Version July 2025
Allergies/common cold/hay fever: Oral: Note: OTC dosing recommendations may vary by product and/or manufacturer. 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. No dose adjustment required when converting between different acetaminophen formulations.
Acetaminophen 325 mg/phenylephrine 5 mg: Acetaminophen 650 mg/phenylephrine 10 mg every 4 to 6 hours as needed. Refer to product-specific labeling for maximum daily dosage (maximum dosage range: acetaminophen 2.6 to 3.25 g/phenylephrine 40 to 50 mg per 24 hours).
Acetaminophen 500 mg/phenylephrine 5 mg: Acetaminophen 1 g/phenylephrine 10 mg every 4 to 6 hours as needed; maximum: acetaminophen 4 g/phenylephrine 40 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. Limited, low-dose therapy is usually well tolerated in hepatic disease/cirrhosis; however, cases of hepatotoxicity at daily acetaminophen dosages <4 g/day have been reported. Avoid chronic use in hepatic impairment. Also see Acetaminophen monograph.
Refer to adult dosing.
(For additional information see "Acetaminophen (paracetamol) and phenylephrine: Pediatric drug information")
Allergies/common cold/hay fever:
Note: OTC dosing recommendations may vary by product and/or manufacturer. 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. Multiple formulations of tablet strengths exist; pay close attention to the strength when ordering or administering.
Acetaminophen 325 mg/phenylephrine 5 mg per tablet (eg, Tylenol Sinus + Headache, Sudafed PE Pressure + Pain): Children ≥12 years and Adolescents: Oral: 2 tablets every 4 hours as needed; maximum daily dose range: 10 to 12 tablets/24 hours; maximum daily dose varies by product; see product-specific labeling for details.
Acetaminophen 500 mg/phenylephrine 5 mg per tablet (eg, Contact Cold & Flu Day, Cetafen Cold & Sinus Relief): Children ≥12 years and Adolescents: Oral: 2 tablets every 4 to 6 hours as needed; maximum daily dose: 8 tablets/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. Limited, low-dose therapy is usually well tolerated in hepatic disease/cirrhosis; however, cases of hepatotoxicity at recommended daily acetaminophen dosages have been reported. Avoid chronic use in hepatic impairment. Also see Acetaminophen monograph.
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, phenylephrine, or any component of the formulation; longer than 7 days (for pain), 3 days (for fever), or 2 days (sore throat).
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 adults). In addition, long-term daily dosing may also result in liver damage in some patients.
• 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.
• Hypersensitivity/anaphylactic reactions: Hypersensitivity and anaphylactic reactions have been reported; discontinue immediately if symptoms of allergic or hypersensitivity reactions occur.
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 alcoholic drinks/day.
• G6PD deficiency: Use with caution in patients with known G6PD deficiency.
• Hepatic impairment: Use with caution in patients with hepatic impairment or active liver disease.
• 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:
• Older adult: Use with caution in older adults; more likely to experience adverse reactions to sympathomimetics.
Other warnings/precautions:
• Dosage limit: Limit acetaminophen dose from all sources <4 g/day (adults).
• Self-medication (OTC use): When used for self-medication (OTC), discontinue use and notify health care provider if pain or nasal congestion does not improve or gets worse within 7 days or are accompanied by fever; fever gets worse or lasts >3 days; if any new symptoms or nervousness, dizziness, or sleeplessness occur; or if redness or swelling is present. If sore throat persists for >2 days, is accompanied or followed by a fever, headache, rash, nausea, or vomiting, contact health care provider.
Hepatoxicity has been reported in patients using acetaminophen. In pediatric patients, this is most commonly associated with supratherapeutic dosing, more frequent administration than recommended, and use of multiple acetaminophen-containing products; however, hepatotoxicity has been rarely reported with recommended dosages (AAP [Sullivan 2011]; Heard 2014). All sources of acetaminophen (eg, prescription, OTC, combination) should be considered when evaluating a patient's maximum daily dose. To lower the risk for hepatotoxicity, the maximum daily acetaminophen dose should be limited to ≤75 mg/kg/day (maximum of 5 daily doses), not to exceed 4,000 mg/day (AAP [Sullivan 2011]; Heard 2014; Krenzelok 2012; Lavonas 2010). Acetaminophen avoidance or a lower total daily dose (2,000 to 3,000 mg/day) has been suggested for adults with increased risk for acetaminophen hepatotoxicity (eg, malnutrition, certain liver diseases, use of drugs that interact with acetaminophen metabolism); similar data are unavailable in pediatric patients (Hayward 2016; Larson 2007; Worriax 2007).
Safety and efficacy for the use of cough and cold products in pediatric patients <4 years of age is limited; the AAP warns against the use of these products for respiratory illnesses in young children. Serious adverse effects including death have been reported (in some cases, high blood concentrations of pseudoephedrine were found). Many of these products contain multiple active ingredients, increasing the risk of accidental overdose when used with other products. The FDA does not recommend OTC uses for these products in pediatric patients <2 years of age and recommends to use with caution in pediatric patients ≥2 years of age. Health care providers are reminded to ask caregivers about the use of OTC cough and cold products in order to avoid exposure to multiple medications containing the same ingredient (AAP 2018; CDC 2007; FDA 2017; FDA 2018). Multiple formulations of tablet strengths exist; pay close attention to the strength when ordering or administering.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product.
Caplet, oral:
Contac Cold + Flu Maximum Strength Non Drowsy: Acetaminophen 500 mg and phenylephrine hydrochloride 5 mg
Mapap Sinus PE, Sudafed PE Pressure + Pain: Acetaminophen 325 mg and phenylephrine hydrochloride 5 mg
Tylenol Sinus + Headache: Acetaminophen 325 mg and phenylephrine hydrochloride 5 mg
Tablet, oral:
Cetafen Cold: Acetaminophen 500 mg and phenylephrine hydrochloride 5 mg
GoodSense Pressure/Pain PE: Acetaminophen 325 mg and phenylephrine hydrochloride 5 mg [DSC]
GoodSense Sinus + Headache: Acetaminophen 325 mg and phenylephrine hydrochloride 5 mg
Mygrex: Acetaminophen 500 mg and phenylephrine hydrochloride 5 mg
Robitussin Peak Cold Nasal Relief: Acetaminophen 325 mg and phenylephrine hydrochloride 5 mg
Sinus Pain & Pressure: Acetaminophen 500 mg and phenylephrine hydrochloride 5 mg
Generic: Acetaminophen 325 mg and phenylephrine hydrochloride 5 mg
Yes: Caplet, tablet
Tablets (Mygrex Oral)
5-500 mg (per each): $0.10
Tablets (Panadol Cold/Flu Oral)
5-325 mg (per each): $0.27
Tablets (Sudafed PE Sinus Pressure+Pain Oral)
5-325 mg (per each): $0.29
Tablets (Tylenol Sinus+Headache Oral)
5-325 mg (per each): $0.30
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: Some products should be swallowed whole (do not crush, chew, or dissolve); refer to product information.
Oral: Swallow caplets whole; do not crush, chew, or dissolve.
Allergies/common cold/hay fever: Temporary relief of symptoms (nasal congestion, sinus congestion/pressure, minor aches and pain, headache, fever, sore throat) associated with hay fever, other respiratory allergies, and the common cold.
Duplicate therapy issues: This product contains acetaminophen, which may be a component of 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.
Alcohol (Ethyl): May increase hepatotoxic effects of Acetaminophen. Risk C: Monitor
Alpha1-Blockers: May decrease vasoconstricting effects of Phenylephrine (Systemic). 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
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
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
Linezolid: May increase hypertensive effects of Sympathomimetics. Management: Consider initial dose reductions of sympathomimetic agents, and closely monitor for enhanced blood pressure elevations, in patients receiving linezolid. Risk D: Consider Therapy Modification
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
Melperone: May decrease therapeutic effects of Phenylephrine (Systemic). Risk C: Monitor
Metergoline: May increase adverse/toxic effects of Alpha1-Agonists. 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: May increase hypertensive effects of Alpha1-Agonists. While linezolid is expected to interact via this mechanism, management recommendations differ from other monoamine oxidase inhibitors. Refer to linezolid specific monographs for details. 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
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
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
Tricyclic Antidepressants: May increase therapeutic effects of Alpha1-Agonists. Tricyclic Antidepressants may decrease therapeutic effects of Alpha1-Agonists. 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 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.
Phenylephrine: Causes vasoconstriction of the arterioles of the nasal mucosa.
See individual agents.
