Version July 2025
Note: When calculating the maximum daily dose, consider all sources of acetaminophen (prescription and OTC) and all routes of administration. Do not exceed the maximum recommended daily dose.
Cold and flu symptoms: Oral:
Acetaminophen 325 mg/dextromethorphan 10 mg/phenylephrine 5 mg per capsule/tablet: Two capsules/tablets every 4 hours. Refer to product-specific labeling for maximum daily dosage; varies by product (maximum dosage range: 8 to 10 capsules/tablets [acetaminophen 2,600 to 3,250 mg/dextromethorphan 80 to 100 mg/phenylephrine 40 to 50 mg] per 24 hours).
Acetaminophen 325 mg/dextromethorphan 10 mg/phenylephrine 5 mg per 15 mL (liquid/syrup): 30 mL every 4 hours. Refer to product-specific labeling for maximum daily dosage; varies by product (maximum: 120 to 150 mL [acetaminophen 2,600 to 3,250 mg/dextromethorphan 80 to 100 mg/phenylephrine 40 to 50 mg] per 24 hours).
Acetaminophen 500 mg/dextromethorphan 20 mg/phenylephrine 10 mg per packet (as powder for solution): One packet every 4 hours (maximum: 6 packets [acetaminophen 3,000 mg/dextromethorphan 120 mg/phenylephrine 60 mg] per 24 hours).
Acetaminophen 650 mg/dextromethorphan 20 mg/phenylephrine 10 mg per packet (as powder for solution): One packet every 4 hours (maximum: 5 packets [acetaminophen 3,250 mg/dextromethorphan 100 mg/phenylephrine 50 mg] per 24 hours).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling.
There are no dosage adjustments provided in the manufacturer's labeling; use with caution in patients with hepatic impairment or active liver disease.
Refer to adult dosing.
Cold and flu symptoms: Oral:
Children 6 to 11 years: Vicks DayQuil Cold & Flu Multi-Symptom Liquid: Acetaminophen 325 mg/dextromethorphan 10 mg/phenylephrine 5 mg per 15 mL: 15 mL every 4 hours (maximum: 60 mL [acetaminophen 1,300 mg/dextromethorphan 40 mg/phenylephrine 20 mg] per 24 hours)
Children ≥12 years and Adolescents: Refer to adult dosing.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling.
There are no dosage adjustments provided in the manufacturer's labeling; use with caution in patients with hepatic impairment or active liver disease.
See individual agents.
OTC labeling: When used for self-medication, do not use with any other drug containing acetaminophen; in combination with or within 14 days of stopping a monoamine oxidase inhibitor (MAOI); if you are hypersensitive to acetaminophen, dextromethorphan, phenylephrine, or any component of the formulation; children <12 years of age.
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Concerns related to adverse effects:
• Hepatotoxicity: Acetaminophen has been associated with acute liver failure, at times resulting in liver transplant and death. Hepatotoxicity is usually associated with excessive acetaminophen intake and often involves more than one product that contains acetaminophen. Do not exceed the maximum recommended daily dose (>4 g daily). In addition, long-term daily dosing may also result in liver damage in some patients.
• Hypersensitivity/anaphylactic reactions: Hypersensitivity and anaphylactic reactions have been reported; discontinue immediately if symptoms of allergic or hypersensitivity reactions occur.
• Skin reactions: Serious and potentially fatal skin reactions, including acute generalized exanthematous pustulosis (AGEP), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), have occurred rarely with acetaminophen use. Discontinue therapy at the first appearance of skin rash.
Disease-related concerns:
• Cardiovascular disease: Use with caution in patients with cardiovascular disease (including hypertension and ischemic heart disease).
• Diabetes: Use with caution in patients with diabetes mellitus.
• Ethanol use: Use with caution in patients with alcoholic liver disease; consuming ≥3 alcoholic drinks/day may increase the risk of liver damage. Avoid ethanol or limit to <3 drinks/day.
• Hepatic impairment: Use caution in patients with hepatic impairment or active liver disease.
• Increased intraocular pressure/glaucoma: Use with caution in patients with increased intraocular pressure or glaucoma.
• Prostatic hyperplasia/urinary obstruction: Use with caution in patients with prostatic hyperplasia and/or GU obstruction.
• Thyroid dysfunction: Use with caution in patients with thyroid dysfunction.
Special populations:
• CYP2D6 poor metabolizers: Dextromethorphan is metabolized by hepatic CYP2D6. Poor metabolizers of CYP2D6 may have exaggerated or prolonged effects of dextromethorphan. Increased risk may be seen with concomitant use of potent CYP2D6 inhibitors; use with caution (Abduljalil 2010; Jurica 2012; Sager 2014; Zhou 2009).
• Older adult: Use with caution in the elderly; more likely to experience adverse reactions to sympathomimetics.
Dosage form specific issues:
• Benzyl alcohol and derivatives: Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer’s labeling.
• Phenylalanine: Some products may contain phenylalanine.
• Propylene glycol: Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Zar 2007).
• Sodium: Some products may contain sodium; use with caution in sodium restricted patients.
Other warnings/precautions:
• Dosage limit: Limit acetaminophen dose from all sources <4 g/day.
• Self-medication (OTC use): When used for self-medication (OTC), discontinue use and notify health care provider if pain, cough, or nasal congestion gets worse or lasts more than 7 days; fever gets worse or lasts >3 days; if any new symptoms or nervousness, dizziness, or sleeplessness occur; if redness or swelling is present; or if cough comes back or occurs with rash or headache that lasts. If sore throat is severe, persists for >2 days, is accompanied or followed by a fever, headache, rash, nausea, or vomiting, contact health care provider. For persistent or chronic cough (as with smoking, asthma, emphysema) or if cough is accompanied by excessive phlegm, consult a health care provider prior to use.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Caplet, oral:
Comtrex Maximum Strength, Non-Drowsy Cold & Cough: Acetaminophen 325 mg, dextromethorphan hydrobromide 10 mg, and phenylephrine hydrochloride 5 mg
Mapap Multi-Symptom Cold: Acetaminophen 325 mg, dextromethorphan hydrobromide 10 mg, and phenylephrine hydrochloride 5 mg [cool blast flavor]
Sudafed PE Pressure+Pain+Cough: Acetaminophen 325 mg, dextromethorphan hydrobromide 10 mg, and phenylephrine hydrochloride 5 mg [DSC]
Theraflu ExpressMax Daytime Severe Cold & Cough: Acetaminophen 325 mg, dextromethorphan hydrobromide 10 mg, and phenylephrine hydrochloride 5 mg
Tylenol Cold Max: Acetaminophen 325 mg, dextromethorphan hydrobromide 10 mg, and phenylephrine hydrochloride 5 mg [DSC]
Capsule, liquid filled, oral:
Alka-Seltzer Plus Day Cold: Acetaminophen 325 mg, dextromethorphan hydrobromide 10 mg, and phenylephrine hydrochloride 5 mg
GoodSense Daytime: Acetaminophen 325 mg, dextromethorphan hydrobromide 10 mg, and phenylephrine hydrochloride 5 mg [DSC]
GoodSense Daytime Cold & Flu: Acetaminophen 325 mg, dextromethorphan hydrobromide 10 mg, and phenylephrine hydrochloride 5 mg
Mucinex Fast-Max Congestion & Headache: Acetaminophen 325 mg, dextromethorphan hydrobromide 10 mg, and phenylephrine hydrochloride 5 mg [contains soybean lecithin]
Mucinex Fast-Max Severe Cold & Sinus: Acetaminophen 325 mg, dextromethorphan hydrobromide 10 mg, and phenylephrine hydrochloride 5 mg [contains soybean lecithin]
Vicks DayQuil Cold & Flu Multi-Symptom: Acetaminophen 325 mg, dextromethorphan hydrobromide 10 mg, and phenylephrine hydrochloride 5 mg
Generic: Acetaminophen 325 mg, dextromethorphan hydrobromide 10 mg, and phenylephrine hydrochloride 5 mg
Liquid, oral:
GoodSense Daytime Cold & Flu: Acetaminophen 325 mg, dextromethorphan hydrobromide 10 mg, and phenylephrine hydrochloride 5 mg per 15 mL (237 mL, 354 mL) [alcohol free, gluten free; contains edetate disodium, polyethylene glycol, propylene glycol, sodium 7 mg/15 mL]
Tylenol Cold Max: Acetaminophen 325 mg, dextromethorphan hydrobromide 10 mg, and phenylephrine hydrochloride 5 mg per 15 mL (240 mL [DSC]) [contains propylene glycol, sodium 5 mg/15 mL, sodium benzoate; citrus burst flavor]
Vicks DayQuil Cold & Flu Multi-Symptom: Acetaminophen 325 mg, dextromethorphan hydrobromide 10 mg, and phenylephrine hydrochloride 5 mg per 15 mL (180 mL, 300 mL) [ethanol free, sugar free; contains propylene glycol, sodium 50 mg/15 mL, sodium benzoate]
Powder for solution, oral:
GoodSense Daytime Flu & Severe Cold: Acetaminophen 500 mg, dextromethorphan hydrobromide 20 mg, and phenylephrine hydrochloride 10 mg per packet (6s) [contains phenylalanine 22 mg/packet, potassium 10 mg/packet, and sodium 20 mg/packet; green tea and honey lemon flavors]
Theraflu Daytime Severe Cold & Cough: Acetaminophen 650 mg, dextromethorphan hydrobromide 20 mg, and phenylephrine hydrochloride 10 mg per packet (6s) [contains phenylalanine 14 mg/packet, potassium 10 mg/packet, and sodium 20 mg/packet; berry-green tea-menthol flavor]
Theraflu Multi-Symptom Severe Cold: Acetaminophen 500 mg, dextromethorphan hydrobromide 20 mg, and phenylephrine hydrochloride 10 mg per packet (6s) [contains phenylalanine 20 mg/packet, potassium 10 mg/packet, and sodium 19 mg/packet; Lipton green tea and honey lemon flavors]
Syrup, oral:
Theraflu ExpressMax Daytime Severe Cold & Cough: Acetaminophen 325 mg, dextromethorphan hydrobromide 10 mg, and phenylephrine hydrochloride 5 mg per 15 mL (245.5 mL) [contains ethanol, potassium 12 mg/15 mL, propylene glycol, sodium 8 mg/15 mL, sodium benzoate; berry flavor]
Tablet, Oral:
Mapap Cold Formula Multi-Symptom: Acetaminophen 325 mg, dextromethorphan hydrobromide 10 mg, and phenylephrine hydrochloride 5 mg (24s)
Theraflu ExpressMax Severe Cold/Cough: Acetaminophen 325 mg, dextromethorphan hydrobromide 10 mg, and phenylephrine hydrochloride 5 mg (20s)
Theraflu Severe Cold/Cough Day: Acetaminophen 325 mg, dextromethorphan hydrobromide 10 mg, and phenylephrine hydrochloride 5 mg (24s)
Theraflu Severe Cold Daytime: Acetaminophen 325 mg, dextromethorphan hydrobromide 15 mg, and phenylephrine hydrochloride 5 mg (24s)
Yes
Capsules (Mucinex Fast-Max Cong Headache Oral)
10-5-325 mg (per each): $0.93
Capsules (Mucinex Sinus-Max Sev Cong/Pn Oral)
10-5-325 mg (per each): $0.93
Liquid (Theraflu ExpressMax Oral)
20-10-650 mg/30 mL (per mL): $0.05
Misc (Theraflu PowerPods Severe Cold Oral)
20-10-650 mg (per each): $1.42
Pack (Theraflu Severe Cold Oral)
20-10-500 mg (per each): $1.87
Pack (Theraflu Severe Cold Relief Oral)
20-10-650 mg (per each): $1.87
Tablets (Comtrex Cold & Cough Max St Oral)
10-5-325 mg (per each): $0.14
Tablets (Mapap Cold Formula Multi-Sympt Oral)
10-5-325 mg (per each): $0.11
Tablets (Theraflu ExpressMax Sev Cld/Cg Oral)
10-5-325 mg (per each): $0.31
Tablets (Theraflu Severe Cold Daytime Oral)
15-5-325 mg (per each): $0.18
Tablets (Theraflu Severe Cold/Cgh Day Oral)
10-5-325 mg (per each): $0.19
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Oral:
Capsules: Administer with water.
Powder for solution: Dissolve one packet in 240 mL hot water; consume within 10 to 15 minutes. If using microwave, add one packet to 240 mL of cool water and stir briskly before and after heating; do not overheat.
Syrup: Administer using enclosed dosing cup.
Tablets: Swallow whole; do not crush, chew, or dissolve.
Oral:
Capsules: Children ≥12 years and Adolescents: Administer with water.
Powder for solution: Children ≥12 years and Adolescents: Dissolve one packet in 240 mL hot water; consume within 10 to 15 minutes. If using microwave, add one packet to 240 mL of cool water and stir briskly before and after heating; do not overheat.
Syrup: Children ≥6 years and Adolescents: Administer using enclosed dosing cup.
Tablets: Children ≥12 years and Adolescents: Swallow whole; do not crush, chew, or dissolve.
Cold and flu symptoms: Temporary relief of common cold and flu symptoms (eg, cough due to minor throat and bronchial irritation, fever, headache, minor aches and pains, nasal congestion, sinus congestion/pressure, sore throat).
Duplicate therapy issues: This product contains acetaminophen, which may be a component of other combination products. Do not exceed the maximum recommended daily dose of acetaminophen.
Refer to individual components.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Ajmaline: May increase serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor
Alcohol (Ethyl): May increase hepatotoxic effects of Acetaminophen. Risk C: Monitor
Alpha1-Blockers: May decrease vasoconstricting effects of Phenylephrine (Systemic). Risk C: Monitor
Artemether and Lumefantrine: May increase serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor
Atazanavir: May increase serum concentration of UGT1A1 Substrates. Management: Do not use UGT1A1 substrates for which small increases in exposure can cause serious adverse effects together with atazanavir, and use caution with any UGT1A1 substrate, even when small changes in exposure are less likely to cause serious adverse effects. Risk D: Consider Therapy Modification
Atomoxetine: May increase hypertensive effects of Sympathomimetics. Atomoxetine may increase tachycardic effects of Sympathomimetics. Risk C: Monitor
Atropine (Systemic): May increase hypertensive effects of Alpha1-Agonists. Risk C: Monitor
Belumosudil: May increase serum concentration of UGT1A1 Substrates. Management: Avoid coadministration of belumosudil with substrates of UGT1A1 for which minimal concentration increases can cause serious adverse effects. If coadministration is required, dose reductions of the UGT1A1 substrate may be required. Risk D: Consider Therapy Modification
Benzylpenicilloyl Polylysine: Coadministration of Alpha1-Agonists and Benzylpenicilloyl Polylysine may alter diagnostic results. Management: Consider delaying skin testing until alpha1-agonists are no longer required, or use of a histamine skin test as a positive control to assess a patient's ability to mount a wheal and flare response. Risk D: Consider Therapy Modification
Bornaprine: Sympathomimetics may increase anticholinergic effects of Bornaprine. Risk C: Monitor
Bromocriptine: May increase hypertensive effects of Alpha1-Agonists. Management: Consider alternatives to this combination when possible. If combined, monitor for hypertension and tachycardia, and do not coadminister these agents for more than 10 days. Risk D: Consider Therapy Modification
Busulfan: Acetaminophen may increase serum concentration of Busulfan. Risk C: Monitor
Cannabinoid-Containing Products: May increase tachycardic effects of Sympathomimetics. Risk C: Monitor
CarBAMazepine: May increase metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor
Chloroprocaine (Systemic): May increase hypotensive effects of Phenylephrine (Systemic). Risk C: Monitor
CloZAPine: May decrease therapeutic effects of Phenylephrine (Systemic). Risk C: Monitor
Cocaine (Topical): May increase hypertensive effects of Sympathomimetics. Management: Consider alternatives to use of this combination when possible. Monitor closely for substantially increased blood pressure or heart rate and for any evidence of myocardial ischemia with concurrent use. Risk D: Consider Therapy Modification
CYP2D6 Inhibitors (Moderate): May increase serum concentration of Dextromethorphan. Risk C: Monitor
CYP2D6 Inhibitors (Strong): May increase serum concentration of Dextromethorphan. Risk C: Monitor
Dapsone (Topical): May increase adverse/toxic effects of Methemoglobinemia Associated Agents. Risk C: Monitor
Dasatinib: Acetaminophen may increase hepatotoxic effects of Dasatinib. Dasatinib may increase serum concentration of Acetaminophen. Management: Avoid coadministration of acetaminophen and dasatinib if possible. If coadministration is unavoidable, monitor for signs/symptoms of hepatotoxicity, particularly in patients with greater acetaminophen exposure. Risk D: Consider Therapy Modification
Dihydralazine: Sympathomimetics may decrease therapeutic effects of Dihydralazine. Risk C: Monitor
Disulfiram: May increase adverse/toxic effects of Products Containing Ethanol. Management: Do not use disulfiram with dosage forms that contain ethanol. Risk X: Avoid
Doxofylline: Sympathomimetics may increase adverse/toxic effects of Doxofylline. Risk C: Monitor
Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates): May increase vasoconstricting effects of Alpha1-Agonists. Risk X: Avoid
Esketamine (Injection): May increase adverse/toxic effects of Sympathomimetics. Specifically, the risk for elevated heart rate, hypertension, and arrhythmias may be increased. Risk C: Monitor
FentaNYL: Decongestants may decrease serum concentration of FentaNYL. Risk C: Monitor
Flucloxacillin: May increase adverse/toxic effects of Acetaminophen. Specifically, the risk for high anion gap metabolic acidosis may be increased. Risk C: Monitor
Fosphenytoin-Phenytoin: May decrease serum concentration of Acetaminophen. Specifically, serum concentrations of acetaminophen may be decreased (leading to decreased efficacy), but the formation of the toxic N-acetyl-p-benzoquinone imine (NAPQI) metabolite may be increased (leading to increased hepatotoxicity). Risk C: Monitor
Guanethidine: May increase hypertensive effects of Sympathomimetics. Guanethidine may increase arrhythmogenic effects of Sympathomimetics. Risk C: Monitor
Hyaluronidase: May increase vasoconstricting effects of Phenylephrine (Systemic). Management: Do not use hyaluronidase to enhance the dispersion or absorption of phenylephrine. Use of hyaluronidase for other purposes in patients receiving phenylephrine may be considered as clinically indicated. Risk D: Consider Therapy Modification
Imatinib: Acetaminophen may increase hepatotoxic effects of Imatinib. Risk C: Monitor
Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies): Acetaminophen may decrease therapeutic effects of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor
Iobenguane Radiopharmaceutical Products: Alpha1-Agonists may decrease therapeutic effects of Iobenguane Radiopharmaceutical Products. Management: Discontinue all drugs that may inhibit or interfere with catecholamine transport or uptake for at least 5 biological half-lives before iobenguane administration. Do not administer these drugs until at least 7 days after each iobenguane dose. Risk X: Avoid
Isoniazid: May increase hepatotoxic effects of Acetaminophen. Isoniazid may increase metabolism of Acetaminophen. Specifically, formation of the hepatotoxic NAPQI metabolite may be increased. Risk C: Monitor
Kratom: May increase adverse/toxic effects of Sympathomimetics. Risk X: Avoid
LamoTRIgine: Acetaminophen may decrease serum concentration of LamoTRIgine. Risk C: Monitor
Landiolol: Sympathomimetics may decrease therapeutic effects of Landiolol. Risk C: Monitor
Levothyroxine: May increase therapeutic effects of Sympathomimetics. Sympathomimetics may increase therapeutic effects of Levothyroxine. Levothyroxine may increase adverse/toxic effects of Sympathomimetics. Specifically, the risk of coronary insufficiency may be increased in patients with coronary artery disease. Risk C: Monitor
Lisuride: May increase hypertensive effects of Alpha1-Agonists. Risk X: Avoid
Local Anesthetics: Methemoglobinemia Associated Agents may increase adverse/toxic effects of Local Anesthetics. Specifically, the risk for methemoglobinemia may be increased. Risk C: Monitor
Lorlatinib: May decrease serum concentration of Acetaminophen. Risk C: Monitor
Mavorixafor: May increase serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk X: Avoid
Melperone: May decrease therapeutic effects of Phenylephrine (Systemic). Risk C: Monitor
Memantine: NMDA Receptor Antagonists may increase adverse/toxic effects of Memantine. Risk C: Monitor
Metergoline: May increase adverse/toxic effects of Alpha1-Agonists. Risk C: Monitor
Methotrimeprazine: May increase CNS depressant effects of Products Containing Ethanol. Management: Avoid products containing alcohol in patients treated with methotrimeprazine. Risk X: Avoid
MetroNIDAZOLE (Systemic): May increase adverse/toxic effects of Products Containing Ethanol. A disulfiram-like reaction may occur. Risk X: Avoid
MetroNIDAZOLE (Topical): May increase adverse/toxic effects of Products Containing Ethanol. A disulfiram-like reaction may occur. Risk C: Monitor
MetyraPONE: May increase serum concentration of Acetaminophen. More importantly, by inhibiting the conjugative metabolism of acetaminophen, metyrapone may shift the metabolism towards the oxidative route that produces a hepatotoxic metabolite. Risk X: Avoid
Mitapivat: May decrease serum concentration of UGT1A1 Substrates. Risk C: Monitor
Monoamine Oxidase Inhibitors: Dextromethorphan may increase serotonergic effects of Monoamine Oxidase Inhibitors. This may cause serotonin syndrome. Risk X: Avoid
Nitric Oxide: May increase adverse/toxic effects of Methemoglobinemia Associated Agents. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Risk C: Monitor
Parecoxib: May increase serum concentration of Dextromethorphan. Risk C: Monitor
Peginterferon Alfa-2b: May decrease serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Peginterferon Alfa-2b may increase serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor
Pergolide: May increase hypertensive effects of Alpha1-Agonists. Risk C: Monitor
PHENobarbital: May increase metabolism of Acetaminophen. Specifically, formation of the hepatotoxic NAPQI metabolite may be increased. Risk C: Monitor
Prilocaine: Methemoglobinemia Associated Agents may increase adverse/toxic effects of Prilocaine. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Management: Monitor for signs of methemoglobinemia when prilocaine is used in combination with other agents associated with development of methemoglobinemia. Avoid use of these agents with prilocaine/lidocaine cream in infants less than 12 months of age. Risk C: Monitor
Primaquine: Methemoglobinemia Associated Agents may increase adverse/toxic effects of Primaquine. Specifically, the risk for methemoglobinemia may be increased. Management: Avoid concomitant use of primaquine and other drugs that are associated with methemoglobinemia when possible. If combined, monitor methemoglobin levels closely. Risk D: Consider Therapy Modification
Primidone: May increase metabolism of Acetaminophen. Specifically, formation of the hepatotoxic NAPQI metabolite may be increased. Risk C: Monitor
Probenecid: May increase serum concentration of Acetaminophen. Probenecid may also limit the formation of at least one major non-toxic metabolite, possibly increasing the potential for formation of the toxic NAPQI metabolite. Management: Consider limiting acetaminophen use in combination with probenecid. Probenecid may reduce clearance of acetaminophen to one of its non-toxic metabolities, increasing the risk for acetaminophen toxicity, even a lower doses. Risk D: Consider Therapy Modification
Propacetamol: May increase serum concentration of Phenylephrine (Systemic). Management: Monitor patients closely for increased side effects of phenylephrine if propacetamol is used concomitantly. Patients with underlying blood pressure issues or arrhythmias may need closer monitoring and may warrant consideration of alternative therapies. Risk C: Monitor
RifAMPin: May increase hepatotoxic effects of Acetaminophen. RifAMPin may decrease serum concentration of Acetaminophen. Risk C: Monitor
Secnidazole: Products Containing Ethanol may increase adverse/toxic effects of Secnidazole. Risk X: Avoid
Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors): Dextromethorphan may increase serotonergic effects of Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors). This could result in serotonin syndrome. Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors) may increase serum concentration of Dextromethorphan. Management: Consider alternatives to this drug combination. The dose of dextromethorphan/bupropion product should not exceed 1 tablet once daily. Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity. Risk D: Consider Therapy Modification
Serotonergic Agents (High Risk): Dextromethorphan may increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Sodium Nitrite: Methemoglobinemia Associated Agents may increase adverse/toxic effects of Sodium Nitrite. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Risk C: Monitor
Solriamfetol: Sympathomimetics may increase hypertensive effects of Solriamfetol. Sympathomimetics may increase tachycardic effects of Solriamfetol. Risk C: Monitor
SORAfenib: Acetaminophen may increase hepatotoxic effects of SORAfenib. SORAfenib may increase serum concentration of Acetaminophen. Management: Avoid coadministration of acetaminophen and sorafenib if possible. If coadministration is unavoidable, monitor for signs/symptoms of hepatotoxicity, particularly in patients with greater acetaminophen exposure. Risk D: Consider Therapy Modification
Sympathomimetics: May increase adverse/toxic effects of Sympathomimetics. Risk C: Monitor
Tedizolid: May increase adverse/toxic effects of Sympathomimetics. Specifically, the risk for increased blood pressure and heart rate may be increased. Risk C: Monitor
Vaccines: Acetaminophen may decrease therapeutic effects of Vaccines. Management: Consider avoiding routine prophylactic use of acetaminophen before or during vaccine administration when possible. Acetaminophen is still recommended to treat fevers and/or pain that occurs after vaccination. Risk D: Consider Therapy Modification
Vitamin K Antagonists: Acetaminophen may increase anticoagulant effects of Vitamin K Antagonists. This appears most likely with daily acetaminophen doses exceeding 1.3 or 2 g/day for multiple consecutive days. Risk C: Monitor
Refer to individual monographs.
Refer to individual monographs.
Some products may contain phenylalanine, potassium, and/or sodium.
Acetaminophen: Although not fully elucidated, the analgesic effects are believed to be due to activation of descending serotonergic inhibitory pathways in the CNS. Interactions with other nociceptive systems may be involved as well (Smith 2009). Antipyresis is produced from inhibition of the hypothalamic heat-regulating center.
Dextromethorphan: Controls cough by depressing the medullary cough center.
Phenylephrine: Causes vasoconstriction of the arterioles of the nasal mucosa.
See individual agents.
