Acetaminophen (paracetamol) and diphenhydramine: Drug information

(For additional information see "Acetaminophen (paracetamol) and diphenhydramine: Patient drug information" and see "Acetaminophen (paracetamol) and diphenhydramine: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)

Brand Names: US

Acetaminophen PM Ex St [OTC] [DSC];
Acetaminophen PM [OTC];
Excedrin PM [OTC];
FT Pain Reliever PM Extra Str [OTC];
GoodSense Headache PM [OTC] [DSC];
GoodSense Pain Relief PM Ex St [OTC];
Healthy Mama eaZZZe the Pain [OTC];
Mapap PM [OTC] [DSC];
Night Time Pain Medicine Ex St [OTC];
Non-Aspirin PM Extra Strength [OTC] [DSC];
Non-Aspirin PM [OTC];
Panadol PM Extra Strength [OTC];
Tylenol PM Extra Strength [OTC]

Pharmacologic Category

Analgesic, Nonopioid

Dosing: Adult

Insomnia and pain, occasional

Insomnia and pain, occasional:

Note: Routine use is not recommended (Ref). When used, limit long-term use (>4 weeks) to cases for which nonpharmacologic treatments are not available or not effective and benefits are felt to outweigh risks (Ref).

General dosing guidelines; refer also to specific product labeling: Oral: Acetaminophen 500 to 1,000 mg and diphenhydramine hydrochloride 25 to 50 mg (38 to 76 mg diphenhydramine citrate) at bedtime or as directed by physician; do not exceed recommended dosage.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Hepatic Impairment: Adult

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.

Dosing: Older Adult

Avoid use (Ref).

Dosing: Pediatric

(For additional information see "Acetaminophen (paracetamol) and diphenhydramine: Pediatric drug information")

Note: All sources of acetaminophen and diphenhydramine (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 of acetaminophen 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).

Insomnia and pain

Insomnia and pain:

Tablet: Acetaminophen 500 mg/diphenhydramine hydrochloride 25 mg per tablet (eg, Panadol PM, Tylenol PM):

Children ≥12 years and Adolescents: Oral: 2 tablets every 24 hours at bedtime as needed. Maximum daily dose: 2 tablets per 24 hours.

Oral solution: Acetaminophen 1,000 mg/diphenhydramine hydrochloride 50 mg per 30 mL (eg, Tylenol PM Extra Strength Liquid):

Children ≥12 years and Adolescents: Oral: 30 mL every 24 hours at bedtime as needed. Maximum daily dose: 30 mL per 24 hours.

Oral powder: Acetaminophen 500 mg/diphenhydramine citrate 38 mg per powder packet (eg, Goody's PM):

Children ≥12 years and Adolescents: Oral: 2 packets every 24 hours at bedtime as needed. Maximum daily dose: 2 powder packets per 24 hours.

Dosing: Kidney Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Hepatic Impairment: Pediatric

Adverse Reactions

See individual agents.

Contraindications

OTC labeling: When used for self-medication, do not use if you have hypersensitivity to acetaminophen, diphenhydramine, or any component of the formulation, concurrently with other products containing acetaminophen or diphenhydramine (including topical), or in children <12 years of age.

Warnings/Precautions

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 that require mental alertness (eg, operating machinery, driving).

• Hepatotoxicity: May cause severe hepatic toxicity on acute overdose; in addition, chronic daily dosing in adults has resulted 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, and toxic epidermal necrolysis. 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.

Special populations:

• Pediatric: Do not exceed pediatric dosing recommendations. If no recommendations exist on OTC labeling for patient's age, the product should not be administered without the guidance of a physician.

Other warnings/precautions:

• Dosage limit: Limit acetaminophen dose to <4 g/day (adults) or <2.6 g/day (children <12 years of age).

• Self-medication (OTC use): Prior to self-medication, patients should contact health care provider if they have had liver disease, emphysema, chronic bronchitis, glaucoma, enlarged prostate, or are currently taking sedative drugs or alcohol. Consuming ≥3 alcoholic beverages/day or taking longer than recommended may increase the risk of liver damage. Discontinue use and contact health care provider if insomnia lasts >14 days, pain gets worse or lasts >10 days, fever gets worse or lasts >3 days, if redness or swelling occurs, or if any new symptoms occur.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Liquid, Oral:

Tylenol PM Extra Strength: Acetaminophen 1000 mg and diphenhydramine hydrochloride 50 mg per 30 mL (240 mL [DSC]) [contains fd&c blue #1 (brilliant blue), fd&c red #40 (allura red ac dye), polyethylene glycol (macrogol), propylene glycol, sodium benzoate]

Tablet, Oral:

Acetaminophen PM: Acetaminophen 500 mg and diphenhydramine hydrochloride 25 mg [contains fd&c blue #1 (brill blue) aluminum lake, quinoline (d&c yellow #10) aluminum lake]

Acetaminophen PM Ex St: Acetaminophen 500 mg and diphenhydramine hydrochloride 25 mg [DSC] [contains fd&c blue #1 (brilliant blue)]

Excedrin PM: Acetaminophen 500 mg and diphenhydramine citrate 38 mg [contains benzoic acid, fd&c blue #1 (brilliant blue)]

FT Pain Reliever PM Extra Str: Acetaminophen 500 mg and diphenhydramine hydrochloride 25 mg [contains corn starch, fd&c blue #1 (brill blue) aluminum lake]

GoodSense Headache PM: Acetaminophen 500 mg and diphenhydramine hydrochloride 25 mg [DSC] [aspirin free, gluten free; contains fd&c blue #1 (brill blue) aluminum lake, fd&c blue #2 (indigo carm) aluminum lake]

GoodSense Pain Relief PM Ex St: Acetaminophen 500 mg and diphenhydramine hydrochloride 25 mg [contains fd&c blue #1 (brilliant blue), fd&c blue #2 (indigo carm) aluminum lake, fd&c red #40 (allura red ac dye), fd&c red #40(allura red ac)aluminum lake, fd&c yellow #6(sunset yellow)alumin lake, quinoline yellow (d&c yellow #10)]

GoodSense Pain Relief PM Ex St: Acetaminophen 500 mg and diphenhydramine hydrochloride 25 mg [gluten free; contains corn starch, fd&c blue #1 (brill blue) aluminum lake]

GoodSense Pain Relief PM Ex St: Acetaminophen 500 mg and diphenhydramine hydrochloride 25 mg [gluten free; contains fd&c blue #1 (brill blue) aluminum lake, fd&c blue #2 (indigo carm) aluminum lake]

Healthy Mama eaZZZe the Pain: Acetaminophen 500 mg and diphenhydramine hydrochloride 25 mg

Mapap PM: Acetaminophen 500 mg and diphenhydramine hydrochloride 25 mg [DSC]

Night Time Pain Medicine Ex St: Acetaminophen 500 mg and diphenhydramine hydrochloride 25 mg [contains fd&c blue #1 (brill blue) aluminum lake, fd&c blue #2 (indigo carm) aluminum lake]

Night Time Pain Medicine Ex St: Acetaminophen 500 mg and diphenhydramine hydrochloride 25 mg [DSC] [contains fd&c blue #1 (brilliant blue)]

Non-Aspirin PM: Acetaminophen 500 mg and diphenhydramine hydrochloride 25 mg [DSC] [contains fd&c blue #1 (brill blue) aluminum lake]

Non-Aspirin PM: Acetaminophen 500 mg and diphenhydramine hydrochloride 25 mg [contains fd&c blue #1 (brilliant blue)]

Non-Aspirin PM Extra Strength: Acetaminophen 500 mg and diphenhydramine hydrochloride 25 mg [DSC] [contains fd&c blue #1 (brill blue) aluminum lake, fd&c blue #2 (indigo carm) aluminum lake]

Panadol PM Extra Strength: Acetaminophen 500 mg and diphenhydramine hydrochloride 25 mg

Tylenol PM Extra Strength: Acetaminophen 500 mg and diphenhydramine hydrochloride 25 mg [contains fd&c blue #1 (brill blue) aluminum lake]

Generic Equivalent Available: US

May be product dependent

Pricing: US

Tablets (Excedrin PM Oral)

500-38 mg (per each): $0.21

Tablets (Healthy Mama eaZZZe the Pain Oral)

500-25 mg (per each): $0.14

Tablets (Panadol PM Extra Strength Oral)

25-500 mg (per each): $0.25

Tablets (Tylenol PM Extra Strength Oral)

500-25 mg (per each): $0.17

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.

Administration: Adult

Oral: Administer without regard to food.

Administration: Pediatric

Oral: Administer at bedtime, without regard to food.

Powder packet: Administer full glass of water with each dose; may stir powder into water or other liquid prior to administration.

Use: Labeled Indications

Insomnia and pain, occasional: Temporary relief of occasional headaches and minor aches and pains accompanied by insomnia.

Limitations of use: American Academy of Sleep Medicine guidelines for the treatment of chronic insomnia suggest diphenhydramine not be used for sleep-onset or sleep-maintenance insomnia in adults due to the absence of evidence for clinically significant improvement (AASM [Sateia 2017]). The US Department of Veterans Affairs/Department of Defense guidelines for the chronic management of insomnia disorder and obstructive sleep apnea suggest against the use of diphenhydramine for chronic insomnia (VA/DoD 2019).

Medication Safety Issues

Sound-alike/look-alike issues:

Excedrin may be confused with Dexedrine

Percogesic may be confused with paregoric, Percodan

Tylenol may be confused with atenolol, timolol, Tylox

Tylenol PM may be confused with Tylenol

Older Adult: High-Risk Medication:

Beers Criteria: Diphenhydramine (oral), a first-generation antihistamine, is identified in the Beers Criteria as a potentially inappropriate medication to be avoided in patients ≥65 years (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. However, use of diphenhydramine may be appropriate in certain situations such as acute treatment of severe allergic reaction (Beers Criteria [AGS 2023]).

Other safety concerns:

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.

International issues:

Benadryl brand name for acetaminophen, diphenhydramine, and phenylephrine [US], but also the brand name for cetirizine [Great Britain, Phillipines] and acrivastine and pseudoephedrine [Great Britain]

Metabolism/Transport Effects

Refer to individual components.

Drug Interactions

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 Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Acetylcholinesterase Inhibitors: May diminish the therapeutic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Risk C: Monitor therapy

Aclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination

Alcohol (Ethyl): May enhance the hepatotoxic effect of Acetaminophen. Risk C: Monitor therapy

Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Amantadine: May enhance the anticholinergic effect of Anticholinergic Agents. Risk C: Monitor therapy

Amezinium: Antihistamines may enhance the stimulatory effect of Amezinium. Risk C: Monitor therapy

Anticholinergic Agents: May enhance the adverse/toxic effect of other Anticholinergic Agents. Risk C: Monitor therapy

Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Benzylpenicilloyl Polylysine: Antihistamines may diminish the diagnostic effect of Benzylpenicilloyl Polylysine. 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 diminish the therapeutic effect of Betahistine. Betahistine may diminish the therapeutic effect of Antihistamines. Risk C: Monitor therapy

Blonanserin: CNS Depressants may enhance the CNS depressant effect 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

Botulinum Toxin-Containing Products: May enhance the anticholinergic effect of Anticholinergic Agents. Risk C: Monitor therapy

Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Risk C: Monitor therapy

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Bromopride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Buprenorphine: CNS Depressants may enhance the CNS depressant effect 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

Busulfan: Acetaminophen may increase the serum concentration of Busulfan. Risk C: Monitor therapy

Cannabinoid-Containing Products: Anticholinergic Agents may enhance the tachycardic effect of Cannabinoid-Containing Products. Risk C: Monitor therapy

Cannabinoid-Containing Products: CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products. Risk C: Monitor therapy

CarBAMazepine: May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy

Chloral Betaine: May enhance the adverse/toxic effect of Anticholinergic Agents. Risk C: Monitor therapy

Chlormethiazole: May enhance the CNS depressant effect 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 enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy

Chlorprothixene: Anticholinergic Agents may enhance the anticholinergic effect of Chlorprothixene. Risk C: Monitor therapy

Cimetropium: Anticholinergic Agents may enhance the anticholinergic effect of Cimetropium. Risk X: Avoid combination

CloZAPine: Anticholinergic Agents may enhance the constipating effect 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 enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy

Dapsone (Topical): May enhance the adverse/toxic effect of Methemoglobinemia Associated Agents. Risk C: Monitor therapy

Daridorexant: May enhance the CNS depressant effect 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

Dasatinib: Acetaminophen may enhance the hepatotoxic effect of Dasatinib. Dasatinib may increase the 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 enhance the CNS depressant effect 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

Difelikefalin: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Disulfiram: May enhance the adverse/toxic effect of Products Containing Ethanol. Management: Do not use disulfiram with dosage forms that contain ethanol. Risk X: Avoid combination

Doxylamine: CNS Depressants may enhance the CNS depressant effect of Doxylamine. Risk C: Monitor therapy

DroPERidol: May enhance the CNS depressant effect 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: Anticholinergic Agents may enhance the constipating effect of Eluxadoline. Risk X: Avoid combination

Esketamine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Flucloxacillin: May enhance the adverse/toxic effect of Acetaminophen. Specifically, the risk for high anion gap metabolic acidosis may be increased. Risk C: Monitor therapy

Flunarizine: CNS Depressants may enhance the CNS depressant effect of Flunarizine. Risk X: Avoid combination

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect 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

Fosphenytoin-Phenytoin: May decrease the 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 therapy

Gastrointestinal Agents (Prokinetic): Anticholinergic Agents may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Risk C: Monitor therapy

Glucagon: Anticholinergic Agents may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Risk C: Monitor therapy

Glycopyrrolate (Oral Inhalation): Anticholinergic Agents may enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation). Risk X: Avoid combination

Glycopyrronium (Topical): May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination

Hyaluronidase: Antihistamines may diminish the therapeutic effect of Hyaluronidase. Risk C: Monitor therapy

HydrOXYzine: May enhance the CNS depressant effect 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 enhance the hepatotoxic effect of Imatinib. Risk C: Monitor therapy

Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies): Acetaminophen may diminish the therapeutic effect of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor therapy

Ipratropium (Oral Inhalation): May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination

Isoniazid: May enhance the hepatotoxic effect of Acetaminophen. Isoniazid may increase the metabolism of Acetaminophen. Specifically, formation of the hepatotoxic NAPQI metabolite may be increased. Risk C: Monitor therapy

Isoproterenol: DiphenhydrAMINE (Systemic) may enhance the therapeutic effect of Isoproterenol. Risk C: Monitor therapy

Itopride: Anticholinergic Agents may diminish the therapeutic effect of Itopride. Risk C: Monitor therapy

Ixabepilone: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Kava Kava: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Kratom: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

LamoTRIgine: Acetaminophen may decrease the serum concentration of LamoTRIgine. Risk C: Monitor therapy

Lemborexant: May enhance the CNS depressant effect 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

Levosulpiride: Anticholinergic Agents may diminish the therapeutic effect of Levosulpiride. Risk X: Avoid combination

Lisuride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Local Anesthetics: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Local Anesthetics. Specifically, the risk for methemoglobinemia may be increased. Risk C: Monitor therapy

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Lorlatinib: May decrease the serum concentration of Acetaminophen. Risk C: Monitor therapy

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Methotrimeprazine: Products Containing Ethanol may enhance the adverse/toxic effect of Methotrimeprazine. Specifically, a disulfiram-like reaction may occur and CNS depressant effects may be increased. Management: Avoid products containing alcohol in patients treated with methotrimeprazine. Risk X: Avoid combination

Metoclopramide: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

MetyraPONE: May increase the 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 combination

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy

Mianserin: May enhance the anticholinergic effect of Anticholinergic Agents. Risk C: Monitor therapy

Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Mipomersen: Acetaminophen may enhance the hepatotoxic effect of Mipomersen. Risk C: Monitor therapy

Mirabegron: Anticholinergic Agents may enhance the adverse/toxic effect of Mirabegron. Risk C: Monitor therapy

Mitapivat: May decrease the serum concentration of UGT1A1 Substrates. Risk C: Monitor therapy

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Nitric Oxide: May enhance the adverse/toxic effect of Methemoglobinemia Associated Agents. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Risk C: Monitor therapy

Nitroglycerin: Anticholinergic Agents may decrease the absorption of Nitroglycerin. Specifically, anticholinergic agents may decrease the dissolution of sublingual nitroglycerin tablets, possibly impairing or slowing nitroglycerin absorption. Risk C: Monitor therapy

Olopatadine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Opioid Agonists: CNS Depressants may enhance the CNS depressant effect 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

Ornidazole: May enhance the adverse/toxic effect of Products Containing Ethanol. Specifically, a disulfiram-like reaction may occur. Risk X: Avoid combination

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination

Oxatomide: May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Oxybate Salt Products: CNS Depressants may enhance the CNS depressant effect 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

OxyCODONE: CNS Depressants may enhance the CNS depressant effect 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

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

PHENobarbital: May increase the metabolism of Acetaminophen. Specifically, formation of the hepatotoxic NAPQI metabolite may be increased. Risk C: Monitor therapy

Phenylephrine (Systemic): Acetaminophen may increase the serum concentration of Phenylephrine (Systemic). Risk C: Monitor therapy

Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Risk C: Monitor therapy

Pitolisant: Antihistamines may diminish the therapeutic effect of Pitolisant. Risk X: Avoid combination

Potassium Chloride: Anticholinergic Agents may enhance the ulcerogenic effect 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 combination

Potassium Citrate: Anticholinergic Agents may enhance the ulcerogenic effect 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 combination

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Risk C: Monitor therapy

Pramlintide: May enhance the anticholinergic effect of Anticholinergic Agents. These effects are specific to the GI tract. Risk X: Avoid combination

Prilocaine: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Prilocaine. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Management: Monitor patients for signs of methemoglobinemia (e.g., hypoxia, cyanosis) when prilocaine is used in combination with other agents associated with development of methemoglobinemia. Avoid lidocaine/prilocaine in infants receiving such agents. Risk C: Monitor therapy

Primidone: May increase the metabolism of Acetaminophen. Specifically, formation of the hepatotoxic NAPQI metabolite may be increased. Risk C: Monitor therapy

Probenecid: May increase the 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 enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Ramosetron: Anticholinergic Agents may enhance the constipating effect of Ramosetron. Risk C: Monitor therapy

Revefenacin: Anticholinergic Agents may enhance the anticholinergic effect of Revefenacin. Risk X: Avoid combination

RifAMPin: May enhance the hepatotoxic effect of Acetaminophen. RifAMPin may decrease the serum concentration of Acetaminophen. Risk C: Monitor therapy

Rivastigmine: Anticholinergic Agents may diminish the therapeutic effect of Rivastigmine. Rivastigmine may diminish the therapeutic effect of Anticholinergic Agents. 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 enhance the adverse/toxic effect 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 enhance the sedative effect of ROPINIRole. Risk C: Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Risk C: Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy

Secnidazole: Products Containing Ethanol may enhance the adverse/toxic effect of Secnidazole. Risk X: Avoid combination

Secretin: Anticholinergic Agents may diminish the therapeutic effect 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 enhance the adverse/toxic effect of Sodium Nitrite. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Risk C: Monitor therapy

SORAfenib: Acetaminophen may enhance the hepatotoxic effect of SORAfenib. SORAfenib may increase the 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 enhance the CNS depressant effect 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 enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination

Thiazide and Thiazide-Like Diuretics: Anticholinergic Agents may increase the serum concentration of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy

Thioridazine: CYP2D6 Inhibitors (Weak) may increase the serum concentration of Thioridazine. Management: Consider avoiding concomitant use of thioridazine and weak CYP2D6 inhibitors. If combined, monitor closely for QTc interval prolongation and arrhythmias. Some weak CYP2D6 inhibitors list use with thioridazine as a contraindication. Risk D: Consider therapy modification

Tiotropium: Anticholinergic Agents may enhance the anticholinergic effect of Tiotropium. Risk X: Avoid combination

Topiramate: Anticholinergic Agents may enhance the adverse/toxic effect of Topiramate. Risk C: Monitor therapy

Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Umeclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination

Vaccines: Acetaminophen may diminish the therapeutic effect 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 enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Vitamin K Antagonists (eg, warfarin): Acetaminophen may enhance the anticoagulant effect 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 therapy

Zolpidem: CNS Depressants may enhance the CNS depressant effect 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

Zuranolone: May enhance the CNS depressant effect 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

Pregnancy Considerations

Refer to individual monographs.

Breastfeeding Considerations

Refer to individual monographs.

Dietary Considerations

Some products may contain potassium and/or sodium.

Pharmacokinetics (Adult Data Unless Noted)

See individual agents.

Brand Names: International

International Brand Names by Country

For country code abbreviations (show table)

(AE) United Arab Emirates: Panadol night;
(AU) Australia: Amcal paracetamol plus diphenhydramine | Apohealth night pain relief | Blooms the chemist night pain relief | Chemists own paracetamol plus diphenhydramine | Chemists' own night pain relief | Combolieve day & night pain relief | Combolieve night pain relief | Mersynonight | Panadol night | Paracetamol/diphenhydramine nhpl | Pharmacy choice night pain relief | Vidalife night pain;
(BG) Bulgaria: Apap night;
(CN) China: An fen la ming | Tai nuo an;
(CO) Colombia: Dolofen | Dolofen sleep;
(DO) Dominican Republic: Tylenol pm;
(EE) Estonia: Tylenol extra s. p | Tylenol pm;
(EG) Egypt: Awadist plus | Cold Control | Excedrin pm;
(ES) Spain: Antidolnait | Dolomidina;
(GB) United Kingdom: Calcold Six Plus | Dozol | Panadol night | Tixylix plus | Tixyplus;
(ID) Indonesia: Tadur;
(IE) Ireland: Dozol | Dozol fortified | Panadol night | Paralief night | Teedex;
(IQ) Iraq: Piodol night | Samadol night;
(JO) Jordan: Pamol night | Panadol night | Panda h | Panda night;
(JP) Japan: Kids bufferin syrup s;
(KE) Kenya: Tylenol pm;
(KR) Korea, Republic of: Nopaincool | Notongphen cool | Penzal night | Phenclean night | Tylenol p.m. | Zaropen | Zolimin;
(KW) Kuwait: Adol pm | Panadol night;
(LB) Lebanon: Panadol night;
(LT) Lithuania: Tylenol pm;
(LV) Latvia: Tailenol pm | Tylenol pm;
(MX) Mexico: Bio dual | Bio electro noche | Nocsin pm | Syncol nocturno;
(NG) Nigeria: Bioramol night | Cenpain | Fimin | Kosi syrup | My baby teething | Panda night | Rotanight plus | Silapen night;
(PH) Philippines: Insomed;
(PL) Poland: Apap noc | Paracetamol + difenhydramina hasco noc;
(PR) Puerto Rico: Acetaminophen pm | Legatrin pm | Pain Relief PM;
(PY) Paraguay: Gripidol;
(QA) Qatar: Adol PM | Panadol Night;
(RU) Russian Federation: Migrenol pm;
(SA) Saudi Arabia: Adol pm | Panadol night;
(UA) Ukraine: Dolaren night pain;
(ZA) South Africa: Mypaid night pain | Tylenol nighttime | Tylenol pm

2023 American Geriatrics Society Beers Criteria Update Expert Panel. American Geriatrics Society 2023 updated AGS Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2023;71(7):2052-2081. doi:10.1111/jgs.18372 [PubMed 37139824]
Bagheri H, Bernhard NB, Montastruc JL. Potentiation of the Acenocoumarol Anticoagulant Effect by Acetaminophen. Ann Pharmacother. 1999;33(4):506. [PubMed 10332548]
Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How safe is acetaminophen use in patients treated with vitamin K antagonists? A systematic review and meta-analysis. Thromb Res. 2015;135(1):58-61. [PubMed 25456003]
Gadisseur AP, Van Der Meer FJ, Rosendaal FR. Sustained Intake of Paracetamol (Acetaminophen) During Oral Anticoagulant Therapy With Coumarins Does Not Cause Clinically Important INR Changes: A Randomized Double-Blind Clinical Trial. J Thromb Haemost. 2003;1(4):714-717. [PubMed 12871405]
Gebauer MG, Nyfort-Hansen K, Henschke PJ, et al. Warfarin and Acetaminophen Interaction. Pharmacotherapy. 2003;23(1):109-112. [PubMed 12523469]
Heard K, Bui A, Mlynarchek SL, et al. Toxicity from repeated doses of acetaminophen in children: assessment of causality and dose in reported cases. Am J Ther. 2014;21(3):174-183. [PubMed 22407198]
Hylek EM, Heiman H, Skates SJ, et al. Acetaminophen and Other Risk Factors for Excessive Warfarin Anticoagulation. JAMA. 1998;279(9):657-662. [PubMed 9496982]
Kwan D, Bartle WR, Walker SE. The Effects of Acute and Chronic Acetaminophen Dosing on the Pharmacodynamics and Pharmacokinetics of (R)- and (S)-Warfarin. Clin Pharmacol Ther. 1995;57:212.
Lavonas EJ, Reynolds KM, Dart RC. Therapeutic acetaminophen is not associated with liver injury in children: a systematic review. Pediatrics. 2010;126(6):e1430-e1444. [PubMed 21098156]
Panadol PM (acetaminophen, diphenhydramine) [prescribing information]. Warren, NJ: GSK Consumer Healthcare; received 2022.
Panadol Extra Strength PM (acetaminophen, diphenhydramine) [prescribing information]. Warren, NJ: GSK Consumer Healthcare; received April 2020.
Qaseem A, Kansagara D, Forciea MA, Cooke M, Denberg TD; Clinical Guidelines Committee of the American College of Physicians. Management of chronic insomnia disorder in adults: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2016;165(2):125-133. doi:10.7326/M15-2175 [PubMed 27136449]
Sateia MJ, Buysse DJ, Krystal AD, Neubauer DN, Heald JL. Clinical practice guideline for the pharmacologic treatment of chronic insomnia in adults: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med. 2017;13(2):307-349. doi:10.5664/jcsm.6470 [PubMed 27998379]
Sullivan JE, Farrar HC. Fever and antipyretic use in children. Pediatrics. 2011;127(3):580-587. [PubMed 21357332]
Tylenol PM Extra Strength (acetaminophen, diphenhydramine) [prescribing information]. Fort Washington, PA: Johnson & Johnson Consumer Inc; 2018.
US Department of Veterans Affairs/Department of Defense (VA/DoD). VA/DoD clinical practice guideline for the management of chronic insomnia disorder and obstructive sleep apnea. https://www.healthquality.va.gov/guidelines/CD/insomnia/VADoDSleepCPGFinal508.pdf. Published October 2019. Accessed April 16, 2020.
van den Bemt PM, Geven LM, Kuitert NA, et al. The Potential Interaction Between Oral Anticoagulants and Acetaminophen in Everyday Practice. Pharm World Sci. 2002;24(5):201-204. [PubMed 12426965]

Topic 9165 Version 377.0

خرید پکیج

Acetaminophen (paracetamol) and diphenhydramine: Drug information