Applies to acetaminophen / aspirin / caffeine: oral packet, oral tablet.

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.
• Signs of bleeding like throwing up or coughing up blood; vomit that looks like coffee grounds; blood in the urine; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a cause or that get bigger; or bleeding you cannot stop.
• Feeling confused.
• Feeling very tired or weak.
• Very bad dizziness or passing out.
• Ringing in ears.
• Hearing loss.
• Very bad headache or if headache is not better after the first dose.
• 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.
• Very bad stomach ulcers or bleeding can happen with this drug. Taking it in high doses or for a long time, smoking, or drinking alcohol raises the chance of these side effects. Taking this drug with food will not lower the chance of these effects. Call your doctor or get medical help right away if you get very bad stomach or back pain; black, tarry, or bloody stools; throwing up blood or throw up that looks like coffee grounds; or weight gain or swelling that is not normal.

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:

• Stomach pain or heartburn.
• Upset stomach.

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/aspirin/caffeine: oral powder for reconstitution, oral tablet.

General

The more commonly reported adverse events may include nausea dyspepsia, nervousness, irritability, sleeplessness, and palpitations.^[Ref]

Hepatic

Acetaminophen (paracetamol):

Frequency not reported: Liver failure

Aspirin:

Frequency not reported: Hepatotoxicity, cholestatic hepatitis, aminotransferase elevations^[Ref]

Gastrointestinal

Acetaminophen (paracetamol):

Frequency not reported: Nausea, vomiting

Aspirin:

Frequency not reported: Epigastric distress, abdominal discomfort, nausea, vomiting, hemorrhage, peptic ulcers, perforation, esophageal ulcerations, dyspepsia, gastritis^[Ref]

Hypersensitivity

Acetaminophen (paracetamol):

Postmarketing reports: Anaphylaxis, hypersensitivity reactions

Aspirin:

Very common (10% or more): Hypersensitivity reactions in asthmatics who are aspirin-sensitive (e.g., with the clinical triad of aspirin sensitivity, bronchial asthma, and nasal polyps)

Frequency not reported: Hypersensitivity reactions include bronchospasm, rhinitis, conjunctivitis, urticaria, angioedema, skin reactions, and anaphylaxis^[Ref]

Dermatologic

Acetaminophen (paracetamol):

Very rare (less than 0.01%): Serious skin reactions including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP)

Aspirin:

Frequency not reported: Stevens-Johnson syndrome, lichenoid eruption^[Ref]

Renal

Aspirin:

Frequency not reported: Renal dysfunction, renal failure, increased blood uric acid levels^[Ref]

Hematologic

Acetaminophen (paracetamol):

Frequency not reported: Blood dyscrasias including thrombocytopenia, agranulocytosis

Aspirin:

Frequency not reported: Predictable antiplatelet effects, hemorrhage, increased blood fibrinolytic activity, hypoprothrombinemia, thrombocytopenia, thrombocyturia, megaloblastic anemia, pancytopenia, aplastic anemia, ecchymosis^[Ref]

Respiratory

Aspirin:

Frequency not reported: Bronchospasm (in patients sensitive to aspirin and other NSAID)^[Ref]

Cardiovascular

Acetaminophen (paracetamol):

Frequency not reported: Hypotension

Aspirin:

Frequency not reported: Salicylate-induced variant angina, ventricular ectopy, conduction abnormalities, and hypotension, particularly during salicylate toxicity

Caffeine:

Frequency not reported: Palpitations^[Ref]

Metabolic

Acetaminophen (paracetamol):

Frequency not reported: Hypokalemia, hypoglycemia

Aspirin:

Frequency not reported: Dehydration, hyperkalemia, hypoglycemia, sodium and fluid retention, respiratory alkalosis and metabolic acidosis (particularly during salicylate toxicity)^[Ref]

Nervous system

Acetaminophen (paracetamol):

Frequency not reported: Headache, dizziness, dystonia

Aspirin:

Frequency not reported: Dizziness, headache

Caffeine:

Frequency not reported: Dizziness, tremor^[Ref]

Other

Acetaminophen (paracetamol):

Frequency not reported: Malaise, fatigue

Aspirin:

Frequency not reported: Reye's syndrome, tinnitus, temporary hearing loss

Caffeine:

Frequency not reported: Fibrocystic breast disease^[Ref]