Acetaminophen and chlorpheniramine

Acetaminophen is a pain reliever and a fever reducer.

Chlorpheniramine is an antihistamine that reduces the natural chemical histamine in the body. Histamine can produce symptoms of sneezing, itching, watery eyes, and runny nose.

Acetaminophen and chlorpheniramine is a combination medicine used to treat headache, runny nose, sneezing, watery eyes, and pain or fever caused by allergies, the common cold, or the flu.

Acetaminophen and chlorpheniramine may also be used for other purposes not listed in this medication guide.

Ask a doctor or pharmacist before using any other cold, allergy, pain, or sleep medication. Acetaminophen (sometimes abbreviated as APAP) is contained in many combination medicines. Taking certain products together can cause you to get too much acetaminophen which can lead to a fatal overdose. Check the label to see if a medicine contains acetaminophen or APAP.

Avoid drinking alcohol. It may increase your risk of liver damage while taking acetaminophen.

This medication may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

In rare cases, acetaminophen may cause a severe skin reaction that can be fatal. This could occur even if you have taken acetaminophen in the past and had no reaction. Stop taking this medicine and call your doctor right away if you have skin redness or a rash that spreads and causes blistering and peeling. If you have this type of reaction, you should never again take any medicine that contains acetaminophen.

Stop using the medicine and call your doctor at once if you have:

• fast, pounding, or uneven heartbeats;

• confusion, severe dizziness or drowsiness;

• tremor, restless muscle movements;

• little or no urinating;

• flu symptoms, easy bruising, unusual bleeding, pale skin, feeling light-headed or short of breath; or

• nausea, pain in your upper stomach pain, itching, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

Common side effects may include:

• constipation;

• dry eyes, blurred vision, dry mouth or nose;

• mild dizziness or drowsiness, trouble concentrating;

• feeling restless or excited (especially in children); or

• mild skin rash.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

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 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.

Applies to acetaminophen / chlorpheniramine: oral tablet

Hepatic

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]

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.

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

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]

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.

A recent 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.[Ref]

Hypersensitivity

Hypersensitivity side effects of acetaminophen have included anaphylaxis and fixed drug eruptions.[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. Acute thrombocytopenia has also been reported as having been caused by sensitivity to acetaminophen glucuronide, the major metabolite of acetaminophen. 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. 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]

Respiratory

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

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]

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]

Nervous system

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]

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.[Ref]

Ocular

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

Genitourinary

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

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

2 tablets orally every 4 to 6 hours
Maximum dose: 12 in 24 hours or as directed by a doctor

The elimination of chlorpheniramine may be prolonged in patients with renal dysfunction. These patients should be monitored for excessive sedation and other adverse effects that may result from chlorpheniramine accumulation.

Use with caution in patients with liver disease. Chronic use of acetaminophen is not recommended in patients with liver disease.