Acetaminophen, dextromethorphan, and diphenhydramine

Name: Acetaminophen, dextromethorphan, and diphenhydramine

What should I discuss with my healthcare provider before taking this medicine?

Ask a doctor before taking medicine that contains acetaminophen if you have ever had liver disease, or if you drink more than 3 alcoholic beverages per day.

Do not use this medicine if you have taken an MAO inhibitor in the past 14 days. A dangerous drug interaction could occur. MAO inhibitors include furazolidone, isocarboxazid, linezolid, phenelzine, rasagiline, selegiline, and tranylcypromine.

You should not use this medicine if you are allergic to acetaminophen (Tylenol), dextromethorphan, or diphenhydramine, or if you have:

  • severe constipation, blockage in your stomach or intestines;

  • untreated or uncontrolled diseases--glaucoma, asthma, high blood pressure, heart disease, coronary artery disease, overactive thyroid; or

  • if you are unable to urinate.

Ask a doctor or pharmacist before taking this medicine if you have any medical condition, especially:

  • kidney disease;

  • cough with mucus, or cough caused by emphysema or chronic bronchitis;

  • an enlarged prostate, problems with urination;

  • a history of alcoholism; or

  • if you take potassium (Cytra, Epiklor, K-Lyte, K-Phos, Kaon, Klor-Con, Polycitra, Urocit-K).

It is not known whether this medicine will harm an unborn baby. Do not use cough and cold medicine without a doctor's advice if you are pregnant.

This medicine may pass into breast milk and may harm a nursing baby. Antihistamines may also slow breast milk production. Do not use cough and cold medicine without a doctor's advice if you are breast-feeding a baby.

Artificially sweetened liquid medicine may contain phenylalanine. Check the medication label if you have phenylketonuria (PKU).

Always ask a doctor before giving a cough or cold medicine to a child. Death can occur from the misuse of cough and cold medicines in very young children.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. An overdose of acetaminophen can be fatal.

The first signs of an acetaminophen overdose include loss of appetite, nausea, vomiting, stomach pain, sweating, and confusion or weakness. Later symptoms may include pain in your upper stomach, dark urine, and yellowing of your skin or the whites of your eyes.

What other drugs will affect acetaminophen, dextromethorphan, and diphenhydramine?

Ask a doctor or pharmacist before using this medicine if you are also using any other drugs, including prescription and over-the-counter medicines, vitamins, and herbal products. Some medicines can cause unwanted or dangerous effects when used together. Not all possible interactions are listed in this medication guide.

Taking this medicine with other drugs that make you sleepy or slow your breathing can worsen these effects. Ask your doctor before taking acetaminophen, dextromethorphan, and diphenhydramine with a sleeping pill, narcotic pain medicine, muscle relaxer, or medicine for anxiety, depression, or seizures.

What are some other side effects of this drug?

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

  • Feeling sleepy.
  • Feeling nervous and excitable.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

For Healthcare Professionals

Applies to acetaminophen / dextromethorphan / diphenhydramine: oral liquid

Cardiovascular

Two cases hypotension have been reported following the administration of acetaminophen. Both patients experienced significant decreases in blood pressure. One of the two patients required pressor agents to maintain adequate mean arterial pressures. Neither episode was associated with symptoms of anaphylaxis. Neither patient was rechallenged after resolution of the initial episode.[Ref]

Cardiovascular side effects of acetaminophen have included two cases of hypotension.

Cardiovascular side effects of diphenhydramine have included hypotension, tachycardia, and palpitations.[Ref]

Gastrointestinal

Gastrointestinal side effects of diphenhydramine have been usually mild and included nausea and dry mouth.

Gastrointestinal side effects of dextromethorphan have included stomach upset.[Ref]

Genitourinary

Genitourinary side effects of diphenhydramine have included urinary retention and dysuria as a result of the anticholinergic effects of diphenhydramine.[Ref]

Hematologic

Hematologic side effects of acetaminophen have included rare cases of thrombocytopenia. Methemoglobinemia with resulting cyanosis has also been observed in the setting of acute overdose.

Hematologic side effects of diphenhydramine have included rare reports of hemolytic anemia, thrombocytopenia, and agranulocytosis.[Ref]

Hypersensitivity

Most commonly, hypersensitivity to diphenhydramine has manifested itself in patients receiving systemic drug after being sensitized to it by topical application. Sensitization with systemic administration has also been reported.[Ref]

Hypersensitivity side effects of diphenhydramine have included rash, pruritus and eczema. Photosensitivity reactions have also been reported.

Hypersensitivity side effects of dextromethorphan have included rare reports of fixed-drug eruptions.[Ref]

Nervous system

The CNS depressant effect of diphenhydramine parallels its plasma concentrations. The plasma concentration threshold for sedation is 30 to 42 ng/mL, and to cause mental impairment is 58 to 74 ng/mL. Patients should be warned against driving while taking diphenhydramine. Dystonic reactions have been accompanied by dizziness, mental confusion, rigidity, lip and tongue protrusion, trismus, torticollis, and swallowing difficulties and generally resolve spontaneously. Toxic encephalopathy has been reported in a child with chicken pox treated generously with topical diphenhydramine. Delirium has been reported in elderly patients with mild dementia following a small oral dose of diphenhydramine.[Ref]

Nervous system side effects of diphenhydramine have included frequent reports of depression with drowsiness and sedation. Motor skills may be impaired. Dystonic reactions have been reported after single doses of diphenhydramine.

Nervous system side effects of dextromethorphan have included drowsiness and dizziness. Other side effects such as excitation, mental confusion, and opioid like respiratory depression have been rare and occurred at higher dosages. In some cases of abuse, patients experienced euphoria, hyperactivity, mania, and auditory and visual hallucinations.[Ref]

Ocular

Ocular side effects of diphenhydramine have included blurred vision, diplopia, and dry eyes due to anticholinergic effects.[Ref]

Dermatologic

Dermatologic side effects acetaminophen have included rare reports of erythematous skin rashes. Acetaminophen associated bullous erythema and purpura fulminans have been reported. One case of toxic epidermal necrolysis associated with acetaminophen administered to a pediatric patient has been reported. Acetaminophen has been associated with a risk of rare but potentially fatal serious skin reactions known as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP).[Ref]

Hepatic

Alcoholic patients may develop hepatotoxicity after even modest doses of acetaminophen. In healthy patients, approximately 15 grams of acetaminophen is necessary to deplete liver glutathione stores by 70% in a 70 kg person. However, hepatotoxicity has been reported following smaller doses. Glutathione concentrations may be repleted by the antidote N-acetylcysteine. One case report has suggested that hypothermia may also be beneficial in decreasing liver damage during overdose.

In a recent retrospective study of 306 patients admitted for acetaminophen overdose, 6.9% had severe liver injury but all recovered. None of the 306 patients died.

One study has suggested that acetaminophen may precipitate acute biliary pain and cholestasis. The mechanism of this effect may be related to inhibition of prostaglandin and alterations in the regulation of the sphincter of Oddi.

Cases of acute pancreatitis have been reported rarely.

A 19-year-old female developed hepatotoxicity, reactive plasmacytosis and agranulocytosis followed by a leukemoid reaction after acute acetaminophen toxicity.[Ref]

Hepatic side effects of acetaminophen have included severe and sometimes fatal dose dependent hepatitis in alcoholic patients. Hepatotoxicity has been increased during fasting.[Ref]

Renal

Renal side effects of acetaminophen have included rare reports of acute renal failure, acute tubular necrosis, and interstitial nephritis. Adverse renal effects are most often observed after overdose, after chronic abuse (often with multiple analgesics), or in association with acetaminophen-related hepatotoxicity.[Ref]

Acute tubular necrosis usually occurs in conjunction with liver failure, but has been observed as an isolated finding in rare cases. A possible increase in the risk of renal cell carcinoma has been associated with chronic acetaminophen use as well.

One case-control study of patients with end-stage renal disease suggested that long term consumption of acetaminophen may significantly increase the risk of end-stage renal disease particularly in patients taking more than two pills per day.

However, a recent cohort study of analgesia use of initially healthy men concluded that moderate use of analgesics including acetaminophen was not associated with increased risk of renal disease.[Ref]

Metabolic

Metabolic side effects of acetaminophen have included metabolic acidosis following a massive overdose of acetaminophen.[Ref]

In the case of metabolic acidosis, causality is uncertain as more than one drug was ingested. The case of metabolic acidosis followed the ingestion of 75 grams of acetaminophen, 1.95 grams of aspirin, and a small amount of a liquid household cleaner The patient also had a history of seizures which the authors reported may have contributed to an increased lactate level indicative of metabolic acidosis.[Ref]

Respiratory

Respiratory side effects of acetaminophen have included a case of eosinophilic pneumonia.[Ref]

Some side effects of acetaminophen / dextromethorphan / diphenhydramine may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Usual Adult Dose for Cold Symptoms

Acetaminophen/dextromethorphan/diphenhydramine 325 mg-10 mg-12.5 mg/5 mL:
10 mL orally every 4 to 6 hours not to exceed 6 doses daily.

Usual Adult Dose for Influenza

Acetaminophen/dextromethorphan/diphenhydramine 325 mg-10 mg-12.5 mg/5 mL:
10 mL orally every 4 to 6 hours not to exceed 6 doses daily.

Liver Dose Adjustments

Data not available

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