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Medication Advisor 2007.4: Acetaminophen/Diphenhydramine, Oral Health Library

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Acetaminophen/Diphenhydramine, Oral

What are other names for this medicine?

Type of medicine: antihistamine; analgesic (painkiller)

Generic and brand names: acetaminophen and diphenhydramine, oral; Acetaminophen PM; Excedrin PM; Legatrin PM; Tylenol Severe Allergy; Tylenol PM; Unisom with Pain Relief

What is this medicine used for?

This medicine combines a pain reliever with an antihistamine that causes drowsiness. It is taken by mouth to relieve nighttime pain and to help you fall asleep.

What should my healthcare provider know before I take this medicine?

Tell your healthcare provider if you have ever had:

  • an allergic reaction to any medicine
  • a stomach ulcer
  • glaucoma
  • kidney disease
  • liver disease
  • lung problems such as asthma, emphysema, or chronic obstructive pulmonary disease (COPD)
  • thyroid problems
  • trouble urinating or an enlarged prostate.

Tell your healthcare provider or pharmacist if you are taking any other medicines, including any nonprescription products, to avoid the risk of taking an overdose.

Females of childbearing age: Tell your healthcare provider if you are pregnant. Do not breast-feed while you are taking this medicine without your healthcare provider's approval.

How do I take it?

You can buy some forms of this medicine without a prescription. Follow the directions on the package or take this medicine exactly as prescribed. You may take this medicine with or without food.

Do not take more of it or take it more often than recommended. Taking too much can make you very drowsy and can damage your liver. Do not give this medicine to young children.

What should I watch out for?

Many prescription and nonprescription medicines for pain, headache, and sinus congestion contain acetaminophen. If you are not sure if you are taking more than the recommended dosage per day, ask your healthcare provider and pharmacist to review all of your medicines.

Important notice: Taking an overdose of this medicine can cause very serious problems. If you think you have taken an overdose, get medical care right away.

Do not take this medicine for more than 2 weeks. If you still have trouble sleeping after 2 weeks, contact your healthcare provider.

This medicine increases the effects of alcohol and other drugs that slow down the nervous system. Alcohol may increase the chance of liver damage by this medicine. Do not drink alcohol while taking this medicine. Ask your healthcare provider about this.

When taken at bedtime, this medicine may make you drowsy the next day. Do not drive or operate machinery unless you are fully alert.

What are the possible side effects?

Along with its needed effects, your medicine may cause some unwanted side effects. Some side effects may be very serious. Some side effects may go away as your body adjusts to the medicine. Tell your healthcare provider if you have any side effects that continue or get worse.

Serious (report these to your doctor right away): Severe tiredness, weakness, fever, yellowing of the skin or eyes, nausea, abdominal pain, unusual bleeding or bruising.

Other: Drowsiness, heavier phlegm, sore throat, dry mouth.

What products might interact with this medicine?

When you take this medicine with other medicines, it can change the way this or any of the other medicines work. Nonprescription medicines, vitamins, natural remedies, and certain foods may also interact. Using these products together might cause harmful side effects. Talk to your healthcare provider if you are taking:

  • antianxiety medicines such as diazepam (Valium), clonazepam (Klonopin), clorazepate (Tranxene), chlordiazepoxide (Librium), flurazepam (Dalmane), alprazolam (Xanax), temazepam (Restoril), triazolam (Halcion), oxazepam (Serax) and lorazepam (Ativan)
  • anticholinergic medicines such as benztropine (Cogentin), dicyclomine (Bentyl), atropine sulfate, belladonna, propantheline (Pro-Banthine), methscopolamine (Pamine), l-hyoscyamine (Levsin, Levsinex), amantadine (Symmetrel), procyclidine (Kemadrin), and trihexyphenidyl (Artane)
  • anticonvulsants such as carbamazepine (Tegretol), primidone (Mysoline), gabapentin (Neurontin), felbamate (Felbatol), lamotrigine (Lamictal), levetiracetam (Keppra), topiramate (Topamax), valproic acid (Depacon, Depakene, Depakote), oxcarbazepine (Trileptal), tiagabine (Gabitril) and phenytoin (Dilantin)
  • antihistamines such as hydroxyzine (Atarax, Vistaril) and chlorpheniramine (Chlor-Trimeton)
  • antinausea medicines such as prochlorperazine (Compazine) and promethazine (Phenergan)
  • antipsychotic medicines such as chlorpromazine (Thorazine), fluphenazine (Permitil, Prolixin), perphenazine, trifluoperazine (Stelazine), thioridazine, haloperidol (Haldol), clozapine (Clozaril), and olanzapine (Zyprexa)
  • cholestyramine (Questran)
  • diflunisal (Dolobid)
  • herbs with sedative effects such as kava, St. John's wort, gotu kola, and valerian
  • isoniazid (Laniazid)
  • MAO inhibitor antidepressants such as isocarboxazid (Marplan), phenelzine (Nardil), and tranylcypromine (Parnate) (Do not take an MAO inhibitor and this medicine within 14 days of each other.)
  • muscle relaxants such as cyclobenzaprine (Flexeril), carisoprodol (Soma), tizanidine (Zanaflex), methocarbamol (Robaxin), and baclofen (Lioresal)
  • narcotic analgesics such as codeine, hydrocodone (Vicodin, Lortab), oxycodone (Percocet, Tylox, OxyContin), morphine (MS Contin), propoxyphene (Darvocet N-100), pentazocine (Talwin), meperidine (Demerol), fentanyl (Duragesic patches), methadone (Dolophine), and hydromorphone (Dilaudid)
  • other cough, cold, allergy, fever, diet, pain, or sleep medicines that may contain acetaminophen or diphenhydramine
  • rifampin (Rifadin, Rimactane)
  • sedatives such as phenobarbital (Solfoton), pentobarbital (Nembutal), and butabarbital (Butisol)
  • sleeping pills such as zolpidem (Ambien), zaleplon (Sonata), and chloral hydrate
  • SSRI antidepressants such as sertraline (Zoloft), fluoxetine (Prozac), citalopram (Celexa), escitalopram (Lexapro), paroxetine (Paxil), venlafaxine (Effexor), and fluvoxamine (Luvox)
  • tricyclic antidepressants such as amitriptyline, nortriptyline (Aventyl, Pamelor), imipramine (Tofranil), trazodone (Desyrel), desipramine (Norpramin), and doxepin (Sinequan)
  • warfarin (Coumadin).

Do not drink alcohol while taking this medicine.

Keep a list of all your medicines (prescription, nonprescription, supplements, natural remedies, and vitamins) with you. Be sure that you tell all healthcare providers who treat you about all the products you are taking.

How should I store this medicine?

Store this medicine at room temperature. Keep the container tightly closed. Protect it from heat, high humidity, and bright light.


This advisory includes selected information only and may not include all side effects of this medicine or interactions with other medicines. Ask your healthcare provider or pharmacist for more information or if you have any questions.

Ask your pharmacist for the best way to dispose of outdated medicine or medicine you have not used. Do not throw medicines in the trash.

Keep all medicines out of the reach of children.

Do not share medicines with other people.

Developed by McKesson Corporation
Published by McKesson Corporation.
Last modified: 2007-10-24
Last reviewed: 2007-09-17
This content is reviewed periodically and is subject to change as new health information becomes available. The information is intended to inform and educate and is not a replacement for medical evaluation, advice, diagnosis or treatment by a healthcare professional.
Copyright © 2007 McKesson Corporation and/or one of its subsidiaries. All Rights Reserved.
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