms of serotonin syndrome may include tremor, agitation, diaphoresis, hyperreflexia, clonus, tachycardia, hyperthermia, and muscle rigidity.(3,4) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturers of milnacipran and levomilnacipran state that concurrent administration with a MAOI, including linezolid, is contraindicated. At least 5 days should elapse between discontinuing milnacipran and initiating linezolid,(1) and at least 7 days should elapse between discontinuing levomilnacipran and initiating linezolid.(2) In emergency situations in patients maintained on milnacipran or levomilnacipran, weigh the availability and safety of alternatives to linezolid against the risk of serotonin syndrome. If linezolid therapy is required, the patient's milnacipran or levomilnacipran should be immediately discontinued. Patients should be monitored for serotonin syndrome for 5 days (2 weeks in the case of levomilnacipran) or until 24 hours after the last dose of linezolid, whichever comes first. Do not initiate milnacipran or levomilnacipran therapy in patients receiving linezolid until 24 hours after the last dose of linezolid. DISCUSSION: Concurrent use or switching between agents without a sufficient washout period may result in serotonin syndrome. Therefore, the US manufacturers of milnacipran and levomilnacipran state that concurrent administration with a MAOI, including linezolid, is contraindicated. At least 5 days should elapse between discontinuing milnacipran and initiating linezolid,(1) and at least 7 days should elapse between discontinuing levomilnacipran and initiating linezolid.(2) Symptoms of serotonin syndrome may include tremor, agitation, diaphoresis, hyperreflexia, clonus, tachycardia, hyperthermia, and muscle rigidity.(3,4) Many authors state that linezolid is a weak MAOI and rarely causes serotonin toxicity. Cases of serotonin toxicity were rapidly reversible with discontinuation of the offending agent(s) and supportive care. Some authors suggest that use of serotonergic medications should not preclude the use of linezolid but that the clinical situation should be assessed. If concurrent use or use of linezolid without a washout is warranted, the patient should be closely monitored.(5-10) |
FETZIMA, SAVELLA |
| MAOIs/Metoclopramide SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: In patients treated with MAOIs, metoclopramide may result in the release of a large quantity of catecholamines.(1) CLINICAL EFFECTS: Use of metoclopramide in patients treated with a MAOI may result in hypertensive crisis.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Avoid the concurrent use of metoclopramide and MAOIs. If concurrent use is warranted, monitor patients closely for hypertensive crisis.(1) DISCUSSION: In patients treated with MAOIs, metoclopramide may result in the release of a large quantity of catecholamines, which may result in hypertensive crisis.(1) Metaxalone is a weak inhibitor of MAO.(2,3) |
GIMOTI, METOCLOPRAMIDE HCL, REGLAN |
| Mixed;Indirect Sympathomimetics/Selected MAOIs SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Catecholamine stores increased by MAOIs can be released by indirect acting sympathomimetics such as ephedrine and amphetamine. MAO inhibitors also interfere with gut and liver metabolism of direct acting sympathomimetics (e.g oral phenylephrine). CLINICAL EFFECTS: Concurrent use of MAOIs may result in potentiation of sympathomimetic effects, which may result in headaches, hypertensive crisis, toxic neurological effects, and malignant hyperpyrexia. Fatalities have occurred with combinations of sympathomimetics and MAO-A inhibitors. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Concurrent use of MAO-A inhibitors and sympathomimetics is contraindicated. The manufacturers of sympathomimetic agents recommend waiting 14 days after discontinuation of MAO inhibitors before initiating the sympathomimetic. Patients receiving direct or indirect acting sympathomimetics should not receive linezolid unless they are monitored for potential increases in blood pressure. Initial dosages of dopamine and epinephrine should be reduced. At recommended dosages, oral selegiline and transdermal selegiline up to 6mg/day are selective for MAO-B; however, at higher dosages they have been shown to lose their selectivity. Patients receiving higher dosages of selegiline should be considered susceptive to this interaction. DISCUSSION: Indirect acting sympathomimetic amines may cause abrupt elevation of blood pressure when administered to patients taking monoamine oxidase inhibitors, resulting in a potentially fatal hypertensive crisis. Mixed (direct and indirect) acting sympathomimetics have also been shown to interact with monoamine oxidase inhibitors depending on their degree of indirect action. The direct-acting sympathomimetics have not been reported to interact. Dopamine is metabolized by monoamine oxidase, and its pressor effect is enhanced by monoamine oxidase inhibitors. Furazolidone, an antibacterial with monoamine oxidase inhibitor action, has also been shown to interact with indirect acting sympathomimetics. Foods containing large amounts of tyramine have also been implicated in this interaction. A significant pressor response was observed in normal subjects receiving linezolid and tyramine doses of more than 100 mg. Administration of linezolid (600 mg BID for 3 days) with pseudoephedrine (60 mg q 4 hours for 2 doses) increased blood pressure by 32 mmHg. Administration of linezolid (600 mg BID for 3 days) with phenylpropanolamine (25 mg q 4 hours for 2 doses) increased blood pressure by 38 mmHg. One or more of the drug pairs linked to this monograph have been included in a list of interactions that should be considered "high-priority" for inclusion and should not be inactivated in EHR systems. This DDI subset was vetted by an expert panel commissioned by the U.S. Office of the National Coordinator (ONC) for Health Information Technology. |
ADDERALL, ADDERALL XR, ADIPEX-P, ADZENYS XR-ODT, AKOVAZ, AMINO ACID 4.5%-D10W-HEPARIN, AMPHETAMINE SULFATE, APTENSIO XR, AZSTARYS, BENZPHETAMINE HCL, BIORPHEN, BROMFED DM, BROMPHENIRAMINE-PSEUDOEPHED-DM, CLARINEX-D 12 HOUR, CLINIMIX, CLINIMIX E, COCAINE HCL, CONCERTA, COTEMPLA XR-ODT, DAYTRANA, DESOXYN, DEXEDRINE, DEXMETHYLPHENIDATE HCL, DEXMETHYLPHENIDATE HCL ER, DEXTROAMPHETAMINE SULFATE, DEXTROAMPHETAMINE SULFATE ER, DEXTROAMPHETAMINE-AMPHET ER, DEXTROAMPHETAMINE-AMPHETAMINE, DIETHYLPROPION HCL, DIETHYLPROPION HCL ER, DOPAMINE HCL, DOPAMINE HCL IN 5% DEXTROSE, DYANAVEL XR, EMERPHED, EPHEDRINE HCL, EPHEDRINE SULFATE, EPHEDRINE SULFATE-0.9% NACL, EPHEDRINE SULFATE-NACL, EVEKEO, FOCALIN, FOCALIN XR, GOPRELTO, HYDROXYAMPHETAMINE HBR, IMMPHENTIV, ISOMETHEPTENE MUCATE, JORNAY PM, LISDEXAMFETAMINE DIMESYLATE, LOMAIRA, METADATE CD, METADATE ER, METHAMPHETAMINE HCL, METHYLIN, METHYLPHENIDATE, METHYLPHENIDATE ER, METHYLPHENIDATE ER (LA), METHYLPHENIDATE HCL, METHYLPHENIDATE HCL CD, METHYLPHENIDATE HCL ER (CD), MYDAYIS, NUMBRINO, PHENDIMETRAZINE TARTRATE, PHENDIMETRAZINE TARTRATE ER, PHENTERMINE HCL, PHENYLEPHRINE HCL, PHENYLEPHRINE HCL-0.9% NACL, PHENYLEPHRINE HCL-NACL, PHENYLEPHRINE HCL-WATER, PROCENTRA, PROMETHAZINE VC, PROMETHAZINE-PHENYLEPHRINE HCL, PSEUDOEPHEDRINE HCL, QSYMIA, QUILLICHEW ER, QUILLIVANT XR, RELEXXII, RESPA A.R., REZIPRES, RITALIN, RITALIN LA, VAZCULEP, VYVANSE, XELSTRYM, ZENZEDI |
| Deferiprone/Selected Myelosuppressive Agents SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Concurrent use of deferiprone with other drugs known to be associated with neutropenia or agranulocytosis may increase the frequency or risk for severe toxicity.(1) CLINICAL EFFECTS: Concurrent use of deferiprone and myelosuppressive agents may result in severe neutropenia or agranulocytosis, which may be fatal. PREDISPOSING FACTORS: Agranulocytosis may be less common in patients receiving deferiprone for thalassemia, and more common in patients treated for other systemic iron overload conditions (e.g. myelodysplastic syndromes, sickle cell disease).(2,3) Inadequate monitoring appears to increase the risk for severe outcomes. Manufacturer post market surveillance found that in all fatal cases of agranulocytosis reported between 1999 and 2005, data on weekly white blood count (WBC) monitoring was missing. In three fatal cases, deferiprone was continued for two to seven days after the detection of neutropenia or agranulocytosis.(2) PATIENT MANAGEMENT: If possible, discontinue one of the drugs associated with risk for neutropenia or agranulocytosis. If alternative therapy is not available, documentation and adherence to the deferiprone monitoring protocol is essential. Baseline absolute neutrophil count (ANC) must be at least 1,500/uL prior to starting deferiprone. Monitor ANC weekly during therapy. If infection develops, interrupt deferiprone therapy and monitor ANC more frequently. If ANC is less than 1,500/uL but greater than 500/uL, discontinue deferiprone and any other drugs possibly associated with neutropenia. Initiate ANC and platelet counts daily until recovery (i.e. ANC at least 1,500/uL). If ANC is less than 500/uL, discontinue deferiprone, evaluate patient and hospitalize if appropriate. Do not resume deferiprone unless potential benefits outweigh potential risks.(1) DISCUSSION: Drugs linked to this monograph have an FDA Boxed Warning for risk of neutropenia, agranulocytosis, or pancytopenia, or have > 5% risk for neutropenia and/or warnings describing risk for myelosuppression in manufacturer prescribing information.(1-25) In pooled clinical studies submitted to the FDA, 6.1% of deferiprone patients met criteria for neutropenia and 1.7% of patients developed agranulocytosis.(1) The time to onset of agranulocytosis was highly variable with a range of 65 days to 9.2 years (median, 161 days).(3) |
DEFERIPRONE, DEFERIPRONE (3 TIMES A DAY), FERRIPROX, FERRIPROX (2 TIMES A DAY), FERRIPROX (3 TIMES A DAY) |
| Clozapine/Selected Myelosuppressive Agents SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Clozapine and other myelosuppressive agents may be associated with neutropenia or agranulocytosis.(2) CLINICAL EFFECTS: Moderate neutropenia, even if due to combination therapy, may require abrupt discontinuation of clozapine resulting in decompensation of the patient's psychiatric disorder (e.g. schizophrenia). The disease treated by the myelosuppressive agent may be compromised if myelosuppression requires dose reduction, delay, or discontinuation of the myelosuppressive agent. Undetected severe neutropenia or agranulocytosis may be fatal. PREDISPOSING FACTORS: Low white blood counts prior to initiation of the myelosuppressive agent may increase risk for clinically significant neutropenia. PATIENT MANAGEMENT: If a patient stabilized on clozapine therapy requires treatment with a myelosuppressive agent, the clozapine prescriber should consult with prescriber of the myelosuppressive agent (e.g. oncologist) to discuss treatment and monitoring options.(2) More frequent ANC monitoring or treatment alternatives secondary to neutropenic episodes may need to be considered. Clozapine is only available through a restricted distribution system which requires documentation of the absolute neutrophil count (ANC) prior to dispensing.(1-2) For most clozapine patients, clozapine treatment must be interrupted for a suspected clozapine-induced ANC < 1000 cells/microliter. For patients with benign ethnic neutropenia (BEN), treatment must be interrupted for suspected clozapine-induced neutropenia < 500 cells/microliter.(2) DISCUSSION: Clozapine is only available through a restricted distribution system which requires documentation of the ANC prior to dispensing.(1) Agents linked to this interaction generally have > 5% risk for neutropenia and/or warnings describing risk for myelosuppression in manufacturer prescribing information.(3-26) |
CLOZAPINE, CLOZAPINE ODT, CLOZARIL, VERSACLOZ |
| Trazodone (Greater Than 100 mg)/MAOIs SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Trazodone is primarily an inhibitor of 5HT2A serotonin receptors, H1 histamine, and alpha-1 receptors.(1) At low doses, inhibition of serotonin reuptake is weak and estimated to be 1/20th of 5HT2A inhibiting activity. At high trazodone doses receptor specificity may be diminished and serotonin reuptake inhibition could be clinically important. In addition, one route of trazodone metabolism leads to formation of an active metabolite, m-chlorophenylpiperazine (mCPP) which is pharmacologically distinct from trazodone in that it is an agonist at a variety of serotonin receptors.(1) MCPP concentrations may be clinically important at antidepressant doses of trazodone. MCPP is converted to an inactive metabolite by CYP2D6.(3) MAO Inhibitors increase serotonin levels via inhibition of its metabolism. CLINICAL EFFECTS: Concurrent administration could increase the risk for serotonin syndrome. Symptoms of serotonin syndrome may include tremor, agitation, diaphoresis, hyperreflexia, clonus, tachycardia, hyperthermia, and muscle rigidity.(2) PREDISPOSING FACTORS: Serotonin syndrome risk is dose-related. Higher systemic concentrations of trazodone, mCPP or more potent MAO inhibitors would be predicted to increase risk for serotonin toxicity.(2) Concomitant therapy with multiple agents which increase brain serotonin concentrations may also increase risk for serotonin syndrome.(2) Concomitant treatment with inhibitors of CYP2D6 (e.g. bupropion, cinacalcet, dacomitinib, fluoxetine, paroxetine, quinidine, or systemic terbinafine)(4) may increase mCPP concentration, increasing the risk for serotonin toxicity. Patients who are poor metabolizers at CYP2D6 would be expected to have higher mCPP concentrations compared with extensive metabolizers. PATIENT MANAGEMENT: Trazodone doses greater than 100 mg should not be prescribed in patients who require treatment with any MAOI and a strong inhibitor of CYP2D6 (e.g. bupropion, cinacalcet, dacomitinib, fluoxetine, paroxetine, quinidine, systemic terbinafine) or any other agent with serotonin-increasing effects (e.g. tramadol, meperidine, most antidepressants). Patients known to be poor metabolizers of CYP2D6 should not receive greater than 100 mg of trazodone per day if they require treatment with a MAOI. To minimize serotonin reuptake inhibition and accumulation of mCPP, limit dosage of trazodone to less than or equal to 100 mg daily in patients receiving MAO inhibitors. If the benefit of higher dose trazodone is judged to be greater than the risk for serotonin toxicities, assure that the patient and health care team are aware of and monitor for signs and symptoms of serotonin syndrome. If concurrent therapy is warranted, patients should be monitored for signs and symptoms of serotonin syndrome. Instruct patients to report muscle twitching, tremors, shivering and stiffness, fever, heavy sweating, heart palpitations, restlessness, confusion, agitation, trouble with coordination, or severe diarrhea. DISCUSSION: In a case report, a 37 year-old male developed serotonin syndrome following the addition of linezolid to citalopram and trazodone.(5) In a case report, a patient developed serotonin syndrome with concurrent trazodone, isocarboxazid, and methylphenidate.(6) In a case report, a patient developed serotonin syndrome following the abrupt replacement of trazodone with moclobemide.(7) An open study evaluated the efficacy and safety of low dose trazodone for the treatment of MAOI-associated insomnia. Twenty-one patients successfully treated with a MAOI for unipolar or bipolar depression but with persistent insomnia participated in the study. Trazodone 25 to 75 mg was given at bedtime. Patients with a fair or good response to trazodone were monitored for a minimum of 4 months to assess efficacy and safety of treatment. Eleven patients had a resolution of insomnia, 9 had a partial response, and one had no benefit. Side effects noted were nausea in 2 patients, persistent morning grogginess in one patient and memory problems in one patient.(8) A small double-blind placebo controlled study evaluated the efficacy and safety of trazodone 50 mg to treat insomnia due to brofaromine, a MAO-A inhibitor. All seven patients had responded to brofaromine and had been in remission for at least 3 months. Three patients received trazodone on week 1, followed by placebo on week 2, while the other 4 patients received placebo on week 1 and trazodone on week 2. At the end of the trial 4 patients elected to continue trazodone and 3 patients discontinued therapy due to adverse effects (nausea, constipation, vertigo, dry mouth, palpitations, or heartburn). The authors stated no patients had symptoms suggestive of serotonin syndrome.(9) Metaxalone is a weak inhibitor of MAO.(10,11) The FDA AERS contains reports of serotonin syndrome with the concurrent use of linezolid and citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, and venlafaxine as well as reports of serotonin syndrome with concurrent injectable methylene blue and citalopram, clomipramine, escitalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, and venlafaxine. The risk of serotonin syndrome with linezolid and other psychiatric drugs is unclear.(12,13) |
RALDESY, TRAZODONE HCL |
| Linezolid/Tryptophan SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Concurrent use may result in additive effects on serotonin levels. MAOIs may potentiate the effects of tryptophan.(1) CLINICAL EFFECTS: Concurrent administration of tryptophan with a MAO Inhibitor may result in serotonin syndrome and/or hypertensive crisis.(1) Symptoms of serotonin syndrome may include tremor, agitation, diaphoresis, hyperreflexia, clonus, tachycardia, hyperthermia, and muscle rigidity.(2) In addition to these effects, disorientation, delirium, agitation, hypomania, shivering, ocular oscillation, and Babinski signs have been reported with concurrent tryptophan and phenelzine.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Patients receiving linezolid should not be administered tryptophan unless they can be closely monitored for serotonin syndrome. If concurrent therapy is warranted, patients should be monitored for signs and symptoms of serotonin syndrome. Instruct patients to report muscle twitching, tremors, shivering and stiffness, fever, heavy sweating, heart palpitations, restlessness, confusion, agitation, trouble with coordination, or severe diarrhea. DISCUSSION: In a case report, a patient receiving metoclopramide and a TPN containing tryptophan developed serotonin syndrome following the addition of linezolid to therapy.(3) In a study in nine subjects, the administration of a single intravenous dose of tryptophan with tranylcypromine significantly increased the normal prolactin response to tryptophan. Four of the nine subjects developed a distinctive neuromotor syndrome characterized by hyperreflexia, ankle clonus, nystagmus, incoordination, tremor, myoclonic jerks, and nausea.(4) Another set of authors reported eight cases of delirium, ranging from mild to severe, in patients who received concurrent tranylcypromine and tryptophan. Symptoms developed within two days to 4 weeks of beginning concurrent therapy.(5) In a case report, the addition of tryptophan to a tranylcypromine regimen resulted in hypomania.(6) In another report, a patient developed hyperventilation, shivering, hyperthermia, increased muscle tone, and hyperreflexia when tryptophan was added to tranylcypromine therapy.(7) There are two reports of fatalities following the concurrent administration of tryptophan and tranylcypromine. In the first report, a a patient had been receiving chlorpromazine, lithium, and tryptophan when phenelzine was initiated. Four weeks later, the patient developed neuroleptic malignant syndrome and expired despite resuscitation efforts.(8) In the second report, a patient had been receiving fluoxetine, levothyroxine, propranolol, quinidine, and hydroxyzine. Fluoxetine was discontinued and tranylcypromine, thioridazine, and tryptophan were initiated. The patient developed neuroleptic malignant syndrome two and one-half hours after the first tryptophan dose and expired 24 hours later. (9) In a case report, the addition of tryptophan to a regimen that included phenelzine resulted in an acute behavioral and neurologic syndrome. The patient's symptoms resolved 24 hours after the discontinuation of both agents.(10) In another report, a patient developed hypomania following the addition of tryptophan to phenelzine therapy.(6) Another report describes the development of delirium following the addition of tryptophan to phenelzine.(11) One set of authors reported three cases of myoclonus, hyperreflexia, and diaphoresis following the addition of tryptophan to phenelzine therapy.(12) Some studies have shown that the addition of tryptophan to MAO Inhibitor therapy may have beneficial results, including greater improvement in depression and faster onset of effects.(13,14) |
AA 2%-D10W-CALCIUM, AA 2%-D10W-CALCIUM-HEPARIN, AA 2%-D10W-LOW CALCIUM-HEPARIN, AA 2%-D5W-CALCIUM-HEPARIN, AA 2.5%-D10W-CALCIUM-HEPARIN, AA 3%-D10W-CALCIUM, AA 3%-D10W-CALCIUM-HEPARIN, AA 3%-D10W-LOW CALCIUM-HEPARIN, AA 3%-D5W-CALCIUM, AA 3%-D5W-CALCIUM-HEPARIN, AA 3%-D5W-LOW CALCIUM-HEPARIN, AA 3.5%-D10W-CALCIUM, AA 3.5%-D10W-CALCIUM-HEPARIN, AA 3.5%-D10W-LO CALCIUM-HEPARN, AA 4%-D10W-CALCIUM-HEPARIN, AA 6%-D10W-CALCIUM-HEPARIN, AMINO ACID 3%-D10W, AMINO ACID 3.5%-D10W, AMINO ACID 3.5%-D10W-HEPARIN, AMINO ACID 4%-D10W, AMINO ACID 4.5%-D10W-HEPARIN, AMINO ACIDS 2.5%-D10W, AMINOSYN II, AMINOSYN-PF, CLINIMIX, CLINIMIX E, CLINISOL, KABIVEN, PERIKABIVEN, PLENAMINE, PREMASOL, PROSOL, TRAVASOL |
| Selected Opioids; Dextromethorphan-Quinidine/Linezolid SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Selected opioids inhibit neural reuptake of serotonin. Linezolid may increase neuronal serotonin concentrations via inhibition of MAO-A.(22) CLINICAL EFFECTS: The concurrent use of some opioids with MAOIs has resulted in serotonin syndrome. Severe cases of serotonin syndrome may be fatal. Symptoms of serotonin syndrome may include tremor, agitation, diaphoresis, hyperreflexia, clonus, tachycardia, hyperthermia, and muscle rigidity.(22) PREDISPOSING FACTORS: Higher opioid concentrations (e.g., due to inhibition of opioid clearance, patient specific genomic factors such as poor metabolizer status for a cytochrome P450 enzyme, or high opioid dosage) may increase the risk for a severe interaction. PATIENT MANAGEMENT: Diamorphine, meperidine, and tapentadol should not be used in patients taking linezolid. Use alternative agents for cough or pain. DISCUSSION: The interaction between meperidine and MAOIs has been well documented. There is one case report of serotonin syndrome with concurrent meperidine and linezolid. Many authors state that linezolid is a weak MAOI and rarely causes serotonin toxicity. Cases of serotonin toxicity were rapidly reversible with discontinuation of the offending agent(s) and supportive care. Some authors suggest that use of serotonergic medications should not preclude the use of linezolid but that the clinical situation should be assessed. If concurrent use or use of linezolid without a washout is warranted, the patient should be closely monitored.(21-26) |
DEMEROL, MEPERIDINE HCL, MEPERIDINE HCL-0.9% NACL, NUCYNTA, NUCYNTA ER, NUEDEXTA |
| Tramadol/Linezolid SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Tramadol and linezolid may lower the seizure threshold.(1-3) Both tramadol and linezolid may increase serotonin and norepinephrine. Tramadol inhibits neuronal reuptake of serotonin and norepinephrine, while linezolid impairs metabolism of serotonin and norepinephrine via inhibition of monoamine oxidase(MAO).(1-3) CLINICAL EFFECTS: Concurrent use of tramadol and linezolid may result in seizures or serotonin syndrome.(1-3) Symptoms of serotonin syndrome may include tremor, agitation, diaphoresis, hyperreflexia, clonus, tachycardia, hyperthermia, and muscle rigidity.(4) PREDISPOSING FACTORS: CYP2D6 poor metabolizers,(5) or patients also taking strong CYP2D6 inhibitors (e.g. bupropion, fluoxetine, paroxetine, terbinafine) will have reduced tramadol metabolism leading higher systemic levels of tramadol. Risk of seizures may be increased in patients with epilepsy, a history of seizures, head trauma, metabolic disorders, alcohol or drug withdrawal, or infections of the central nervous system.(1) The risk for seizures may also be increased in patients receiving more than the upper daily dose limit of tramadol, or in patients taking additional medications which lower the seizure threshold.(1) PATIENT MANAGEMENT: Evaluate the patient for predisposing factors (other drugs, diseases or conditions) which may further increase the risk for serotonin syndrome or seizures. When possible and clinically appropriate, change to an alternative analgesic or antibiotic, particularly when predisposing factors are present. If concomitant therapy is necessary, monitor patient for signs of serotonin toxicity (e.g. tremor, agitation, diaphoresis, hyperreflexia, clonus, tachycardia, hyperthermia, muscle rigidity) or seizures, especially after tramadol dose increases. Manufacturer prescribing recommendations: The US manufacturer of tramadol states that tramadol should be used with caution in patients taking monoamine oxidase inhibitors.(1) In contrast, an Australian manufacturer of tramadol states that it is contraindicated in patients who are currently receiving monoamine oxidase inhibitors or who have received them in the previous 14 days.(2) The US manufacturer of linezolid does not have specific recommendations regarding concurrent treatment with tramadol but does state that linezolid should not be used in patients receiving serotonergic drugs (e.g. SSRIs, TCAs, meperidine) unless clinically appropriate and patients are carefully observed for signs and symptoms of serotonin syndrome.(3) DISCUSSION: Tramadol and its M1 metabolite are pharmacologically active. Tramadol inhibits the reuptake of norepinephrine and serotonin with minimal opioid receptor binding. The active M1 metabolite has 200 times greater binding affinity for the mu-opioid receptor than tramadol and is 6 times more potent in producing analgesia.(1) CYP P-450-2D6 converts tramadol to M1.(1,5) A study in surgery patients included 2D6 EM patients who received concomitant treatment with tramadol and 2D6 inhibitors. Levels of the M1 metabolite were decreased by 80-90% compared with EM patients not taking 2D6 inhibitors. Authors noted some EM patients were converted to the PM phenotype.(6) |
CONZIP, QDOLO, TRAMADOL HCL, TRAMADOL HCL ER, TRAMADOL HCL-ACETAMINOPHEN |
| Droxidopa/MAOIs SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: MAOIs inhibit the enzyme responsible for degradation of norepinephrine which is formed by droxidopa. CLINICAL EFFECTS: Concurrent use of MAOIs and droxidopa may result in increased effects of droxidopa, including headache, dizziness, nausea, and hypertensive crisis. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of droxidopa recommends concurrent use with non-selective MAOIs should be avoided. Selective MAO-B inhibitors, including rasagiline and selegiline, were used concurrently in clinical trials without an increase in risk of hypertensive crisis. If concurrent therapy is warranted, monitor patient closely for increases in blood pressure. DISCUSSION: Hypertensive reactions are possible as a result of this interaction. This interaction may be possible for several weeks after the discontinuation of a MAO inhibitor. Furazolidone and linezolid have been shown to inhibit MAO. Metaxalone is a weak inhibitor of MAO. |
DROXIDOPA, NORTHERA |
| Valbenazine/MAOIs SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Valbenazine inhibits the vesicular monoamine transporter 2 (VMAT2) that regulates monoamine uptake from the cytoplasm to the synaptic vesicle for storage and release. Concomitant use with MAOIs may increase the concentration of monoamine neurotransmitters in synapses. CLINICAL EFFECTS: The concurrent use of valbenazine with MAOIs may result in serotonin syndrome. Symptoms of serotonin syndrome may include tremor, agitation, diaphoresis, hyperreflexia, clonus, tachycardia, hyperthermia, and muscle rigidity. Concomitant use of MAOIs with valbenazine may reduce the effectiveness of valbenazine. PREDISPOSING FACTORS: Treatment with multiple medications which increase serotonin levels or with medications which inhibit the metabolism of serotonin increasing drugs are risk factors for serotonin syndrome. PATIENT MANAGEMENT: This combination should be avoided if possible. If concurrent therapy is warranted, patients should be monitored for adverse effects. If concurrent therapy is warranted, patients should be monitored for signs and symptoms of serotonin syndrome. Instruct patients to report muscle twitching, tremors, shivering and stiffness, fever, heavy sweating, heart palpitations, restlessness, confusion, agitation, trouble with coordination, or severe diarrhea. DISCUSSION: Concomitant use of valbenazine with MAOIs may increase the concentration of monoamine neurotransmitters in synapses. Metaxalone is a weak inhibitor of MAO. |
INGREZZA, INGREZZA INITIATION PK(TARDIV), INGREZZA SPRINKLE |
| Iobenguane I 123/Agents that Affect Catecholamines SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Many compounds that reduce catecholamine uptake or that deplete catecholamine stores may interfere with iobenguane uptake into cells.(1) CLINICAL EFFECTS: Compounds that reduce catecholamine uptake or that deplete catecholamine stores may interfere with imaging completed with iobenguane.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Discuss the use of agents that affect catecholamines. Discontinue drugs that reduce catecholamine uptake or deplete catecholamine stores prior to imaging with iobenguane. Before imaging with iobenguane, discontinue agents that affect catecholamines for at least 5 biological half-lives, as clinically tolerated.(1) DISCUSSION: Many agents may reduce catecholamine uptake or deplete catecholamine stores.(1) Examples include: - CNS stimulants or amphetamines (e.g. cocaine, methylphenidate, dextroamphetamine) - norepinephrine and dopamine reuptake inhibitors (e.g. phentermine) - norepinephrine and serotonin reuptake inhibitors (e.g. tramadol) - monoamine oxidase inhibitors (e.g. phenelzine, linezolid) - central monoamine depleting drugs (e.g. reserpine) - non-select beta adrenergic blocking drugs (e.g. labetalol) - alpha agonists or alpha/beta agonists (e.g. pseudoephedrine, phenylephrine, ephedrine, phenylpropanolamine, naphazoline) - tricyclic antidepressants or norepinephrine reuptake inhibitors (e.g. amitriptyline, bupropion, duloxetine, mirtazapine, venlafaxine) - botanicals that may inhibit reuptake of norepinephrine, serotonin or dopamine (e.g. ephedra, ma huang, St. John's Wort, yohimbine) |
ADREVIEW |
| Tricyclic; Tetracyclic Agents; Carbamazepine/Linezolid SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Linezolid is a weak, reversible inhibitor of monoamine oxidase.(1) Tricyclic and tetracyclic compounds may sensitize post-synaptic receptors to amines that are accumulating extraneuronally as a result of MAO inhibition.(2) Carbamazepine is structurally related to the tricyclic antidepressants.(3) Similarity between cyclobenzaprine and tricyclics warrants consideration of tricyclic interactions for cyclobenzaprine.(4) Mirtazapine, a tetracyclic antidepressant, should also be considered for this interaction.(5) CLINICAL EFFECTS: Concurrent use with linezolid may result in a severe reaction including hyperpyrexia, convulsions, excitability, fluctuations in blood pressure, convulsions, grand mal seizures, serotonin syndrome, coma, and death.(1) Symptoms of serotonin syndrome may include tremor, agitation, diaphoresis, hyperreflexia, clonus, tachycardia, hyperthermia, and muscle rigidity.(6) PREDISPOSING FACTORS: High doses of tricyclics or tetracyclics, or concurrent use of multiple drugs which increase CNS serotonin levels may increase risk for serotonin syndrome. PATIENT MANAGEMENT: The manufacturers of the tricyclic antidepressants, carbamazepine, cyclobenzaprine and mirtazapine state that coadministration with MAO inhibitors is contraindicated. Concurrent linezolid is specifically contraindicated by the manufacturers of clomipramine, desipramine, mirtazapine, nortriptyline, and trimipramine.(1,3-5,7-12) The manufacturer of linezolid does not contraindicate the use of serotonergic agents but states that they should not be coadministered unless clinically appropriate and the patient is closely monitored.(1) This recommendation is consistent with the 2011 FDA Drug Safety Communication on linezolid and serotonergic psychiatric medications.(13,14) In non-emergency situations in patients maintained on tricyclics or tetracyclics when linezolid therapy is planned, discontinue the patient's tricyclic or tetracyclic at least 2 weeks in advance of linezolid therapy. In emergency situations in patients maintained on tricyclics or tetracyclics, weigh the availability and safety of alternatives to linezolid against the risk of serotonin syndrome. If linezolid therapy is required, the patient's tricyclic or tetracyclic should be immediately discontinued. Patients should be monitored for serotonin syndrome for 2 weeks or until 24 hours after the last dose of linezolid, whichever comes first. The patient's tricyclic or tetracyclic therapy may be resumed 24 hours after the last dose of linezolid.(13) Clinical studies have found a low incidence of serotonin syndrome in patients on concomitant linezolid and serotonergic agents, ranging from 0.24% to 4%, depending on the quality and size of the study. While linezolid-associated serotonin syndrome is potentially serious and fatal, if treated early, it is quickly reversible with discontinuation of offending agents and supportive care. Therefore, some authors suggest that use of serotonergic medications should not preclude the use of linezolid but that the clinical situation should be assessed. If concurrent use or use of linezolid without a washout is warranted, the patient should be closely monitored.(15-20) If concurrent therapy is warranted, patients should be monitored for signs and symptoms of serotonin syndrome. Instruct patients to report muscle twitching, tremors, shivering and stiffness, fever, heavy sweating, heart palpitations, restlessness, confusion, agitation, trouble with coordination, or severe diarrhea. DISCUSSION: It should be noted that if this interaction occurs, the consequences will be immediate and severe. Effects may continue to be seen for several days after discontinuing linezolid. The FDA FAERS contains reports of serotonin syndrome with the concurrent use of linezolid and citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, and venlafaxine. The risk of serotonin syndrome with other psychiatric drugs is unclear.(14) |
AMITRIPTYLINE HCL, AMOXAPINE, AMRIX, ANAFRANIL, CARBAMAZEPINE, CARBAMAZEPINE ER, CARBATROL, CHLORDIAZEPOXIDE-AMITRIPTYLINE, CLOMIPRAMINE HCL, CYCLOBENZAPRINE HCL, CYCLOBENZAPRINE HCL ER, CYCLOPAK, CYCLOTENS, DESIPRAMINE HCL, DOXEPIN HCL, EPITOL, EQUETRO, FEXMID, IMIPRAMINE HCL, IMIPRAMINE PAMOATE, MIRTAZAPINE, MIRTAZAPINE ANHYDROUS, NORPRAMIN, NORTRIPTYLINE HCL, PAMELOR, PERPHENAZINE-AMITRIPTYLINE, PROTRIPTYLINE HCL, REMERON, SILENOR, TEGRETOL, TEGRETOL XR, TRIMIPRAMINE MALEATE |
| Bupropion; Solriamfetol/Linezolid SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Bupropion and solriamfetol increase dopamine and norepinephrine concentrations via blockade of the dopamine and norepinephrine reuptake transporters.(1-4) Linezolid is a weak, nonselective monoamine oxidase inhibitor (MAOI) that blocks the metabolism of norepinephrine and dopamine, also leading to increased neuronal concentrations of norepinephrine and dopamine.(5) CLINICAL EFFECTS: The concurrent administration of bupropion or solriamfetol and linezolid may increase the risk for serotonin syndrome and/or severe hypertensive, or other adverse reactions, including mania, psychosis or agitation with bupropion, and headache, nausea, anorexia, or anxiety with solriamfetol.(1-2) Symptoms of serotonin syndrome may include tremor, agitation, diaphoresis, hyperreflexia, clonus, tachycardia, hyperthermia, and muscle rigidity. PREDISPOSING FACTORS: Patients with pre-existing hypertension may be more likely to experience treatment-emergent hypertension.(1) Patients with moderate to severe renal impairment may be at higher risk for increases in blood pressure and heart rate from solriamfetol due to prolonged drug exposure.(2) PATIENT MANAGEMENT: The US manufacturers of bupropion and solriamfetol state that concurrent use of bupropion or solriamfetol with a MAOI is contraindicated due to the risk for hypertensive reactions.(1,2) The manufacturer of linezolid does not contraindicate the use of serotonergic agents but states that they should not be coadministered unless clinically appropriate and the patient is closely monitored.(5) This recommendation is consistent with the 2011 FDA Drug Safety Communication on linezolid and serotonergic psychiatric medications.(6,7) In non-emergency situations in patients maintained on bupropion or solriamfetol when linezolid therapy is planned, discontinue the patient's bupropion or solriamfetol at least 2 weeks in advance of linezolid therapy.(1,6) In emergency situations in patients maintained on bupropion or solriamfetol, weigh the availability and safety of alternatives to linezolid against the risk of acute hypertension. If linezolid therapy is required, the patient's bupropion or solriamfetol should be immediately discontinued. Patients' blood pressure should be closely monitored for 2 weeks or until 24 hours after the last dose of linezolid, whichever comes first.(1,6) The patient's bupropion or solriamfetol therapy may be resumed 24 hours after the last dose of linezolid.(1,6) Clinical studies have found a low incidence of serotonin syndrome in patients on concomitant linezolid and serotonergic agents, ranging from 0.24% to 4%, depending on the quality and size of the study. While linezolid-associated serotonin syndrome is potentially serious and fatal, if treated early, it is quickly reversible with discontinuation of offending agents and supportive care. Therefore, some authors suggest that use of serotonergic medications should not preclude the use of linezolid but that the clinical situation should be assessed. If concurrent use of linezolid without a washout is warranted, the patient should be closely monitored.(8-13) If concurrent therapy is warranted, patients should be monitored for signs and symptoms of serotonin syndrome. Instruct patients to report muscle twitching, tremors, shivering and stiffness, fever, heavy sweating, heart palpitations, restlessness, confusion, agitation, trouble with coordination, or severe diarrhea. DISCUSSION: The US manufacturers of bupropion and solriamfetol state that concurrent use of bupropion or solriamfetol with a MAOI is contraindicated.(1,2) An FDA alert in July 2011(6) described the risk for serotonin syndrome when bupropion is used concurrently with linezolid. In October 2011 FDA updated these alerts, describing the risk for serotonin syndrome when MAOIs are combined with bupropion (and selected other psychiatric agents not associated with case reports of serotonin syndrome) as unclear.(7) Subsequent bupropion and solriamfetol prescribing information describes an increased risk for hypertensive reactions when co-prescribed with MAOIs.(1,2) |
APLENZIN, AUVELITY, BUPROPION HCL, BUPROPION HCL SR, BUPROPION XL, CONTRAVE, FORFIVO XL, SUNOSI, WELLBUTRIN SR, WELLBUTRIN XL |
| Buspirone; Dexfenfluramine; Fenfluramine/Linezolid SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Linezolid is a weak, reversible inhibitor of monoamine oxidase. Buspirone is a 5-HT1A and moderate D2 agonist, while fenfluramine is an agonist of 5HT-2. Combination of these agents may result an increase in endogenous serotonin and dopamine.(1-6) CLINICAL EFFECTS: Concurrent use of buspirone, dexfenfluramine or fenfluramine with linezolid may result in elevated blood pressure leading to hypertensive crisis.(1-3) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturers of buspirone and fenfluramine state that concurrent use of linezolid is contraindicated.(1,2) The manufacturer of linezolid does not contraindicate the use of serotonergic agents but states that they should not be coadministered unless clinically appropriate and the patient is closely monitored.(3) This recommendation is consistent with the 2011 FDA Drug Safety Communication on linezolid and serotonergic psychiatric medications.(8,9) In non-emergency situations in patients maintained on buspirone, dexfenfluramine or fenfluramine, when linezolid therapy is planned, discontinue the patient's buspirone, dexfenfluramine or fenfluramine at least 2 weeks in advance of linezolid therapy.(6) In emergency situations in patients maintained on buspirone, dexfenfluramine or fenfluramine, weigh the availability and safety of alternatives to linezolid against the risk of hypertensive crisis. If linezolid therapy is required, the patient's buspirone, dexfenfluramine or fenfluramine should be immediately discontinued. Patients should be monitored for hypertensive crisis for 2 weeks or until 24 hours after the last dose of linezolid, whichever comes first.(6) The patient's buspirone, dexfenfluramine or fenfluramine therapy may be resumed 24 hours after the last dose of linezolid.(6) If concurrent therapy is warranted, patients should be monitored closely for hypertensive crisis. DISCUSSION: Several cases of elevated blood pressure have been reported in patients receiving MAOIs who were given buspirone.(1) No adverse sequelae have been reported in these patients. |
BUSPIRONE HCL, FINTEPLA |
| Fentanyl; Levomethadone; Methadone/Linezolid SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Fentanyl, levomethadone, and methadone may inhibit neuronal reuptake of serotonin. Linezolid increases neuronal serotonin concentration via inhibition of monoamine oxidase. CLINICAL EFFECTS: The concurrent use of fentanyl and methadone with MAOIs has been associated with serotonin syndrome.(1-4) Levomethadone is an enantiomer of methadone.(5) Symptoms of serotonin syndrome may include tremor, agitation, diaphoresis, hyperreflexia, clonus, tachycardia, hyperthermia, and muscle rigidity. PREDISPOSING FACTORS: Higher opioid concentrations as may occur due to inhibition of opioid clearance, patient specific genomic factors (e.g. poor metabolizer status for a specific P450 enzyme), or high opioid dosage may increase the risk for a severe interaction. PATIENT MANAGEMENT: Recommendations regarding concomitant use of MAOIs like linezolid with fentanyl, levomethadone, and methadone vary in different regions. In general, the combination of linezolid with these opioids is not recommended.(1-9) Some regions make stronger recommendations for certain agents. In Australia, fentanyl and methadone are contraindicated with MAOIs.(6-8) In the UK, methadone is contraindicated with MAOIs.(9) In Sweden, levomethadone is contraindicated with MAOIs.(5) The US manufacturer of linezolid does not contraindicate the use of serotonergic agents but states that they should not be coadministered unless clinically appropriate and the patient is closely monitored.(10) Clinical studies have found a low incidence of serotonin syndrome in patients on concomitant linezolid and serotonergic agents, ranging from 0.24% to 4%, depending on the quality and size of the study. While linezolid-associated serotonin syndrome is potentially serious and fatal, if treated early, it is quickly reversible with discontinuation of offending agents and supportive care. Therefore, some authors suggest that use of serotonergic medications should not preclude the use of linezolid but that the clinical situation should be assessed. If concurrent use or use of linezolid without a washout is warranted, the patient should be closely monitored.(11-16) If concurrent therapy is warranted, patients should be monitored for signs and symptoms of serotonin syndrome. Instruct patients to report muscle twitching, tremors, shivering and stiffness, fever, heavy sweating, heart palpitations, restlessness, confusion, agitation, trouble with coordination, or severe diarrhea. DISCUSSION: The interaction between another opioid, meperidine, and MAOIs has been well documented.(17,18) There are two reports of potential interactions between MAOIs and dextromethorphan.(19,20) At least one fatality has been reported from the use of fentanyl during surgery in a patient receiving an MAOI.(21) FDA performed a search of its adverse event database for cases of serotonin syndrome with selected opiates for the period of January 1, 1969 to June 12, 2013; five cases were associated with methadone use during this 43 year period.(22) |
DISKETS, FENTANYL, FENTANYL CITRATE, FENTANYL CITRATE-0.9% NACL, FENTANYL CITRATE-D5W, FENTANYL CITRATE-STERILE WATER, FENTANYL CITRATE-WATER, FENTANYL-BUPIVACAINE-0.9% NACL, FENTANYL-BUPIVACAINE-NACL, FENTANYL-ROPIVACAINE-0.9% NACL, METHADONE HCL, METHADONE HCL-0.9% NACL, METHADONE HCL-NACL, METHADONE INTENSOL, METHADOSE |
| Sodium Iodide I 131/Myelosuppressives; Immunomodulators SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Sodium iodide I 131 can cause depression of the hematopoetic system. Myelosuppressives and immunomodulators also suppress the immune system.(1) CLINICAL EFFECTS: Concurrent use of sodium iodide I 131 with agents that cause bone marrow depression, including myelosuppressives or immunomodulators, may result in an enhanced risk of hematologic disorders, including anemia, blood dyscrasias, bone marrow depression, leukopenia, and thrombocytopenia. Bone marrow depression may increase the risk of serious infections and bleeding.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of sodium iodide I 131 states that concurrent use with bone marrow depressants may enhance the depression of the hematopoetic system caused by large doses of sodium iodide I 131.(1) Sodium iodide I 131 causes a dose-dependent bone marrow suppression, including neutropenia or thrombocytopenia, in the 3 to 5 weeks following administration. Patients may be at increased risk of infections or bleeding during this time. Monitor complete blood counts within one month of therapy. If results indicate leukopenia or thrombocytopenia, dosimetry should be used to determine a safe sodium iodide I 131 activity.(1) DISCUSSION: Hematologic disorders including death have been reported with sodium iodide I 131. The most common hematologic disorders reported include anemia, blood dyscrasias, bone marrow depression, leukopenia, and thrombocytopenia.(1) |
HICON, SODIUM IODIDE I-131 |
| Fecal Microbiota Spores/Antibiotics SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Fecal microbiota spores is a suspension of live bacterial spores, which may be compromised by concurrent use of antibiotics.(1) CLINICAL EFFECTS: Antibiotics may decrease the effectiveness of fecal microbiota spores.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Antibiotics should not be used concurrently with fecal microbiota spores. Antibacterial treatment should be completed for 2 to 4 days before initiating treatment with fecal microbiota spores.(1) DISCUSSION: Antibiotics may compromise the effectiveness of fecal microbiota spores. |
VOWST |
| Foslevodopa; Levodopa/Linezolid SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Linezolid is a weak, nonselective monoamine oxidase inhibitor (MAOI) that blocks the metabolism of dopamine and norepinephrine, which are formed by levodopa. Also, storage and release of dopamine and norepinephrine is increased.(1-2) Foslevodopa is a prodrug of levodopa. CLINICAL EFFECTS: Concurrent use of linezolid may result in increased effects of levodopa, including tremor, hypertensive crisis, and postural hypotension. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of carbidopa/levodopa states that the concurrent use of nonselective MAO inhibitors is contraindicated.(1) The Canadian manufacturer of foslevodopa/foscarbidopa states that concurrent use of nonselective MAO inhibitors and selective MAO type A inhibitors is contraindicated. MAO inhibitors should be stopped at least 2 weeks prior to initiation of foslevodopa/foscarbidopa therapy.(2) The manufacturer of linezolid does not contraindicate the use of adrenergic agents but states that they should not be coadministered unless the patient is closely monitored for potential increases in blood pressure.(3) If concurrent therapy is warranted, patients should be monitored closely for hypertensive crisis. The addition of a decarboxylase inhibitor to the combination of a non-selective MAO inhibitor and levodopa may minimize risk of adverse effects. Phentolamine has been effective in treating hypertension caused by this interaction. DISCUSSION: Hypertensive reactions, flushing, and palpitations have been reported as a result of the interaction between levodopa and other MAO inhibitors. In a case report, an 89-year-old female with COPD, sick sinus syndrome, atrial fibrillation, hypertension, history of CVA, ischemic colitis, and Parkinson's disease on many medications including carbidopa-levodopa for 6 years took linezolid for 8 days and developed seizure-like activity. The patient was afebrile and normotensive, but was tachycardic, lethargic, agitated, and exhibited clonus on examination 2 days after linezolid was discontinued.(4) |
CARBIDOPA-LEVODOPA, CARBIDOPA-LEVODOPA ER, CREXONT, DHIVY, DUOPA, INBRIJA, LEVODOPA, RYTARY, SINEMET, VYALEV |
| Carbidopa-Levodopa-Entacapone/Linezolid SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Since monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT) are the two major enzymes responsible for the metabolism of catecholamines, the combination of carbidopa-levodopa-entacapone and a non-selective MAOI may inhibit the majority of catecholamine metabolism pathways.(1-5) Linezolid is a weak, nonselective monoamine oxidase inhibitor (MAOI).(6) CLINICAL EFFECTS: Concurrent administration of carbidopa-levodopa-entacapone with linezolid may result in elevated levels of catecholamines, which may result in elevated heart rate and blood pressure.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of carbidopa-levodopa-entacapone states that concomitant use with a non-selective MAOI is contraindicated. Nonselective MAOI should be discontinued at least 2 weeks prior to initiating therapy with carbidopa-levodopa-entacapone.(1) The US manufacturer of carbidopa-levodopa states that the concurrent use of nonselective MAO inhibitors is contraindicated. Carbidopa-levodopa may be administered with recommended dosages of selective MAO-B inhibitors.(2) The Canadian(5) and UK(3) manufacturers of entacapone state that concomitant use of either a non-selective MAOI or a selective MAO-A inhibitor with a selective MAO-B inhibitor with entacapone is contraindicated. Nonselective MAOI should be discontinued at least 2 weeks prior to initiating entacapone therapy. The manufacturer of linezolid does not contraindicate the use of adrenergic agents but states that they should not be coadministered unless the patient is closely monitored for potential increases in blood pressure.(6) If concurrent therapy is warranted, patients should be monitored closely for hypertensive crisis. The addition of a decarboxylase inhibitor to the combination of a non-selective MAO inhibitor and levodopa may minimize risk of adverse effects. Phentolamine has been effective in treating hypertension caused by this interaction. DISCUSSION: Hypertensive reactions, flushing, and palpitations have been reported as a result of the interaction between levodopa and other MAO inhibitors. Monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT) are the two major enzymes systems involved in the metabolism of catecholamines. Therefore, theoretically, the combination of either entacapone, tolcapone, or opicapone with a non-selective MAO inhibitor will result in inhibition of the majority of catecholamine metabolism pathways.(1-5) In a case report, an 89-year-old female with COPD, sick sinus syndrome, atrial fibrillation, hypertension, history of CVA, ischemic colitis, and Parkinson's disease on many medications including carbidopa-levodopa for 6 years took linezolid for 8 days and developed seizure-like activity. The patient was afebrile and normotensive, but was tachycardic, lethargic, agitated, and exhibited clonus on examination 2 days after linezolid was discontinued.(7) |
CARBIDOPA-LEVODOPA-ENTACAPONE |
| Selected 5-HT1D Agonists/Linezolid SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Monoamine oxidase inhibitors (MAOIs) inhibit the metabolism of rizatriptan,(1) sumatriptan,(2-9) and zolmitriptan.(10) Linezolid is a weak, reversible, nonselective MAOI.(12) CLINICAL EFFECTS: Concurrent use of linezolid may result in increased levels and effects of rizatriptan, sumatriptan or zolmitriptan.(1-11) PREDISPOSING FACTORS: Patients with a history of cardiovascular disease, e.g. coronary artery disease (CAD), transient ischemic attack (TIA), stroke, cardiac conduction disorders or poorly controlled hypertension, are not considered candidates for 5-HT1D agonist therapy and would be at greater risk for toxicity due to this interaction. PATIENT MANAGEMENT: Concurrent administration of rizatriptan and a MAOI or administration of rizatriptan within two weeks of the discontinuation of a MAOI is contraindicated according to product labeling for rizatriptan.(1) Concurrent administration of sumatriptan and a MAOI within two weeks of the discontinuation of a MAOI is contraindicated according to the Australian, Canada, UK, and US product labeling for these agents.(2-9) Concurrent administration of zolmitriptan and a MAO-A Inhibitor or the administration of zolmitriptan within two weeks of discontinuation of a MAO-A Inhibitor is contraindicated according to US labeling.(10) The UK manufacturer states that a maximum of 7.5 mg of zolmitriptan should be administered within 24 hours of a MAO-A inhibitor.(11) The manufacturer of linezolid does not contraindicated the use of 5-HT1D agonists but states that they should not be coadministered unless clinically appropriate and patients are carefully observed for signs and symptoms of serotonin syndrome.(12) Eletriptan and frovatriptan are not metabolized by MAO-A(13,14) and may be an alternative in patients who require treatment with linezolid. DISCUSSION: The combination of linezolid and 5-HT1D agonists has not been studied. Other MAOIs have been reported to interact with 5-HT1D agonists. Rizatriptan is metabolized by the 'A' subtype of monoamine oxidase. In a study with 12 subjects, the concurrent administration of rizatriptan (10 mg) with moclobemide (450 mg daily, a selective, reversible MAO-A inhibitor) resulted in increases in the rizatriptan area-under-curve (AUC) and maximum concentration (Cmax) by 119% and 41%, respectively. The AUC of the active metabolite, N-monodesmethyl rizatriptan, increased over 400%. Plasma concentrations of rizatriptan may be increased by selective MAO-A inhibitors or by nonselective MAO-A&B inhibitors, although the interaction is expected to be greater with selective MAO-A inhibitors. The manufacturer also states that no interaction is expected with selective MAO-B inhibitors.(1) Sumatriptan oral bioavailability is approximately 15%, primarily due to presystemic clearance by MAO-A in the gut and liver. A small study found an approximately 7-fold increase in systemic sumatriptan exposure when an MAO-A inhibitor was given prior to a 25 mg oral dose of sumatriptan.(4) In another study, pretreatment with an MAO-A inhibitor prior to administration of injectable sumatriptan resulted in a 2-fold increase in sumatriptan AUC and a 40% increase in elimination half-life.(8) Pretreatment with a MAO-B inhibitor did not produce any significant changes in sumatriptan pharmacokinetics. The effect of a MAOI on nasal sumatriptan systemic absorption is expected to be less than that seen with oral sumatriptan but greater than that seen with injectable sumatriptan.(6) Administration of moclobemide, a MAO-A inhibitor, for one week (150 mg twice daily) resulted in a 25% increase in zolmitriptan AUC and a three-fold increase in Cmax and AUC for zolmitriptan's active N-desmethyl metabolite.(10,11) |
IMITREX, MAXALT, MAXALT MLT, MIGRANOW, ONZETRA XSAIL, RIZATRIPTAN, SUMATRIPTAN, SUMATRIPTAN SUCC-NAPROXEN SOD, SUMATRIPTAN SUCCINATE, SYMBRAVO, TOSYMRA, TREXIMET, ZEMBRACE SYMTOUCH, ZOLMITRIPTAN, ZOLMITRIPTAN ODT, ZOMIG |
There are 4 moderate interactions.
The clinician should assess the patient’s characteristics and take action as needed. Actions required for moderate interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration.
| Drug Interaction | Drug Names |
|---|---|
| Selected Antidiabetics/MAOIs SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The exact mechanism by which MAO inhibitors affect carbohydrate metabolism and subsequent enhancement of the hypoglycemic action of insulin is not clear. The adrenergic response to hypoglycemia may be blocked by insulin release caused by MAOI's. In vitro studies have shown that MAO inhibitors are capable of both potentiating and inhibiting insulin release, depending on their concentrations. Stimulation of glucose-mediated insulin secretion is believed to be related to the MAO inhibitory effects of the drugs. CLINICAL EFFECTS: The hypoglycemic response to both insulin and glucose lowering agents including alpha glucosidase inhibitors, meglitinides, and sulfonylurea may be increased. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Concurrent MAO inhibitor therapy for depression in a diabetic patient will often require reduction in dosage of the hypoglycemic agent because of enhanced hypoglycemic effects. Since the extent of the reaction is highly unpredictable, any diabetic patients receiving MAO inhibitors should be monitored for possible excessive hypoglycemia. DISCUSSION: This interaction is likely to occur. The interaction between MAOIs and insulin is well documented. Additional documentation is necessary to confirm the potential interaction of MAOI's with other glucose lowering agents including alpha glucosidase inhibitors, meglitinides, and sulfonylureas but is expected to occur based on pharmacologic similarity. It may take several weeks for the full hypoglycemic effect of the MAOI to occur. Conversely, it may take several weeks for the effect to dissipate after stopping the MAOI. Furazolidone is known to be a monoamine oxidase inhibitor. Methylene blue, when administered intravenously, has been shown to reach sufficient concentrations to be a potent inhibitor of MAO-A. Metaxalone is a weak inhibitor of MAO. |
ACARBOSE, ADMELOG, ADMELOG SOLOSTAR, AFREZZA, APIDRA, APIDRA SOLOSTAR, BASAGLAR KWIKPEN U-100, BASAGLAR TEMPO PEN U-100, DUETACT, FIASP, FIASP FLEXTOUCH, FIASP PENFILL, FIASP PUMPCART, GLIMEPIRIDE, GLIPIZIDE, GLIPIZIDE ER, GLIPIZIDE XL, GLIPIZIDE-METFORMIN, GLUCOTROL XL, GLYBURIDE, GLYBURIDE MICRONIZED, GLYBURIDE-METFORMIN HCL, HUMALOG, HUMALOG JUNIOR KWIKPEN, HUMALOG KWIKPEN U-100, HUMALOG KWIKPEN U-200, HUMALOG MIX 50-50 KWIKPEN, HUMALOG MIX 75-25, HUMALOG MIX 75-25 KWIKPEN, HUMALOG TEMPO PEN U-100, HUMULIN R U-500, HUMULIN R U-500 KWIKPEN, INSULIN ASPART, INSULIN ASPART FLEXPEN, INSULIN ASPART PENFILL, INSULIN ASPART PROT MIX 70-30, INSULIN DEGLUDEC, INSULIN DEGLUDEC PEN (U-100), INSULIN DEGLUDEC PEN (U-200), INSULIN GLARGINE MAX SOLOSTAR, INSULIN GLARGINE SOLOSTAR, INSULIN GLARGINE-YFGN, INSULIN LISPRO, INSULIN LISPRO JUNIOR KWIKPEN, INSULIN LISPRO KWIKPEN U-100, INSULIN LISPRO PROTAMINE MIX, LANTUS, LANTUS SOLOSTAR, LYUMJEV, LYUMJEV KWIKPEN U-100, LYUMJEV KWIKPEN U-200, LYUMJEV TEMPO PEN U-100, MIGLITOL, MYXREDLIN, NATEGLINIDE, NOVOLOG, NOVOLOG FLEXPEN, NOVOLOG MIX 70-30, NOVOLOG MIX 70-30 FLEXPEN, NOVOLOG PENFILL, PIOGLITAZONE-GLIMEPIRIDE, PRECOSE, REZVOGLAR KWIKPEN, SEMGLEE (YFGN), SEMGLEE (YFGN) PEN, SOLIQUA 100-33, TOUJEO MAX SOLOSTAR, TOUJEO SOLOSTAR, TRESIBA, TRESIBA FLEXTOUCH U-100, TRESIBA FLEXTOUCH U-200, XULTOPHY 100-3.6 |
| Linezolid/Rifampin SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The exact mechanism is unknown, but may involve induction of linezolid metabolism by CYP2D6(1) or induction of linezolid excretion by P-glycoprotein.(2,3) CLINICAL EFFECTS: Concurrent or recent use of rifampin may result in decreased levels and effectiveness of linezolid.(1-3) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Monitor linezolid levels and clinical response in patients who are receiving concurrent rifampin or who have recently discontinued rifampin. The dosage of linezolid may need to be adjusted. DISCUSSION: In a study in 16 healthy males, pretreatment with oral rifampin (600 mg daily for 8 days) decreased the maximum concentration (Cmax) and area-under-curve (AUC) of a single oral dose of linezolid by 21% and 32%, respectively. when compared to the administration of linezolid alone.(1) In a study in 8 healthy males, administration of a single intravenous dose of rifampin (600 mg) decreased the plasma levels of a single intravenous dose of linezolid (600 mg) by 10% at 6 hours post-dose, 20% at 9 hours post-dose, and by 35% at 12 hours post-dose when compared to the administration of linezolid alone.(2) In a case report, low linezolid levels and slow clinical response were noted in a 31 year-old female undergoing concurrent treatment with linezolid and rifampin.(3) |
RIFADIN, RIFAMPIN |
| Trazodone (Less Than or Equal To 100 mg)/MAOIs SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Trazodone is primarily an inhibitor of 5HT2A serotonin receptors, H1 histamine, and alpha-1 receptors.(1) Inhibition of serotonin reuptake is weak and estimated to be 1/20th of 5HT2A inhibiting activity. Metabolism of trazodone leads to formation of an active metabolite, m-chlorophenylpiperazine (mCPP) which is an agonist at a variety of serotonin receptors.(1) MCPP is further converted to an inactive metabolite by CYP2D6.(3) MAO Inhibitors increase serotonin levels via inhibition of its metabolism. CLINICAL EFFECTS: Concurrent administration could increase the risk for serotonin syndrome. Symptoms of serotonin syndrome may include tremor, agitation, diaphoresis, hyperreflexia, clonus, tachycardia, hyperthermia, and muscle rigidity.(2) PREDISPOSING FACTORS: Serotonin syndrome risk is dose-related. Higher systemic concentrations of trazodone, mCPP or more potent MAO inhibitors would be predicted to increase risk for serotonin toxicity.(2) Concomitant therapy with multiple agents which increase brain serotonin concentrations may also increase risk for serotonin syndrome.(2) Concomitant treatment with inhibitors of CYP2D6 (e.g. bupropion, cinacalcet, dacomitinib, fluoxetine, paroxetine, quinidine, or systemic terbinafine)(4) may increase mCPP concentration, increasing the risk for serotonin toxicity. Patients who are poor metabolizers at CYP2D6 would be expected to have higher mCPP concentrations compared with extensive metabolizers. PATIENT MANAGEMENT: It would be prudent to seek trazodone alternatives in patients who require treatment with a MAOI and a strong inhibitor of CYP2D6 (e.g. bupropion, cinacalcet, dacomitinib, fluoxetine, paroxetine, quinidine, systemic terbinafine) or another serotonergic agent. Assess patient for additional predisposing risk factors then change/adjust medications or monitor accordingly. To minimize accumulation of mCPP, limit dosage of trazodone to less than or equal to 100 mg daily. Assure careful monitoring for signs and symptoms of serotonin syndrome when the dose of either agent is increased. If concurrent therapy is warranted, patients should be monitored for signs and symptoms of serotonin syndrome. Instruct patients to report muscle twitching, tremors, shivering and stiffness, fever, heavy sweating, heart palpitations, restlessness, confusion, agitation, trouble with coordination, or severe diarrhea. DISCUSSION: In a case report, a 37 year-old male developed serotonin syndrome following the addition of linezolid to citalopram and trazodone.(5) In a case report, a patient developed serotonin syndrome with concurrent trazodone, isocarboxazid, and methylphenidate.(6) In a case report, a patient developed serotonin syndrome following the abrupt replacement of trazodone with moclobemide.(7) An open study evaluated the efficacy and safety of low dose trazodone for the treatment of MAOI-associated insomnia. Twenty-one patients successfully treated with a MAOI for unipolar or bipolar depression but with persistent insomnia participated in the study. Trazodone 25 to 75 mg was given at bedtime. Patients with a fair or good response to trazodone were monitored for a minimum of 4 months to assess efficacy and safety of treatment. Eleven patients had a resolution of insomnia, 9 had a partial response, and one had no benefit. Side effects noted were nausea in 2 patients, persistent morning grogginess in one patient and memory problems in one patient.(8) A small double-blind placebo controlled study evaluated the efficacy and safety of trazodone 50 mg to treat insomnia due to brofaromine, a MAO-A inhibitor. All seven patients had responded to brofaromine and had been in remission for at least 3 months. Three patients received trazodone on week 1, followed by placebo on week 2, while the other 4 patients received placebo on week 1 and trazodone on week 2. At the end of the trial 4 patients elected to continue trazodone and 3 patients discontinued therapy due to adverse effects (nausea, constipation, vertigo, dry mouth, palpitations, or heartburn). The authors stated no patients had symptoms suggestive of serotonin syndrome.(9) Metaxalone is a weak inhibitor of MAO.(10,11) The FDA AERS contains reports of serotonin syndrome with the concurrent use of linezolid and citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, and venlafaxine as well as reports of serotonin syndrome with concurrent injectable methylene blue and citalopram, clomipramine, escitalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, and venlafaxine. The risk of serotonin syndrome with other psychiatric drugs is unclear.(12,13) |
TRAZODONE HCL |
| Selected Anticoagulants (Vitamin K antagonists)/Linezolid SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The exact mechanism is unknown. Linezolid may interfere with vitamin K-producing gut flora. CLINICAL EFFECTS: Concurrent use of linezolid may increase may result in increased anticoagulant effects with possible bleeding. PREDISPOSING FACTORS: High anticoagulant doses, hepatic or renal impairment, and poor nutrition may increase the risk of bleeding. The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g., thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g., NSAIDs). PATIENT MANAGEMENT: Consider using an alternative antibiotic. If concurrent therapy is warranted, monitor prothrombin activity and adjust the anticoagulant dosage accordingly. Monitor patients for signs of blood loss, including decreased hemoglobin, hematocrit, fecal occult blood, and decreased blood pressure and promptly evaluate patients with any symptoms. When applicable, perform agent-specific laboratory test (e.g., INR, aPTT) to monitor efficacy and safety of anticoagulation. Discontinue anticoagulation in patients with active pathologic bleeding. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling. The time of highest risk for a coumarin-type drug interaction is when the precipitant drug is initiated or discontinued. Contact the prescriber before initiating, altering the dose or discontinuing either drug. DISCUSSION: A retrospective study examined 16 patients with left ventricular assist system for severe heart failure taking warfarin (goal INR 3-4) and started on linezolid. INR increased non-significantly (from 3.74 to 4.06) but warfarin dose decreased (3.23 mg/day to 2.69 mg/day (p=0.001)) and INR/warfarin dose ratio increased significantly. Patients with fever (temperature > 38 degrees C), potentially interacting medications, on liquid diet or TPN or with decreased food intake were excluded.(1) A retrospective study of 6 patients on warfarin and linezolid after cardiovascular surgery found that INR increased from 1.62 to 3 on day 4-5 of concomitant therapy then decreased by day 10 after dose reduction or withdrawal of warfarin. Patients on potentially interacting medications were excluded.(2) In a case series, 4 patients who were 2-5 days post aortic or mitral valve replacement and started on acenocoumarol and linezolid all experienced increased INR ranging from >5 to >10.(3) A case report describes a patient stable on acenocoumarol for a prosthetic aortic valve who developed INR of 5.6 three days after starting linezolid.(4) Another case report describes a patient who experienced INR of 5.2 three days after concomitant therapy with acenocoumarol and linezolid.(5) |
ANISINDIONE, DICUMAROL, JANTOVEN, PHENINDIONE, WARFARIN SODIUM |
The following contraindication information is available for LINEZOLID (linezolid):
Drug contraindication overview.
Linezolid is contraindicated in patients with known hypersensitivity to linezolid or any ingredient in the formulation. Linezolid should not be used in patients who are receiving (or have received within the last 2 weeks) drugs that inhibit monoamine oxidase (MAO) A or B, including MAO inhibitor antidepressants (e.g., isocarboxazid, phenelzine). (See Monoamine Oxidase Inhibitors under Drug Interactions.)
Linezolid is contraindicated in patients with known hypersensitivity to linezolid or any ingredient in the formulation. Linezolid should not be used in patients who are receiving (or have received within the last 2 weeks) drugs that inhibit monoamine oxidase (MAO) A or B, including MAO inhibitor antidepressants (e.g., isocarboxazid, phenelzine). (See Monoamine Oxidase Inhibitors under Drug Interactions.)
There are 1 contraindications.
Absolute contraindication.
| Contraindication List |
|---|
| Serotonin syndrome |
There are 5 severe contraindications.
Adequate patient monitoring is recommended for safer drug use.
| Severe List |
|---|
| Carcinoid syndrome |
| Clostridioides difficile infection |
| Hypertension |
| Pheochromocytoma |
| Thyrotoxicosis |
There are 7 moderate contraindications.
Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.
| Moderate List |
|---|
| Anemia |
| Bone marrow depression |
| Hyponatremia |
| Leukopenia |
| Seizure disorder |
| SIADH syndrome |
| Thrombocytopenic disorder |
The following adverse reaction information is available for LINEZOLID (linezolid):
Adverse reaction overview.
Adverse effects occurring in 2% or more of adults receiving linezolid include GI effects (diarrhea, nausea, vomiting), headache, anemia, rash, and dizziness. Adverse effects reported in 2% or more of pediatric patients receiving linezolid in clinical studies include GI effects (diarrhea, nausea, vomiting, localized or generalized abdominal pain, loose stools), headache, anemia, and thrombocytopenia.
Adverse effects occurring in 2% or more of adults receiving linezolid include GI effects (diarrhea, nausea, vomiting), headache, anemia, rash, and dizziness. Adverse effects reported in 2% or more of pediatric patients receiving linezolid in clinical studies include GI effects (diarrhea, nausea, vomiting, localized or generalized abdominal pain, loose stools), headache, anemia, and thrombocytopenia.
There are 36 severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Anemia Diarrhea Headache disorder Vomiting |
Abnormal hepatic function tests Oral candidiasis Skin rash Thrombocytopenic disorder |
| Rare/Very Rare |
|---|
|
Anaphylaxis Angioedema Bone marrow depression Bullous dermatitis Clostridioides difficile infection Eosinophilia Fungal infection Gastrointestinal hemorrhage Heart failure Hypersensitivity angiitis Hypertension Hypoglycemic disorder Hypokalemia Hyponatremia Lactic acidosis Leukopenia Obstructive hyperbilirubinemia Optic neuropathy Pancytopenia Peripheral neuropathy Pure red cell aplasia Rhabdomyolysis Seizure disorder Serotonin syndrome SIADH syndrome Sideroblastic anemia Stevens-johnson syndrome Toxic epidermal necrolysis |
There are 18 less severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Nausea |
Dizziness Dysgeusia Loose stools Vulvovaginal candidiasis |
| Rare/Very Rare |
|---|
|
Abdominal pain with cramps Acute cognitive impairment Anorexia Dental discoloration Drowsy Dyspepsia Dyspnea Ecchymosis Fever Flatulence Pruritus of skin Tongue discoloration Vertigo |
The following precautions are available for LINEZOLID (linezolid):
Safety and efficacy of linezolid for the treatment of community-acquired pneumonia (CAP), nosocomial pneumonia, complicated skin and skin structure infections, and vancomycin-resistant Enterococcus faecium infections in pediatric patients are supported by adequate and well-controlled studies in adults, pharmacokinetic studies in pediatric patients, and additional data from a comparator-controlled study of gram-positive infections in neonates and children through 11 years of age. Safety and efficacy of the drug for the treatment of CAP in pediatric patients also is supported by evidence from an uncontrolled study in patients 8 months through 12 years of age. Safety and efficacy of linezolid for the treatment of uncomplicated skin and skin structure infections in pediatric patients have been established in a comparator-controlled study in pediatric patients 5-17 years of age.
While some pharmacokinetic parameters (i.e., peak plasma concentration, volume of distribution) are similar in children of all ages, linezolid clearance varies with age. Excluding neonates younger than 1 week of age, clearance is most rapid in the youngest age groups (i.e., those 7 days to 11 years of age); as children age, the clearance of linezolid decreases and clearance values in adolescents approach those observed in adults. Systemic exposure (mean daily area under the plasma concentration-time curve (AUC)) in pediatric patients younger than 12 years of age receiving linezolid every 8 hours generally is similar to that in adults and adolescents receiving the drug every 12 hours.
There is wider intraindividual variability in linezolid clearance and in systemic drug exposure in all pediatric age groups relative to adults. The manufacturer states that linezolid is not recommended for empiric treatment of CNS infections in pediatric patients; therapeutic concentrations of the drug were not consistently achieved or maintained in CSF of pediatric patients with ventriculoperitoneal shunts. Inadequate systemic exposure, site and severity of infection, and underlying medical conditions should be considered in children with a suboptimal response to linezolid, especially those with infections caused by gram-positive bacteria that have minimum inhibitory concentrations (MICs) of 4 mcg/mL.
Contraindicated
Severe Precaution
Management or Monitoring Precaution
While some pharmacokinetic parameters (i.e., peak plasma concentration, volume of distribution) are similar in children of all ages, linezolid clearance varies with age. Excluding neonates younger than 1 week of age, clearance is most rapid in the youngest age groups (i.e., those 7 days to 11 years of age); as children age, the clearance of linezolid decreases and clearance values in adolescents approach those observed in adults. Systemic exposure (mean daily area under the plasma concentration-time curve (AUC)) in pediatric patients younger than 12 years of age receiving linezolid every 8 hours generally is similar to that in adults and adolescents receiving the drug every 12 hours.
There is wider intraindividual variability in linezolid clearance and in systemic drug exposure in all pediatric age groups relative to adults. The manufacturer states that linezolid is not recommended for empiric treatment of CNS infections in pediatric patients; therapeutic concentrations of the drug were not consistently achieved or maintained in CSF of pediatric patients with ventriculoperitoneal shunts. Inadequate systemic exposure, site and severity of infection, and underlying medical conditions should be considered in children with a suboptimal response to linezolid, especially those with infections caused by gram-positive bacteria that have minimum inhibitory concentrations (MICs) of 4 mcg/mL.
Contraindicated
| None |
Severe Precaution
| None |
Management or Monitoring Precaution
| None |
Available data from published and postmarketing case reports regarding use of linezolid in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In studies in mice, rats, and rabbits, linezolid was not teratogenic; however, embryofetal toxicities were reported. These nonteratogenic effects included increased post-implantational embryo death, decreased fetal body weights, and increased incidence of costal cartilage fusion in mice; decreased fetal body weights, reduced ossification of sternebrae, and decreased survival of pups in rats; and reduced fetal body weight in rabbits.
Linezolid is distributed into human milk. It is not known whether the drug affects the breast-fed infant or affects milk production. Available data suggest that a breast-fed infant would receive approximately 6-9% of the recommended daily therapeutic infant dose (10 mg/kg every 8 hours).
The benefits of breast-feeding and the importance of linezolid to the woman should be considered along with the potential adverse effects on the breast-fed child from the drug or from the underlying maternal condition. If linezolid is used in a nursing woman, the manufacturer recommends that the breast-fed infant be monitored for diarrhea and vomiting since these are the most common adverse reactions reported in infants being treated with linezolid.
The benefits of breast-feeding and the importance of linezolid to the woman should be considered along with the potential adverse effects on the breast-fed child from the drug or from the underlying maternal condition. If linezolid is used in a nursing woman, the manufacturer recommends that the breast-fed infant be monitored for diarrhea and vomiting since these are the most common adverse reactions reported in infants being treated with linezolid.
No overall differences in safety, efficacy, or pharmacokinetics have been observed in geriatric adults 65 years of age or older compared with younger adults. Other clinical experience has not revealed age-related differences in response, but the possibility of greater sensitivity in some older patients cannot be ruled out.
The following prioritized warning is available for LINEZOLID (linezolid):
No warning message for this drug.
No warning message for this drug.
The following icd codes are available for LINEZOLID (linezolid)'s list of indications:
| Complicated skin and skin structure s. aureus infection | |
| B95.6 | Staphylococcus aureus as the cause of diseases classified elsewhere |
| B95.61 | Methicillin susceptible staphylococcus aureus infection as the cause of diseases classified elsewhere |
| B95.62 | Methicillin resistant staphylococcus aureus infection as the cause of diseases classified elsewhere |
| H00.03 | Abscess of eyelid |
| H00.031 | Abscess of right upper eyelid |
| H00.032 | Abscess of right lower eyelid |
| H00.033 | Abscess of eyelid right eye, unspecified eyelid |
| H00.034 | Abscess of left upper eyelid |
| H00.035 | Abscess of left lower eyelid |
| H00.036 | Abscess of eyelid left eye, unspecified eyelid |
| H00.039 | Abscess of eyelid unspecified eye, unspecified eyelid |
| H60.0 | Abscess of external ear |
| H60.00 | Abscess of external ear, unspecified ear |
| H60.01 | Abscess of right external ear |
| H60.02 | Abscess of left external ear |
| H60.03 | Abscess of external ear, bilateral |
| H60.1 | Cellulitis of external ear |
| H60.10 | Cellulitis of external ear, unspecified ear |
| H60.11 | Cellulitis of right external ear |
| H60.12 | Cellulitis of left external ear |
| H60.13 | Cellulitis of external ear, bilateral |
| J34.0 | Abscess, furuncle and carbuncle of nose |
| K61 | Abscess of anal and rectal regions |
| K61.0 | Anal abscess |
| K61.1 | Rectal abscess |
| K61.2 | Anorectal abscess |
| K61.3 | Ischiorectal abscess |
| K61.4 | Intrasphincteric abscess |
| L02 | Cutaneous abscess, furuncle and carbuncle |
| L02.0 | Cutaneous abscess, furuncle and carbuncle of face |
| L02.01 | Cutaneous abscess of face |
| L02.03 | Carbuncle of face |
| L02.1 | Cutaneous abscess, furuncle and carbuncle of neck |
| L02.11 | Cutaneous abscess of neck |
| L02.13 | Carbuncle of neck |
| L02.2 | Cutaneous abscess, furuncle and carbuncle of trunk |
| L02.21 | Cutaneous abscess of trunk |
| L02.211 | Cutaneous abscess of abdominal wall |
| L02.212 | Cutaneous abscess of back [any part, except buttock] |
| L02.213 | Cutaneous abscess of chest wall |
| L02.214 | Cutaneous abscess of groin |
| L02.215 | Cutaneous abscess of perineum |
| L02.216 | Cutaneous abscess of umbilicus |
| L02.219 | Cutaneous abscess of trunk, unspecified |
| L02.23 | Carbuncle of trunk |
| L02.231 | Carbuncle of abdominal wall |
| L02.232 | Carbuncle of back [any part, except buttock] |
| L02.233 | Carbuncle of chest wall |
| L02.234 | Carbuncle of groin |
| L02.235 | Carbuncle of perineum |
| L02.236 | Carbuncle of umbilicus |
| L02.239 | Carbuncle of trunk, unspecified |
| L02.3 | Cutaneous abscess, furuncle and carbuncle of buttock |
| L02.31 | Cutaneous abscess of buttock |
| L02.33 | Carbuncle of buttock |
| L02.4 | Cutaneous abscess, furuncle and carbuncle of limb |
| L02.41 | Cutaneous abscess of limb |
| L02.411 | Cutaneous abscess of right axilla |
| L02.412 | Cutaneous abscess of left axilla |
| L02.413 | Cutaneous abscess of right upper limb |
| L02.414 | Cutaneous abscess of left upper limb |
| L02.415 | Cutaneous abscess of right lower limb |
| L02.416 | Cutaneous abscess of left lower limb |
| L02.419 | Cutaneous abscess of limb, unspecified |
| L02.43 | Carbuncle of limb |
| L02.431 | Carbuncle of right axilla |
| L02.432 | Carbuncle of left axilla |
| L02.433 | Carbuncle of right upper limb |
| L02.434 | Carbuncle of left upper limb |
| L02.435 | Carbuncle of right lower limb |
| L02.436 | Carbuncle of left lower limb |
| L02.439 | Carbuncle of limb, unspecified |
| L02.5 | Cutaneous abscess, furuncle and carbuncle of hand |
| L02.51 | Cutaneous abscess of hand |
| L02.511 | Cutaneous abscess of right hand |
| L02.512 | Cutaneous abscess of left hand |
| L02.519 | Cutaneous abscess of unspecified hand |
| L02.53 | Carbuncle of hand |
| L02.531 | Carbuncle of right hand |
| L02.532 | Carbuncle of left hand |
| L02.539 | Carbuncle of unspecified hand |
| L02.6 | Cutaneous abscess, furuncle and carbuncle of foot |
| L02.61 | Cutaneous abscess of foot |
| L02.611 | Cutaneous abscess of right foot |
| L02.612 | Cutaneous abscess of left foot |
| L02.619 | Cutaneous abscess of unspecified foot |
| L02.63 | Carbuncle of foot |
| L02.631 | Carbuncle of right foot |
| L02.632 | Carbuncle of left foot |
| L02.639 | Carbuncle of unspecified foot |
| L02.8 | Cutaneous abscess, furuncle and carbuncle of other sites |
| L02.81 | Cutaneous abscess of other sites |
| L02.811 | Cutaneous abscess of head [any part, except face] |
| L02.818 | Cutaneous abscess of other sites |
| L02.83 | Carbuncle of other sites |
| L02.831 | Carbuncle of head [any part, except face] |
| L02.838 | Carbuncle of other sites |
| L02.9 | Cutaneous abscess, furuncle and carbuncle, unspecified |
| L02.91 | Cutaneous abscess, unspecified |
| L02.93 | Carbuncle, unspecified |
| L03 | Cellulitis and acute lymphangitis |
| L03.0 | Cellulitis and acute lymphangitis of finger and toe |
| L03.01 | Cellulitis of finger |
| L03.011 | Cellulitis of right finger |
| L03.012 | Cellulitis of left finger |
| L03.019 | Cellulitis of unspecified finger |
| L03.02 | Acute lymphangitis of finger |
| L03.021 | Acute lymphangitis of right finger |
| L03.022 | Acute lymphangitis of left finger |
| L03.029 | Acute lymphangitis of unspecified finger |
| L03.03 | Cellulitis of toe |
| L03.031 | Cellulitis of right toe |
| L03.032 | Cellulitis of left toe |
| L03.039 | Cellulitis of unspecified toe |
| L03.04 | Acute lymphangitis of toe |
| L03.041 | Acute lymphangitis of right toe |
| L03.042 | Acute lymphangitis of left toe |
| L03.049 | Acute lymphangitis of unspecified toe |
| L03.1 | Cellulitis and acute lymphangitis of other parts of limb |
| L03.11 | Cellulitis of other parts of limb |
| L03.111 | Cellulitis of right axilla |
| L03.112 | Cellulitis of left axilla |
| L03.113 | Cellulitis of right upper limb |
| L03.114 | Cellulitis of left upper limb |
| L03.115 | Cellulitis of right lower limb |
| L03.116 | Cellulitis of left lower limb |
| L03.119 | Cellulitis of unspecified part of limb |
| L03.12 | Acute lymphangitis of other parts of limb |
| L03.121 | Acute lymphangitis of right axilla |
| L03.122 | Acute lymphangitis of left axilla |
| L03.123 | Acute lymphangitis of right upper limb |
| L03.124 | Acute lymphangitis of left upper limb |
| L03.125 | Acute lymphangitis of right lower limb |
| L03.126 | Acute lymphangitis of left lower limb |
| L03.129 | Acute lymphangitis of unspecified part of limb |
| L03.2 | Cellulitis and acute lymphangitis of face and neck |
| L03.21 | Cellulitis and acute lymphangitis of face |
| L03.211 | Cellulitis of face |
| L03.212 | Acute lymphangitis of face |
| L03.22 | Cellulitis and acute lymphangitis of neck |
| L03.221 | Cellulitis of neck |
| L03.222 | Acute lymphangitis of neck |
| L03.3 | Cellulitis and acute lymphangitis of trunk |
| L03.31 | Cellulitis of trunk |
| L03.311 | Cellulitis of abdominal wall |
| L03.312 | Cellulitis of back [any part except buttock] |
| L03.313 | Cellulitis of chest wall |
| L03.314 | Cellulitis of groin |
| L03.315 | Cellulitis of perineum |
| L03.316 | Cellulitis of umbilicus |
| L03.317 | Cellulitis of buttock |
| L03.319 | Cellulitis of trunk, unspecified |
| L03.32 | Acute lymphangitis of trunk |
| L03.321 | Acute lymphangitis of abdominal wall |
| L03.322 | Acute lymphangitis of back [any part except buttock] |
| L03.323 | Acute lymphangitis of chest wall |
| L03.324 | Acute lymphangitis of groin |
| L03.325 | Acute lymphangitis of perineum |
| L03.326 | Acute lymphangitis of umbilicus |
| L03.327 | Acute lymphangitis of buttock |
| L03.329 | Acute lymphangitis of trunk, unspecified |
| L03.8 | Cellulitis and acute lymphangitis of other sites |
| L03.81 | Cellulitis of other sites |
| L03.811 | Cellulitis of head [any part, except face] |
| L03.818 | Cellulitis of other sites |
| L03.89 | Acute lymphangitis of other sites |
| L03.891 | Acute lymphangitis of head [any part, except face] |
| L03.898 | Acute lymphangitis of other sites |
| L03.9 | Cellulitis and acute lymphangitis, unspecified |
| L03.90 | Cellulitis, unspecified |
| L03.91 | Acute lymphangitis, unspecified |
| L05.0 | Pilonidal cyst and sinus with abscess |
| L05.01 | Pilonidal cyst with abscess |
| L05.02 | Pilonidal sinus with abscess |
| L08.0 | Pyoderma |
| M72.6 | Necrotizing fasciitis |
| N48.22 | Cellulitis of corpus cavernosum and penis |
| N75.1 | Abscess of bartholin's gland |
| N76.4 | Abscess of vulva |
| O91 | Infections of breast associated with pregnancy, the puerperium and lactation |
| O91.0 | Infection of nipple associated with pregnancy, the puerperium and lactation |
| O91.01 | Infection of nipple associated with pregnancy |
| O91.011 | Infection of nipple associated with pregnancy, first trimester |
| O91.012 | Infection of nipple associated with pregnancy, second trimester |
| O91.013 | Infection of nipple associated with pregnancy, third trimester |
| O91.019 | Infection of nipple associated with pregnancy, unspecified trimester |
| O91.02 | Infection of nipple associated with the puerperium |
| O91.03 | Infection of nipple associated with lactation |
| O91.1 | Abscess of breast associated with pregnancy, the puerperium and lactation |
| O91.11 | Abscess of breast associated with pregnancy |
| O91.111 | Abscess of breast associated with pregnancy, first trimester |
| O91.112 | Abscess of breast associated with pregnancy, second trimester |
| O91.113 | Abscess of breast associated with pregnancy, third trimester |
| O91.119 | Abscess of breast associated with pregnancy, unspecified trimester |
| O91.12 | Abscess of breast associated with the puerperium |
| O91.13 | Abscess of breast associated with lactation |
| Complicated skin structure s. agalactiae infection | |
| B95.1 | Streptococcus, group b, as the cause of diseases classified elsewhere |
| H00.03 | Abscess of eyelid |
| H00.031 | Abscess of right upper eyelid |
| H00.032 | Abscess of right lower eyelid |
| H00.033 | Abscess of eyelid right eye, unspecified eyelid |
| H00.034 | Abscess of left upper eyelid |
| H00.035 | Abscess of left lower eyelid |
| H00.036 | Abscess of eyelid left eye, unspecified eyelid |
| H00.039 | Abscess of eyelid unspecified eye, unspecified eyelid |
| H60.0 | Abscess of external ear |
| H60.00 | Abscess of external ear, unspecified ear |
| H60.01 | Abscess of right external ear |
| H60.02 | Abscess of left external ear |
| H60.03 | Abscess of external ear, bilateral |
| H60.1 | Cellulitis of external ear |
| H60.10 | Cellulitis of external ear, unspecified ear |
| H60.11 | Cellulitis of right external ear |
| H60.12 | Cellulitis of left external ear |
| H60.13 | Cellulitis of external ear, bilateral |
| J34.0 | Abscess, furuncle and carbuncle of nose |
| K61 | Abscess of anal and rectal regions |
| K61.0 | Anal abscess |
| K61.1 | Rectal abscess |
| K61.2 | Anorectal abscess |
| K61.3 | Ischiorectal abscess |
| K61.4 | Intrasphincteric abscess |
| L02 | Cutaneous abscess, furuncle and carbuncle |
| L02.0 | Cutaneous abscess, furuncle and carbuncle of face |
| L02.01 | Cutaneous abscess of face |
| L02.03 | Carbuncle of face |
| L02.1 | Cutaneous abscess, furuncle and carbuncle of neck |
| L02.11 | Cutaneous abscess of neck |
| L02.13 | Carbuncle of neck |
| L02.2 | Cutaneous abscess, furuncle and carbuncle of trunk |
| L02.21 | Cutaneous abscess of trunk |
| L02.211 | Cutaneous abscess of abdominal wall |
| L02.212 | Cutaneous abscess of back [any part, except buttock] |
| L02.213 | Cutaneous abscess of chest wall |
| L02.214 | Cutaneous abscess of groin |
| L02.215 | Cutaneous abscess of perineum |
| L02.216 | Cutaneous abscess of umbilicus |
| L02.219 | Cutaneous abscess of trunk, unspecified |
| L02.23 | Carbuncle of trunk |
| L02.231 | Carbuncle of abdominal wall |
| L02.232 | Carbuncle of back [any part, except buttock] |
| L02.233 | Carbuncle of chest wall |
| L02.234 | Carbuncle of groin |
| L02.235 | Carbuncle of perineum |
| L02.236 | Carbuncle of umbilicus |
| L02.239 | Carbuncle of trunk, unspecified |
| L02.3 | Cutaneous abscess, furuncle and carbuncle of buttock |
| L02.31 | Cutaneous abscess of buttock |
| L02.33 | Carbuncle of buttock |
| L02.4 | Cutaneous abscess, furuncle and carbuncle of limb |
| L02.41 | Cutaneous abscess of limb |
| L02.411 | Cutaneous abscess of right axilla |
| L02.412 | Cutaneous abscess of left axilla |
| L02.413 | Cutaneous abscess of right upper limb |
| L02.414 | Cutaneous abscess of left upper limb |
| L02.415 | Cutaneous abscess of right lower limb |
| L02.416 | Cutaneous abscess of left lower limb |
| L02.419 | Cutaneous abscess of limb, unspecified |
| L02.43 | Carbuncle of limb |
| L02.431 | Carbuncle of right axilla |
| L02.432 | Carbuncle of left axilla |
| L02.433 | Carbuncle of right upper limb |
| L02.434 | Carbuncle of left upper limb |
| L02.435 | Carbuncle of right lower limb |
| L02.436 | Carbuncle of left lower limb |
| L02.439 | Carbuncle of limb, unspecified |
| L02.5 | Cutaneous abscess, furuncle and carbuncle of hand |
| L02.51 | Cutaneous abscess of hand |
| L02.511 | Cutaneous abscess of right hand |
| L02.512 | Cutaneous abscess of left hand |
| L02.519 | Cutaneous abscess of unspecified hand |
| L02.53 | Carbuncle of hand |
| L02.531 | Carbuncle of right hand |
| L02.532 | Carbuncle of left hand |
| L02.539 | Carbuncle of unspecified hand |
| L02.6 | Cutaneous abscess, furuncle and carbuncle of foot |
| L02.61 | Cutaneous abscess of foot |
| L02.611 | Cutaneous abscess of right foot |
| L02.612 | Cutaneous abscess of left foot |
| L02.619 | Cutaneous abscess of unspecified foot |
| L02.63 | Carbuncle of foot |
| L02.631 | Carbuncle of right foot |
| L02.632 | Carbuncle of left foot |
| L02.639 | Carbuncle of unspecified foot |
| L02.8 | Cutaneous abscess, furuncle and carbuncle of other sites |
| L02.81 | Cutaneous abscess of other sites |
| L02.811 | Cutaneous abscess of head [any part, except face] |
| L02.818 | Cutaneous abscess of other sites |
| L02.83 | Carbuncle of other sites |
| L02.831 | Carbuncle of head [any part, except face] |
| L02.838 | Carbuncle of other sites |
| L02.9 | Cutaneous abscess, furuncle and carbuncle, unspecified |
| L02.91 | Cutaneous abscess, unspecified |
| L02.93 | Carbuncle, unspecified |
| L03 | Cellulitis and acute lymphangitis |
| L03.0 | Cellulitis and acute lymphangitis of finger and toe |
| L03.01 | Cellulitis of finger |
| L03.011 | Cellulitis of right finger |
| L03.012 | Cellulitis of left finger |
| L03.019 | Cellulitis of unspecified finger |
| L03.02 | Acute lymphangitis of finger |
| L03.021 | Acute lymphangitis of right finger |
| L03.022 | Acute lymphangitis of left finger |
| L03.029 | Acute lymphangitis of unspecified finger |
| L03.03 | Cellulitis of toe |
| L03.031 | Cellulitis of right toe |
| L03.032 | Cellulitis of left toe |
| L03.039 | Cellulitis of unspecified toe |
| L03.04 | Acute lymphangitis of toe |
| L03.041 | Acute lymphangitis of right toe |
| L03.042 | Acute lymphangitis of left toe |
| L03.049 | Acute lymphangitis of unspecified toe |
| L03.1 | Cellulitis and acute lymphangitis of other parts of limb |
| L03.11 | Cellulitis of other parts of limb |
| L03.111 | Cellulitis of right axilla |
| L03.112 | Cellulitis of left axilla |
| L03.113 | Cellulitis of right upper limb |
| L03.114 | Cellulitis of left upper limb |
| L03.115 | Cellulitis of right lower limb |
| L03.116 | Cellulitis of left lower limb |
| L03.119 | Cellulitis of unspecified part of limb |
| L03.12 | Acute lymphangitis of other parts of limb |
| L03.121 | Acute lymphangitis of right axilla |
| L03.122 | Acute lymphangitis of left axilla |
| L03.123 | Acute lymphangitis of right upper limb |
| L03.124 | Acute lymphangitis of left upper limb |
| L03.125 | Acute lymphangitis of right lower limb |
| L03.126 | Acute lymphangitis of left lower limb |
| L03.129 | Acute lymphangitis of unspecified part of limb |
| L03.2 | Cellulitis and acute lymphangitis of face and neck |
| L03.21 | Cellulitis and acute lymphangitis of face |
| L03.211 | Cellulitis of face |
| L03.212 | Acute lymphangitis of face |
| L03.22 | Cellulitis and acute lymphangitis of neck |
| L03.221 | Cellulitis of neck |
| L03.222 | Acute lymphangitis of neck |
| L03.3 | Cellulitis and acute lymphangitis of trunk |
| L03.31 | Cellulitis of trunk |
| L03.311 | Cellulitis of abdominal wall |
| L03.312 | Cellulitis of back [any part except buttock] |
| L03.313 | Cellulitis of chest wall |
| L03.314 | Cellulitis of groin |
| L03.315 | Cellulitis of perineum |
| L03.316 | Cellulitis of umbilicus |
| L03.317 | Cellulitis of buttock |
| L03.319 | Cellulitis of trunk, unspecified |
| L03.32 | Acute lymphangitis of trunk |
| L03.321 | Acute lymphangitis of abdominal wall |
| L03.322 | Acute lymphangitis of back [any part except buttock] |
| L03.323 | Acute lymphangitis of chest wall |
| L03.324 | Acute lymphangitis of groin |
| L03.325 | Acute lymphangitis of perineum |
| L03.326 | Acute lymphangitis of umbilicus |
| L03.327 | Acute lymphangitis of buttock |
| L03.329 | Acute lymphangitis of trunk, unspecified |
| L03.8 | Cellulitis and acute lymphangitis of other sites |
| L03.81 | Cellulitis of other sites |
| L03.811 | Cellulitis of head [any part, except face] |
| L03.818 | Cellulitis of other sites |
| L03.89 | Acute lymphangitis of other sites |
| L03.891 | Acute lymphangitis of head [any part, except face] |
| L03.898 | Acute lymphangitis of other sites |
| L03.9 | Cellulitis and acute lymphangitis, unspecified |
| L03.90 | Cellulitis, unspecified |
| L03.91 | Acute lymphangitis, unspecified |
| L05.0 | Pilonidal cyst and sinus with abscess |
| L05.01 | Pilonidal cyst with abscess |
| L05.02 | Pilonidal sinus with abscess |
| L08.0 | Pyoderma |
| L08.89 | Other specified local infections of the skin and subcutaneous tissue |
| N48.21 | Abscess of corpus cavernosum and penis |
| N48.22 | Cellulitis of corpus cavernosum and penis |
| N75.1 | Abscess of bartholin's gland |
| N76.4 | Abscess of vulva |
| O91 | Infections of breast associated with pregnancy, the puerperium and lactation |
| O91.0 | Infection of nipple associated with pregnancy, the puerperium and lactation |
| O91.01 | Infection of nipple associated with pregnancy |
| O91.011 | Infection of nipple associated with pregnancy, first trimester |
| O91.012 | Infection of nipple associated with pregnancy, second trimester |
| O91.013 | Infection of nipple associated with pregnancy, third trimester |
| O91.019 | Infection of nipple associated with pregnancy, unspecified trimester |
| O91.02 | Infection of nipple associated with the puerperium |
| O91.03 | Infection of nipple associated with lactation |
| O91.1 | Abscess of breast associated with pregnancy, the puerperium and lactation |
| O91.11 | Abscess of breast associated with pregnancy |
| O91.111 | Abscess of breast associated with pregnancy, first trimester |
| O91.112 | Abscess of breast associated with pregnancy, second trimester |
| O91.113 | Abscess of breast associated with pregnancy, third trimester |
| O91.119 | Abscess of breast associated with pregnancy, unspecified trimester |
| O91.12 | Abscess of breast associated with the puerperium |
| O91.13 | Abscess of breast associated with lactation |
| Complicated skin structure s. pyogenes infection | |
| B95.0 | Streptococcus, group a, as the cause of diseases classified elsewhere |
| H00.03 | Abscess of eyelid |
| H00.031 | Abscess of right upper eyelid |
| H00.032 | Abscess of right lower eyelid |
| H00.033 | Abscess of eyelid right eye, unspecified eyelid |
| H00.034 | Abscess of left upper eyelid |
| H00.035 | Abscess of left lower eyelid |
| H00.036 | Abscess of eyelid left eye, unspecified eyelid |
| H00.039 | Abscess of eyelid unspecified eye, unspecified eyelid |
| H60.0 | Abscess of external ear |
| H60.00 | Abscess of external ear, unspecified ear |
| H60.01 | Abscess of right external ear |
| H60.02 | Abscess of left external ear |
| H60.03 | Abscess of external ear, bilateral |
| J34.0 | Abscess, furuncle and carbuncle of nose |
| K61 | Abscess of anal and rectal regions |
| K61.0 | Anal abscess |
| K61.1 | Rectal abscess |
| K61.2 | Anorectal abscess |
| K61.3 | Ischiorectal abscess |
| K61.4 | Intrasphincteric abscess |
| L02 | Cutaneous abscess, furuncle and carbuncle |
| L02.0 | Cutaneous abscess, furuncle and carbuncle of face |
| L02.01 | Cutaneous abscess of face |
| L02.03 | Carbuncle of face |
| L02.1 | Cutaneous abscess, furuncle and carbuncle of neck |
| L02.11 | Cutaneous abscess of neck |
| L02.13 | Carbuncle of neck |
| L02.2 | Cutaneous abscess, furuncle and carbuncle of trunk |
| L02.21 | Cutaneous abscess of trunk |
| L02.211 | Cutaneous abscess of abdominal wall |
| L02.212 | Cutaneous abscess of back [any part, except buttock] |
| L02.213 | Cutaneous abscess of chest wall |
| L02.214 | Cutaneous abscess of groin |
| L02.215 | Cutaneous abscess of perineum |
| L02.216 | Cutaneous abscess of umbilicus |
| L02.219 | Cutaneous abscess of trunk, unspecified |
| L02.23 | Carbuncle of trunk |
| L02.231 | Carbuncle of abdominal wall |
| L02.232 | Carbuncle of back [any part, except buttock] |
| L02.233 | Carbuncle of chest wall |
| L02.234 | Carbuncle of groin |
| L02.235 | Carbuncle of perineum |
| L02.236 | Carbuncle of umbilicus |
| L02.239 | Carbuncle of trunk, unspecified |
| L02.3 | Cutaneous abscess, furuncle and carbuncle of buttock |
| L02.31 | Cutaneous abscess of buttock |
| L02.33 | Carbuncle of buttock |
| L02.4 | Cutaneous abscess, furuncle and carbuncle of limb |
| L02.41 | Cutaneous abscess of limb |
| L02.411 | Cutaneous abscess of right axilla |
| L02.412 | Cutaneous abscess of left axilla |
| L02.413 | Cutaneous abscess of right upper limb |
| L02.414 | Cutaneous abscess of left upper limb |
| L02.415 | Cutaneous abscess of right lower limb |
| L02.416 | Cutaneous abscess of left lower limb |
| L02.419 | Cutaneous abscess of limb, unspecified |
| L02.43 | Carbuncle of limb |
| L02.431 | Carbuncle of right axilla |
| L02.432 | Carbuncle of left axilla |
| L02.433 | Carbuncle of right upper limb |
| L02.434 | Carbuncle of left upper limb |
| L02.435 | Carbuncle of right lower limb |
| L02.436 | Carbuncle of left lower limb |
| L02.439 | Carbuncle of limb, unspecified |
| L02.5 | Cutaneous abscess, furuncle and carbuncle of hand |
| L02.51 | Cutaneous abscess of hand |
| L02.511 | Cutaneous abscess of right hand |
| L02.512 | Cutaneous abscess of left hand |
| L02.519 | Cutaneous abscess of unspecified hand |
| L02.53 | Carbuncle of hand |
| L02.531 | Carbuncle of right hand |
| L02.532 | Carbuncle of left hand |
| L02.539 | Carbuncle of unspecified hand |
| L02.6 | Cutaneous abscess, furuncle and carbuncle of foot |
| L02.61 | Cutaneous abscess of foot |
| L02.611 | Cutaneous abscess of right foot |
| L02.612 | Cutaneous abscess of left foot |
| L02.619 | Cutaneous abscess of unspecified foot |
| L02.63 | Carbuncle of foot |
| L02.631 | Carbuncle of right foot |
| L02.632 | Carbuncle of left foot |
| L02.639 | Carbuncle of unspecified foot |
| L02.8 | Cutaneous abscess, furuncle and carbuncle of other sites |
| L02.81 | Cutaneous abscess of other sites |
| L02.811 | Cutaneous abscess of head [any part, except face] |
| L02.818 | Cutaneous abscess of other sites |
| L02.83 | Carbuncle of other sites |
| L02.831 | Carbuncle of head [any part, except face] |
| L02.838 | Carbuncle of other sites |
| L02.9 | Cutaneous abscess, furuncle and carbuncle, unspecified |
| L02.91 | Cutaneous abscess, unspecified |
| L02.93 | Carbuncle, unspecified |
| L03 | Cellulitis and acute lymphangitis |
| L03.0 | Cellulitis and acute lymphangitis of finger and toe |
| L03.01 | Cellulitis of finger |
| L03.011 | Cellulitis of right finger |
| L03.012 | Cellulitis of left finger |
| L03.019 | Cellulitis of unspecified finger |
| L03.02 | Acute lymphangitis of finger |
| L03.021 | Acute lymphangitis of right finger |
| L03.022 | Acute lymphangitis of left finger |
| L03.029 | Acute lymphangitis of unspecified finger |
| L03.03 | Cellulitis of toe |
| L03.031 | Cellulitis of right toe |
| L03.032 | Cellulitis of left toe |
| L03.039 | Cellulitis of unspecified toe |
| L03.04 | Acute lymphangitis of toe |
| L03.041 | Acute lymphangitis of right toe |
| L03.042 | Acute lymphangitis of left toe |
| L03.049 | Acute lymphangitis of unspecified toe |
| L03.1 | Cellulitis and acute lymphangitis of other parts of limb |
| L03.11 | Cellulitis of other parts of limb |
| L03.111 | Cellulitis of right axilla |
| L03.112 | Cellulitis of left axilla |
| L03.113 | Cellulitis of right upper limb |
| L03.114 | Cellulitis of left upper limb |
| L03.115 | Cellulitis of right lower limb |
| L03.116 | Cellulitis of left lower limb |
| L03.119 | Cellulitis of unspecified part of limb |
| L03.12 | Acute lymphangitis of other parts of limb |
| L03.121 | Acute lymphangitis of right axilla |
| L03.122 | Acute lymphangitis of left axilla |
| L03.123 | Acute lymphangitis of right upper limb |
| L03.124 | Acute lymphangitis of left upper limb |
| L03.125 | Acute lymphangitis of right lower limb |
| L03.126 | Acute lymphangitis of left lower limb |
| L03.129 | Acute lymphangitis of unspecified part of limb |
| L03.2 | Cellulitis and acute lymphangitis of face and neck |
| L03.21 | Cellulitis and acute lymphangitis of face |
| L03.211 | Cellulitis of face |
| L03.212 | Acute lymphangitis of face |
| L03.22 | Cellulitis and acute lymphangitis of neck |
| L03.221 | Cellulitis of neck |
| L03.222 | Acute lymphangitis of neck |
| L03.3 | Cellulitis and acute lymphangitis of trunk |
| L03.31 | Cellulitis of trunk |
| L03.311 | Cellulitis of abdominal wall |
| L03.312 | Cellulitis of back [any part except buttock] |
| L03.313 | Cellulitis of chest wall |
| L03.314 | Cellulitis of groin |
| L03.315 | Cellulitis of perineum |
| L03.316 | Cellulitis of umbilicus |
| L03.317 | Cellulitis of buttock |
| L03.319 | Cellulitis of trunk, unspecified |
| L03.32 | Acute lymphangitis of trunk |
| L03.321 | Acute lymphangitis of abdominal wall |
| L03.322 | Acute lymphangitis of back [any part except buttock] |
| L03.323 | Acute lymphangitis of chest wall |
| L03.324 | Acute lymphangitis of groin |
| L03.325 | Acute lymphangitis of perineum |
| L03.326 | Acute lymphangitis of umbilicus |
| L03.327 | Acute lymphangitis of buttock |
| L03.329 | Acute lymphangitis of trunk, unspecified |
| L03.8 | Cellulitis and acute lymphangitis of other sites |
| L03.81 | Cellulitis of other sites |
| L03.811 | Cellulitis of head [any part, except face] |
| L03.818 | Cellulitis of other sites |
| L03.89 | Acute lymphangitis of other sites |
| L03.891 | Acute lymphangitis of head [any part, except face] |
| L03.898 | Acute lymphangitis of other sites |
| L03.9 | Cellulitis and acute lymphangitis, unspecified |
| L03.90 | Cellulitis, unspecified |
| L03.91 | Acute lymphangitis, unspecified |
| L05.0 | Pilonidal cyst and sinus with abscess |
| L05.01 | Pilonidal cyst with abscess |
| L05.02 | Pilonidal sinus with abscess |
| L08.0 | Pyoderma |
| L08.89 | Other specified local infections of the skin and subcutaneous tissue |
| L08.9 | Local infection of the skin and subcutaneous tissue, unspecified |
| M72.6 | Necrotizing fasciitis |
| N48.21 | Abscess of corpus cavernosum and penis |
| N48.22 | Cellulitis of corpus cavernosum and penis |
| N75.1 | Abscess of bartholin's gland |
| N76.4 | Abscess of vulva |
| O91 | Infections of breast associated with pregnancy, the puerperium and lactation |
| O91.0 | Infection of nipple associated with pregnancy, the puerperium and lactation |
| O91.01 | Infection of nipple associated with pregnancy |
| O91.011 | Infection of nipple associated with pregnancy, first trimester |
| O91.012 | Infection of nipple associated with pregnancy, second trimester |
| O91.013 | Infection of nipple associated with pregnancy, third trimester |
| O91.019 | Infection of nipple associated with pregnancy, unspecified trimester |
| O91.02 | Infection of nipple associated with the puerperium |
| O91.03 | Infection of nipple associated with lactation |
| O91.1 | Abscess of breast associated with pregnancy, the puerperium and lactation |
| O91.11 | Abscess of breast associated with pregnancy |
| O91.111 | Abscess of breast associated with pregnancy, first trimester |
| O91.112 | Abscess of breast associated with pregnancy, second trimester |
| O91.113 | Abscess of breast associated with pregnancy, third trimester |
| O91.119 | Abscess of breast associated with pregnancy, unspecified trimester |
| O91.12 | Abscess of breast associated with the puerperium |
| O91.13 | Abscess of breast associated with lactation |
| Diabetic foot infection due to gram-positive bacteria | |
| E08.621 | Diabetes mellitus due to underlying condition with foot ulcer |
| E09.621 | Drug or chemical induced diabetes mellitus with foot ulcer |
| E10.621 | Type 1 diabetes mellitus with foot ulcer |
| E11.621 | Type 2 diabetes mellitus with foot ulcer |
| E13.621 | Other specified diabetes mellitus with foot ulcer |
| Nosocomial pneumonia due to streptococcus pneumoniae | |
| J13 | Pneumonia due to streptococcus pneumoniae |
| Skin and skin structure strep. pyogenes infection | |
| B95.0 | Streptococcus, group a, as the cause of diseases classified elsewhere |
| B95.4 | Other streptococcus as the cause of diseases classified elsewhere |
| L08.89 | Other specified local infections of the skin and subcutaneous tissue |
| L08.9 | Local infection of the skin and subcutaneous tissue, unspecified |
| Staphylococcal pneumonia | |
| J15.2 | Pneumonia due to staphylococcus |
| J15.20 | Pneumonia due to staphylococcus, unspecified |
| J15.21 | Pneumonia due to staphylococcus aureus |
| J15.211 | Pneumonia due to methicillin susceptible staphylococcus aureus |
| J15.212 | Pneumonia due to methicillin resistant staphylococcus aureus |
| J15.29 | Pneumonia due to other staphylococcus |
| Staphylococcus aureus skin and skin structure infection | |
| B95.6 | Staphylococcus aureus as the cause of diseases classified elsewhere |
| H60.1 | Cellulitis of external ear |
| H60.10 | Cellulitis of external ear, unspecified ear |
| H60.11 | Cellulitis of right external ear |
| H60.12 | Cellulitis of left external ear |
| H60.13 | Cellulitis of external ear, bilateral |
| J34.0 | Abscess, furuncle and carbuncle of nose |
| L02 | Cutaneous abscess, furuncle and carbuncle |
| L02.0 | Cutaneous abscess, furuncle and carbuncle of face |
| L02.02 | Furuncle of face |
| L02.03 | Carbuncle of face |
| L02.1 | Cutaneous abscess, furuncle and carbuncle of neck |
| L02.12 | Furuncle of neck |
| L02.13 | Carbuncle of neck |
| L02.2 | Cutaneous abscess, furuncle and carbuncle of trunk |
| L02.22 | Furuncle of trunk |
| L02.221 | Furuncle of abdominal wall |
| L02.222 | Furuncle of back [any part, except buttock] |
| L02.223 | Furuncle of chest wall |
| L02.224 | Furuncle of groin |
| L02.225 | Furuncle of perineum |
| L02.226 | Furuncle of umbilicus |
| L02.229 | Furuncle of trunk, unspecified |
| L02.23 | Carbuncle of trunk |
| L02.231 | Carbuncle of abdominal wall |
| L02.232 | Carbuncle of back [any part, except buttock] |
| L02.233 | Carbuncle of chest wall |
| L02.234 | Carbuncle of groin |
| L02.235 | Carbuncle of perineum |
| L02.236 | Carbuncle of umbilicus |
| L02.239 | Carbuncle of trunk, unspecified |
| L02.3 | Cutaneous abscess, furuncle and carbuncle of buttock |
| L02.32 | Furuncle of buttock |
| L02.33 | Carbuncle of buttock |
| L02.4 | Cutaneous abscess, furuncle and carbuncle of limb |
| L02.42 | Furuncle of limb |
| L02.421 | Furuncle of right axilla |
| L02.422 | Furuncle of left axilla |
| L02.423 | Furuncle of right upper limb |
| L02.424 | Furuncle of left upper limb |
| L02.425 | Furuncle of right lower limb |
| L02.426 | Furuncle of left lower limb |
| L02.429 | Furuncle of limb, unspecified |
| L02.43 | Carbuncle of limb |
| L02.431 | Carbuncle of right axilla |
| L02.432 | Carbuncle of left axilla |
| L02.433 | Carbuncle of right upper limb |
| L02.434 | Carbuncle of left upper limb |
| L02.435 | Carbuncle of right lower limb |
| L02.436 | Carbuncle of left lower limb |
| L02.439 | Carbuncle of limb, unspecified |
| L02.5 | Cutaneous abscess, furuncle and carbuncle of hand |
| L02.52 | Furuncle hand |
| L02.521 | Furuncle right hand |
| L02.522 | Furuncle left hand |
| L02.529 | Furuncle unspecified hand |
| L02.53 | Carbuncle of hand |
| L02.531 | Carbuncle of right hand |
| L02.532 | Carbuncle of left hand |
| L02.539 | Carbuncle of unspecified hand |
| L02.6 | Cutaneous abscess, furuncle and carbuncle of foot |
| L02.62 | Furuncle of foot |
| L02.621 | Furuncle of right foot |
| L02.622 | Furuncle of left foot |
| L02.629 | Furuncle of unspecified foot |
| L02.63 | Carbuncle of foot |
| L02.631 | Carbuncle of right foot |
| L02.632 | Carbuncle of left foot |
| L02.639 | Carbuncle of unspecified foot |
| L02.8 | Cutaneous abscess, furuncle and carbuncle of other sites |
| L02.82 | Furuncle of other sites |
| L02.821 | Furuncle of head [any part, except face] |
| L02.828 | Furuncle of other sites |
| L02.83 | Carbuncle of other sites |
| L02.831 | Carbuncle of head [any part, except face] |
| L02.838 | Carbuncle of other sites |
| L02.9 | Cutaneous abscess, furuncle and carbuncle, unspecified |
| L02.92 | Furuncle, unspecified |
| L02.93 | Carbuncle, unspecified |
| L03.01 | Cellulitis of finger |
| L03.011 | Cellulitis of right finger |
| L03.012 | Cellulitis of left finger |
| L03.019 | Cellulitis of unspecified finger |
| L03.03 | Cellulitis of toe |
| L03.031 | Cellulitis of right toe |
| L03.032 | Cellulitis of left toe |
| L03.039 | Cellulitis of unspecified toe |
| L03.1 | Cellulitis and acute lymphangitis of other parts of limb |
| L03.11 | Cellulitis of other parts of limb |
| L03.111 | Cellulitis of right axilla |
| L03.112 | Cellulitis of left axilla |
| L03.113 | Cellulitis of right upper limb |
| L03.114 | Cellulitis of left upper limb |
| L03.115 | Cellulitis of right lower limb |
| L03.116 | Cellulitis of left lower limb |
| L03.119 | Cellulitis of unspecified part of limb |
| L03.2 | Cellulitis and acute lymphangitis of face and neck |
| L03.21 | Cellulitis and acute lymphangitis of face |
| L03.211 | Cellulitis of face |
| L03.22 | Cellulitis and acute lymphangitis of neck |
| L03.221 | Cellulitis of neck |
| L03.3 | Cellulitis and acute lymphangitis of trunk |
| L03.31 | Cellulitis of trunk |
| L03.311 | Cellulitis of abdominal wall |
| L03.312 | Cellulitis of back [any part except buttock] |
| L03.313 | Cellulitis of chest wall |
| L03.314 | Cellulitis of groin |
| L03.315 | Cellulitis of perineum |
| L03.316 | Cellulitis of umbilicus |
| L03.317 | Cellulitis of buttock |
| L03.319 | Cellulitis of trunk, unspecified |
| L03.8 | Cellulitis and acute lymphangitis of other sites |
| L03.81 | Cellulitis of other sites |
| L03.811 | Cellulitis of head [any part, except face] |
| L03.818 | Cellulitis of other sites |
| L03.9 | Cellulitis and acute lymphangitis, unspecified |
| L03.90 | Cellulitis, unspecified |
| L08.89 | Other specified local infections of the skin and subcutaneous tissue |
| L08.9 | Local infection of the skin and subcutaneous tissue, unspecified |
| N48.22 | Cellulitis of corpus cavernosum and penis |
| Staphylococcus nosocomial pneumonia | |
| J15.2 | Pneumonia due to staphylococcus |
| J15.20 | Pneumonia due to staphylococcus, unspecified |
| J15.21 | Pneumonia due to staphylococcus aureus |
| J15.212 | Pneumonia due to methicillin resistant staphylococcus aureus |
| J15.29 | Pneumonia due to other staphylococcus |
| Streptococcal pneumonia | |
| J13 | Pneumonia due to streptococcus pneumoniae |
| J15.3 | Pneumonia due to streptococcus, group B |
| J15.4 | Pneumonia due to other streptococci |
| Vancomycin resistant enterococcus faecium bacteremia | |
| A41.81 | Sepsis due to enterococcus |
| Z16.21 | Resistance to vancomycin |
| Vancomycin-resistant enterococcus faecium infection | |
| A41.81 | Sepsis due to enterococcus |
| B95.2 | Enterococcus as the cause of diseases classified elsewhere |
| Z16.21 | Resistance to vancomycin |
Formulary Reference Tool