Effect of Fluconazole, Clarithromycin, and Rifabutin on the Pharmacokinetics of Sulfamethoxazole-Trimethoprim and Dapsone and Their Hydroxylamine Metabolites
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| ClinicalTrials.gov Identifier: NCT00000826 |
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Recruitment Status :
Completed
First Posted : August 31, 2001
Last Update Posted : October 29, 2021
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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 or disease | Intervention/treatment | Phase |
|---|---|---|
| Bacterial Infections Mycoses HIV Infections | Drug: Clarithromycin Drug: Rifabutin Drug: Sulfamethoxazole-Trimethoprim Drug: Dapsone Drug: Fluconazole | Phase 1 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Enrollment : | 48 participants |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Effect of Fluconazole, Clarithromycin, and Rifabutin on the Pharmacokinetics of Sulfamethoxazole and Dapsone and Their Hydroxylamine Metabolites |
| Actual Study Completion Date : | May 1999 |
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| Ages Eligible for Study: | 18 Years to 65 Years (Adult, Older 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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 |
Other Publications:
| Responsible Party: | National Institute of Allergy and Infectious Diseases (NIAID) |
| ClinicalTrials.gov Identifier: | NCT00000826 |
| Other Study ID Numbers: |
ACTG 283 11259 ( Registry Identifier: DAIDS ES Registry Number ) |
| First Posted: | August 31, 2001 Key Record Dates |
| Last Update Posted: | October 29, 2021 |
| Last Verified: | October 2021 |
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Rifabutin Trimethoprim-Sulfamethoxazole Combination AIDS-Related Opportunistic Infections Dapsone Drug Interactions |
Fluconazole Acquired Immunodeficiency Syndrome AIDS-Related Complex Clarithromycin Sulfamethoxazole-Trimethoprim |
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Infections Communicable Diseases Mycoses Bacterial Infections Disease Attributes Pathologic Processes Bacterial Infections and Mycoses 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 Hormone Antagonists Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs Cytochrome P-450 CYP2C9 Inhibitors Cytochrome P-450 CYP2C19 Inhibitors Anti-Infective Agents, Urinary |