Effect of Fluconazole, Clarithromycin, and Rifabutin on the Pharmacokinetics of Sulfamethoxazole-Trimethoprim and Dapsone and Their Hydroxylamine Metabolites
Information source: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Bacterial Infections; Mycoses; HIV Infections
Intervention: Clarithromycin (Drug); Rifabutin (Drug); Sulfamethoxazole-Trimethoprim (Drug); Dapsone (Drug); Fluconazole (Drug)
Phase: Phase 1
Status: Completed
Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID) Official(s) and/or principal investigator(s):
Unadkat J, Study Chair
Trapnell CB, Study Chair
Summary
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.
Clinical Details
Official title: Effect of Fluconazole, Clarithromycin, and Rifabutin on the Pharmacokinetics of Sulfamethoxazole and Dapsone and Their Hydroxylamine Metabolites
Study design: Endpoint Classification: Pharmacokinetics Study, Masking: Open Label, Primary Purpose: Treatment
Detailed description:
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
Minimum age: 18 Years.
Maximum age: 65 Years.
Gender(s): Both.
Criteria:
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.
Locations and Contacts
Ucsf Aids Crs, San Francisco, California, United States
University of Washington AIDS CRS, Seattle, Washington 98122, United States
Additional Information
Click here for more information about fluconazole Click here for more information about sulfamethoxazole-trimethoprim
Related publications: Cheng B. Preventing opportunistic infections. PI Perspect. 1995 May;(no 16):14-5.
Last updated: May 1, 2012
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