ADVERSE REACTIONS
MYCOBUTIN Capsules were generally well tolerated in the controlled clinical trials. Discontinuation of therapy due to an adverse event was required in 16% of patients receiving MYCOBUTIN compared to 8% of patients receiving placebo in these trials. Primary reasons for discontinuation of MYCOBUTIN were rash (4% of treated patients), gastrointestinal intolerance (3%), and neutropenia (2%).
The following table enumerates adverse experiences that occurred at a frequency of 1% or greater, among the patients treated with MYCOBUTIN in studies 023 and 027.
| CLINICAL ADVERSE EXPERIENCES REPORTED IN ≥1% OF PATIENTS TREATED WITH MYCOBUTIN |
|---|
| ADVERSE EVENT | MYCOBUTIN
(n = 566) % | PLACEBO
(n = 580) % |
|---|
| BODY AS A WHOLE | | |
| Abdominal Pain | 4 | 3 |
| Asthenia | 1 | 1 |
| Chest Pain | 1 | 1 |
| Fever | 2 | 1 |
| Headache | 3 | 5 |
| Pain | 1 | 2 |
| DIGESTIVE SYSTEM | | |
| Anorexia | 2 | 2 |
| Diarrhea | 3 | 3 |
| Dyspepsia | 3 | 1 |
| Eructation | 3 | 1 |
| Flatulence | 2 | 1 |
| Nausea | 6 | 5 |
| Nausea and Vomiting | 3 | 2 |
| Vomiting | 1 | 1 |
| MUSCULOSKELETAL SYSTEM | | |
| Myalgia | 2 | 1 |
| NERVOUS SYSTEM | | |
| Insomnia | 1 | 1 |
| SKIN AND APPENDAGES | | |
| Rash | 11 | 8 |
| SPECIAL SENSES | | |
| Taste Perversion | 3 | 1 |
| UROGENITAL SYSTEM | | |
| Discolored Urine | 30 | 6 |
CLINICAL ADVERSE EVENTS REPORTED IN <1% OF PATIENTS WHO RECEIVED MYCOBUTIN
Considering data from the 023 and 027 pivotal trials, and from other clinical studies, MYCOBUTIN appears to be a likely cause of the following adverse events which occurred in less than 1% of treated patients: flu-like syndrome, hepatitis, hemolysis, arthralgia, myositis, chest pressure or pain with dyspnea, and skin discoloration.
The following adverse events have occurred in more than one patient receiving MYCOBUTIN, but an etiologic role has not been established: seizure, paresthesia, aphasia, confusion, and non-specific T wave changes on electrocardiogram.
When MYCOBUTIN was administered at doses from 1050 mg/day to 2400 mg/day, generalized arthralgia and uveitis were reported. These adverse experiences abated when MYCOBUTIN was discontinued.
The following table enumerates the changes in laboratory values that were considered as laboratory abnormalities in studies 023 and 027.
| PERCENTAGE OF PATIENTS WITH LABORATORY ABNORMALITIES |
|---|
| LABORATORY ABNORMALITIES | MYCOBUTIN
(n = 566) % | PLACEBO
(n = 580) % |
|---|
| INCLUDES GRADE 3 OR 4 TOXICITIES AS SPECIFIED: |
| Chemistry: | | |
| Increased Alkaline Phosphatase all values >450 U/L | < 1 | 3 |
| Increased SGOT
| 7 | 12 |
| Increased SGPT | 9 | 11 |
| Hematology: | | |
| Anemia all hemoglobin values < 8.0 g/dL | 6 | 7 |
| Eosinophilia | 1 | 1 |
| Leukopenia all WBC values < 1,500/mm 3 | 17 | 16 |
| Neutropenia all ANC values < 750/mm 3 | 25 | 20 |
| Thrombocytopenia all platelet count values < 50,000/mm 3 | 5 | 4 |
The incidence of neutropenia in patients treated with MYCOBUTIN was significantly greater than in patients treated with placebo (p = 0.03). Although thrombocytopenia was not significantly more common among patients treated with MYCOBUTIN in these trials, MYCOBUTIN has been clearly linked to thrombocytopenia in rare cases. One patient in study 023 developed thrombotic thrombocytopenic purpura, which was attributed to MYCOBUTIN.
Uveitis is rare when MYCOBUTIN is used as a single agent at 300 mg/day for prophylaxis of MAC in HIV-infected persons, even with the concomitant use of fluconazole and/or macrolide antibiotics. However, if higher doses of MYCOBUTIN are administered in combination with these agents, the incidence of uveitis is higher.
Patients who developed uveitis had mild to severe symptoms that resolved after treatment with corticosteroids and/or mydriatic eye drops; in some severe cases, however, resolution of symptoms occurred after several weeks.
When uveitis occurs, temporary discontinuance of MYCOBUTIN and ophthalmologic evaluation are recommended. In most mild cases, MYCOBUTIN may be restarted; however, if signs or symptoms recur, use of MYCOBUTIN should be discontinued (Morbidity and Mortality Weekly Report, September 9, 1994).
|
