ADVERSE REACTIONS
Clinical Studies Experience
The data described below reflect exposure to APRISO in 557 patients, including 354 exposed for at least 6 months and 250 exposed for greater than one year. APRISO was studied in two placebo-controlled trials (n = 367 treated with APRISO) and in one open-label, long-term study (n = 190 additional patients). The population consisted of patients with ulcerative colitis; the mean age was 47 years, 54% were female, and 93% were white. Patients received doses of APRISO 1.5 g administered orally once per day for six months in the placebo-controlled trials and for up to 24 months in the open-label study.
Because clinical studies 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 practice.
In the two placebo-controlled trials, 59% of APRISO-treated patients experienced an adverse reaction compared with 64% of placebo patients. Most adverse reactions with APRISO were mild or moderate in severity. Severe adverse reactions occurred in 6% of APRISO-treated patients and 5% of placebo-treated patients. Discontinuations due to adverse reactions occurred in 11% of APRISO-treated patients and 17% of placebo-treated patients; the most common adverse reaction resulting in study discontinuation was recurrence of ulcerative colitis (APRISO 6%, placebo 14%). The most common reactions reported with APRISO (≥3%) are shown in Table 1 below.
Table 1: Treatment-Emergent Adverse Reactions during Clinical Trials Occurring in at Least 3% of APRISO-Treated Patients and at a Greater Rate than with Placebo | MedDRA Preferred Term | APRISO
1.5g/day
N=367 |
Placebo
N=185 |
|---|
| Headache | 11% | 8%
|
| Diarrhea | 8% | 7% |
| Abdominal Pain Upper | 5% | 3% |
| Nausea | 4% | 3% |
| Nasopharyngitis | 4% | 3% |
| Influenza & Influenza-like illness | 4% | 4% |
| Sinusitis | 3% | 3% |
The following adverse reactions, presented by body system, were reported at a frequency less than 3% in patients treated with APRISO for up to 24 months in controlled and open-label trials.
Ear and Labyrinth Disorders: tinnitus, vertigo
Dermatological Disorder: alopecia
Gastrointestinal: abdominal pain lower, rectal hemorrhage
Laboratory Abnormalities: increased triglycerides, decreased hematocrit and hemoglobin
General Disorders and Administration Site Disorders: fatigue
Hepatic: hepatitis cholestatic, transaminases increased
Renal Disorders: creatinine clearance decreased, hematuria
Musculoskeletal: pain, arthralgia
Respiratory: dyspnea
Adverse Reaction Information from Other Sources
The following adverse reactions have been identified during clinical trials of a product similar to APRISO and post approval use of other mesalamine-containing products such as APRISO. Because many of these reactions are reported voluntarily from a population of unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Body as a Whole: lupus-like syndrome, drug fever
Cardiovascular: pericarditis, pericardial effusion, myocarditis
Gastrointestinal: pancreatitis, cholecystitis, gastritis, gastroenteritis, gastrointestinal bleeding, perforated peptic ulcer
Hepatic: jaundice, cholestatic jaundice, hepatitis, liver necrosis, liver failure, Kawasaki-like syndrome including changes in liver enzymes
Hematologic: agranulocytosis, aplastic anemia
Neurological/Psychiatric: peripheral neuropathy, Guillain-Barré syndrome, transverse myelitis
Respiratory/Pulmonary: eosinophilic pneumonia, interstitial pneumonitis
Skin: psoriasis, pyoderma gangrenosum, erythema nodosum
Renal/Urogenital: reversible oligospermia
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