Note: This document contains side effect information about acetaminophen / phenyltoloxamine. Some dosage forms listed on this page may not apply to the brand name Acuflex.

Applies to acetaminophen / phenyltoloxamine: oral liquid, oral tablet.

Get emergency medical help if you have any of these signs of an allergic reaction while taking acetaminophen / phenyltoloxamine: hives; difficulty 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 this medication and call your doctor at once if you have:

• confusion, hallucinations, unusual thoughts or behavior;

• little or no urinating; or

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

Common side effects may include:

• dizziness, drowsiness;

• feeling restless or excited (especially in children);

• constipation;

• blurred vision; or

• dry mouth, nose, or throat.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects.

For Healthcare Professionals

Applies to acetaminophen / phenyltoloxamine: oral liquid, oral tablet, oral tablet extended release.

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.

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

Hepatic side effects including severe and sometimes fatal dose dependent hepatitis has been reported with the use of acetaminophen 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]

Gastrointestinal

Gastrointestinal side effects including nausea, vomiting, and abdominal pain have been reported frequently with the use of butalbital. Gastrointestinal side effects are rare with acetaminophen use, except in alcoholics and after overdose. Cases of acute pancreatitis have been reported rarely with the use of acetaminophen.^[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

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]

Renal side effects have been rare with the use of acetaminophen and 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]

Hypersensitivity

Hypersensitivity side effects, including anaphylaxis and fixed drug eruptions, have been reported rarely in association with acetaminophen use.^[Ref]

Hematologic

Hematologic side effects including rare cases of thrombocytopenia associated with acetaminophen have been reported. 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 such as hemolytic anemia, thrombocytopenia, and agranulocytosis have been rarely caused by antihistamines.^[Ref]

Dermatologic

Dermatologic side effects including erythematous skin rashes associated with acetaminophen have been reported, but are rare. Acetaminophen associated bullous erythema and purpura fulminans have also been reported.^[Ref]

Respiratory

Respiratory side effects including a case of acetaminophen-induced eosinophilic pneumonia have been reported.^[Ref]

Cardiovascular

Cardiovascular side effects including two cases of hypotension have been reported following the administration of acetaminophen.

Cardiovascular side effects from the use of antihistamines 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

Metabolic side effects including metabolic acidosis have been reported 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]