ADVERSE REACTIONS
Worldwide, approximately 80,500 patients have been treated with pantoprazole in clinical trials involving various dosages and duration of treatment.
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.
Gastroesophageal Reflux Disease (GERD)
Safety in nine randomized comparative US clinical trials in patients with GERD included 1,473 patients on oral pantoprazole (20 mg or 40 mg), 299 patients on an H2-receptor antagonist, 46 patients on another proton pump inhibitor, 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 I.V. pantoprazole 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 I.V. pantoprazole.
Table 1: Adverse Reactions Reported in Clinical Trials of Adult Patients with GERD at a Frequency of > 2%
|
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 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
Zollinger-Ellison Syndrome
In clinical studies of Zollinger-Ellison Syndrome, adverse reactions reported in 35 patients taking PROTONIX 80 mg/day to 240 mg/day for up to 2 years were similar to those reported in adult patients with GERD.
Postmarketing Experience
The following adverse reactions have been identified during postapproval use of PROTONIX. 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)
Investigations: weight changes
Skin and Subcutaneous Tissue Disorders: severe dermatologic reactions (some fatal), including erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis (TEN), and angioedema (Quincke's edema)
Musculoskeletal Disorders: rhabdomyolysis, bone fracture
Renal and Urinary Disorders: interstitial nephritis
Hepatobiliary Disorders: hepatocellular damage leading to jaundice and hepatic failure
Psychiatric Disorder: hallucinations, confusion, insomnia, somnolence
Metabolism and Nutritional Disorders: hyponatremia, hypomagnesemia
Infections and Infestations:
Clostridium difficile associated diarrhea
Hematologic: pancytopenia, agranulocytosis
Nervous: ageusia, dysgeusia
|