What are the adverse effects of famotidine (Pepcid)?

Famotidine (Pepcid) Side Effects

Famotidine is generally well tolerated with the most common side effects being headache, dizziness, and constipation, each occurring in ≥1% of patients, while serious adverse reactions like anaphylaxis, cardiac arrhythmias, and severe skin reactions are rare but documented. 1

Common Side Effects (≥1% incidence)

The FDA-approved labeling identifies the following adverse reactions occurring in at least 1% of famotidine-treated patients in clinical trials: 1

• Headache 1
• Dizziness 1
• Constipation 1

Less Common Side Effects (<1% incidence)

The following adverse reactions occurred in less than 1% of patients during clinical trials: 1

Systemic Effects

• Fever, asthenia (weakness), and fatigue 1

Cardiovascular

• Palpitations 1

Gastrointestinal

• Elevated liver enzymes, vomiting, nausea, abdominal discomfort, anorexia, and dry mouth 1

Hematologic

• Thrombocytopenia (low platelet count) 1

Hypersensitivity Reactions

• Orbital edema, rash, conjunctival injection, and bronchospasm 1

Musculoskeletal

• Musculoskeletal pain and arthralgia (joint pain) 1

Neuropsychiatric

• Seizure, hallucinations, depression, anxiety, decreased libido, insomnia, and somnolence 1

Dermatologic

• Pruritus (itching), dry skin, and flushing 1

Other

• Tinnitus, taste disorder, and impotence 1

Serious Postmarketing Adverse Reactions

The following serious adverse reactions have been reported after FDA approval, though their frequency cannot be reliably estimated: 1

Life-Threatening Reactions

• Anaphylaxis - IgE-mediated anaphylaxis has been documented, with potential cross-reactivity to other H2-receptor antagonists (nizatidine, ranitidine) 1, 2
• Toxic epidermal necrolysis/Stevens-Johnson syndrome 1
• Agranulocytosis and pancytopenia (severe blood cell deficiencies) 1

Cardiovascular

• Arrhythmia, AV block, and prolonged QT interval 1

Hepatic

• Cholestatic jaundice and hepatitis 1

Respiratory

• Interstitial pneumonia 1

Neurologic

• Confusion, agitation, and paresthesia 1

Musculoskeletal

• Rhabdomyolysis (muscle breakdown) and muscle cramps 1

Hypersensitivity

• Angioedema, facial edema, and urticaria 1

Important Clinical Context

Overall Safety Profile

• Famotidine has an excellent tolerability profile based on data from approximately 18.8 million patients treated worldwide since 1985 3
• The drug does not notably bind to cytochrome P-450 or gastric alcohol dehydrogenase, resulting in minimal clinically significant drug interactions 3

Specific Advantages

• Unlike proton pump inhibitors, famotidine does not interfere with clopidogrel's antiplatelet activity, making it the preferred acid suppression agent in patients on dual antiplatelet therapy 4, 5, 6

Important Limitation

• Tachyphylaxis (tolerance) develops within 6 weeks of continuous H2-receptor antagonist therapy, significantly limiting effectiveness for long-term use 5, 6

Premedication Use

• When famotidine is used as premedication (e.g., before tagraxofusp infusion for BPDCN), it helps mitigate acute infusion-related adverse effects such as fever, chills, and nausea 4

Special Populations

• Famotidine is generally well tolerated in patients with cardiovascular, renal, or hepatic dysfunction 3
• Elimination half-life is prolonged nonlinearly in patients with decreased renal function 7