Side Effects of Pantoprazole
Pantoprazole is generally well tolerated with most adverse effects being mild and occurring in less than 12% of patients, with headache being the most common side effect. 1
Common Side Effects (Occurring in >2% of Patients)
Based on clinical trial data in adults with GERD, the following adverse reactions occur with pantoprazole: 1
- Headache (12.2%) - the most frequently reported adverse effect 1
- Diarrhea (8.8%) 1
- Nausea (7.0%) 1
- Abdominal pain (6.2%) 1
- Vomiting (4.3%) 1
- Flatulence (3.9%) 1
- Dizziness (3.0%) 1
- Arthralgia (2.8%) 1
Less Common Side Effects (≤2% Frequency)
Additional adverse reactions reported in clinical trials include: 1
- Gastrointestinal: constipation, dry mouth, hepatitis 1
- Hematologic: leukopenia, thrombocytopenia 1
- Metabolic: elevated creatine kinase, generalized edema, elevated triglycerides, elevated liver enzymes 1
- Musculoskeletal: myalgia 1
- Neurologic: depression, vertigo 1
- Dermatologic: urticaria, rash, pruritus 1
- Ophthalmologic: blurred vision 1
- Other: allergic reaction, pyrexia, photosensitivity reaction, facial edema 1
Serious Adverse Effects with Long-Term Use
Bone Fracture Risk
Long-term PPI use has been associated with increased risk of bone fractures, particularly in adults 65 years and older. 2 This risk is consistently reported across multiple observational studies, though primarily based on lower-quality evidence. 3
Kidney Disease
Both acute and chronic kidney disease have been associated with PPI use, with increased risks consistently reported in observational studies. 2, 3 Interstitial nephritis has been reported in postmarketing surveillance. 1
Gastrointestinal Infections
- Clostridium difficile-associated diarrhea has been reported with pantoprazole use 1, 2
- In the only high-quality randomized controlled trial evaluating chronic pantoprazole use, enteric infections occurred significantly more frequently compared to placebo 3
- The American College of Gastroenterology notes this as a recognized risk with PPI therapy 3
Nutritional Deficiencies
Vitamin B-12 deficiency: Pantoprazole reduces stomach acid needed for proper vitamin B-12 absorption, particularly concerning after more than 3 years of treatment. 1, 2
Hypomagnesemia (low magnesium): This serious complication can occur in patients taking PPIs for at least 3 months, usually after a year of treatment. 1, 2, 3 Symptoms include: 1
- Seizures
- Dizziness
- Abnormal or fast heartbeat
- Jitteriness
- Jerking movements or tremors
- Muscle weakness, spasms, or cramps
- Spasm of the voice box
Gastric Changes
Chronic atrophic gastritis (long-lasting inflammation of the stomach lining) may develop with prolonged pantoprazole use. 1
Severe Postmarketing Adverse Reactions
The following serious reactions have been identified during postapproval use: 1
- Hematologic: pancytopenia, agranulocytosis 1
- Hepatobiliary: hepatocellular damage leading to jaundice and hepatic failure 1
- Immune: anaphylaxis including anaphylactic shock 1
- Musculoskeletal: rhabdomyolysis 1
- Dermatologic: severe reactions including erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (some fatal), and angioedema 1
- Psychiatric: hallucination, confusion, insomnia, somnolence 1
- Neurologic: ageusia (loss of taste), dysgeusia (altered taste) 1
- Other: hyponatremia, weight changes 1
Pediatric Considerations
In children ages 1-16 years, the most common adverse reactions (>4%) include: 1
- Upper respiratory infection
- Headache
- Fever
- Diarrhea
- Vomiting
- Rash
- Abdominal pain
Drug Interaction Considerations
Clopidogrel interaction: Pantoprazole reduces the bioavailability of clopidogrel by raising gastric pH from 2.2 to 5.9, decreasing peak plasma concentration by 40% and AUC by 20-40%. 4 However, the American Heart Association and American College of Cardiology note that clinical outcome data does not demonstrate consistent adverse cardiovascular effects with this combination, and pantoprazole may be preferred over omeprazole when a PPI is needed with clopidogrel. 4
Clinical Context and Safety Profile
Pantoprazole has been used for over 13 years in more than 100 countries with an excellent overall safety profile. 5 Short-term use (8-10 weeks) causes few adverse effects, with tolerability similar to other PPIs and better than H2-receptor antagonists. 6, 7 The medication has minimal potential for drug-drug interactions compared to other PPIs. 6, 7, 5
Important caveat: Most serious long-term adverse effects are based on observational data subject to bias and confounding. 3 The American College of Gastroenterology continues to recommend PPIs as first-line treatment for GERD and upper GI bleeding despite these concerns. 3