6 ADVERSE REACTIONS
The following serious adverse reactions are described below and elsewhere in labeling:
- •
- Injection Site Reactions [see Warnings and Precautions (5.2)]
- •
- Potential for Exacerbation of Zinc Deficiency [see Warnings and Precautions (5.3)]
- •
- Acute Tubulointerstitial Nephritis [see Warnings and Precautions (5.4)]
- •
- Clostridium difficile-Associated Diarrhea [see Warnings and Precautions (5.5)]
- •
- Bone Fracture [see Warnings and Precautions (5.6)]
- •
- Severe Cutaneous Adverse Reactions [see Warnings and Precautions (5.7)]
- •
- Cutaneous and Systemic Lupus Erythematosus [see Warnings and Precautions (5.8)]
- •
- Hepatic Effects [see Warnings and Precautions (5.9)]
- •
- Hypomagnesemia and Mineral Metabolism [see Warnings and Precautions (5.10)]
- •
- Fundic Gland Polyps [see Warnings and Precautions (5.11)]
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
Worldwide, approximately 80,500 patients have been treated with pantoprazole in clinical trials involving various dosages and duration of treatment.
Gastroesophageal Reflux Disease (GERD)
Safety in nine randomized comparative US clinical trials in patients with GERD included 1,473 patients on oral PROTONIX (20 mg or 40 mg), 299 patients on an H2-receptor antagonist, 46 patients on another PPI, and 82 patients on placebo. The most frequently occurring adverse reactions are listed in Table 1.
The number of patients treated in comparative studies with PROTONIX I.V. is limited; however, the adverse reactions seen were similar to those seen in the oral studies. Thrombophlebitis was the only new adverse reaction identified with PROTONIX I.V.
| Oral PROTONIX (n=1473) % | Comparators (n=345) % | Placebo (n=82) % | |
|---|---|---|---|
Headache | 12.2 | 12.8 | 8.5 |
Diarrhea | 8.8 | 9.6 | 4.9 |
Nausea | 7.0 | 5.2 | 9.8 |
Abdominal pain | 6.2 | 4.1 | 6.1 |
Vomiting | 4.3 | 3.5 | 2.4 |
Flatulence | 3.9 | 2.9 | 3.7 |
Dizziness | 3.0 | 2.9 | 1.2 |
Arthralgia | 2.8 | 1.4 | 1.2 |
Additional adverse reactions that were reported for oral PROTONIX in US clinical trials with a frequency of ≤2% are listed below by body system:
Body as a Whole: allergic reaction, fever, photosensitivity reaction, facial edema, thrombophlebitis (I.V. only)
Gastrointestinal: constipation, dry mouth, hepatitis
Hematologic: leukopenia (reported in ex-US clinical trials only), thrombocytopenia
Metabolic/Nutritional: elevated CPK (creatine phosphokinase), generalized edema, elevated triglycerides, liver function tests abnormal
Musculoskeletal: myalgia
Nervous: depression, vertigo
Skin and Appendages: urticaria, rash, pruritus
Special Senses: blurred vision
6.2 Postmarketing Experience
The following adverse reactions have been identified during postapproval use of PROTONIX and PROTONIX I.V. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
These adverse reactions are listed below by body system:
General Disorders and Administration Conditions: asthenia, fatigue, malaise
Immune System Disorders: anaphylaxis (including anaphylactic shock), systemic lupus erythematosus
Investigations: weight changes
Skin and Subcutaneous Tissue Disorders: severe dermatologic reactions (some fatal), including erythema multiforme, SJS/TEN, DRESS, AGEP, angioedema (Quincke's edema) and cutaneous lupus erythematosus
Musculoskeletal Disorders: rhabdomyolysis, bone fracture
Renal and Genitourinary Disorders: acute tubulointerstitial nephritis, erectile dysfunction
Hepatobiliary Disorders: hepatocellular damage leading to jaundice and hepatic failure
Psychiatric Disorder: hallucinations, confusion, insomnia, somnolence
Metabolism and Nutritional Disorders: hyponatremia, hypomagnesemia, hypocalcemia, hypokalemia, hyponatremia
Infections and Infestations: Clostridium difficile associated diarrhea
Hematologic: pancytopenia, agranulocytosis
Nervous: ageusia, dysgeusia
Gastrointestinal Disorders: fundic gland polyps