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

Applies to acetaminophen / caffeine / isometheptene mucate: oral tablet.

Serious side effects of MigraTen

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.
• Feeling confused.
• 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 of MigraTen

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:

• Dizziness.

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/caffeine/isometheptene mucate: oral capsule, oral tablet.

Hepatic

Hepatic side effects including severe and sometimes fatal dose dependent hepatitis have been reported in alcoholic patients with the use of acetaminophen. 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]

General

General side effects including caffeinism have been reported. Caffeinism is a syndrome characterized by anxiety, restlessness, and sleep disorders (similar to anxiety states). Caffeine may cause anxiety and panic in panic disorder patients and may aggravate PMS.^[Ref]

Consumption of higher doses of caffeine (>600 mg/day) has been reported to have lead to caffeinism. It has also been reported that chronic, heavy caffeine ingestion may be associated with depression.^[Ref]

Other

Other side effects including an increased incidence of fibrocystic breast disease have been reported with caffeine use.^[Ref]

In one study of the effects of caffeine, 634 women with fibrocystic breast disease (compared to 1066 women without the disease), the occurrence of fibrocystic breast disease was positively associated with average daily consumption of caffeine. Women who consumed 31 to 250 mg/day of caffeine were reported to have a 1.5 times increase in odds to have the disease. Women who consumed over 500 mg/day of caffeine were reported to have a 2.3 times increase in odds.^[Ref]

Gastrointestinal

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]

Gastrointestinal side effects have been rare with the use of acetaminophen, except in alcoholics and after overdose. Cases of acute pancreatitis have been reported rarely with the use of acetaminophen. In clinical trials of caffeine citrate, five cases of necrotizing enterocolitis were reported among the 46 infants exposed to the caffeine citrate injection.^[Ref]

Renal

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]

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, 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. Methemoglobinemia with resulting cyanosis has also been observed in the setting of acute overdose.^[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. Acetaminophen has been associated with a risk of rare but potentially fatal serious skin reactions know as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP).^[Ref]

Respiratory

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

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 including two cases of hypotension have been reported following the administration of acetaminophen.^[Ref]