Applies to acetaminophen / chlorpheniramine / dextromethorphan: oral liquid, oral syrup.

Serious side effects

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.
• Not able to pass urine or change in how much urine is passed.
• A very bad skin reaction (Stevens-Johnson syndrome/toxic epidermal necrolysis) may happen. It can cause very bad health problems that may not go away, and sometimes death. Get medical help right away if you have signs like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in your mouth, throat, nose, or eyes.

Other side effects

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 1-800-332-1088. You may also report side effects at https://www.fda.gov/medwatch.

For Healthcare Professionals

Applies to acetaminophen/chlorpheniramine/dextromethorphan: oral liquid, oral suspension, oral syrup, oral tablet.

Cardiovascular

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

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

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]

Nervous system

Nervous system side effects of chlorpheniramine have included depression resulting in drowsiness in 75% or more of treated patients. Dyskinesias have rarely been reported following chronic use of chlorpheniramine.

Nervous system side effects of dextromethorphan have included drowsiness and dizziness. Other side effects such as excitation, mental confusion, and opiate-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]

Few cases of dyskinesias and tremors, often of the face, have been reported in patients whose chronic use of chlorpheniramine extended over a period of 3 to 10 years. Some of these cases were only partially relieved by discontinuation of the drug. Haloperidol was successful in relieving symptoms.^[Ref]

Gastrointestinal

Gastrointestinal side effects of acetaminophen have been rare, except in alcoholics and after overdose. Cases of acute pancreatitis have been reported rarely with the use of acetaminophen.

Gastrointestinal side effects of chlorpheniramine have included dry mouth and constipation in up to one-third of treated patients.

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

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.^[Ref]

Hypersensitivity

Hypersensitivity side effects of acetaminophen have included anaphylaxis and fixed drug eruptions.

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

Genitourinary

Genitourinary side effects of chlorpheniramine have included dysuria, urinary hesitancy, and decreased urine flow.^[Ref]

Respiratory

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

Hepatic side effects of acetaminophen have included severe and sometimes fatal dose dependent hepatitis in alcoholic patients. Hepatotoxicity has been increased during fasting. Several cases of hepatotoxicity from chronic acetaminophen therapy at therapeutic doses have also been reported despite a lack of risk factors for toxicity.^[Ref]

Renal

Renal side effects of acetaminophen have included 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]

Hematologic

A fatal case of agranulocytosis has been reported in a patient taking chlorpheniramine, pseudoephedrine, acetaminophen, dextromethorphan, phenylpropanolamine, and aspirin. Chlorpheniramine was felt to be the cause.^[Ref]

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 chlorpheniramine have included bone marrow suppression, thrombocytopenia, and aplastic anemia.^[Ref]

Dermatologic

Dermatologic side effects of acetaminophen have included erythematous skin rashes. Bullous erythema and purpura fulminans have also been reported.^[Ref]

Metabolic

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]

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

Ocular

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