Interactions Between HIV Protease Inhibitors and Calcium Channel Blockers
Condition: HIV Infections; Cardiovascular Diseases; Hypertension
MeSH terms: Cardiovascular Diseases
Study type: Interventional
Phase: Phase 1

Summary: 
      Diltiazem CD and amlodipine are drugs used to treat heart disease and high blood pressure.
      The purpose of this study is to find out if these drugs interact with the anti-HIV drugs
      indinavir and ritonavir. The study will also look at the safety of taking the study drugs
      together.

      Heart disease and high blood pressure are major health concerns for people with HIV. Standard
      treatment for these illnesses often includes calcium channel blockers (CCBs). There is a
      potential for significant drug interactions between CCBs and HIV protease inhibitors (PIs)
      that may influence the dosing, monitoring, and choosing of CCBs and PIs when used in people
      infected with HIV. This study will examine the drug interactions between 2 commonly used CCBs
      and the PI combination indinavir and ritonavir (IDV/RTV). This information should help
      doctors choose the appropriate treatment for high blood pressure or heart disease in people
      taking PIs.
    

Detailed description: 
      Ischemic cardiovascular disease and hypertension occur in persons with HIV infection, and the
      incidence and prevalence may increase over time as the infected population ages. Standard
      pharmacologic interventions for these illnesses often include calcium channel blockers
      (CCBs). Many of the calcium channel blockers are metabolized by cytochrome P450 3A4 (CYP
      3A4), which is inhibited by some protease inhibitors (PIs). Thus, there is potential for
      clinically significant interactions between CCBs and PIs. The presence of significant
      drug-drug interactions may influence the dosing, monitoring, and choosing of CCBs and/or PIs
      when used in persons with HIV infection. Because of the potential concomitant use of CCBs
      with the PI combination IDV/RTV, this study will evaluate bi-directional drug-drug
      interactions between 2 commonly used CCBs and IDV/RTV. This information should assist
      clinicians in choosing the appropriate CCBs to treat hypertension or cardiovascular disease
      in persons taking PIs.

      Patients are randomized to 1 of the following 2 arms:

      Arm A: diltiazem CD interaction with IDV and RTV. Arm B: amlodipine interaction with IDV and
      RTV. From Days 1 to 7, patients take diltiazem CD (Arm A) or amlodipine (Arm B). Plasma is
      collected for PK over a 24-hour period beginning on Day 7. From Days 8 to 19, patients stop
      taking their assigned CCB and take IDV and RTV. Plasma is collected for PK over a 12-hour
      period on Day 19. From Days 20 to 26, patients continue to take IDV and RTV and add diltiazem
      CD (Arm A) or amlodipine (Arm B). Patients stop all 3 drugs after the last dose on Day 26.
      Plasma is collected for PK for a 24-hour period beginning on Day 26. Blood work, liver and
      kidney function tests, urinalysis, and an electrocardiogram (EKG) are performed at some
      visits.
    

Intervention name(s): Indinavir sulfate; Ritonavir; Amlodipine; Diltiazem HCl
Intervention type(s): Drug; Drug; Drug; Drug
Intervention MeSH terms: Ritonavir; Indinavir; Amlodipine; Diltiazem
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Drug Interactions; HIV Protease Inhibitors; Ritonavir; Indinavir; Calcium Channel Blockers; Pharmacokinetics; Diltiazem; Amlodipine