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Effect of Fluconazole, Clarithromycin, and Rifabutin on the Pharmacokinetics of Sulfamethoxazole-Trimethoprim and Dapsone and Their Hydroxylamine Metabolites
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Purpose
To determine the effects of fluconazole and either rifabutin or clarithromycin, alone and in combination, on the pharmacokinetics of first sulfamethoxazole-trimethoprim and then dapsone in HIV-infected patients.
Although prophylaxis for more than one opportunistic infection is emerging as a common clinical practice in patients with advanced HIV disease, little is known about possible adverse drug interactions. The need exists to define pharmacokinetics and pharmacodynamic adverse interactions of the many combination prophylactic regimens that may be prescribed.
| Condition | Intervention | Phase |
|---|---|---|
| Bacterial Infections Mycoses HIV Infections | Drug: Clarithromycin Drug: Rifabutin Drug: Sulfamethoxazole-Trimethoprim Drug: Dapsone Drug: Fluconazole | Phase 1 |
| Study Type: | Interventional |
| Study Design: | Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Effect of Fluconazole, Clarithromycin, and Rifabutin on the Pharmacokinetics of Sulfamethoxazole and Dapsone and Their Hydroxylamine Metabolites |
| Estimated Enrollment: | 48 |
| Study Completion Date: | May 1999 |
Although prophylaxis for more than one opportunistic infection is emerging as a common clinical practice in patients with advanced HIV disease, little is known about possible adverse drug interactions. The need exists to define pharmacokinetics and pharmacodynamic adverse interactions of the many combination prophylactic regimens that may be prescribed.
In Part A, patients receive sulfamethoxazole-trimethoprim (SMX/TMP) alone for 2 weeks, then in combination with fluconazole, rifabutin, or both drugs, each over 2-week periods in a randomly assigned order. Patients in Part B receive the same regimens except with clarithromycin substituted for rifabutin. In Part C, patients receive dapsone alone for 2 weeks, then in combination with fluconazole, rifabutin, or both drugs in the same manner as in Part A. Part D patients receive the same regimen as those in Part C, except with clarithromycin substituted for rifabutin. Patients are followed every 2 weeks.
Eligibility| Ages Eligible for Study: | 18 Years to 65 Years (Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria
Concurrent Medication:
Allowed:
- Antiretroviral therapy provided patient has been on a stable dose for at least 4 weeks prior to study entry.
- Methadone for drug abuse programs provided patient has been on a stable dose for at least 4 weeks prior to the study.
Patients must have:
- HIV infection.
- CD4 count >= 200 cells/mm3.
- No active opportunistic infection.
Prior Medication:
Allowed:
- Antiretroviral therapy.
- Methadone for drug abuse therapy.
Exclusion Criteria
Co-existing Condition:
Patients with the following symptoms or conditions are excluded:
- Suspicion of gastrointestinal malabsorption problems (at discretion of investigator).
- Known hypersensitivity to dapsone, SMX, or other sulfonamides, trimethoprim, clarithromycin, rifabutin or other rifamycins, fluconazole, or other azoles.
- G-6-PD deficiency or methemoglobinemia (in Part C and D patients only).
Concurrent Medication:
Excluded:
- Cytolytic agents.
- Amiodarone.
- Anesthetics, general.
- Astemizole.
- Azithromycin.
- Barbiturates.
- Carbamazepine.
- Cimetidine.
- Ciprofloxacin.
- Cisapride.
- Clarithromycin (except as required on study).
- Clotrimazole.
- Dexamethasone.
- Disulfiram.
- Erythromycin.
- Fluoroquinolones.
- Fluoxetine.
- Gestodene.
- Hydrochlorothiazide.
- Hypoglycemics, oral.
- Isoniazid.
- Itraconazole.
- Ketoconazole.
- Levomepromazine.
- Loratadine.
- MAO inhibitors.
- Methoxsalen.
- Miconazole.
- Nafcillin.
- Narcotic analgesics.
- Naringenin.
- Nifedipine.
- Norethindrone.
- Pentazocine.
- Phenothiazines.
- Phenytoin.
- Protease inhibitors.
- Quinidine.
- Ranitidine.
- Rifabutin (except as required on study).
- Rifampin.
- Sedative hypnotics.
- Sulfaphenazole.
- Terfenadine.
- Tranquilizers (unless allowed by investigator).
- Tricyclic and tetracyclic antidepressants.
- Troleandomycin.
- Warfarin.
Concurrent Treatment:
Excluded:
- Radiation therapy.
Prior Medication:
Excluded:
- Cytolytic agents within 5 years prior to study entry.
- Rifabutin and/or rifampin within 4 weeks prior to study entry.
- Fluconazoles or other azoles within 4 weeks prior to study entry.
- Glutathione, glutathione precursors, or related prodrugs within 2 weeks prior to study entry.
Excluded within 72 hours prior to study entry:
- Amiodarone.
- Anesthetics, general.
- Astemizole.
- Azithromycin.
- Cimetidine.
- Ciprofloxacin.
- Cisapride.
- Clarithromycin.
- Dexamethasone.
- Disulfiram.
- Erythromycin.
- Fluoroquinolones.
- Fluoxetine.
- Hydrochlorothiazide.
- Hypoglycemics, oral.
- Isoniazid.
- Levomepromazine.
- Loratadine.
- MAO inhibitors.
- Methoxsalen.
- Nafcillin.
- Narcotic analgesics.
- Naringenin.
- Nifedipine.
- Norethindrone.
- Pentazocine.
- Phenothiazines.
- Phenytoin.
- Protease inhibitors.
- Quinidine.
- Ranitidine.
- Sedative hypnotics.
- Sulfaphenazole.
- Terfenadine.
- Tranquilizers (unless allowed by investigator).
- Troleandomycin.
- Warfarin.
Excluded within 4 weeks prior to study entry:
- Barbiturates.
- Carbamazepine.
- Clotrimazole.
- Gestodene.
- Itraconazole.
- Ketoconazole.
- Miconazole.
- Omeprazole.
- Rifabutin.
- Rifampin.
- Tricyclic and tetracyclic antidepressants.
Prior Treatment:
Excluded:
- Blood transfusion within 1 week prior to study entry.
- Radiation therapy within 5 years prior to study entry.
Active drug or alcohol abuse or dependence that would preclude completion of study.
Contacts and LocationsPlease refer to this study by its ClinicalTrials.gov identifier: NCT00000826
| United States, California | |
| Ucsf Aids Crs | |
| San Francisco, California, United States | |
| United States, Washington | |
| University of Washington AIDS CRS | |
| Seattle, Washington, United States, 98122 | |
| Study Chair: | Unadkat J | |
| Study Chair: | Trapnell CB |
More Information
Publications:
| Responsible Party: | National Institute of Allergy and Infectious Diseases (NIAID) |
| ClinicalTrials.gov Identifier: | NCT00000826 History of Changes |
| Other Study ID Numbers: |
ACTG 283 11259 ( Registry Identifier: DAIDS ES Registry Number ) |
| Study First Received: | November 2, 1999 |
| Last Updated: | May 1, 2012 |
Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
|
Rifabutin Trimethoprim-Sulfamethoxazole Combination AIDS-Related Opportunistic Infections Dapsone Drug Interactions |
Fluconazole Acquired Immunodeficiency Syndrome AIDS-Related Complex Clarithromycin Sulfamethoxazole-Trimethoprim |
Additional relevant MeSH terms:
|
Infection Communicable Diseases HIV Infections Mycoses Bacterial Infections Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases Clarithromycin Dapsone |
Rifabutin Trimethoprim, Sulfamethoxazole Drug Combination Fluconazole Trimethoprim Sulfamethoxazole Anti-Bacterial Agents Anti-Infective Agents Protein Synthesis Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Cytochrome P-450 CYP3A Inhibitors Cytochrome P-450 Enzyme Inhibitors Antifungal Agents 14-alpha Demethylase Inhibitors Steroid Synthesis Inhibitors |
ClinicalTrials.gov processed this record on July 24, 2017