Medically Reviewed on 2/23/2023

Generic Name: acetaminophen/diphenhydramine/dextromethorphan

Brand Name: Diabetic Tussin Nighttime Cold and Flu

Drug Class: Cough/Cold, Non-narcotic Combos; Analgesic/Antihistamine/Antitussive Combos

What is acetaminophen/diphenhydramine/dextromethorphan, and what is it used for?

Acetaminophen/diphenhydramine/dextromethorphan is a combination medication used for the temporary relief of common cold and flu symptoms, including fever, headache, muscular aches, cough, sore throat, runny nose, and sneezing. The three drugs are combined in specific dosages and the combination drug is available over the counter (OTC).

Each medication in the combination works in a different way and together they provide more effective relief than any of them as a single agent.

  • Acetaminophen is an analgesic and antipyretic drug used to relieve pain and fever. Acetaminophen relieves pain by blocking pain impulse generation and inhibiting the synthesis of prostaglandin in the central nervous system (CNS). Prostaglandin is a natural substance in the body that initiates inflammation. Acetaminophen reduces fever by acting on the hypothalamus region of the brain which regulates temperature.
  • Diphenhydramine binds to and blocks histamine from binding to histamine H1 receptors, protein particles on cell membranes that an initial inflammatory response when activated by histamine. Histamine is an inflammatory compound responsible for reactions such as swelling, itching, redness, and pain, and is released by the immune system in response to injury or exposure to allergens or other irritants. Diphenhydramine enters the central nervous system and can also induce sedation.
  • Dextromethorphan suppresses cough by reducing the sensitivity of cough receptors in the brain region that stimulate the cough reflex and preventing the transmission of cough impulses.


  • Do not use acetaminophen/diphenhydramine/dextromethorphan in patients with known hypersensitivity to acetaminophen, diphenhydramine, dextromethorphan, or any of the components in the formulation.
  • Do not take concurrently with any other drug containing acetaminophen, or diphenhydramine, including the topical diphenhydramine formulation.
  • Acetaminophen can damage the liver, especially with prolonged high dosages. Risk of liver damage is higher with concurrent use of other acetaminophen products, and in alcoholics. Advise patients to ideally avoid or at least limit alcohol intake.
  • Do not use acetaminophen/diphenhydramine/dextromethorphan in the following conditions:
  • Avoid repeated administration in patients with anemia or heart, lung, or kidney disease.
  • Do not use acetaminophen/diphenhydramine/dextromethorphan to treat premature newborns or nursing mothers.
  • Do not take concurrently or within 14 days after treatment with monoamine oxidase inhibitor (MAOI) type of antidepressant medications.
  • Use acetaminophen/diphenhydramine/dextromethorphan with caution in patients with G6PD enzyme deficiency, a genetic disorder.
  • Check with your physician before taking the combo medication if you have:
  • Some formulations may contain phenylalanine which should be avoided in patients with phenylketonuria, a disorder with the inability to metabolize phenylalanine.
  • There have been rare reports of life-threatening skin reactions including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP) with symptoms such as blisters, rash, and redness. Discontinue the drug if such symptoms develop.


Which illness is known as a viral upper respiratory tract infection? See Answer

What are the side effects of acetaminophen/diphenhydramine/dextromethorphan?

Common side effects of acetaminophen/diphenhydramine/dextromethorphan include:

Less common side effects of acetaminophen/diphenhydramine/dextromethorphan include:

  • Confusion
  • Disorientation
  • Decreased cognitive function in elderly patients
  • Dry mouth (xerostomia)
  • Dryness of nasal mucous membrane
  • Dryness of throat
  • Gastrointestinal hemorrhage
  • Liver toxicity
  • Liver failure
  • Kidney toxicity
  • Lung inflammation (pneumonitis)
  • Allergic skin reactions including:
  • Hives (urticaria)
  • Itchy flat and raised skin lesions (pruritic maculopapular rash)
  • Stevens-Johnson syndrome
  • Toxic epidermal necrolysis
  • Hypersensitivity reactions including:
  • Swelling under the skin and in mucous tissue (angioedema)
  • Swelling of voice box (laryngeal edema)
  • Severe allergy-like (anaphylactoid) reactions
  • Blood disorders including:
  • Severely low blood count of granulocyte immune cells (agranulocytosis)
  • Low count of neutrophil immune cells (neutropenia)
  • Low count of leukocyte immune cells (leukopenia)
  • Low count of all types of blood cells (pancytopenia)
  • Low platelet count (thrombocytopenia)
  • Easy bruising due to thrombocytopenia (thrombocytopenic purpura)

Call your doctor immediately if you experience any of the following symptoms or serious side effects while using this drug:

  • Serious heart symptoms include fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness;
  • Severe headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
  • Severe nervous system reaction with very stiff muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, and feeling like you might pass out; or
  • Serious eye symptoms include blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

What are the dosages of acetaminophen/diphenhydramine/dextromethorphan?

Oral Solution

  • 325 mg/12.5 mg/10 mg/5 mL

Cold and Flu

  • Indicated for relief of cold and flu symptoms


  • 10 mL orally every 4 hours as needed; not to exceed 6 doses/24 hours


  • Children below 6 years: Safety and efficacy not established
  • Children 6-12 years: 5 mL orally every 4 hours as needed; not to exceed 6 doses/24 hours
  • Children above 12 years: As adults; 10 mL every 4 hours as needed; not to exceed 6 doses/24 hours


What drugs interact with acetaminophen/diphenhydramine/dextromethorphan?

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

  • Severe interactions of acetaminophen/diphenhydramine/dextromethorphan include:
    • eliglustat
  • Serious interactions of acetaminophen/diphenhydramine/dextromethorphan include:
  • Acetaminophen/diphenhydramine/dextromethorphan has moderate interactions with at least 289 different drugs.
  • Acetaminophen/diphenhydramine/dextromethorphan has mild interactions with at least 82 different drugs.

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider about all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or healthcare provider if you have any questions about the medication.

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Pregnancy and breastfeeding

  • Acetaminophen/diphenhydramine/dextromethorphan should be used by pregnant women only if clearly needed.
  • Acetaminophen/diphenhydramine/dextromethorphan is present in breastmilk. Do not use this combination if you are a nursing mother.
  • If you are pregnant or breastfeeding, do not take any OTC drug, including acetaminophen/diphenhydramine/dextromethorphan, without first checking with your healthcare provider.

What else should I know about acetaminophen/diphenhydramine/dextromethorphan?

  • Take acetaminophen/diphenhydramine/dextromethorphan exactly as prescribed or as per label instructions.
  • Do not take higher or more frequent doses, do not exceed daily recommended dosage, and do not take for prolonged periods.
  • Avoid overdose by checking product labels carefully. Acetaminophen is found in many dosage forms and many combination products.
  • Discontinue immediately if you develop hypersensitivity reactions.
  • Discontinue use and consult with your healthcare provider if:
    • Your sore throat persists for longer than two days, or is accompanied by fever, rash, headache, nausea, or vomiting
    • Your cough lasts longer than seven days, reoccurs, or occurs with fever, rash, or persistent headaches
    • Your fever gets worse or lasts longer than three days
    • You have skin redness or swelling, or develop severe skin reactions
    • You develop new symptoms
  • If you have chronic cough associated with smoking, asthma, or emphysema, or if it occurs with heavy phlegm or mucus, check with your physician before taking acetaminophen/diphenhydramine/dextromethorphan.
  • Avoid taking sedatives or tranquilizers, and avoid or limit intake of alcohol while on treatment with acetaminophen/diphenhydramine/dextromethorphan, it can worsen the drowsiness induced by the drug.
  • Avoid hazardous tasks such as driving or operating heavy machinery while taking acetaminophen/diphenhydramine/dextromethorphan.
  • Store safely out of reach of children.
  • In case of overdose, seek immediate medical help or contact Poison Control.


Acetaminophen/diphenhydramine/dextromethorphan is a combination medication used for the temporary relief of common cold and flu symptoms, including fever, headache, muscular aches, cough, sore throat, runny nose, and sneezing. Common side effects of acetaminophen/diphenhydramine/dextromethorphan include drowsiness, dizziness, sedation, blurred vision, uncontrolled eye movements (nystagmus), constipation, nausea, vomiting, and thick sputum. Consult with your doctor if pregnant or breastfeeding.

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You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.

Medically Reviewed on 2/23/2023