Concurrent Medication:
Allowed:
- Antiviral therapy (e.g., zidovudine).
- Prophylaxis (including aerosolized pentamidine) for Pneumocystis carinii pneumonia
(PCP).
Concurrent Treatment:
Allowed:
- Radiation therapy for mucocutaneous Kaposi's sarcoma.
Patients must be oriented to person, place, and time and able to give written informed
consent.
- Patients must have had an acute episode of cryptococcal meningitis that was documented
by recovery and identification of cryptococcus from lumbar cerebrospinal fluid (CSF)
culture within 4 months of study entry.
- Adequate therapy will consist of 6 - 16 weeks of treatment with amphotericin B alone,
amphotericin B + oral flucytosine, or a period of the combination followed by
amphotericin alone. Adequate regimens will include:
- A minimum total amphotericin B dose of 2 grams as monotherapy.
- 6 weeks of flucytosine at 150 mg/kg/day (or levels of 20 to 100 mcg/ml demonstrated)
plus amphotericin B at an average daily dose of at least 0.3 mg/kg/day or to a total
dose of 1 gram.
- After a shorter period of the combination amphotericin/flucytosine therapy, an
additional Y grams of amphotericin B monotherapy will make therapy adequate where Y =
2 gm-(X weeks combination therapy / 3 weeks).
- For example, a patient who received 3 weeks of combination followed by amphotericin
alone would need an additional 2 gm - 3 weeks/3 weeks = 1 gm of amphotericin B.
- Patients need not be receiving amphotericin B at the time of randomization but must
begin study maintenance therapy within 3 weeks of cessation of primary amphotericin B
therapy.
Prior Medication:
Allowed:
- Antiviral therapy (e.g., zidovudine (AZT)).
- Prophylaxis (including aerosolized pentamidine) for Pneumocystis carinii pneumonia
(PCP).
Co-existing Condition:
Patients with the following are excluded:
- Clinical evidence of acute or chronic meningitis based upon any etiology other than
cryptococcosis.
- History of allergy or intolerance of imidazoles, azoles, or amphotericin B.
- Moderate or severe liver disease.
Concurrent Medication:
Excluded:
- Intrathecal amphotericin B.
- Coumarin-type anticoagulants.
- Oral hypoglycemics.
- Barbiturates.
- Phenytoin.
- Immunostimulants.
- Investigational drugs or approved (licensed) drugs for investigational indications.
Concurrent Treatment:
Excluded:
- Lymphocyte replacement.
Patients with the following are excluded:
- Clinical evidence of acute or chronic meningitis based upon any etiology other than
cryptococcosis.
- History of allergy or intolerance of imidazoles, azoles, or amphotericin B.
- Moderate or severe liver disease defined by specific lab values.
- Inability to take oral medications reliably.
Prior Medication:
Excluded:
- Intrathecal amphotericin B.
- Coumarin-type anticoagulants.
- Oral hypoglycemics.
- Barbiturates.
- Phenytoin.
- Immunostimulants.
- Investigational drugs or approved (licensed) drugs for investigational indications.
Prior Treatment:
Excluded:
- Lymphocyte replacement.