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Drug overview for ALKA-SELTZER PLUS-D SINUS-COLD (dextromethorphan/pseudoephedrine/acetaminophen/chlorpheniram):
Generic name: dextromethorphan/pseudoephedrine/acetaminophen/chlorpheniram
Drug class: Amphetamines/Anorexiants/Stimulants
Therapeutic class: Respiratory Therapy Agents
Acetaminophen is a synthetic nonopiate derivative of p-aminophenol that Chlorpheniramine is an alkylamine (propylamine)-derivative, first Dextromethorphan, a derivative of levorphanol, is an antitussive agent. Pseudoephedrine is a sympathomimetic agent that occurs naturally in plants generation antihistamine. of the genus Ephedra; the drug acts directly on both alpha- and, to a produces analgesia and antipyresis. lesser degree, beta-adrenergic receptors.
Acetaminophen is used extensively in the treatment of mild to moderate pain Dextromethorphan is used for the temporary relief of coughs caused by minor Pseudoephedrine is used as a nasal decongestant for self-medication for the and fever. temporary relief of nasal congestion associated with upper respiratory throat and bronchial irritation such as may occur with common colds or with allergy and to provide temporary relief of sinus congestion and pressure. inhaled irritants.
Dextromethorphan is most effective in the treatment of chronic, nonproductive cough. The drug is a common ingredient in commercial The drug also has been used for self-medication in the symptomatic cough mixtures available without prescription. prevention of otitic barotrauma+ (aerotitis ( barotitis) media).
Pseudoephedrine also has been misused for clandestine synthesis of Although cough and cold preparations that contain cough suppressants methamphetamine and methcathinone for illicit use. (including dextromethorphan), nasal decongestants, antihistamines, and/or expectorants commonly are used in pediatric patients younger than 2 years of age, systematic reviews of controlled trials have concluded that nonprescription (over-the-counter, OTC) cough and cold preparations are not more effective than placebo in reducing acute cough and other symptoms of upper respiratory tract infection in these patients. Furthermore, adverse events, including deaths, have been (and continue to be) reported in pediatric patients younger than 2 years of age receiving these preparations.
(See Cautions: Pediatric Precautions and see Acute Toxicity: Manifestations.) For information on abuse of dextromethorphan, see Cautions. For use of dextromethorphan hydrobromide in fixed combination with quinidine sulfate in the treatment of pseudobulbar affect (PBA), see Dextromethorphan Hydrobromide and Quinidine Sulfate 28:92.
Generic name: dextromethorphan/pseudoephedrine/acetaminophen/chlorpheniram
Drug class: Amphetamines/Anorexiants/Stimulants
Therapeutic class: Respiratory Therapy Agents
Acetaminophen is a synthetic nonopiate derivative of p-aminophenol that Chlorpheniramine is an alkylamine (propylamine)-derivative, first Dextromethorphan, a derivative of levorphanol, is an antitussive agent. Pseudoephedrine is a sympathomimetic agent that occurs naturally in plants generation antihistamine. of the genus Ephedra; the drug acts directly on both alpha- and, to a produces analgesia and antipyresis. lesser degree, beta-adrenergic receptors.
Acetaminophen is used extensively in the treatment of mild to moderate pain Dextromethorphan is used for the temporary relief of coughs caused by minor Pseudoephedrine is used as a nasal decongestant for self-medication for the and fever. temporary relief of nasal congestion associated with upper respiratory throat and bronchial irritation such as may occur with common colds or with allergy and to provide temporary relief of sinus congestion and pressure. inhaled irritants.
Dextromethorphan is most effective in the treatment of chronic, nonproductive cough. The drug is a common ingredient in commercial The drug also has been used for self-medication in the symptomatic cough mixtures available without prescription. prevention of otitic barotrauma+ (aerotitis ( barotitis) media).
Pseudoephedrine also has been misused for clandestine synthesis of Although cough and cold preparations that contain cough suppressants methamphetamine and methcathinone for illicit use. (including dextromethorphan), nasal decongestants, antihistamines, and/or expectorants commonly are used in pediatric patients younger than 2 years of age, systematic reviews of controlled trials have concluded that nonprescription (over-the-counter, OTC) cough and cold preparations are not more effective than placebo in reducing acute cough and other symptoms of upper respiratory tract infection in these patients. Furthermore, adverse events, including deaths, have been (and continue to be) reported in pediatric patients younger than 2 years of age receiving these preparations.
(See Cautions: Pediatric Precautions and see Acute Toxicity: Manifestations.) For information on abuse of dextromethorphan, see Cautions. For use of dextromethorphan hydrobromide in fixed combination with quinidine sulfate in the treatment of pseudobulbar affect (PBA), see Dextromethorphan Hydrobromide and Quinidine Sulfate 28:92.
DRUG IMAGES
ALKA-SELTZER PLUS-D SINUS-COLD
The following indications for ALKA-SELTZER PLUS-D SINUS-COLD (dextromethorphan/pseudoephedrine/acetaminophen/chlorpheniram) have been approved by the FDA:
Indications:
Cold symptoms
Cough
Fever
Flu-like symptoms
Headache disorder
Nasal congestion
Rhinorrhea
Professional Synonyms:
Cephalgia
Cephalodynia
Febrile reaction
Febrile
Nasal stuffiness
Pyrexia
Indications:
Cold symptoms
Cough
Fever
Flu-like symptoms
Headache disorder
Nasal congestion
Rhinorrhea
Professional Synonyms:
Cephalgia
Cephalodynia
Febrile reaction
Febrile
Nasal stuffiness
Pyrexia
The following dosing information is available for ALKA-SELTZER PLUS-D SINUS-COLD (dextromethorphan/pseudoephedrine/acetaminophen/chlorpheniram):
Dosage of chlorpheniramine and dexchlorpheniramine should be individualized according to the patient's response and tolerance. Dosage of dexchlorpheniramine maleate is approximately 50% that of chlorpheniramine maleate.
Dosages of dextromethorphan hydrobromide and dextromethorphan polistirex are expressed in terms of dextromethorphan hydrobromide.
The usual dosage of dextromethorphan hydrobromide for adults and children 12 years of age or older is 10-20 mg every 4 hours or 30 mg every 6-8 hours, not to exceed 120 mg daily, or as directed by a clinician. The usual dosage for children 6 to younger than 12 years of age is 5-10 mg every 4 hours or 15 mg every 6-8 hours, not to exceed 60 mg daily, or as directed by a clinician. Children 2 to younger than 6 years of age may receive 2.5-5
mg every 4 hours or 7.5 mg every 6-8 hours, not to exceed 30 mg daily, or as directed by a clinician. Dosage in children younger than 2 years of age must be individualized.
Suggested dosages for children younger than 2 years of age+ for some cough and cold preparations have been published in various references for prescribing and parenting. Using recommended dosages for adults and older children, some clinicians have extrapolated dosages for these preparations based on the weight or age of children younger than 2 years of age. However, these extrapolations were based on assumptions that pathology of the disease and pharmacology of the drugs are similar in adults and pediatric patients.
There currently are no specific dosage recommendations (i.e., approved by the US Food and Drug Administration (FDA)) for cough and cold preparations for this patient population. (See Cautions: Pediatric Precautions.)
The usual dosage of dextromethorphan hydrobromide as the extended-release oral suspension containing the polistirex for adults and children 12 years of age or older is 60 mg twice daily. The usual dosage as the extended-release oral suspension for children 6 to younger than 12 years of age is 30 mg twice daily; children 2 to younger than 6 years of age may receive 15 mg twice daily.
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.)
Dosages of dextromethorphan hydrobromide and dextromethorphan polistirex are expressed in terms of dextromethorphan hydrobromide.
The usual dosage of dextromethorphan hydrobromide for adults and children 12 years of age or older is 10-20 mg every 4 hours or 30 mg every 6-8 hours, not to exceed 120 mg daily, or as directed by a clinician. The usual dosage for children 6 to younger than 12 years of age is 5-10 mg every 4 hours or 15 mg every 6-8 hours, not to exceed 60 mg daily, or as directed by a clinician. Children 2 to younger than 6 years of age may receive 2.5-5
mg every 4 hours or 7.5 mg every 6-8 hours, not to exceed 30 mg daily, or as directed by a clinician. Dosage in children younger than 2 years of age must be individualized.
Suggested dosages for children younger than 2 years of age+ for some cough and cold preparations have been published in various references for prescribing and parenting. Using recommended dosages for adults and older children, some clinicians have extrapolated dosages for these preparations based on the weight or age of children younger than 2 years of age. However, these extrapolations were based on assumptions that pathology of the disease and pharmacology of the drugs are similar in adults and pediatric patients.
There currently are no specific dosage recommendations (i.e., approved by the US Food and Drug Administration (FDA)) for cough and cold preparations for this patient population. (See Cautions: Pediatric Precautions.)
The usual dosage of dextromethorphan hydrobromide as the extended-release oral suspension containing the polistirex for adults and children 12 years of age or older is 60 mg twice daily. The usual dosage as the extended-release oral suspension for children 6 to younger than 12 years of age is 30 mg twice daily; children 2 to younger than 6 years of age may receive 15 mg twice daily.
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.)
Chlorpheniramine maleate and dexchlorpheniramine maleate are administered orally. Dextromethorphan preparations are administered orally. Lozenges containing dextromethorphan hydrobromide should not be used in children younger than 6 years of age and liquid-filled capsules containing the drug should not be used in children younger than 12 years of age, unless otherwise directed by a clinician.
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.
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 ALKA-SELTZER PLUS-D SINUS-COLD (dextromethorphan/pseudoephedrine/acetaminophen/chlorpheniram):
There are 5 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 |
|---|---|
| Sympathomimetics (Indirect & Mixed Acting)/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 |
| Selected Opioids; Dextromethorphan/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: Selected opioids inhibit neural reuptake of serotonin. MAOIs may increase neuronal serotonin concentrations via inhibition of MAO-A.(26) CLINICAL EFFECTS: The concurrent use of selected opioids with MAOIs has resulted in hypotension, hyperpyrexia, sedation, somnolence, and death. Symptoms of serotonin syndrome may include tremor, agitation, diaphoresis, hyperreflexia, clonus, tachycardia, hyperthermia, and muscle rigidity.(26) 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 P450 enzyme), or high opioid dosage may increase the risk for a severe interaction. PATIENT MANAGEMENT: Dextromethorphan, diamorphine, meperidine, and tapentadol should not be used in patients taking MAOIs. Use alternative agents for cough or pain. The US manufacturer of Nuedexta(dextromethorphan-quinidine) states Nuedexta is contraindicated within 14 days of MAOI administration.(28) Quinidine increases systemic dextromethorphan concentrations 10 to 20-fold. Other strong CYP2D6 inhibitors such as bupropion, fluoxetine and paroxetine could similarly increase dextromethorphan levels. The US manufacturer of selegiline states that concurrent use with dextromethorphan or meperidine is contraindicated. The US manufacturers of meperidine and tapentadol and the UK manufacturer of diamorphine state that they should not be used concurrently with or within 14 days of taking an MAOI. DISCUSSION: The interaction between meperidine and MAOIs has been well documented. There are at least two reports of potential interactions between MAOIs and dextromethorphan. Concomitant use of quinidine, a strong CYP2D6 inhibitor, increases systemic dextromethorphan concentrations 10 to 20-fold. Other strong CYP2D6 inhibitors such as bupropion, fluoxetine and paroxetine could similarly increase dextromethorphan levels and risk for serotonin toxicity in patients also receiving MAOIs. 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. 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. |
AZILECT, EMSAM, FURAZOLIDONE, MARPLAN, MATULANE, METHYLENE BLUE, NARDIL, PARNATE, PHENELZINE SULFATE, PROCARBAZINE HCL, PROVAYBLUE, RASAGILINE MESYLATE, SELEGILINE HCL, TRANYLCYPROMINE SULFATE, XADAGO, ZELAPAR |
| Selected Antihistamines/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: MAOIs prolong and intensify the effects of antihistamines.(1-6) CLINICAL EFFECTS: Concurrent use of antihistamines and a MAOI may result in severe hypotension.(1-6) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Concurrent use of antihistamines and a MAOI is contraindicated.(1-6) DISCUSSION: MAOIs may prolong and intensify the effects of antihistamines, resulting in severe hypotension.(1-6) A case report describes a patient having cyproheptadine added to their phenelzine therapy in an attempt to relieve the patients anorgasmia. The patient began to suddenly experience visual hallucination after taking the cyproheptadine for two months. Once the medication was terminated, the hallucinations stopped occurring within 48 hours.(7) Methylene blue, when administered intravenously, has been shown to reach sufficient concentrations to be a potent inhibitor of MAO-A.(8,9) |
AZILECT, EMSAM, FURAZOLIDONE, MARPLAN, MATULANE, METHYLENE BLUE, NARDIL, PARNATE, PHENELZINE SULFATE, PROCARBAZINE HCL, PROVAYBLUE, RASAGILINE MESYLATE, SELEGILINE HCL, TRANYLCYPROMINE SULFATE, XADAGO, ZELAPAR |
| Dextromethorphan/Metaxalone 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: Dextromethorphan inhibits neural reuptake of serotonin. Metaxalone, a weak inhibitor of MAO, may increase neuronal serotonin concentrations.(1) CLINICAL EFFECTS: The concurrent use of dextromethorphan with MAOIs may result in hypotension, hyperpyrexia, sedation, somnolence, and death. Symptoms of serotonin syndrome may include tremor, agitation, diaphoresis, hyperreflexia, clonus, tachycardia, hyperthermia, and muscle rigidity.(1) 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 P450 enzyme), or high opioid dosage may increase the risk for a severe interaction. PATIENT MANAGEMENT: Dextromethorphan should not be used in patients taking MAOIs such as metaxalone. Use alternative agents for cough. The US manufacturer of Nuedexta (dextromethorphan-quinidine) states Nuedexta is contraindicated within 14 days of MAOI administration.(1) Quinidine increases systemic dextromethorphan concentrations 10 to 20-fold. DISCUSSION: Metaxalone is a weak inhibitor of MAO.(2,3) There are at least two reports of potential interactions between MAOIs and dextromethorphan. Concomitant use of quinidine, a strong CYP2D6 inhibitor, increases systemic dextromethorphan concentrations 10 to 20-fold. Other strong CYP2D6 inhibitors such as bupropion, fluoxetine and paroxetine could similarly increase dextromethorphan levels and risk for serotonin toxicity in patients also receiving MAOIs.(4,5) |
METAXALONE |
| Selected CYP2D6 Substrates/Mavorixafor 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: Mavorixafor is a strong inhibitor of CYP2D6 and is expected to inhibit the metabolism of agents through this pathway.(1) CLINICAL EFFECTS: Concurrent use of mavorixafor may result in elevated levels of and toxicity from agents metabolized by CYP2D6.(1) PREDISPOSING FACTORS: With tricyclic antidepressants, the risk of seizures may be increased in patients with a history of head trauma or prior seizure; CNS tumor; severe hepatic cirrhosis; excessive use of alcohol or sedatives; addiction to opiates, cocaine, or stimulants; use of over-the-counter stimulants and anorectics; diabetics treated with oral hypoglycemics or insulin; or with concomitant medications known to lower seizure threshold (antipsychotics, theophylline, systemic steroids). With anticholinergic agents, the risk of anticholinergic toxicities including cognitive decline, delirium, falls and fractures is increased in geriatric patients using more than one medicine with anticholinergic properties.(2) PATIENT MANAGEMENT: The US manufacturer of mavorixafor states concurrent use with CYP2D6 substrate that are highly dependent on CYP2D6 metabolism is contraindicated.(1) DISCUSSION: Mavorixafor (400 mg) increased dextromethorphan (CYP2D6 substrate) maximum concentration (Cmax) and area-under-curve (AUC) by 6-fold and 9-fold, respectively.(1) Selected CYP2D6 substrates linked to this monograph include: aripiprazole, brexpiprazole, desipramine, deutetrabenazine, dextromethorphan, doxepin, encainide, fenfluramine, metoclopramide, methoxyphenamine, metoprolol, mexiletine, nebivolol, paroxetine, perphenazine, risperidone, tetrabenazine, trimipramine, venlafaxine, and yohimbine. |
XOLREMDI |
There are 15 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. |
DIHYDROERGOTAMINE MESYLATE, ERGOLOID MESYLATES, ERGOMAR, ERGOTAMINE TARTRATE, ERGOTAMINE-CAFFEINE, METHYLERGONOVINE MALEATE, METHYSERGIDE MALEATE, MIGERGOT, MIGRANAL, TRUDHESA |
| Solid Oral Potassium Tablets/Anticholinergics SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Concentrated potassium may damage the lining of the GI tract. Anticholinergics delay gastric emptying, resulting in the potassium product remaining in the gastrointestinal tract for a longer period of time.(1-16) CLINICAL EFFECTS: Use of solid oral dosage forms of potassium in patients treated with anticholinergics may result in gastrointestinal erosions, ulcers, stenosis and bleeding.(1-16) PREDISPOSING FACTORS: Diseases or conditions which may increase risk for GI damage include: preexisting dysphagia, strictures, cardiomegaly, diabetic gastroparesis, elderly status, or insufficient oral intake to allow dilution of potassium.(1-10,21) Other drugs which may add to risk for GI damage include: nonsteroidal anti-inflammatory drugs (NSAIDs), bisphosphonates, or tetracyclines.(21) PATIENT MANAGEMENT: Regulatory agency and manufacturer recommendations regarding this interaction: - In the US, all solid oral dosage forms (including tablets and extended release capsules) of potassium are contraindicated in patients receiving anticholinergics at sufficient dosages to result in systemic effects.(2-8) Patients receiving such anticholinergic therapy should use a liquid form of potassium chloride.(2) - In Canada, solid oral potassium is contraindicated in any patient with a cause for arrest or delay in tablet/capsule passage through the gastrointestinal tract and the manufacturers recommend caution with concurrent anticholinergic medications.(1,9-10) Evaluate each patient for predisposing factors which may increase risk for GI damage. In patients with multiple risk factors for harm, consider use of liquid potassium supplements, if tolerated. For patients receiving concomitant therapy, assure any potassium dose form is taken after meals with a large glass of water or other fluid. To decrease potassium concentration in the GI tract, limit each dose to 20 meq; if more than 20 meq daily is required, give in divided doses.(2) If concurrent therapy is warranted, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin, hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. Patients should be instructed to immediately report any difficulty swallowing, abdominal pain, distention, severe vomiting, or gastrointestinal 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. DISCUSSION: In clinical trials, there was a higher incidence of gastric and duodenal lesions in patients receiving a high dose of a wax-matrix controlled-release formulation with a concurrent anticholinergic agent. Some lesions were asymptomatic and not accompanied by bleeding, as shown by a lack of positive Hemoccult tests.(1-17) Several studies suggest that the incidence of gastric and duodenal lesions may be less with the microencapsulated formulation of potassium chloride.(14-17) |
K-TAB ER, KLOR-CON 10, KLOR-CON 8, KLOR-CON M10, KLOR-CON M15, KLOR-CON M20, POTASSIUM CHLORIDE, POTASSIUM CITRATE ER, UROCIT-K |
| Solid Oral Potassium Capsules/Anticholinergics SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Concentrated potassium may damage the lining of the GI tract. Anticholinergics delay gastric emptying, resulting in the potassium product remaining in the gastrointestinal tract for a longer period of time.(1-16)) CLINICAL EFFECTS: Use of solid oral dosage forms of potassium in patients treated with anticholinergics may result in gastrointestinal erosions, ulcers, stenosis and bleeding.(1-16) PREDISPOSING FACTORS: Diseases or conditions which may increase risk for GI damage include: preexisting dysphagia, strictures, cardiomegaly, diabetic gastroparesis, elderly status, or insufficient oral intake to allow dilution of potassium.(1-10,21) Other drugs which may add to risk for GI damage include: nonsteroidal anti-inflammatory drugs (NSAIDs), bisphosphonates, or tetracyclines.(21) PATIENT MANAGEMENT: Regulatory agency and manufacturer recommendations regarding this interaction: - In the US, all solid oral dosage forms (including tablets and extended release capsules) of potassium are contraindicated in patients receiving anticholinergics at sufficient dosages to result in systemic effects.(2-8) Patients receiving such anticholinergic therapy should use a liquid form of potassium chloride.(2) - In Canada, solid oral potassium is contraindicated in any patient with a cause for arrest or delay in tablet/capsule passage through the gastrointestinal tract and the manufacturers recommend caution with concurrent anticholinergic medications.(1,9-10) Evaluate each patient for predisposing factors which may increase risk for GI damage. In patients with multiple risk factors for harm, consider use of liquid potassium supplements, if tolerated. For patients receiving concomitant therapy, assure any potassium dose form is taken after meals with a large glass of water or other fluid. To decrease potassium concentration in the GI tract, limit each dose to 20 meq; if more than 20 meq daily is required, give in divided doses.(2) If concurrent therapy is warranted, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin, hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. Patients should be instructed to immediately report any difficulty swallowing, abdominal pain, distention, severe vomiting, or gastrointestinal 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. DISCUSSION: In clinical trials, there was a higher incidence of gastric and duodenal lesions in patients receiving a high dose of a wax-matrix controlled-release formulation with a concurrent anticholinergic agent. The lesions were asymptomatic and not accompanied by bleeding, as shown by a lack of positive Hemoccult tests.(1-17) Several studies suggest that the incidence of gastric and duodenal lesions may be less with the microencapsulated formulation of potassium chloride.(14-17) |
POTASSIUM CHLORIDE |
| 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. |
EMSAM, LINEZOLID, LINEZOLID-0.9% NACL, LINEZOLID-D5W, SELEGILINE HCL, XADAGO, ZELAPAR, ZYVOX |
| Radioactive Iodide/Agents that Affect Iodide SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Many compounds can affect iodide protein binding and alter iodide pharmacokinetics and pharmacodynamics.(1) CLINICAL EFFECTS: Compounds that affect iodide pharmacokinetics and pharmacodynamics may impact the effectiveness of radioactive iodide.(1) PREDISPOSING FACTORS: Compounds that affect iodide pharmacokinetics and pharmacodynamics are expected to have the most impact during therapy using radioactive iodide. Diagnostic procedures would be expected to be impacted less. PATIENT MANAGEMENT: Discuss the use of agents that affect iodide pharmacokinetics and pharmacodynamics with the patient's oncologist.(1) DISCUSSION: Many agents interact with radioactive iodine. The average duration of effect is: anticoagulants - 1 week antihistamines - 1 week anti-thyroid drugs, e.g: carbimazole, methimazole, propylthiouracil - 3-5 days corticosteroids - 1 week iodide-containing medications, e.g: amiodarone - 1-6 months expectorants - 2 weeks Lugol solution - 3 weeks saturated solution of potassium iodine - 3 weeks vitamins - 10-14 days iodide-containing X-ray contrast agents - up to 1 year lithium - 4 weeks phenylbutazone - 1-2 weeks sulfonamides - 1 week thyroid hormones (natural or synthetic), e.g.: thyroxine - 4 weeks tri-iodothyronine - 2 weeks tolbutamide - 1 week topical iodide - 1-9 months (1) |
ADREVIEW, JEANATOPE, MEGATOPE, SODIUM IODIDE I-123 |
| 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 |
| Selected CYP2D6 Substrates/Panobinostat SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Panobinostat is a moderate inhibitor of CYP2D6 and is expected to inhibit the metabolism of agents through this pathway.(1) CLINICAL EFFECTS: Concurrent use of panobinostat may result in elevated levels of and toxicity from agents metabolized by CYP2D6.(1) PREDISPOSING FACTORS: With tricyclic antidepressants, the risk of seizures may be increased in patients with a history of head trauma or prior seizure; CNS tumor; severe hepatic cirrhosis; excessive use of alcohol or sedatives; addiction to opiates, cocaine, or stimulants; use of over-the-counter stimulants and anorectics; diabetics treated with oral hypoglycemics or insulin; or with concomitant medications known to lower seizure threshold (antipsychotics, theophylline, systemic steroids). With anticholinergic agents, the risk of anticholinergic toxicities including cognitive decline, delirium, falls and fractures is increased in geriatric patients using more than one medicine with anticholinergic properties.(4) PATIENT MANAGEMENT: Avoid the concurrent use of panobinostat with agents that are sensitive CYP2D6 or CYP2D6 substrates with a narrow therapeutic index. If concurrent use is warranted, monitor patients for toxicity.(1) DISCUSSION: In a study in 14 subjects with advanced cancer, panobinostat (20 mg daily on Days 3, 5, and 8) increased the maximum concentration (Cmax) and area-under-curve (AUC) of a single dose of dextromethorphan (60 mg) by 20-200% and 20-130%, respectively. Dextromethorphan exposures were extremely variable.(1) Selected CYP2D6 substrates linked to this monograph include: desipramine, deutetrabenazine, dextromethorphan, doxepin, encainide, methoxyphenamine, metoprolol, nebivolol, paroxetine, perphenazine, risperidone, tetrabenazine, trimipramine, venlafaxine, and yohimbine. |
FARYDAK |
| Selected CYP1A2 or CYP2D6 Substrates/Givosiran SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Givosiran interferes with the first and rate-limiting step in hepatic heme biosynthesis, which may lower hepatic heme levels and decrease production and/or activity of cytochrome P450 enzymes.(1,2) CLINICAL EFFECTS: Concurrent use of givosiran may result in elevated levels of and toxicity from agents metabolized by CYP1A2 or CYP2D6.(1) PREDISPOSING FACTORS: With tricyclic antidepressants, the risk of seizures may be increased in patients with a history of head trauma or prior seizure; CNS tumor; severe hepatic cirrhosis; excessive use of alcohol or sedatives; addiction to opiates, cocaine, or stimulants; use of over-the-counter stimulants and anorectics; diabetics treated with oral hypoglycemics or insulin; or with concomitant medications known to lower seizure threshold (antipsychotics, theophylline, systemic steroids). With anticholinergic agents, the risk of anticholinergic toxicities including cognitive decline, delirium, falls and fractures is increased in geriatric patients using more than one medicine with anticholinergic properties.(3) PATIENT MANAGEMENT: Avoid the concurrent use of givosiran with agents that are sensitive substrates of CYP1A2 or CYP2D6, or CYP1A2 or CYP2D6 substrates with a narrow therapeutic index. If concurrent use is unavoidable, decrease the dose of the CYP1A2 or CYP2D6 substrate and monitor patients for toxicity. DISCUSSION: A study of 9 patients with acute intermittent porphyria found that givosiran decreased the maximum concentration (Cmax) and area-under-curve (AUC) of caffeine (a CYP1A2 substrate) by 1.3- and 3.1-fold, respectively, compared to caffeine alone. Givosiran also decreased the Cmax and AUC of dextromethorphan (a CYP2D6 substrate) by 2- and 2.4-fold, respectively, compared to dextromethorphan alone.(1,2) Selected CYP2D6 substrates linked to this monograph include: desipramine, deutetrabenazine, dextromethorphan, doxepin, encainide, methoxyphenamine, metoprolol, nebivolol, nefazodone, paroxetine, perphenazine, risperidone, tetrabenazine, trimipramine, and venlafaxine. Selected CYP1A2 substrates linked to this monograph include: agomelatine, aminophylline, rasagiline, tacrine, theophylline, tizanidine, and yohimbine. |
GIVLAARI |
| Clozapine/Anticholinergics SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Clozapine has potent anticholinergic properties and inhibits serotonin receptors, including 5-HT3.(1-4) Both of these properties may cause inhibition of gastrointestinal (GI) smooth muscle contraction, resulting in decreased peristalsis.(3,4) These effects may be compounded by concurrent use of anticholinergic agents.(1-6) CLINICAL EFFECTS: Concurrent use of clozapine with other anticholinergic agents may increase the risk of constipation (common) and serious bowel complications (uncommon), including complete bowel obstruction, fecal impaction, paralytic ileus and intestinal ischemia or infarction.(1-6) PREDISPOSING FACTORS: The risk for serious bowel complications is higher with increasing age, higher frequency of constipation, and in patients on higher doses of clozapine or multiple anticholinergic agents.(1,5) PATIENT MANAGEMENT: Avoid the use of other anticholinergic agents with clozapine.(1-6) If concurrent use is necessary, evaluate the patient's bowel function regularly. Monitor for symptoms of constipation and GI hypomotility, including having bowel movements less than three times weekly or less than usual, difficulty having a bowel movement or passing gas, nausea, vomiting, and abdominal pain or distention.(2) Consider a prophylactic laxative in those with a history of constipation or bowel obstruction.(2) Review patient medication list for other anticholinergic agents. When possible, decrease the dosage or number of prescribed anticholinergic agents, particularly in the elderly. Counsel the patient about the importance of maintaining adequate hydration. Encourage regular exercise and eating a high-fiber diet.(2) DISCUSSION: In a prospective cohort study of 26,720 schizophrenic patients in the Danish Central Psychiatric Research Registry, the odds ratio (OR) for ileus was 1.99 with clozapine and 1.48 with anticholinergics. The OR for fatal ileus was 6.73 with clozapine and 5.88 with anticholinergics. Use of anticholinergics with 1st generation antipsychotics (FGA) increased the risk of ileus compare to FGA alone, but this analysis was not done with clozapine.(5) A retrospective cohort study of 24,970 schizophrenic patients from the Taiwanese National Health Insurance Research Database found that the hazard ratio (HR) for clozapine-induced constipation increased from 1.64 when clozapine is used alone, to 2.15 when used concomitantly with anticholinergics. However, there was no significant difference in the HR for ileus when clozapine is used with and without anticholinergics (1.95 and 2.02, respectively).(6) In the French Pharmacovigilance Database, 7 of 38 cases of antipsychotic-associated ischemic colitis or intestinal necrosis involved clozapine, and 5 of these cases involved use of concomitant anticholinergic agents. Three patients died, one of whom was on concomitant anticholinergics.(3) In a case series, 4 of 9 cases of fatal clozapine-associated GI dysfunction involved concurrent anticholinergic agents.(4) |
CLOZAPINE, CLOZAPINE ODT, CLOZARIL, VERSACLOZ |
| Zonisamide/Anticholinergics SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Zonisamide can cause decreased sweating and elevated body temperature. Agents with anticholinergic activity can predispose patients to heat-related disorders.(1-2) CLINICAL EFFECTS: Concurrent use of zonisamide with agents with anticholinergic activity may increase the incidence of oligohidrosis and hyperthermia, especially in pediatric or adolescent patients.(1-2) Overheating and dehydration can lead to brain damage and death. PREDISPOSING FACTORS: Pediatric and adolescent patients and patients with dehydration may be more likely to experience heat-related disorders.(1) PATIENT MANAGEMENT: The UK and US manufacturers of zonisamide state that caution should be used in adults when zonisamide is prescribed with other medicinal products that predispose to heat-related disorders, such as agents with anticholinergic activity.(1-2) Pediatric and adolescent patients must not take anticholinergic agents (e.g. clomipramine, hydroxyzine, diphenhydramine, haloperidol, imipramine, and oxybutynin) concurrently with zonisamide.(1) Monitor for signs and symptoms of heat stroke: skin feels very hot with little or no sweating, confusion, muscle cramps, rapid heartbeat, or rapid breathing. Monitor for signs and symptoms of dehydration: dry mouth, urinating less than usual, dark-colored urine, dry skin, feeling tired, dizziness, or irritability. If signs or symptoms of dehydration, oligohidrosis, or elevated body temperature occur, discontinuation of zonisamide should be considered. DISCUSSION: Case reports of decreased sweating and elevated temperature have been reported, especially in pediatric patients. Some cases resulted in heat stroke that required hospital treatment and resulted in death.(1) |
ZONEGRAN, ZONISADE, ZONISAMIDE |
| Eluxadoline/Anticholinergics; Opioids SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Eluxadoline is a mixed mu-opioid and kappa-opioid agonist and delta-opioid antagonist and may alter or slow down gastrointestinal transit.(1) CLINICAL EFFECTS: Constipation related adverse events that sometimes required hospitalization have been reported, including the development of intestinal obstruction, intestinal perforation, and fecal impaction.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Avoid use with other drugs that may cause constipation. If concurrent use is necessary, evaluate the patient's bowel function regularly. Monitor for symptoms of constipation and GI hypomotility, including having bowel movements less than three times weekly or less than usual, difficulty having a bowel movement or passing gas, nausea, vomiting, and abdominal pain or distention.(1) Instruct patients to stop eluxadoline and immediately contact their healthcare provider if they experience severe constipation. Loperamide may be used occasionally for acute management of severe diarrhea, but must be discontinued if constipation develops.(1) DISCUSSION: In phase 3 clinical trials, constipation was the most commonly reported adverse reaction (8%). Approximately 50% of constipation events occurred within the first 2 weeks of treatment while the majority occurred within the first 3 months of therapy. Rates of severe constipation were less than 1% in patients receiving eluxadoline doses of 75 mg and 100 mg.(1) |
VIBERZI |
| 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/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 |
| Glucagon (Diagnostic)/Anticholinergics SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Glucagon and anticholinergic agents may have additive effects on inhibition of gastrointestinal motility.(1) CLINICAL EFFECTS: Concurrent use of glucagon with anticholinergic agents may increase the risk of gastrointestinal hypomotility, including constipation and bowel complications.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Concurrent use of glucagon as a diagnotic aid is not recommended with the use of anticholinergic agents.(1) If concurrent use is necessary, evaluate the patient's bowel function. Monitor for symptoms of constipation and gastrointestinal hypomotility. DISCUSSION: Both glucagon and anticholinergic agents may have additive effects on inhibition of gastrointestinal motility and increase the risk of gastrointestinal adverse effects.(1) |
GLUCAGON HCL |
| Sodium Iodide I 131/Agents that Affect Iodide SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Many compounds can affect iodide protein binding and alter iodide pharmacokinetics and pharmacodynamics.(1,2) CLINICAL EFFECTS: Compounds that affect iodide pharmacokinetics and pharmacodynamics may impact the effectiveness of radioactive iodide.(1,2) PREDISPOSING FACTORS: Compounds that affect iodide pharmacokinetics and pharmacodynamics are expected to have the most impact during therapy using radioactive iodide. Diagnostic procedures would be expected to be impacted less. PATIENT MANAGEMENT: Discuss the use of agents that affect iodide pharmacokinetics and pharmacodynamics with the patient's oncologist.(1,2) DISCUSSION: Many agents interact with radioactive iodine. The average duration of effect is: anticoagulants - 1 week antihistamines - 1 week anti-thyroid drugs, e.g: carbimazole, methimazole, propylthiouracil - 3-5 days corticosteroids - 1 week iodide-containing medications, e.g: amiodarone - 1-6 months expectorants - 2 weeks Lugol solution - 3 weeks saturated solution of potassium iodine - 3 weeks vitamins - 10-14 days iodide-containing X-ray contrast agents - up to 1 year lithium - 4 weeks phenylbutazone - 1-2 weeks sulfonamides - 1 week thyroid hormones (natural or synthetic), e.g.: thyroxine - 4 weeks tri-iodothyronine - 2 weeks tolbutamide - 1 week topical iodide - 1-9 months (1,2) |
HICON, SODIUM IODIDE I-131 |
There are 11 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 |
| Dextromethorphan/Selected SSRIs that Inhibit CYP2D6 SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Fluoxetine and paroxetine, strong inhibitors of CYP2D6, may inhibit the metabolism of dextromethorphan.(1-4) CLINICAL EFFECTS: Patients may experience increased adverse effects of dextromethorphan due to elevated systemic concentrations. Concomitant use of two or more serotonergic agents increases the risk for serotonin syndrome. Serotonin syndrome constitutes a range of toxicities from mild to life threatening.(5) Mild serotonin symptoms may include: shivering, diaphoresis, mydriasis, intermittent tremor, and/or myoclonus.(5) Moderate serotonin symptoms may include: tachycardia, hypertension, hyperthermia, mydriasis, diaphoresis, hyperactive bowel sounds, hyperreflexia, and/OR clonus.(5) Severe serotonin symptoms may include: severe hypertension and tachycardia, shock, agitated delirium, muscular rigidity, and/or hypertonicity.(5) PREDISPOSING FACTORS: Concurrent use of additional drugs which increase CNS serotonin levels would be expected to further increase risk for serotonin syndrome.(5) PATIENT MANAGEMENT: Monitor patients on multiple serotonergic agents for symptoms of serotonin toxicity. Patients in whom serotonin syndrome is suspected should receive immediate medical attention. If the interacting agents are prescribed by different providers, it would be prudent to assure that both are aware of concomitant therapy and monitoring the patient for serotonin toxicities. Advise patients not to exceed recommended dosages of dextromethorphan. 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: An open label parallel group trial evaluated the interaction between dextromethorphan-quinidine 30 mg-30 mg (higher than marketed strength of 20 mg-10 mg) and paroxetine 20 mg in 27 healthy volunteers with a mean age of 33.6 years. Subjects were randomly divided into 2 groups: - Group 1 received paroxetine 20 mg once daily for 12 days, followed by the addition of dextromethorphan-quinidine twice daily for 8 days. - Group 2 received dextromethorphan-quinidine twice daily for 8 days, followed by paroxetine 20 mg daily for 12 days. Results: overall, adverse effects were reported in 19 of 26 subjects who received combination therapy (73%) and 15 of 27 subjects who received monotherapy (56%). Adverse effects from the combination differed somewhat between groups and were more closely associated with the second drug product administered. Group 1 reported dizziness, headache, somnolence, euphoria, nausea, and vomiting after the addition of dextromethorphan-quinidine to paroxetine. Group 2 adverse events were dizziness, headache, nausea, vomiting, insomnia, anxiety, and hyperhidrosis after the addition of paroxetine to dextromethorphan.(1) Two weeks of fluoxetine therapy increased the area-under-curve (AUC) of dextromethorphan by 27-fold.(4) Serotonin syndrome has been reported in patients following the addition of dextromethorphan containing cough syrups to fluoxetine(6,7) and paroxetine.(8) |
FLUOXETINE DR, FLUOXETINE HCL, OLANZAPINE-FLUOXETINE HCL, PAROXETINE CR, PAROXETINE ER, PAROXETINE HCL, PAROXETINE MESYLATE, PAXIL, PAXIL CR, PROZAC, SYMBYAX |
| 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 |
| Selected CYP2D6 Substrates/Desvenlafaxine SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Desvenlafaxine is considered a weak inhibitor of CYP2D6.(1) CLINICAL EFFECTS: Concurrent use of desvenlafaxine may lead to increased serum levels and adverse effects of drugs sensitive to inhibition of the CYP2D6 pathway.(1) Agents linked to this monograph are: atomoxetine, dapoxetine, deutetrabenazine, dextromethorphan, metoprolol, nebivolol, perphenazine, tolterodine, and yohimbine. PREDISPOSING FACTORS: With perphenazine and tolterodine, the risk of anticholinergic toxicities including cognitive decline, delirium, falls and fractures is increased in geriatric patients using more than one medicine with anticholinergic properties.(2) PATIENT MANAGEMENT: Reduce the dose of CYP2D6 substrates by up to one-half when coadministered with desvenlafaxine 400 mg.(1) Studies have shown that desvenlafaxine does not have a clinically relevant effect on CYP2D6 metabolism at the dose of 100 mg daily. CYP2D6 substrates should be dosed at the original level when coadministered with desvenlafaxine 100 mg or lower or when desvenlafaxine is discontinued.(1) DISCUSSION: In a study, coadministration of desvenlafaxine 100 mg daily with desipramine (single dose 50 mg) increased desipramine's maximum concentration (Cmax) and area-under-the-curve (AUC)by 25% and 17%.(1) In a study, coadministration of desvenlafaxine 400 mg daily with desipramine (single dose 50 mg) increased desipramine's maximum concentration (Cmax) and area-under-the-curve (AUC)by 50% and 90%.(1) Selected CYP2D6 substrates linked to this monograph are: atomoxetine, dapoxetine, deutetrabenazine, dextromethorphan, metoprolol, nebivolol, perphenazine, tolterodine, and yohimbine. |
DESVENLAFAXINE ER, DESVENLAFAXINE SUCCINATE ER, PRISTIQ |
| Topiramate/Anticholinergics SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Topiramate can cause decreased sweating and elevated body temperature. Agents with anticholinergic activity can predispose patients to heat-related disorders.(1-2) CLINICAL EFFECTS: Concurrent use of topiramate with agents with anticholinergic activity may increase the incidence of oligohidrosis and hyperthermia, especially in pediatric or adolescent patients.(1-2) Overheating and dehydration can lead to brain damage and death. PREDISPOSING FACTORS: Pediatric and adolescent patients and patients with dehydration may be more likely to experience heat-related disorders.(1) PATIENT MANAGEMENT: The manufacturer of topiramate states that caution should be used when topiramate is prescribed with other medicinal products that predispose to heat-related disorders, such as agents with anticholinergic activity (e.g. clomipramine, hydroxyzine, diphenhydramine, haloperidol, imipramine, and oxybutynin) concurrently with zonisamide.(1) Monitor for signs and symptoms of heat stroke: skin feels very hot with little or no sweating, confusion, muscle cramps, rapid heartbeat, or rapid breathing. Monitor for signs and symptoms of dehydration: dry mouth, urinating less than usual, dark-colored urine, dry skin, feeling tired, dizziness, or irritability. If signs or symptoms of dehydration, oligohidrosis, or elevated body temperature occur, discontinuation of zonisamide should be considered. DISCUSSION: Case reports of decreased sweating and elevated temperature have been reported, especially in pediatric patients. Some cases resulted in heat stroke that required hospital treatment.(1) A 64-year old woman developed non-exertional hyperthemia while taking multiple psychiatric medications with topiramate.(2) |
EPRONTIA, QSYMIA, QUDEXY XR, TOPAMAX, TOPIRAMATE, TOPIRAMATE ER, TROKENDI XR |
| Dextromethorphan/Selected Serotonergic Agents SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Dextromethorphan inhibits neuronal reuptake of serotonin. Concurrent administration with one or more serotonergic agents may increase serotonin effects, leading to serotonin toxicity.(1-11) CLINICAL EFFECTS: The concurrent use of dextromethorphan with serotonergic agents may increase the risk for serotonin syndrome. Serotonin syndrome constitutes a range of toxicities from mild to life threatening.(3) Mild serotonin symptoms may include: shivering, diaphoresis, mydriasis, intermittent tremor, and/or myoclonus.(3) Moderate serotonin symptoms may include: tachycardia, hypertension, hyperthermia, mydriasis, diaphoresis, hyperactive bowel sounds, hyperreflexia, and/OR clonus.(3) Severe serotonin symptoms may include: severe hypertension and tachycardia, shock, agitated delirium, muscular rigidity, and/or hypertonicity.(3) PREDISPOSING FACTORS: Concurrent use of additional drugs which increase CNS serotonin levels would be expected to further increase risk for serotonin syndrome.(1-11) PATIENT MANAGEMENT: Monitor patients on multiple serotonergic agents for symptoms of serotonin toxicity. Patients in whom serotonin syndrome is suspected should receive immediate medical attention. If the interacting agents are prescribed by different providers, it would be prudent to assure that both are aware of concomitant therapy and monitoring the patient for serotonin toxicities. Advise patients not to exceed recommended dosages of dextromethorphan. 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: Dextromethorphan inhibits neuronal reuptake of serotonin and may potentially precipitate dose-dependant serotonin toxicity in conjunction with other serotonergic agents.(4,5) Serotonin syndrome has been reported in patients following the addition of dextromethorphan containing cough syrups to duloxetine,(6) escitalopram,(7) fluoxetine,(8,9) paroxetine,(10) and sertraline.(11) Selected serotonergic agents linked to this monograph include: citalopram, clomipramine, duloxetine, escitalopram, fluvoxamine, imipramine, levomilnacipran, milnacipran, sertraline, venlafaxine, vilazodone and vortioxetine. |
ANAFRANIL, CELEXA, CITALOPRAM HBR, CLOMIPRAMINE HCL, CYMBALTA, DRIZALMA SPRINKLE, DULOXETINE HCL, DULOXICAINE, EFFEXOR XR, ESCITALOPRAM OXALATE, FETZIMA, FLUVOXAMINE MALEATE, FLUVOXAMINE MALEATE ER, IMIPRAMINE HCL, IMIPRAMINE PAMOATE, LEXAPRO, SAVELLA, SERTRALINE HCL, TRINTELLIX, VENLAFAXINE BESYLATE ER, VENLAFAXINE HCL, VENLAFAXINE HCL ER, VIIBRYD, VILAZODONE HCL, ZOLOFT |
| Dextromethorphan/Selected Strong CYP2D6 Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Strong inhibitors of CYP2D6 may inhibit the metabolism of dextromethorphan.(1-4) CLINICAL EFFECTS: Patients may experience increased adverse effects of dextromethorphan due to elevated systemic concentrations. Elevated levels of dextromethorphan or concomitant use of two or more serotonergic agents increases the risk for serotonin syndrome. Serotonin syndrome constitutes a range of toxicities from mild to life threatening.(5) Mild serotonin symptoms may include: shivering, diaphoresis, mydriasis, intermittent tremor, and/or myoclonus.(5) Moderate serotonin symptoms may include: tachycardia, hypertension, hyperthermia, mydriasis, diaphoresis, hyperactive bowel sounds, hyperreflexia, and/OR clonus.(5) Severe serotonin symptoms may include: severe hypertension and tachycardia, shock, agitated delirium, muscular rigidity, and/or hypertonicity.(5) PREDISPOSING FACTORS: Concurrent use of additional drugs which increase CNS serotonin levels would be expected to further increase risk for serotonin syndrome.(5) PATIENT MANAGEMENT: Monitor patients for elevated dextromethorphan levels or on multiple serotonergic agents for symptoms of serotonin toxicity. Patients in whom serotonin syndrome is suspected should receive immediate medical attention. If the interacting agents are prescribed by different providers, it would be prudent to assure that both are aware of concomitant therapy and monitoring the patient for serotonin toxicities. Advise patients not to exceed recommended dosages of dextromethorphan. 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: An open label parallel group trial evaluated the interaction between dextromethorphan-quinidine 30 mg-30 mg (higher than marketed strength of 20 mg-10 mg) and paroxetine 20 mg in 27 healthy volunteers with a mean age of 33.6 years. Subjects were randomly divided into 2 groups: - Group 1 received paroxetine 20 mg once daily for 12 days, followed by the addition of dextromethorphan-quinidine twice daily for 8 days. - Group 2 received dextromethorphan-quinidine twice daily for 8 days, followed by paroxetine 20 mg daily for 12 days. Results: overall, adverse effects were reported in 19 of 26 subjects who received combination therapy (73%) and 15 of 27 subjects who received monotherapy (56%). Adverse effects from the combination differed somewhat between groups and were more closely associated with the second drug product administered. Group 1 reported dizziness, headache, somnolence, euphoria, nausea, and vomiting after the addition of dextromethorphan-quinidine to paroxetine. Group 2 adverse events were dizziness, headache, nausea, vomiting, insomnia, anxiety, and hyperhidrosis after the addition of paroxetine to dextromethorphan.(1) Two weeks of fluoxetine therapy increased the area-under-curve (AUC) of dextromethorphan by 27-fold.(4) Serotonin syndrome has been reported in patients following the addition of dextromethorphan containing cough syrups to fluoxetine(6,7) and paroxetine.(8) Selected strong CYP2D6 inhibitors linked to this monograph include: bupropion, dacomitinib, hydroquinidine, quinidine, and terbinafine.(8) |
APLENZIN, AUVELITY, BUPROPION HCL, BUPROPION HCL SR, BUPROPION XL, CONTRAVE, FORFIVO XL, NUEDEXTA, QUINIDINE GLUCONATE, QUINIDINE SULFATE, TERBINAFINE HCL, VIZIMPRO, WELLBUTRIN SR, WELLBUTRIN XL |
The following contraindication information is available for ALKA-SELTZER PLUS-D SINUS-COLD (dextromethorphan/pseudoephedrine/acetaminophen/chlorpheniram):
Drug contraindication overview.
No enhanced Contraindications information available for this drug.
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 15 severe contraindications.
Adequate patient monitoring is recommended for safer drug use.
| Severe List |
|---|
| Angle-closure glaucoma |
| Benign prostatic hyperplasia |
| Bladder outflow obstruction |
| Chronic idiopathic constipation |
| Diabetes mellitus |
| Disease of liver |
| Gastrointestinal obstruction |
| Hypertension |
| Hyperthyroidism |
| Pheochromocytoma |
| Protein-calorie malnutrition |
| Shock |
| Stenosing peptic ulcer |
| Systemic mastocytosis |
| Urinary retention |
There are 5 moderate contraindications.
Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.
| Moderate List |
|---|
| Chronic obstructive pulmonary disease |
| Hypertension |
| Hyperthyroidism |
| Kidney disease with reduction in glomerular filtration rate (GFr) |
| Severe hepatic disease |
The following adverse reaction information is available for ALKA-SELTZER PLUS-D SINUS-COLD (dextromethorphan/pseudoephedrine/acetaminophen/chlorpheniram):
Adverse reaction overview.
No enhanced Common Adverse Effects information available for this drug.
No enhanced Common Adverse Effects information available for this drug.
There are 28 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 Anaphylaxis Angioedema Blood dyscrasias Drug-induced hepatitis Dyspnea Extrasystoles Hallucinations Hemolytic anemia Hypersensitivity drug reaction Hypertension Hypotension 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 75 less severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Anticholinergic toxicity Dizziness Drowsy Headache disorder Insomnia Thick bronchial secretions |
Agitation Anorexia Dizziness Drowsy Dysuria General weakness Muscle weakness Nausea Nervousness Pallor Sedation Tachycardia Tremor |
| Rare/Very Rare |
|---|
|
Abdominal distension Abdominal pain with cramps Accidental fall Acute abdominal pain Acute cognitive impairment Agitation Anorexia Anticholinergic toxicity Ataxia Blurred vision Cardiac arrhythmia Chest discomfort Chest tightness Chills Constipation Diarrhea Diplopia Dizziness Drowsy Dry nose Dry throat Dyspepsia Dyspnea Dysuria Erythema Euphoria Excitement Fatigue Headache disorder Hyperhidrosis Insomnia Irritability Maculopapular rash Malaise Medication overuse headache Migraine Nausea Nervousness Nightmares Palpitations Paresthesia Pruritus of skin Skin photosensitivity Skin rash Symptoms of anxiety Syncope Tachycardia Tinnitus Tremor Urinary retention Urticaria Vertigo Visual changes Vomiting Wheezing Xerostomia |
The following precautions are available for ALKA-SELTZER PLUS-D SINUS-COLD (dextromethorphan/pseudoephedrine/acetaminophen/chlorpheniram):
No enhanced Pediatric Use information available for this drug.
Contraindicated
Contraindicated
Contraindicated
Severe Precaution
Management or Monitoring Precaution
Contraindicated
| Chlorpheniramine | 30 Days – 2 Years | Risk of serious and life-threatening adverse effects of CNS depression or excitation. Not recommended age <2 years. Avoid using with underlying asthma. |
Contraindicated
| Chlorpheniramine (Oral) | 1 Day – 29 Days | Possible paradoxical CNS excitation. Seizure risk in newborns. |
Contraindicated
| Pseudoephedrine (Immed. Release) | 1 Day – 6 Years | High risk of adverse CNS effects. Not recommended for use age < 6 years. |
Severe Precaution
| Chlorpheniramine | 2 Years – 6 Years | Risk of CNS depression and paradoxical excitation. Consult healthcare provider for age< 6 years. |
Management or Monitoring Precaution
| Acetaminophen (oral,rectal) | 1 Day – 12 Years | Use weight based dosing in children less than 12 years. |
Reproduction studies in animals using dexchlorpheniramine have not been performed to date, but reproduction studies in rabbits and rats using chlorpheniramine maleate dosages up to 50 and 85 times the usual human dosage, respectively, have not revealed evidence of harm to the fetus. Decreased postnatal survival in offspring of rats receiving 33 and 67 times the usual human dosage of chlorpheniramine maleate has been reported. There are no adequate and controlled studies to date using chlorpheniramine or dexchlorpheniramine in pregnant women, and the drugs should be used during the first 2 trimesters only when clearly needed.
In one epidemiologic study, use of chlorpheniramine was not associated with an increased risk of teratogenic effects; however, only a limited number of pregnant women received the drug in this study. Because of the risk of severe reactions (e.g., seizures) to antihistamines in neonates, chlorpheniramine or dexchlorpheniramine should not be used during the third trimester. 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.
In one epidemiologic study, use of chlorpheniramine was not associated with an increased risk of teratogenic effects; however, only a limited number of pregnant women received the drug in this study. Because of the risk of severe reactions (e.g., seizures) to antihistamines in neonates, chlorpheniramine or dexchlorpheniramine should not be used during the third trimester. 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.
| Drug/Drug Class | Severity | Precaution Description | Pregnancy Category Description |
|---|---|---|---|
| Acetaminophen | 2 | Available data suggest no known risk; otc product, no fda pregnancy warnings | No fda rating but may have precautions or warnings; may have animal and/or human studies or pre or post marketing information. |
| Chlorpheniramine | 2 | Low risk, premature infant at risk of retrolental fibroplasia | No fda rating but may have precautions or warnings; may have animal and/or human studies or pre or post marketing information. |
| Dextromethorphan | 2 | Available human data show no increased risk for major birth defects | No fda rating but may have precautions or warnings; may have animal and/or human studies or pre or post marketing information. |
| Pseudoephedrine | 2 | Limited human data are inconclusive on developmental toxicity risk | No fda rating but may have precautions or warnings; may have animal and/or human studies or pre or post marketing information. |
It is not known whether chlorpheniramine or dexchlorpheniramine is distributed into milk, but other antihistamines (e.g., diphenhydramine) have been detected in milk. Because of the potential for serious adverse reactions to antihistamines in nursing infants, a decision should be made whether to discontinue nursing or chlorpheniramine or dexchlorpheniramine, taking into account the importance of the drug to the woman. 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.
Precaution Exists
Precaution exists. (No data or inconclusive human data.) Use of this drug by breast feeding mothers should be evaluated carefully.
No Known Risk
No known risk. This drug has no known risks to nursing infants and does not adversely affect lactation.
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.
Precaution Exists
Precaution exists. (No data or inconclusive human data.) Use of this drug by breast feeding mothers should be evaluated carefully.
| Drug Name | Excretion Potential | Effect on Infant | Notes |
|---|---|---|---|
| Chlorpheniramine | Unknown. It is unknown whether the drug is excreted in human breast milk. | It is not known whether this drug has an adverse effect on the nursing infant. (No data or inconclusive human data) | Insufficient data available; may cause sedation and inhibit lactation |
| Dextromethorphan | Unknown. It is unknown whether the drug is excreted in human breast milk. | It is not known whether this drug has an adverse effect on the nursing infant. (No data or inconclusive human data) | Insufficient data available; molecular wt low enough for possible excretion |
| Pseudoephedrine | Excreted.This drug is known to be excreted in human breast milk. | This drug has been shown to have an adverse effect on the nursing infant. | May decrease milk supply and cause irritability |
No Known Risk
No known risk. This drug has no known risks to nursing infants and does not adversely affect lactation.
| Drug Name | Excretion Potential | Effect on Infant | Notes |
|---|---|---|---|
| Acetaminophen | Excreted.This drug is known to be excreted in human breast milk. | This drug has been shown not to have an adverse effect on the nursing infant. | Low levels excreted with low risk for adverse effects in infant |
No enhanced Geriatric Use information available for this drug.
Precaution Exists
Geriatric management or monitoring precaution exists.
Precaution Exists
Geriatric management or monitoring precaution exists.
| Drug Name | Narrative | REN | HEP | CARDIO | NEURO | PULM | ENDO |
|---|---|---|---|---|---|---|---|
| Acetaminophen (oral,rectal) | Hepatic-Elderly may be more susceptible to hepatotoxicity. Strict adherence to a maximum daily dose is recommended; maximum dose 3000-3800 mg depending on dose form strength used and recommendation source. | N | Y | N | N | N | N |
| Chlorpheniramine | Neuro/Psych-Anticholinergic effects may cause sedation, worsen cognitive impairment and increase fall risk. Non-sedating antihistamine preferred. Gastrointestinal-May cause or worsen pre-existing constipation. Genitourinary-Best avoided in patients with urinary retention from any cause. | N | N | N | Y | N | N |
| Pseudoephedrine | Cardiovascular-Elderly are more sensitive to tachycardia and hypertensive effects. May exacerbate symptomatic coronary insufficiency. Genitourinary-May cause urinary retention. Neuro/Psych-May worsen cognitive impairment in some elderly with dementia. Insomnia risk. | Y | N | Y | Y | N | N |
The following prioritized warning is available for ALKA-SELTZER PLUS-D SINUS-COLD (dextromethorphan/pseudoephedrine/acetaminophen/chlorpheniram):
WARNING: One ingredient in this product is acetaminophen. Taking too much acetaminophen may cause serious (possibly fatal) liver disease. Adults should not take more than 4000 milligrams (4 grams) of acetaminophen a day.
People with liver problems and children should take less acetaminophen. Ask your doctor or pharmacist how much acetaminophen is safe to take. Do not use with any other drug containing acetaminophen without asking your doctor or pharmacist first.
Acetaminophen is in many nonprescription and prescription medications (such as pain/fever drugs or cough-and-cold products). Check the labels on all your medicines to see if they contain acetaminophen, and ask your pharmacist if you are unsure. Get medical help right away if you take too much acetaminophen (overdose), even if you feel well.
Overdose symptoms may include nausea, vomiting, loss of appetite, sweating, stomach/abdominal pain, extreme tiredness, yellowing eyes/skin, and dark urine. Daily alcohol use, especially when combined with acetaminophen, may damage your liver. Avoid alcohol.
WARNING: One ingredient in this product is acetaminophen. Taking too much acetaminophen may cause serious (possibly fatal) liver disease. Adults should not take more than 4000 milligrams (4 grams) of acetaminophen a day.
People with liver problems and children should take less acetaminophen. Ask your doctor or pharmacist how much acetaminophen is safe to take. Do not use with any other drug containing acetaminophen without asking your doctor or pharmacist first.
Acetaminophen is in many nonprescription and prescription medications (such as pain/fever drugs or cough-and-cold products). Check the labels on all your medicines to see if they contain acetaminophen, and ask your pharmacist if you are unsure. Get medical help right away if you take too much acetaminophen (overdose), even if you feel well.
Overdose symptoms may include nausea, vomiting, loss of appetite, sweating, stomach/abdominal pain, extreme tiredness, yellowing eyes/skin, and dark urine. Daily alcohol use, especially when combined with acetaminophen, may damage your liver. Avoid alcohol.
The following icd codes are available for ALKA-SELTZER PLUS-D SINUS-COLD (dextromethorphan/pseudoephedrine/acetaminophen/chlorpheniram)'s list of indications:
| Cold symptoms | |
| J00 | Acute nasopharyngitis [common cold] |
| Cough | |
| R05 | Cough |
| R05.1 | Acute cough |
| R05.2 | Subacute cough |
| R05.3 | Chronic cough |
| R05.9 | Cough, unspecified |
| 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 |
| Flu-like symptoms | |
| J02.9 | Acute pharyngitis, unspecified |
| R05 | Cough |
| R05.1 | Acute cough |
| R05.2 | Subacute cough |
| R05.9 | Cough, unspecified |
| R09.81 | Nasal congestion |
| R50.9 | Fever, unspecified |
| R53.1 | Weakness |
| R53.81 | Other malaise |
| R53.83 | Other fatigue |
| R68.83 | Chills (without fever) |
| Headache disorder | |
| G43 | Migraine |
| G43.0 | Migraine without aura |
| G43.00 | Migraine without aura, not intractable |
| G43.009 | Migraine without aura, not intractable, without status migrainosus |
| G43.01 | Migraine without aura, intractable |
| G43.019 | Migraine without aura, intractable, without status migrainosus |
| G43.1 | Migraine with aura |
| G43.10 | Migraine with aura, not intractable |
| G43.109 | Migraine with aura, not intractable, without status migrainosus |
| G43.11 | Migraine with aura, intractable |
| G43.119 | Migraine with aura, intractable, without status migrainosus |
| G43.4 | Hemiplegic migraine |
| G43.40 | Hemiplegic migraine, not intractable |
| G43.409 | Hemiplegic migraine, not intractable, without status migrainosus |
| G43.41 | Hemiplegic migraine, intractable |
| 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 |
| G43.509 | Persistent migraine aura without cerebral infarction, not intractable, without status migrainosus |
| G43.51 | Persistent migraine aura without cerebral infarction, intractable |
| 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 |
| G43.609 | Persistent migraine aura with cerebral infarction, not intractable, without status migrainosus |
| G43.61 | Persistent migraine aura with cerebral infarction, intractable |
| 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 |
| G43.709 | Chronic migraine without aura, not intractable, without status migrainosus |
| G43.71 | Chronic migraine without aura, intractable |
| G43.719 | Chronic migraine without aura, intractable, without status migrainosus |
| G43.8 | Other migraine |
| G43.80 | Other migraine, not intractable |
| G43.809 | Other migraine, not intractable, without status migrainosus |
| G43.81 | Other migraine, intractable |
| G43.819 | Other migraine, intractable, without status migrainosus |
| G43.82 | Menstrual migraine, not intractable |
| G43.829 | Menstrual migraine, not intractable, without status migrainosus |
| G43.83 | Menstrual migraine, intractable |
| G43.839 | Menstrual migraine, intractable, without status migrainosus |
| G43.9 | Migraine, unspecified |
| G43.90 | Migraine, unspecified, not intractable |
| G43.909 | Migraine, unspecified, not intractable, without status migrainosus |
| G43.91 | Migraine, unspecified, intractable |
| 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.E09 | Chronic migraine with aura, not intractable, without status migrainosus |
| G43.E1 | Chronic migraine with aura, intractable |
| G43.E19 | Chronic migraine with aura, intractable, without status migrainosus |
| G44 | Other headache syndromes |
| G44.0 | Cluster headaches and other trigeminal autonomic cephalgias (TAc) |
| 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 |
| G44.09 | Other trigeminal autonomic cephalgias (TAc) |
| G44.091 | Other trigeminal autonomic cephalgias (TAc), intractable |
| G44.099 | Other trigeminal autonomic cephalgias (TAc), 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 |
| G44.89 | Other headache syndrome |
| R51 | Headache |
| R51.9 | Headache, unspecified |
| Nasal congestion | |
| R09.81 | Nasal congestion |
| Rhinorrhea | |
| R09.82 | Postnasal drip |
Formulary Reference Tool