Nexafed Sinus Pressure-Pain

Drug overview for NEXAFED SINUS PRESSURE-PAIN (pseudoephedrine hcl/acetaminophen):

Generic name: PSEUDOEPHEDRINE HCL/ACETAMINOPHEN
Drug class: Amphetamines/Anorexiants/Stimulants
Therapeutic class: Respiratory Therapy Agents

Pseudoephedrine is a sympathomimetic agent that occurs naturally in plants of the genus Ephedra; the drug acts directly on both alpha- and, to a lesser degree, beta-adrenergic receptors. Acetaminophen is a synthetic nonopiate derivative of p-aminophenol that produces analgesia and antipyresis.

Pseudoephedrine is used as a nasal decongestant for self-medication for the temporary relief of nasal congestion associated with upper respiratory allergy and to provide temporary relief of sinus congestion and pressure. The drug also has been used for self-medication in the symptomatic prevention of otitic barotrauma+ (aerotitis ( barotitis) media). Pseudoephedrine also has been misused for clandestine synthesis of methamphetamine and methcathinone for illicit use. Acetaminophen is used extensively in the treatment of mild to moderate pain and fever.

DRUG IMAGES

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The following indications for NEXAFED SINUS PRESSURE-PAIN (pseudoephedrine hcl/acetaminophen) have been approved by the FDA:

Indications:
Fever
Nasal congestion
Pain
Sinus headache

Professional Synonyms:
Febrile reaction
Febrile
Nasal stuffiness
Pyrexia
Sinus pain

The following dosing information is available for NEXAFED SINUS PRESSURE-PAIN (pseudoephedrine hcl/acetaminophen):

Dosing
Administration
Dosing Information
Generic

Acetaminophen is relatively safe when used at recommended dosages. However, acetaminophen overdosage has been the leading cause of acute liver failure in the US, United Kingdom, and most of Europe, with about 50% of US cases in recent years resulting from inadvertent overdosage (e.g., in patients not recognizing the presence of the drug in multiple over-the-counter (OTC) and/or prescription products that they may be taking). Therefore, patients should be warned about the importance of determining whether acetaminophen is present in their medications (e.g., by examining labels carefully, by consulting their clinician and pharmacist) and of not exceeding recommended dosages or combining acetaminophen-containing preparations.

Acetaminophen should not be used for self-medication of pain for longer than 10 days (in adults or children 12 years of age and older) or 5 days (in children 2-11 years of age), unless directed by a clinician because pain of such intensity and duration may indicate a pathologic condition requiring medical evaluation and supervised treatment.

Acetaminophen should not be used in adults or children for self-medication of marked fever (greater than 39.5degreesC), fever persisting longer than 3 days, or recurrent fever, unless directed by a clinician because such fevers may indicate serious illness requiring prompt medical evaluation.

Acetaminophen should not be used in adults or children for self-medication of sore throat pain (pharyngitis, laryngitis, tonsillitis) for longer than 2 days.

To minimize the risk of overdosage, recommended age-appropriate daily dosages of acetaminophen should not be exceeded. Because severe liver toxicity and death have occurred in children who received multiple excessive doses of acetaminophen as part of therapeutic administration, parents or caregivers should be instructed to use weight-based dosing for acetaminophen, to use only the calibrated measuring device provided with the particular acetaminophen formulation for measuring dosage, to ensure that the correct number of tablets required for the intended dose is removed from the package, and not to exceed the recommended daily dosage because serious adverse effects could result. In addition, patients should be warned that the risk of overdosage and severe liver damage is increased if more than one preparation containing acetaminophen are used concomitantly.

Pharmacists have an important role in preventing acetaminophen-induced hepatotoxicity by advising consumers about the risk of failing to recognize that a wide variety of OTC and prescription preparations contain acetaminophen. Failure to recognize acetaminophen as an ingredient may be particularly likely with prescription drugs because the label of the dispensed drug may not clearly state its presence. Educating consumers about the risk of exceeding recommended acetaminophen dosages also is important.

The US Food and Drug Administration (FDA) recommends that pharmacists receiving prescriptions for fixed-combination preparations containing more than 325 mg of acetaminophen per dosage unit contact the prescriber to discuss use of a preparation containing no more than 325 mg of the drug per dosage unit. (See Preparations.)

Clinicians should exercise caution when prescribing, preparing, and administering IV acetaminophen to avoid dosing errors that could result in accidental overdosage and death. In particular, clinicians should ensure that the dose (in mg) and the volume (in mL) are not confused, the dose for patients weighing less than 50 kg is based on body weight, the infusion pump is programmed correctly, and the total daily dosage of acetaminophen from all sources does not exceed the maximum recommended daily dosage.

In patients with hepatic impairment or active liver disease, reduction of the total daily dosage of acetaminophen may be warranted. In patients with severe renal impairment (creatinine clearance of 30 mL/minute or less), longer dosing intervals and a reduced total daily dosage of acetaminophen may be warranted. (See Cautions: Precautions and Contraindications.)

Pseudoephedrine hydrochloride and sulfate are administered orally. Pseudoephedrine hydrochloride 240-mg extended-release tablets should be administered orally once daily and swallowed whole with water; the extended-release tablets should not be divided, crushed, chewed, or dissolved. Patients should be advised that the tablet does not completely dissolve and may be passed in the stool.

Acetaminophen is administered orally, rectally as suppositories, and by IV infusion over 15 minutes. Acetaminophen preparations for self-medication should not be used unless seals on the tamper-resistant packaging are intact.

No dosing information available.

No generic dosing information available.

The following drug interaction information is available for NEXAFED SINUS PRESSURE-PAIN (pseudoephedrine hcl/acetaminophen):

Contraindicated
Severe
Moderate

There are 2 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
Mixed & Indirect Sympathomimetics; Oral Phenylephrine/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: 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. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Concurrent use of monoamine oxidase inhibitors and sympathomimetics is contraindicated. The manufacturers of sympathomimetic agents recommend waiting 14 days after discontinuation of MAO inhibitors before initiating the sympathomimetic. 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. Since procarbazine, an antineoplastic agent, is a weak monoamine oxidase inhibitor, hypertensive reactions may result from its concurrent use with indirect and mixed acting sympathomimetics. Furazolidone, an antibacterial with monoamine oxidase inhibitor action, has also been shown to interact with indirect acting sympathomimetics. Linezolid is another antibacterial with monoamine oxidase inhibitor properties. Metaxalone is a weak inhibitor of MAO. Foods containing large amounts of tyramine have also been implicated in this interaction. Methylene blue, when administered intravenously, has been shown to reach sufficient concentrations to be a potent inhibitor of MAO-A. At recommended dosages, rasagiline, 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. 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.	EMSAM, FURAZOLIDONE, MARPLAN, MATULANE, METAXALONE, METHYLENE BLUE, NARDIL, PARNATE, PHENELZINE SULFATE, PROCARBAZINE HCL, PROVAYBLUE, SELEGILINE HCL, TRANYLCYPROMINE SULFATE
Dihydroergotamine/Sympathomimetics 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: Concurrent use of dihydroergotamine and sympathomimetics may result in additive or synergistic effect on peripheral blood vessels.(1) CLINICAL EFFECTS: Concurrent use of dihydroergotamine and sympathomimetics may result in increased blood pressure due to peripheral vasoconstriction.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Dihydroergotamine is contraindicated with sympathomimetics because the combination may result in additive or synergistic elevation of blood pressure.(1) DISCUSSION: Significant elevation in blood pressure has been reported in patients treated with dihydroergotamine.(1) Sympathomimetics can be expected to have additional effects on blood pressure.	BREKIYA, DIHYDROERGOTAMINE MESYLATE, MIGRANAL, TRUDHESA

Drug Interaction

Drug Names

Mixed & Indirect Sympathomimetics; Oral Phenylephrine/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: 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.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Concurrent use of monoamine oxidase inhibitors and sympathomimetics is contraindicated. The manufacturers of sympathomimetic agents recommend waiting 14 days after discontinuation of MAO inhibitors before initiating the sympathomimetic.

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. Since procarbazine, an antineoplastic agent, is a weak monoamine oxidase inhibitor, hypertensive reactions may result from its concurrent use with indirect and mixed acting sympathomimetics. Furazolidone, an antibacterial with monoamine oxidase inhibitor action, has also been shown to interact with indirect acting sympathomimetics.

Linezolid is another antibacterial with monoamine oxidase inhibitor properties. Metaxalone is a weak inhibitor of MAO. Foods containing large amounts of tyramine have also been implicated in this interaction.

Methylene blue, when administered intravenously, has been shown to reach sufficient concentrations to be a potent inhibitor of MAO-A. At recommended dosages, rasagiline, 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. 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.

EMSAM, FURAZOLIDONE, MARPLAN, MATULANE, METAXALONE, METHYLENE BLUE, NARDIL, PARNATE, PHENELZINE SULFATE, PROCARBAZINE HCL, PROVAYBLUE, SELEGILINE HCL, TRANYLCYPROMINE SULFATE

Dihydroergotamine/Sympathomimetics

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: Concurrent use of dihydroergotamine and sympathomimetics may result in additive or synergistic effect on peripheral blood vessels.(1)

CLINICAL EFFECTS: Concurrent use of dihydroergotamine and sympathomimetics may result in increased blood pressure due to peripheral vasoconstriction.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Dihydroergotamine is contraindicated with sympathomimetics because the combination may result in additive or synergistic elevation of blood pressure.(1)

DISCUSSION: Significant elevation in blood pressure has been reported in patients treated with dihydroergotamine.(1) Sympathomimetics can be expected to have additional effects on blood pressure.

BREKIYA, DIHYDROERGOTAMINE MESYLATE, MIGRANAL, TRUDHESA

There are 5 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
Ergot Alkaloids/Sympathomimetics SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Concurrent use of ergot alkaloids and sympathomimetics may result in additive or synergistic effect on peripheral blood vessels. CLINICAL EFFECTS: Concurrent use of ergot alkaloids and sympathomimetics may result in increased blood pressure due to peripheral vasoconstriction. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: When possible, avoid the concurrent use of ergot alkaloids and sympathomimetics. If concurrent use is warranted, monitor blood pressure and for signs of vasoconstriction. Decreasing the dose of one or both drugs may be necessary. DISCUSSION: There have been reports of severe vasoconstriction resulting in gangrene in patients receiving intravenous ergonovine with dopamine or norepinephrine.	ERGOLOID MESYLATES, ERGOMAR, ERGOTAMINE TARTRATE, ERGOTAMINE-CAFFEINE, METHYLERGONOVINE MALEATE, METHYSERGIDE MALEATE, MIGERGOT
Mixed & Indirect Sympathomimetics; Oral Phenylephrine/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 indirect acting sympathomimetics should not receive linezolid unless they are monitored for potential increases in blood pressure. Initial dosages of dopamine 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.	EMSAM, LINEZOLID, LINEZOLID-0.9% NACL, LINEZOLID-D5W, SELEGILINE HCL, XADAGO, ZELAPAR, ZYVOX
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
Alprostadil/Acetaminophen; NSAIDs SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Alprostadil is a prostaglandin E1 product used to maintain patency of a patent ductus arteriosus (PDA).(1) Acetaminophen and nonsteroidal anti-inflammatory (NSAID) agents inhibit prostaglandins and may be used for PDA closure in addition to pain/fever management.(2-4) CLINICAL EFFECTS: Simultaneous administration of acetaminophen or NSAIDs may result in decreased clinical effects from alprostadil, including reduction in PDA.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Avoid concurrent administration of acetaminophen or NSAIDs in patients on alprostadil for maintaining patency of a patent ductus arteriosus (PDA).(1) DISCUSSION: NSAIDs and acetaminophen are used as management for patent ductus arteriosus (PDA) closure.(2-4) Alprostadil is used to maintain patency of a PDA.(1) In a case report, a 37-week gestational age neonate with cardiac defects required alprostadil therapy for PDA patency. After multiple doses of acetaminophen for pain, an echocardiogram showed reduction of the PDA requiring increased doses of alprostadil. Additional acetaminophen was discontinued. Follow up echocardiogram showed successful reversal of PDA reduction and alprostadil dose was reduced.(5)	ALPROSTADIL, PROSTAGLANDIN E1, PROSTIN VR PEDIATRIC
Mixed & Indirect Sympathomimetics; Oral Phenylephrine/Rasagiline 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. Hypertensive crisis has been reported in patients taking recommended doses of rasagiline with sympathomimetic agents. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: At recommended dosages, rasagiline is selective for MAO-B; however, at higher dosages it has been shown to lose its selectivity. Patients receiving higher dosages of rasagiline should be considered susceptive to this interaction. Concurrent use should be approached with caution. 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.	AZILECT, RASAGILINE MESYLATE

There are 6 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
Sympathomimetics (Direct, Mixed-Acting)/Guanethidine SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Direct or mixed-acting sympathomimetics may inhibit uptake of guanethidine at the adrenergic neuron. CLINICAL EFFECTS: Decreased antihypertensive effectiveness. Effects may be seen for several days after discontinuation of the direct or mixed-acting sympathomimetic. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Avoid concomitant administration of these drugs. If both drugs are administered, adjust the guanethidine dose as needed based on blood pressure. DISCUSSION: Documentation supports routine monitoring of this interaction. It should be noted that this interaction can occur quickly.	GUANETHIDINE HEMISULFATE
Sympathomimetics/Rauwolfia Alkaloids SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Reserpine depletes catecholamine stores within the peripheral vascular adrenergic nerve endings, thus indirect acting sympathomimetics are unable to trigger the release of catecholamines. The reserpine-induced catecholamine release increases sensitivity to the effects of direct acting sympathomimetics. CLINICAL EFFECTS: Increased effects of direct acting sympathomimetics. Decreased effects of indirect acting sympathomimetics. Mixed acting sympathomimetics will show effects based on the predominance of either direct or indirect activity. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: If these agents are administered concurrently, monitor blood pressure. The dose of the sympathomimetic may need to be adjusted. DISCUSSION: This interaction has been well documented in animal studies and human case reports have confirmed the interaction. Reserpine has been shown to decrease the response to epinephrine administered for hypotension. Reserpine has also been shown to decrease the effectiveness of ophthalmic epinephrine, a direct acting sympathomimetic. Ophthalmic phenylephrine has been shown to decrease the hypotensive effects of reserpine.	RESERPINE
Sympathomimetics (Direct, Mixed-Acting)/Methyldopa SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Unknown. CLINICAL EFFECTS: The pressor response to sympathomimetics may be increased. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Start with low doses of sympathomimetics and monitor blood pressure of patients during concurrent administration of sympathomimetics and methyldopa. DISCUSSION: The pressor response to sympathomimetics has been reported to be increased during methyldopa administration. In addition to increased duration of pressor response, severe hypertension has been reported.	METHYLDOPA, METHYLDOPA-HYDROCHLOROTHIAZIDE, METHYLDOPATE HCL
Acetaminophen/Isoniazid SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Isoniazid may induce the metabolism of acetaminophen to its toxic N-acetyl-p-benzoquinone imine (NAPQI) metabolite by CYP2E1.(1) CLINICAL EFFECTS: Concurrent isoniazid and acetaminophen may result in hepatotoxicity.(1) Symptoms can include nausea, vomiting, jaundice, dark urine, abdominal pain, and unexplained fatigue. PREDISPOSING FACTORS: The interaction may be more severe in fast acetylators. PATIENT MANAGEMENT: Concurrent use of acetaminophen in patients treated with isoniazid should be approached with caution. Consider an alternative analgesic agent. If concurrent therapy is warranted, advise patients not to exceed the maximum recommended daily dose of acetaminophen and to immediately report any symptoms of hepatotoxicity. DISCUSSION: Isoniazid has been shown to induce, after initially inhibiting, the metabolism of acetaminophen to N-acetyl-p-benzoquinone imine (NAPQI), which is hepatotoxicity. Normally, NAPQI is rapidly converted to non-toxic metabolites by glutathione; however, high levels of NAPQI can overwhelm this system.(2-4) In a case report, a patient receiving isoniazid developed severe acetaminophen toxicity following a suicide attempt, despite only having ingested a maximum of 11.5 grams of acetaminophen and having a blood acetaminophen level of 15 mmol/L 13 hours later. Toxicity is usually seen with levels greater than 26 mmol/L.(5) In a retrospective review of 20 deaths in patients taking isoniazid alone or with ethambutol during a 13 year period, two deaths involved patients receiving concurrent isoniazid and acetaminophen.(6,7)	ISONIAZID
Selected Anticoagulants/Acetaminophen SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Acetaminophen may reduce levels of functional Factor VI, thereby increasing the International Normalized Ratio (INR).(1) In one trial factors II and VII levels were also reduced, thereby increasing the INR. (2) CLINICAL EFFECTS: Concurrent use of routine acetaminophen, especially at dosages greater than 2 grams/day, and coumarin anticoagulants may result in elevated anticoagulant effects. PREDISPOSING FACTORS: Routine use of acetaminophen at dosages greater than 2 grams/day may increase the risk of the interaction. PATIENT MANAGEMENT: Patients receiving routine acetaminophen at dosages greater than 2 grams/day with coumarin anticoagulants should be closely monitored for changes in anticoagulant effects. The dosage of the anticoagulant may need to be adjusted. Patients receiving coumarin anticoagulants should be counseled on the use of acetaminophen. DISCUSSION: A large systematic review was performed on 72 warfarin drug-drug interactions studies that reported on bleeding, thromboembolic events, or death. Most studies were retrospective cohorts. A meta-analysis of 4 of those studies found a higher rate of clinically significant bleeding in patients on warfarin and non-NSAID analgesics (OR=2.12; 95% CI 1.65-2.73). Increased bleeding risk was also seen in subgroup analyses with acetaminophen (OR=2.32; 95% CI 1.22-4.44).(3) In a study in 11 patients maintained on warfarin, use of acetaminophen (4 grams daily for 14 days) increased INR values by an average of 1.04.(4) In a study in 36 patients maintained on warfarin, the addition of acetaminophen (2 grams/day or 4 grams/day) increased INR values.(5) In a study in 20 patients maintained on warfarin, the addition of acetaminophen (4 grams/day for 14 days) increased average INR values by 1.20 (from 2.6 to 3.45).(6) In a study, 12 patients maintained on various anticoagulants (anisindione, dicoumarol, phenprocoumon, and warfarin) who received 4 weeks of acetaminophen (2.6 grams/day) were compared to 50 subjects maintained on various anticoagulants who did not receive acetaminophen. By the third week of concurrent acetaminophen, prothrombin times increased from 23 seconds to 28.4 seconds. The average warfarin-equivalent dose decreased by 5.8 mg to 4.4 mg. In another phase, 50 subjects maintained on various anticoagulants received acetaminophen (2.6 grams/day for 14 days). The mean prothrombin increase was 3.6 seconds.(7) There have been case reports of increased INRs following concurrent acetaminophen in patients maintained on warfarin(8-11) and acenocoumarol.(12) In contrast to the above reports, other studies have found no effects on acenocoumarol,(14) phenprocoumon,(13-15) or warfarin(16,17) by acetaminophen. In a study in 45 patients maintained on warfarin, the addition of acetaminophen (2 or 3 grams/day for 10 days) increased average INR by 0.7 and 0.67 with 2 grams/day and 3 grams/day, respectively. This increase was apparent by day 3, and a decrease in factor II and VII was observed.(2) A self-controlled case study of 1,622 oral anticoagulant-precipitant drug pairs were reviewed and found 14% of drug pairs were associated with a statistically significant elevated risk of thromboembolism. Concurrent use of warfarin and acetaminophen resulted in a ratio of rate ratios (95% CI) of 1.28 (1.18-1.38).(18) One or more of the drug pairs linked to this monograph have been included in a list of interactions that could be considered for classification as "non-interruptive" 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.	DICUMAROL, JANTOVEN, WARFARIN SODIUM
Busulfan/Acetaminophen SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Busulfan is eliminated from the body via glutathione conjugation. Acetaminophen reduces glutathione levels in the blood and tissues and therefore could decrease the elimination rate of busulfan.(1,2) CLINICAL EFFECTS: Concurrent use of acetaminophen may result in elevated levels of, prolonged exposure to, and toxicity from busulfan, including myelosuppression, granulocytopenia, thrombocytopenia, anemia, seizures, hepatic veno-occlusive disease, cardiac tamponade, bronchopulmonary dysplasia, or cellular dysplasia.(1,2) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Use acetaminophen concurrent with busulfan with caution.(1) Consider withholding acetaminophen for 72 hours before and during busulfan therapy. If concurrent use cannot be avoided, monitor patients for busulfan toxicity. DISCUSSION: Although a small population study in adult patients found no effect of acetaminophen on busulfan clearance,(3) caution is still warranted.(1)	BUSULFAN, BUSULFEX, MYLERAN

The following contraindication information is available for NEXAFED SINUS PRESSURE-PAIN (pseudoephedrine hcl/acetaminophen):

Overview
Contraindicated
Severe
Moderate

Drug contraindication overview.

No enhanced Contraindications information available for this drug.

There are 6 contraindications. Absolute contraindication.

Contraindication List
Acetaminophen overdose
Acute hepatic failure
Acute hepatitis C
Severe coronary artery disease
Severe uncontrolled hypertension
Urinary retention

There are 9 severe contraindications. Adequate patient monitoring is recommended for safer drug use.

Severe List
Angle-closure glaucoma
Benign prostatic hyperplasia
Diabetes mellitus
Disease of liver
Hypertension
Hyperthyroidism
Pheochromocytoma
Protein-calorie malnutrition
Shock

There are 2 moderate contraindications. Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.

Moderate List
Kidney disease with reduction in glomerular filtration rate (GFr)
Severe hepatic disease

The following adverse reaction information is available for NEXAFED SINUS PRESSURE-PAIN (pseudoephedrine hcl/acetaminophen):

Overview
Severe
Less Severe

Adverse reaction overview.

No enhanced Common Adverse Effects information available for this drug.

There are 22 severe adverse reactions.

More Frequent	Less Frequent
None.	Abnormal hepatic function tests

Rare/Very Rare
Acute generalized exanthematous pustulosis Acute hepatic failure Agranulocytosis Allergic dermatitis Angioedema Drug-induced hepatitis Dyspnea Hallucinations Hypertension Ischemic colitis Laryngeal edema Leukopenia Maculopapular rash Neutropenic disorder Posterior reversible encephalopathy syndrome Reversible cerebral vasoconstriction syndrome Seizure disorder Stevens-johnson syndrome Thrombocytopenic disorder Toxic epidermal necrolysis Vomiting

Rare/Very Rare

Acute generalized exanthematous pustulosis
Acute hepatic failure
Agranulocytosis
Allergic dermatitis
Angioedema
Drug-induced hepatitis
Dyspnea
Hallucinations
Hypertension
Ischemic colitis
Laryngeal edema
Leukopenia
Maculopapular rash
Neutropenic disorder
Posterior reversible encephalopathy syndrome
Reversible cerebral vasoconstriction syndrome
Seizure disorder
Stevens-johnson syndrome
Thrombocytopenic disorder
Toxic epidermal necrolysis
Vomiting

There are 26 less severe adverse reactions.

More Frequent	Less Frequent
Headache disorder Insomnia	Agitation Anorexia Dizziness Drowsy Dysuria General weakness Nausea Nervousness Pallor Tachycardia Tremor

Rare/Very Rare
Abdominal pain with cramps Cardiac arrhythmia Chest tightness Dyspepsia Erythema Excitement Hyperhidrosis Medication overuse headache Palpitations Skin rash Symptoms of anxiety Syncope Urticaria

The following precautions are available for NEXAFED SINUS PRESSURE-PAIN (pseudoephedrine hcl/acetaminophen):

Pediatric
Pregnant
Lactation
Geriatric

No enhanced Pediatric Use information available for this drug.

Contraindicated

None

Severe Precaution

None

Management or Monitoring Precaution

None

Epidemiologic data regarding oral acetaminophen use in pregnant women have shown no increased risk of major congenital malformations in infants exposed in utero to the drug. In a large population-based prospective cohort study involving more than 26,000 women with live-born singleton infants who were exposed to oral acetaminophen during the first trimester of pregnancy, no increase in the risk of congenital malformations was observed in exposed children compared with a control group of unexposed children; the rate of congenital malformations (4.3%) was similar to the rate in the general population. A population-based, case-control study from the National Birth Defects Prevention Study also found no increase in the risk of major birth defects in a group of 11,610 children who had been exposed to acetaminophen during the first trimester of pregnancy compared with a control group of 4500 children.

Animal reproduction studies in pregnant rats given oral acetaminophen during organogenesis at dosages up to 0.85 times the maximum recommended human daily dosage (4 g daily, based on body surface area comparison) showed evidence of fetotoxicity (reduced fetal weight and length) and a dose-related increase in bone variations (reduced ossification and rudimentary rib changes); the offspring showed no evidence of external, visceral, or skeletal malformations. When pregnant rats received oral acetaminophen throughout gestation at a dosage of 1.2

times the maximum recommended human daily dosage, areas of necrosis occurred in both the liver and kidney of pregnant rats and fetuses; these effects did not occur in animals given acetaminophen at dosages of 0.3 times the maximum recommended human dosage. In a continuous breeding study in which pregnant mice were given acetaminophen at dosages approximately equivalent to 0.43,

0.87, or 1.7 times the maximum recommended human daily dosage (based on body surface area comparison), a dose-related reduction in body weight of the fourth and fifth litter offspring of the treated mating pair occurred during lactation and following weaning at all dosages studied.

Animals receiving the highest dosage had a reduced number of litters per mating pair, male offspring with an increased percentage of abnormal sperm, and reduced birth weights in the next-generation pups. Acetaminophen is commonly used during all stages of pregnancy for its analgesic and antipyretic effects. Although acetaminophen has been thought not to be associated with risk in offspring, some recent reports have questioned this assessment, especially with frequent maternal use or in cases involving genetic variability.

FDA reviewed data on a possible association between acetaminophen use during pregnancy and risk of attention deficit hyperactivity disorder (ADHD) in children and announced in January 2015 that the data were inconclusive. Some experts state that as with all drug use during pregnancy, routine use of acetaminophen should be avoided. The manufacturer states that there are no studies of IV acetaminophen in pregnant women and animal reproduction studies have not been conducted with this preparation.

Therefore, the manufacturer states that IV acetaminophen should be used during pregnancy only when clearly needed. Because there are no adequate and well-controlled studies of IV acetaminophen during labor and delivery, the manufacturer states that IV acetaminophen should be used in this setting only after careful assessment of potential benefits and risks.

Acetaminophen is distributed into human milk in small quantities after oral administration. Data from more than 15 nursing women suggest that approximately 1-2% of the maternal daily dosage would be ingested by a nursing infant. A case of maculopapular rash in a breast-fed infant has been reported; the rash resolved when the mother discontinued acetaminophen use and recurred when she resumed acetaminophen therapy.

The American Academy of Pediatrics and other experts state that acetaminophen is an acceptable choice for use in nursing women. The manufacturer states that IV acetaminophen should be used with caution in nursing women.

No enhanced Geriatric Use information available for this drug.

The following icd codes are available for NEXAFED SINUS PRESSURE-PAIN (pseudoephedrine hcl/acetaminophen)'s list of indications:

Fever
R50	Fever of other and unknown origin
R50.2	Drug induced fever
R50.8	Other specified fever
R50.81	Fever presenting with conditions classified elsewhere
R50.82	Postprocedural fever
R50.83	Postvaccination fever
R50.84	Febrile nonhemolytic transfusion reaction
R50.9	Fever, unspecified
Nasal congestion
R09.81	Nasal congestion
Pain
G43	Migraine
G43.0	Migraine without aura
G43.00	Migraine without aura, not intractable
G43.001	Migraine without aura, not intractable, with status migrainosus
G43.009	Migraine without aura, not intractable, without status migrainosus
G43.01	Migraine without aura, intractable
G43.011	Migraine without aura, intractable, with status migrainosus
G43.019	Migraine without aura, intractable, without status migrainosus
G43.1	Migraine with aura
G43.10	Migraine with aura, not intractable
G43.101	Migraine with aura, not intractable, with status migrainosus
G43.109	Migraine with aura, not intractable, without status migrainosus
G43.11	Migraine with aura, intractable
G43.111	Migraine with aura, intractable, with status migrainosus
G43.119	Migraine with aura, intractable, without status migrainosus
G43.4	Hemiplegic migraine
G43.40	Hemiplegic migraine, not intractable
G43.401	Hemiplegic migraine, not intractable, with status migrainosus
G43.409	Hemiplegic migraine, not intractable, without status migrainosus
G43.41	Hemiplegic migraine, intractable
G43.411	Hemiplegic migraine, intractable, with status migrainosus
G43.419	Hemiplegic migraine, intractable, without status migrainosus
G43.5	Persistent migraine aura without cerebral infarction
G43.50	Persistent migraine aura without cerebral infarction, not intractable
G43.501	Persistent migraine aura without cerebral infarction, not intractable, with status migrainosus
G43.509	Persistent migraine aura without cerebral infarction, not intractable, without status migrainosus
G43.51	Persistent migraine aura without cerebral infarction, intractable
G43.511	Persistent migraine aura without cerebral infarction, intractable, with status migrainosus
G43.519	Persistent migraine aura without cerebral infarction, intractable, without status migrainosus
G43.6	Persistent migraine aura with cerebral infarction
G43.60	Persistent migraine aura with cerebral infarction, not intractable
G43.601	Persistent migraine aura with cerebral infarction, not intractable, with status migrainosus
G43.609	Persistent migraine aura with cerebral infarction, not intractable, without status migrainosus
G43.61	Persistent migraine aura with cerebral infarction, intractable
G43.611	Persistent migraine aura with cerebral infarction, intractable, with status migrainosus
G43.619	Persistent migraine aura with cerebral infarction, intractable, without status migrainosus
G43.7	Chronic migraine without aura
G43.70	Chronic migraine without aura, not intractable
G43.701	Chronic migraine without aura, not intractable, with status migrainosus
G43.709	Chronic migraine without aura, not intractable, without status migrainosus
G43.71	Chronic migraine without aura, intractable
G43.711	Chronic migraine without aura, intractable, with status migrainosus
G43.719	Chronic migraine without aura, intractable, without status migrainosus
G43.8	Other migraine
G43.80	Other migraine, not intractable
G43.801	Other migraine, not intractable, with status migrainosus
G43.809	Other migraine, not intractable, without status migrainosus
G43.81	Other migraine, intractable
G43.811	Other migraine, intractable, with status migrainosus
G43.819	Other migraine, intractable, without status migrainosus
G43.82	Menstrual migraine, not intractable
G43.821	Menstrual migraine, not intractable, with status migrainosus
G43.829	Menstrual migraine, not intractable, without status migrainosus
G43.83	Menstrual migraine, intractable
G43.831	Menstrual migraine, intractable, with status migrainosus
G43.839	Menstrual migraine, intractable, without status migrainosus
G43.9	Migraine, unspecified
G43.90	Migraine, unspecified, not intractable
G43.901	Migraine, unspecified, not intractable, with status migrainosus
G43.909	Migraine, unspecified, not intractable, without status migrainosus
G43.91	Migraine, unspecified, intractable
G43.911	Migraine, unspecified, intractable, with status migrainosus
G43.919	Migraine, unspecified, intractable, without status migrainosus
G43.B	Ophthalmoplegic migraine
G43.B0	Ophthalmoplegic migraine, not intractable
G43.B1	Ophthalmoplegic migraine, intractable
G43.C	Periodic headache syndromes in child or adult
G43.C0	Periodic headache syndromes in child or adult, not intractable
G43.C1	Periodic headache syndromes in child or adult, intractable
G43.D	Abdominal migraine
G43.D0	Abdominal migraine, not intractable
G43.D1	Abdominal migraine, intractable
G43.E	Chronic migraine with aura
G43.E0	Chronic migraine with aura, not intractable
G43.E01	Chronic migraine with aura, not intractable, with status migrainosus
G43.E09	Chronic migraine with aura, not intractable, without status migrainosus
G43.E1	Chronic migraine with aura, intractable
G43.E11	Chronic migraine with aura, intractable, with status migrainosus
G43.E19	Chronic migraine with aura, intractable, without status migrainosus
G44	Other headache syndromes
G44.00	Cluster headache syndrome, unspecified
G44.001	Cluster headache syndrome, unspecified, intractable
G44.009	Cluster headache syndrome, unspecified, not intractable
G44.01	Episodic cluster headache
G44.011	Episodic cluster headache, intractable
G44.019	Episodic cluster headache, not intractable
G44.02	Chronic cluster headache
G44.021	Chronic cluster headache, intractable
G44.029	Chronic cluster headache, not intractable
G44.03	Episodic paroxysmal hemicrania
G44.031	Episodic paroxysmal hemicrania, intractable
G44.039	Episodic paroxysmal hemicrania, not intractable
G44.04	Chronic paroxysmal hemicrania
G44.041	Chronic paroxysmal hemicrania, intractable
G44.049	Chronic paroxysmal hemicrania, not intractable
G44.05	Short lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCt)
G44.051	Short lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCt), intractable
G44.059	Short lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCt), not intractable
G44.1	Vascular headache, not elsewhere classified
G44.2	Tension-type headache
G44.20	Tension-type headache, unspecified
G44.201	Tension-type headache, unspecified, intractable
G44.209	Tension-type headache, unspecified, not intractable
G44.21	Episodic tension-type headache
G44.211	Episodic tension-type headache, intractable
G44.219	Episodic tension-type headache, not intractable
G44.22	Chronic tension-type headache
G44.221	Chronic tension-type headache, intractable
G44.229	Chronic tension-type headache, not intractable
G44.3	Post-traumatic headache
G44.30	Post-traumatic headache, unspecified
G44.301	Post-traumatic headache, unspecified, intractable
G44.309	Post-traumatic headache, unspecified, not intractable
G44.31	Acute post-traumatic headache
G44.311	Acute post-traumatic headache, intractable
G44.319	Acute post-traumatic headache, not intractable
G44.32	Chronic post-traumatic headache
G44.321	Chronic post-traumatic headache, intractable
G44.329	Chronic post-traumatic headache, not intractable
G44.4	Drug-induced headache, not elsewhere classified
G44.40	Drug-induced headache, not elsewhere classified, not intractable
G44.41	Drug-induced headache, not elsewhere classified, intractable
G44.5	Complicated headache syndromes
G44.51	Hemicrania continua
G44.52	New daily persistent headache (NDPh)
G44.53	Primary thunderclap headache
G44.59	Other complicated headache syndrome
G44.8	Other specified headache syndromes
G44.81	Hypnic headache
G44.82	Headache associated with sexual activity
G44.83	Primary cough headache
G44.84	Primary exertional headache
G44.85	Primary stabbing headache
G44.86	Cervicogenic headache
G44.89	Other headache syndrome
G50.1	Atypical facial pain
G89	Pain, not elsewhere classified
G89.0	Central pain syndrome
G89.1	Acute pain, not elsewhere classified
G89.11	Acute pain due to trauma
G89.12	Acute post-thoracotomy pain
G89.18	Other acute postprocedural pain
G89.2	Chronic pain, not elsewhere classified
G89.21	Chronic pain due to trauma
G89.22	Chronic post-thoracotomy pain
G89.28	Other chronic postprocedural pain
G89.29	Other chronic pain
G89.3	Neoplasm related pain (acute) (chronic)
G89.4	Chronic pain syndrome
G90.5	Complex regional pain syndrome I (CRPS i)
G90.50	Complex regional pain syndrome i, unspecified
G90.51	Complex regional pain syndrome I of upper limb
G90.511	Complex regional pain syndrome I of right upper limb
G90.512	Complex regional pain syndrome I of left upper limb
G90.513	Complex regional pain syndrome I of upper limb, bilateral
G90.519	Complex regional pain syndrome I of unspecified upper limb
G90.52	Complex regional pain syndrome I of lower limb
G90.521	Complex regional pain syndrome I of right lower limb
G90.522	Complex regional pain syndrome I of left lower limb
G90.523	Complex regional pain syndrome I of lower limb, bilateral
G90.529	Complex regional pain syndrome I of unspecified lower limb
G90.59	Complex regional pain syndrome I of other specified site
H57.1	Ocular pain
H57.10	Ocular pain, unspecified eye
H57.11	Ocular pain, right eye
H57.12	Ocular pain, left eye
H57.13	Ocular pain, bilateral
H92	Otalgia and effusion of ear
H92.0	Otalgia
H92.01	Otalgia, right ear
H92.02	Otalgia, left ear
H92.03	Otalgia, bilateral
H92.09	Otalgia, unspecified ear
K14.6	Glossodynia
M25.5	Pain in joint
M25.50	Pain in unspecified joint
M25.51	Pain in shoulder
M25.511	Pain in right shoulder
M25.512	Pain in left shoulder
M25.519	Pain in unspecified shoulder
M25.52	Pain in elbow
M25.521	Pain in right elbow
M25.522	Pain in left elbow
M25.529	Pain in unspecified elbow
M25.53	Pain in wrist
M25.531	Pain in right wrist
M25.532	Pain in left wrist
M25.539	Pain in unspecified wrist
M25.54	Pain in joints of hand
M25.541	Pain in joints of right hand
M25.542	Pain in joints of left hand
M25.549	Pain in joints of unspecified hand
M25.55	Pain in hip
M25.551	Pain in right hip
M25.552	Pain in left hip
M25.559	Pain in unspecified hip
M25.56	Pain in knee
M25.561	Pain in right knee
M25.562	Pain in left knee
M25.569	Pain in unspecified knee
M25.57	Pain in ankle and joints of foot
M25.571	Pain in right ankle and joints of right foot
M25.572	Pain in left ankle and joints of left foot
M25.579	Pain in unspecified ankle and joints of unspecified foot
M25.59	Pain in other specified joint
M26.62	Arthralgia of temporomandibular joint
M26.621	Arthralgia of right temporomandibular joint
M26.622	Arthralgia of left temporomandibular joint
M26.623	Arthralgia of bilateral temporomandibular joint
M26.629	Arthralgia of temporomandibular joint, unspecified side
M54	Dorsalgia
M54.2	Cervicalgia
M54.4	Lumbago with sciatica
M54.40	Lumbago with sciatica, unspecified side
M54.41	Lumbago with sciatica, right side
M54.42	Lumbago with sciatica, left side
M54.5	Low back pain
M54.50	Low back pain, unspecified
M54.51	Vertebrogenic low back pain
M54.59	Other low back pain
M54.6	Pain in thoracic spine
M54.8	Other dorsalgia
M54.89	Other dorsalgia
M54.9	Dorsalgia, unspecified
M77.4	Metatarsalgia
M77.40	Metatarsalgia, unspecified foot
M77.41	Metatarsalgia, right foot
M77.42	Metatarsalgia, left foot
M79.1	Myalgia
M79.10	Myalgia, unspecified site
M79.11	Myalgia of mastication muscle
M79.12	Myalgia of auxiliary muscles, head and neck
M79.18	Myalgia, other site
M79.6	Pain in limb, hand, foot, fingers and toes
M79.60	Pain in limb, unspecified
M79.601	Pain in right arm
M79.602	Pain in left arm
M79.603	Pain in arm, unspecified
M79.604	Pain in right leg
M79.605	Pain in left leg
M79.606	Pain in leg, unspecified
M79.609	Pain in unspecified limb
M79.62	Pain in upper arm
M79.621	Pain in right upper arm
M79.622	Pain in left upper arm
M79.629	Pain in unspecified upper arm
M79.63	Pain in forearm
M79.631	Pain in right forearm
M79.632	Pain in left forearm
M79.639	Pain in unspecified forearm
M79.64	Pain in hand and fingers
M79.641	Pain in right hand
M79.642	Pain in left hand
M79.643	Pain in unspecified hand
M79.644	Pain in right finger(s)
M79.645	Pain in left finger(s)
M79.646	Pain in unspecified finger(s)
M79.65	Pain in thigh
M79.651	Pain in right thigh
M79.652	Pain in left thigh
M79.659	Pain in unspecified thigh
M79.66	Pain in lower leg
M79.661	Pain in right lower leg
M79.662	Pain in left lower leg
M79.669	Pain in unspecified lower leg
M79.67	Pain in foot and toes
M79.671	Pain in right foot
M79.672	Pain in left foot
M79.673	Pain in unspecified foot
M79.674	Pain in right toe(s)
M79.675	Pain in left toe(s)
M79.676	Pain in unspecified toe(s)
N23	Unspecified renal colic
N64.4	Mastodynia
N94	Pain and other conditions associated with female genital organs and menstrual cycle
N94.0	Mittelschmerz
N94.3	Premenstrual tension syndrome
N94.4	Primary dysmenorrhea
N94.5	Secondary dysmenorrhea
N94.6	Dysmenorrhea, unspecified
R07	Pain in throat and chest
R07.0	Pain in throat
R07.1	Chest pain on breathing
R07.2	Precordial pain
R07.81	Pleurodynia
R07.82	Intercostal pain
R07.89	Other chest pain
R07.9	Chest pain, unspecified
R10	Abdominal and pelvic pain
R10.0	Acute abdomen
R10.1	Pain localized to upper abdomen
R10.10	Upper abdominal pain, unspecified
R10.11	Right upper quadrant pain
R10.12	Left upper quadrant pain
R10.2	Pelvic and perineal pain
R10.20	Pelvic and perineal pain unspecified side
R10.21	Pelvic and perineal pain right side
R10.22	Pelvic and perineal pain left side
R10.23	Pelvic and perineal pain bilateral
R10.24	Suprapubic pain
R10.3	Pain localized to other parts of lower abdomen
R10.30	Lower abdominal pain, unspecified
R10.31	Right lower quadrant pain
R10.32	Left lower quadrant pain
R10.33	Periumbilical pain
R10.8	Other abdominal pain
R10.83	Colic
R10.84	Generalized abdominal pain
R10.85	Abdominal pain of multiple sites
R10.9	Unspecified abdominal pain
R10.A	Pain localized to flank
R10.A0	Flank pain, unspecified side
R10.A1	Flank pain, right side
R10.A2	Flank pain, left side
R10.A3	Flank pain, bilateral
R51	Headache
R51.0	Headache with orthostatic component, not elsewhere classified
R51.9	Headache, unspecified
R52	Pain, unspecified
R68.84	Jaw pain
T82.84	Pain due to cardiac and vascular prosthetic devices, implants and grafts
T82.847	Pain due to cardiac prosthetic devices, implants and grafts
T82.847A	Pain due to cardiac prosthetic devices, implants and grafts, initial encounter
T82.847D	Pain due to cardiac prosthetic devices, implants and grafts, subsequent encounter
T82.848	Pain due to vascular prosthetic devices, implants and grafts
T82.848A	Pain due to vascular prosthetic devices, implants and grafts, initial encounter
T82.848D	Pain due to vascular prosthetic devices, implants and grafts, subsequent encounter
T83.84	Pain due to genitourinary prosthetic devices, implants and grafts
T83.84xA	Pain due to genitourinary prosthetic devices, implants and grafts, initial encounter
T83.84xD	Pain due to genitourinary prosthetic devices, implants and grafts, subsequent encounter
T84.84	Pain due to internal orthopedic prosthetic devices, implants and grafts
T84.84xA	Pain due to internal orthopedic prosthetic devices, implants and grafts, initial encounter
T84.84xD	Pain due to internal orthopedic prosthetic devices, implants and grafts, subsequent encounter
T85.84	Pain due to internal prosthetic devices, implants and grafts, not elsewhere classified
T85.840	Pain due to nervous system prosthetic devices, implants and grafts
T85.840A	Pain due to nervous system prosthetic devices, implants and grafts, initial encounter
T85.840D	Pain due to nervous system prosthetic devices, implants and grafts, subsequent encounter
T85.848	Pain due to other internal prosthetic devices, implants and grafts
T85.848A	Pain due to other internal prosthetic devices, implants and grafts, initial encounter
T85.848D	Pain due to other internal prosthetic devices, implants and grafts, subsequent encounter
Sinus headache
R51	Headache
R51.9	Headache, unspecified