Version July 2025
Pain/fever/hay fever: Oral: Two tablets every 4 to 6 hours as needed (maximum: 10 tablets/day).
There are no dosage adjustments provided in the manufacturer’s labeling; monitor renal function with severe impairment.
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.
Avoid use (Ref).
(For additional information see "Acetaminophen (paracetamol) and phenyltoloxamine: Pediatric drug information")
Note: All sources of acetaminophen (eg, prescription, OTC, combination products) should be considered when evaluating a patient's maximum daily dose. To lower the risk for hepatotoxicity, limit daily dose to ≤75 mg/kg/day (maximum of 5 daily doses), not to exceed 4,000 mg/day; while recommended doses are generally considered safe, hepatotoxicity has been reported (rarely) even with doses below recommendations (Ref).
Pain (minor) or fever: Oral: Dolorex (acetaminophen 325 mg/phenyltoloxamine citrate 25 mg per tablet):
Children 6 to 11 years: 1 tablet every 4 to 6 hours as needed; maximum daily dose: 5 tablets/24 hours
Children ≥12 years and Adolescents: 2 tablets every 4 to 6 hours as needed; maximum daily dose: 10 tablets/24 hours
There are no dosage adjustments provided in the manufacturer's labeling; monitor renal function with severe impairment.
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 <4,000 mg have been reported. Avoid chronic use in hepatic impairment.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Frequency not defined.
Central nervous system: Dizziness, drowsiness, lassitude
Dermatologic: Diaphoresis, pruritus, skin rash
Gastrointestinal: Nausea
Ophthalmic: Blurred vision
OTC labeling: When used for self-medication, do not use if allergic to acetaminophen, phenyltoloxamine, or any component of the formulation or with any other medicine containing acetaminophen or phenyltoloxamine.
Concerns related to adverse effects:
• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
• 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 >1 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: Rarely, acetaminophen may cause serious and potentially fatal skin reactions such as acute generalized exanthematous pustulosis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). Discontinue treatment if severe skin reactions develop.
Disease-related concerns:
• Ethanol use: Use with caution in patients with alcoholic liver disease; consuming ≥3 alcoholic drinks/day may increase the risk of liver damage. Have patients avoid ethanol or limit to <3 drinks/day.
• Hepatic impairment: Use with caution in patients with hepatic impairment; acetaminophen may cause severe hepatic toxicity with acute overdose.
Other warnings/precautions:
• Dosage limit: Limit acetaminophen dose to <4 g/day or <2.6 g/day (children <12 years of age).
• Self-medication (OTC use): When used for self-medication, patients should contact health care provider if they have liver disease and/or are currently taking a blood thinner. Discontinue use and notify health care provider if pain worsens or lasts >10 days in adults (or >5 days in children), fever worsens or lasts >3 days, if any new symptoms occur, or if redness or swelling is present.
Prophylactic use of acetaminophen to reduce fever and discomfort associated with vaccination is not recommended by the Advisory Committee on Immunization Practices (ACIP). Additionally, the ACIP does not recommend prophylactic acetaminophen to reduce risk of febrile seizure in infants and children with or without a history of febrile seizures. Antipyretics have not been shown to prevent febrile seizures (NCIRD/ACIP 2011). One study reported that routine prophylactic administration of acetaminophen to prevent fever prior to vaccination decreased the immune response of some vaccines; in the trial evaluating 459 infants (including 226 who received acetaminophen), antibody geometric mean concentrations (GMCs) for targeted vaccine immune response markers were lower in significantly more infants in the acetaminophen group compared with control. Before the booster dose, children who received prophylactic acetaminophen had lower antibody GMCs for all vaccine serotypes than children in the control group; this effect persisted after boosting even in the absence of additional acetaminophen doses. The clinical significance of this reduction in immune response has not been established (Prymula 2009). Antipyretics may be used to treat fever or discomfort following vaccination (NCIRD/ACIP 2011).
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).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Dolorex: Acetaminophen 325 mg and phenyltoloxamine citrate 25 mg
Yes
Tablets (Dologesic Oral)
30-500 mg (per each): $0.22
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Oral: May be administered without regard to food.
Pain/fever/hay fever: Temporary relief of minor aches and pains due to headache, backache, toothache, menstrual cramps, muscular aches, and minor pain of arthritis; temporarily reduces fever; temporarily reduces itchy and watery eyes due to hay fever.
Beers Criteria: Based on pharmacologic class concerns for first-generation antihistamines in the Beers Criteria, phenyltoloxamine may be a potentially inappropriate medication to be avoided in patients 65 years and older (independent of diagnosis or condition) due to its potent anticholinergic properties resulting in increased risk of confusion, dry mouth, constipation, and other anticholinergic effects or toxicity; use should also be avoided due to reduced clearance with advanced age and tolerance associated with use as a hypnotic. Exposure to concurrent anticholinergic drugs also increases risk of falls, delirium, and dementia; consider total anticholinergic burden when conducting medication reviews (Beers Criteria [AGS 2023]).
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.
Acetylcholinesterase Inhibitors: May decrease therapeutic effects of Agents with Clinically Relevant Anticholinergic Effects. Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Acetylcholinesterase Inhibitors. Risk C: Monitor
Aclidinium: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid
Acrivastine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Acrivastine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Alcohol (Ethyl): May increase hepatotoxic effects of Acetaminophen. Risk C: Monitor
Alizapride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Amantadine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Amezinium: Antihistamines may increase stimulatory effects of Amezinium. Risk C: Monitor
Amisulpride (Oral): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Articaine: May increase CNS depressant effects of CNS Depressants. Management: Consider reducing the dose of articaine if possible when used in patients who are also receiving CNS depressants. Monitor for excessive CNS depressant effects with any combined use. Risk D: Consider Therapy Modification
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
Azelastine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
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
Benperidol: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Benperidol. Risk C: Monitor
Benperidol: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Benztropine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Benztropine. Risk C: Monitor
Benzylpenicilloyl Polylysine: Coadministration of Antihistamines and Benzylpenicilloyl Polylysine may alter diagnostic results. Management: Suspend systemic H1 antagonists for benzylpenicilloyl-polylysine skin testing and delay testing until systemic antihistaminic effects have dissipated. A histamine skin test may be used to assess persistent antihistaminic effects. Risk D: Consider Therapy Modification
Betahistine: Antihistamines may decrease therapeutic effects of Betahistine. Betahistine may decrease therapeutic effects of Antihistamines. Risk C: Monitor
Biperiden: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Biperiden. Risk C: Monitor
Blonanserin: CNS Depressants may increase CNS depressant effects of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider Therapy Modification
Bornaprine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Bornaprine. Risk C: Monitor
Botulinum Toxin-Containing Products: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Brexanolone: CNS Depressants may increase CNS depressant effects of Brexanolone. Risk C: Monitor
Brimonidine (Topical): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Bromopride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Bromperidol: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Buclizine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Buclizine. Risk C: Monitor
Buclizine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Buprenorphine: CNS Depressants may increase CNS depressant effects of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Risk D: Consider Therapy Modification
BusPIRone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Busulfan: Acetaminophen may increase serum concentration of Busulfan. Risk C: Monitor
Cannabinoid-Containing Products: Agents with Clinically Relevant Anticholinergic Effects may increase tachycardic effects of Cannabinoid-Containing Products. Risk C: Monitor
Cannabinoid-Containing Products: CNS Depressants may increase CNS depressant effects of Cannabinoid-Containing Products. 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
Certoparin: Antihistamines may increase therapeutic effects of Certoparin. Risk C: Monitor
Cetirizine (Systemic): May increase CNS depressant effects of CNS Depressants. Management: Consider avoiding this combination if possible. If required, monitor for excessive sedation or CNS depression, limit the dose and duration of combination therapy, and consider CNS depressant dose reductions. Risk D: Consider Therapy Modification
Chloral Hydrate/Chloral Betaine: CNS Depressants may increase CNS depressant effects of Chloral Hydrate/Chloral Betaine. Management: Consider alternatives to the use of chloral hydrate or chloral betaine and additional CNS depressants. If combined, consider a dose reduction of either agent and monitor closely for enhanced CNS depressive effects. Risk D: Consider Therapy Modification
Chlormethiazole: May increase CNS depressant effects of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider Therapy Modification
Chlorphenesin Carbamate: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor
Chlorprothixene: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Chlorprothixene. Risk C: Monitor
Cimetropium: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Cimetropium. Risk X: Avoid
CloZAPine: Agents with Clinically Relevant Anticholinergic Effects may increase constipating effects of CloZAPine. Management: Consider alternatives to this combination whenever possible. If combined, monitor closely for signs and symptoms of gastrointestinal hypomotility and consider prophylactic laxative treatment. Risk D: Consider Therapy Modification
CNS Depressants: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor
Cyclizine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Dantrolene: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Dapsone (Topical): May increase adverse/toxic effects of Methemoglobinemia Associated Agents. Risk C: Monitor
Daridorexant: May increase CNS depressant effects of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider Therapy Modification
Darifenacin: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Darifenacin. 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
DexmedeTOMIDine: CNS Depressants may increase CNS depressant effects of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider Therapy Modification
Dicyclomine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Dicyclomine. Risk C: Monitor
Difelikefalin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Difenoxin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Dihydralazine: CNS Depressants may increase hypotensive effects of Dihydralazine. Risk C: Monitor
Dimethindene (Systemic): Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Dimethindene (Systemic). Risk C: Monitor
Dimethindene (Topical): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Dothiepin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Doxylamine: CNS Depressants may increase CNS depressant effects of Doxylamine. Risk C: Monitor
DroNABinol: Agents with Clinically Relevant Anticholinergic Effects may increase tachycardic effects of DroNABinol. Risk X: Avoid
DroPERidol: May increase CNS depressant effects of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Risk D: Consider Therapy Modification
Eluxadoline: Agents with Clinically Relevant Anticholinergic Effects may increase constipating effects of Eluxadoline. Risk X: Avoid
Emedastine (Systemic): May increase CNS depressant effects of CNS Depressants. Management: Consider avoiding this combination if possible. If required, monitor for excessive sedation or CNS depression, limit the dose and duration of combination therapy, and consider CNS depressant dose reductions. Risk C: Monitor
Entacapone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Esketamine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Fesoterodine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Fesoterodine. 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
Flunarizine: CNS Depressants may increase CNS depressant effects of Flunarizine. Risk X: Avoid
Flunitrazepam: CNS Depressants may increase CNS depressant effects of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider Therapy Modification
FluPHENAZine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. 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
Gastrointestinal Agents (Prokinetic): Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Gastrointestinal Agents (Prokinetic). Risk C: Monitor
Gepotidacin: May decrease anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Glucagon: Agents with Clinically Relevant Anticholinergic Effects may increase adverse/toxic effects of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Risk C: Monitor
Glycopyrrolate (Oral Inhalation): Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Glycopyrrolate (Oral Inhalation). Risk X: Avoid
Glycopyrrolate (Systemic): Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Glycopyrrolate (Systemic). Risk C: Monitor
Glycopyrronium (Topical): May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid
Hyaluronidase: Antihistamines may decrease therapeutic effects of Hyaluronidase. Risk C: Monitor
HydrOXYzine: May increase CNS depressant effects of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. 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
Ipratropium (Nasal): May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Ipratropium (Oral Inhalation): May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. 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
Itopride: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Itopride. Risk C: Monitor
Ixabepilone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Kava Kava: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Ketotifen (Systemic): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Kratom: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
LamoTRIgine: Acetaminophen may decrease serum concentration of LamoTRIgine. Risk C: Monitor
Lemborexant: May increase CNS depressant effects of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider Therapy Modification
Levocetirizine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Levosulpiride: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Levosulpiride. Risk X: Avoid
Lisuride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Local Anesthetics: Methemoglobinemia Associated Agents may increase adverse/toxic effects of Local Anesthetics. Specifically, the risk for methemoglobinemia may be increased. Risk C: Monitor
Lofepramine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Lofexidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Lorlatinib: May decrease serum concentration of Acetaminophen. Risk C: Monitor
Loxapine: CNS Depressants may increase CNS depressant effects of Loxapine. Management: Consider reducing the dose of CNS depressants administered concomitantly with loxapine due to an increased risk of respiratory depression, sedation, hypotension, and syncope. Risk D: Consider Therapy Modification
Magnesium Sulfate: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Maprotiline: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Maprotiline. Risk C: Monitor
Melitracen [INT]: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Melperone: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Mequitazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Metergoline: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Methotrimeprazine: CNS Depressants may increase CNS depressant effects of Methotrimeprazine. Methotrimeprazine may increase CNS depressant effects of CNS Depressants. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider Therapy Modification
Methoxyflurane: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Methscopolamine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Methscopolamine. Risk C: Monitor
Metoclopramide: May increase CNS depressant effects of CNS Depressants. 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
MetyroSINE: CNS Depressants may increase sedative effects of MetyroSINE. Risk C: Monitor
Minocycline (Systemic): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Mirabegron: Agents with Clinically Relevant Anticholinergic Effects may increase adverse/toxic effects of Mirabegron. Risk C: Monitor
Mitapivat: May decrease serum concentration of UGT1A1 Substrates. Risk C: Monitor
Moxonidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Nabilone: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Nalfurafine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
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
Nitroglycerin: Agents with Clinically Relevant Anticholinergic Effects may decrease absorption of Nitroglycerin. Specifically, anticholinergic agents may decrease the dissolution of sublingual nitroglycerin tablets, possibly impairing or slowing nitroglycerin absorption. Risk C: Monitor
Noscapine: CNS Depressants may increase adverse/toxic effects of Noscapine. Risk X: Avoid
OLANZapine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of OLANZapine. Risk C: Monitor
Olopatadine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Opicapone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Opioid Agonists: CNS Depressants may increase CNS depressant effects of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider Therapy Modification
Opipramol: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Opipramol: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Orphenadrine: CNS Depressants may increase CNS depressant effects of Orphenadrine. Risk X: Avoid
Oxatomide: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid
Oxomemazine: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Oxybate Salt Products: CNS Depressants may increase CNS depressant effects of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interrupt oxybate salt treatment during short-term opioid use Risk D: Consider Therapy Modification
OxyBUTYnin: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of OxyBUTYnin. Risk C: Monitor
OxyCODONE: CNS Depressants may increase CNS depressant effects of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider Therapy Modification
Paliperidone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Paraldehyde: CNS Depressants may increase CNS depressant effects of Paraldehyde. Risk X: Avoid
Perampanel: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Perazine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Periciazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Perphenazine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Perphenazine. Risk C: Monitor
PHENobarbital: May increase metabolism of Acetaminophen. Specifically, formation of the hepatotoxic NAPQI metabolite may be increased. Risk C: Monitor
Phenylephrine (Systemic): Acetaminophen may increase serum concentration of Phenylephrine (Systemic). Risk C: Monitor
Pipamperone: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor
Piribedil: CNS Depressants may increase CNS depressant effects of Piribedil. Risk C: Monitor
Pitolisant: Antihistamines may decrease therapeutic effects of Pitolisant. Risk X: Avoid
Pizotifen: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Potassium Chloride: Agents with Clinically Relevant Anticholinergic Effects may increase ulcerogenic effects of Potassium Chloride. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium chloride. Risk X: Avoid
Potassium Citrate: Agents with Clinically Relevant Anticholinergic Effects may increase ulcerogenic effects of Potassium Citrate. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium citrate. Risk X: Avoid
Pramipexole: CNS Depressants may increase sedative effects of Pramipexole. Risk C: Monitor
Pramlintide: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. These effects are specific to the GI tract. Risk X: Avoid
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
Procarbazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Promethazine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Promethazine. Risk C: Monitor
Propantheline: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Propantheline. Risk C: Monitor
Propiverine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
QuiNIDine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Ramosetron: Agents with Clinically Relevant Anticholinergic Effects may increase constipating effects of Ramosetron. Risk C: Monitor
Revefenacin: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Revefenacin. Risk X: Avoid
RifAMPin: May increase hepatotoxic effects of Acetaminophen. RifAMPin may decrease serum concentration of Acetaminophen. Risk C: Monitor
Rilmenidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Rivastigmine: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Rivastigmine. Rivastigmine may decrease therapeutic effects of Agents with Clinically Relevant Anticholinergic Effects. Management: Use of rivastigmine with an anticholinergic agent is not recommended unless clinically necessary. If the combination is necessary, monitor for reduced anticholinergic effects. Risk D: Consider Therapy Modification
Ropeginterferon Alfa-2b: CNS Depressants may increase adverse/toxic effects of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider Therapy Modification
ROPINIRole: CNS Depressants may increase sedative effects of ROPINIRole. Risk C: Monitor
Rotigotine: CNS Depressants may increase sedative effects of Rotigotine. Risk C: Monitor
Scopolamine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Scopolamine. Risk C: Monitor
Secretin: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Secretin. Management: Avoid concomitant use of anticholinergic agents and secretin. Discontinue anticholinergic agents at least 5 half-lives prior to administration of secretin. Risk D: Consider Therapy Modification
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
Sofpironium: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Sofpironium. Risk X: Avoid
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
Suvorexant: CNS Depressants may increase CNS depressant effects of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider Therapy Modification
Thalidomide: CNS Depressants may increase CNS depressant effects of Thalidomide. Risk X: Avoid
Thiazide and Thiazide-Like Diuretics: Agents with Clinically Relevant Anticholinergic Effects may increase serum concentration of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor
Thiothixene: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Thiothixene. Risk C: Monitor
Tiapride: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Tiapride. Risk C: Monitor
Tiotropium: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Tiotropium. Risk X: Avoid
Tolterodine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Tolterodine. Risk C: Monitor
Topiramate: Agents with Clinically Relevant Anticholinergic Effects may increase adverse/toxic effects of Topiramate. Risk C: Monitor
Tranylcypromine: May increase anticholinergic effects of Antihistamines, First Generation. Risk X: Avoid
Tricyclic Antidepressants: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Tricyclic Antidepressants. Risk C: Monitor
Trimeprazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Trimethobenzamide: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Trimethobenzamide. Risk C: Monitor
Trospium: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Trospium. Risk C: Monitor
Umeclidinium: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid
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
Valerian: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
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
Zolpidem: CNS Depressants may increase CNS depressant effects of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider Therapy Modification
Zuclopenthixol: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Zuclopenthixol. Risk C: Monitor
Zuranolone: May increase CNS depressant effects of CNS Depressants. Management: Consider alternatives to the use of zuranolone with other CNS depressants or alcohol. If combined, consider a zuranolone dose reduction and monitor patients closely for increased CNS depressant effects. Risk D: Consider Therapy Modification
Refer to individual monographs.
Refer to individual monographs.
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.
Phenyltoloxamine: An antihistamine (H1-blocking agent) that acts primarily to inhibit secretions in the nose, mouth, and pharynx, as well as causing CNS depression.
