acetaminophen, doxylamine, dextromethorphan, and phenylephrine

Medically Reviewed on 5/2/2023

Generic Name: acetaminophen/doxylamine/dextromethorphan/phenylephrine

Brand Names: Alka-Seltzer Plus Night Cold Formula, Tylenol Cold Multi-Symptom Nighttime Liquid, Alka-Seltzer Plus Night Severe Cold, Cough and Flu, Alka-Seltzer Plus Night Sinus Congestion, Allergy and Cough

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

What is acetaminophen, doxylamine, dextromethorphan, and phenylephrine, and what is it used for?

Acetaminophen/doxylamine/dextromethorphan/phenylephrine is a combination medication used for the temporary relief of common cold and flu symptoms, including fever, headache, body aches, cough, sore throat, runny nose, sneezing, and nasal and sinus congestion. Four drugs are combined in specific dosages in the formulation and the combo drug is available over the counter (OTC). Each medication 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.
  • Doxylamine is an antihistamine that works by blocking the activity of histamine, a natural compound in the body that causes allergy symptoms. Doxylamine binds non-selectively to all H1 receptors, including in the central and peripheral nervous systems, uterus, gastrointestinal tract, large blood vessels and bronchial muscles. Doxylamine produces sedation, reduces nausea and vomiting, and relieves upper respiratory tract allergy symptoms.
  • 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.
  • Phenylephrine belongs to a class of medications known as alpha1 agonists. Phenylephrine stimulates alpha1 adrenergic receptors, protein molecules located in smooth muscle tissues around blood vessels, making the muscles contract. This constricts the blood vessels in the nasal and sinus passages, reducing congestion.


  • Do not use in patients with known hypersensitivity to acetaminophen, doxylamine, dextromethorphan, phenylephrine or any other component of the formulation.
  • Do not use acetaminophen/doxylamine/dextromethorphan/phenylephrine in patients with any of the following conditions:
  • Do not use acetaminophen/doxylamine/dextromethorphan/phenylephrine in children below 12 years of age or for pediatric sedation.
  • Do not use concurrently with any other drug containing acetaminophen.
  • Do not use concurrently or within 14 days after treatment with monoamine oxidase inhibitor (MAOI) type of antidepressant medications.
  • Dextromethorphan may slow the respiratory rate, use with caution.
  • Doxylamine may cause drowsiness and impair mental and physical abilities. Caution patients appropriately.
  • Use acetaminophen/doxylamine/dextromethorphan/phenylephrine with caution in patients with:
  • Use with caution in patients with alcoholic liver disease. Drinking 3 or more alcoholic drinks a day can increase the risk of liver damage. Advise patients to avoid drinking or limit to less than 3 drinks a day.
  • Use with caution in elderly or debilitated patients.
  • 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.


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What are the side effects of acetaminophen, doxylamine, dextromethorphan, and phenylephrine?

Common side effects of acetaminophen/doxylamine/dextromethorphan/phenylephrine include:

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

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, doxylamine, dextromethorphan, and phenylephrine?


  • 325 mg/6.25 mg/10 mg/5 mg

Adult and pediatric:

Congestion, Rhinorrhea, Cough, Sore Throat, Headache, Fever, Minor Aches and Pains

Children below 12 years

  • Ask a pediatrician

Children 12 years and above and adults

  • 2 caps orally once every 4 hours as needed; not to exceed 12 caps/day


  • Overdose of acetaminophen/doxylamine/dextromethorphan/phenylephrine can cause kidney and liver damage with symptoms that include nausea, vomiting, loss of appetite, sweating, abdominal pain, extreme tiredness, yellowing eyes and skin, dark urine, agitation, confusion, irregular heart rhythm, low blood pressure, high temperature, absence of sweating, urinary retention, seizure, muscle breakdown (rhabdomyolysis), respiratory failure and coma.
  • Overdose may be treated with symptomatic and supportive care, including administration of activated charcoal to eliminate undigested drug if it is within one hour of ingestion, and N-acetylcysteine, antidote to acetaminophen.

What drugs interact with acetaminophen, doxylamine, dextromethorphan, and phenylephrine?

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/doxylamine/dextromethorphan/phenylephrine include:
    • iobenguane I 123
    • isocarboxazid
    • linezolid
    • phenelzine
    • procarbazine
    • selegiline transdermal
    • tranylcypromine
  • Acetaminophen/doxylamine/dextromethorphan/phenylephrine has serious interactions with at least 37 different drugs. Acetaminophen/doxylamine/dextromethorphan/phenylephrine has moderate interactions with at least 270 different drugs.
  • Acetaminophen/doxylamine/dextromethorphan/phenylephrine has mild interactions with at least 62 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 of 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 health care provider if you have any questions about the medication.

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Pregnancy and breastfeeding

  • Acetaminophen/doxylamine/dextromethorphan/phenylephrine should be used by pregnant women only if clearly needed. The lowest effective dose for the shortest possible time is recommended.
  • Acetaminophen/doxylamine/dextromethorphan/phenylephrine is present in breastmilk, use with caution if you are a nursing mother.
  • If you are pregnant or breastfeeding, do not take any OTC drug, including acetaminophen/doxylamine/dextromethorphan/phenylephrine, without first checking with your healthcare provider.

What else should I know about acetaminophen, doxylamine, dextromethorphan, and phenylephrine?

  • Take acetaminophen/doxylamine/dextromethorphan/phenylephrine exactly as prescribed or as per label instructions if taking OTC medication.
  • 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 or severe skin reactions.
  • Discontinue use and consult with your healthcare provider if:
    • Symptoms do not get better within 7 days or are accompanied by fever
    • Fever gets worse or lasts longer than 3 days
    • You experience any new symptoms, dizziness, nervousness or sleeplessness.
    • You have redness or swelling
    • Sore throat is severe, lasts longer than two days, or is accompanied by fever, rash, headaches, nausea or vomiting
  • Do not take acetaminophen/doxylamine/dextromethorphan/phenylephrine if you have chronic cough associated with smoking, asthma, or emphysema, or if it occurs with heavy phlegm or mucus, unless directed by your physician.
  • Avoid or limit intake of alcohol while on treatment.
  • Doxylamine in the combination drug can make you drowsy. Avoid hazardous tasks such as driving and operating heavy machinery while under treatment.
  • Store safely out of reach of children.
  • In case of overdose, seek immediate medical help or contact Poison Control.


Acetaminophen/doxylamine/dextromethorphan/phenylephrine is a combination medication used for the temporary relief of common cold and flu symptoms, including fever, headache, body aches, cough, sore throat, runny nose, sneezing, and nasal and sinus congestion. Common side effects of acetaminophen, doxylamine, dextromethorphan, and phenylephrine include dizziness, drowsiness, headache, tremor, excitability, restlessness, constriction of peripheral and abdominal blood vessels, high blood pressure (hypertension), reflex increase in heart rate (reflex tachycardia), gastrointestinal disturbances, and others. Consult 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 5/2/2023