Table of Contents
Understanding and Managing Drug Interactions in HIV Disease
Content
Basic Pharmacokinetic Parameters
Antiretroviral Pharmacodynamics
Potential Consequences of Antiretroviral Interactions
Hospitalizations Due to ADRs and Drug Interactions
Clinical Toxicity Associated with Increased Drug Exposure
Nephrotoxicity and IDV concentrations
Dose-Response Effect of Protease Inhibitors?
TRILEGE: Indinavir Levels in Naïve Patients Taking AZT/3TC/Indinavir
VIRADAPT: Efficacy According to Drug Levels & Randomization Arm
Principles of Drug Interactions
Sites in the Body for Drug Interactions
Absorption Interactions
Antiretroviral-Food Interactions
Gastric pH Interactions
Chelation Interactions
Summary of Antiretroviral Absorption Interactions
P-Glycoprotein
Mechanism of PGP transport
P-Glycoprotein Interactions
P-Glycoprotein and Protease Inhibitors
Increases in Protease CSF concentrations with Ketoconazole (P-gp inhibitor)
Routes of Drug Metabolism
Metabolic Interactions
Cytochrome P450 Enzymes
Substrate
Enzyme Inhibitor
Selectivity - Which CYP Isozymes?
Potency
Enzyme Inhibition Interactions
Enzyme Inducer
Enzyme Induction Interactions
Some Antiretrovirals May Induce and Inhibit CYP450
Effect on CYP450 - Summary
Pharmacokinetically Enhanced Protease Inhibitor Combinations
Dual Protease Combinations
Double Protease Combinations (2)
Steady State Indinavir Plasma Profile
after Indinavir + Ritonavir 400 mg q12h with Food
Ritonavir Boosted PI Regimens
Ritonavir Enhances Kinetics of Other Protease Inhibitors
Impact of Ritonavir on Protease Concentrations
Effect of Drug Dose on the Pharmacokinetics
of Dual Protease Inhibitor Regimens
Advantages of Ritonavir-Boosted Regimens
Boosting Protease Levels May Expand Antiviral Activity
Indinavir 800 mg with Ritonavir 200
mg q12h
Saquinavir Intensification
Disadvantages of Ritonavir Boosted Regimens
Boosted PI Regimens Plus NNRTIs
Effect of Delavirdine on Protease Inhibitor Concentrations
Delavirdine Boosted Regimens (2)
Boosted Regimens - Summary
Undesirable Antiretroviral Interactions
PI-NNRTI Combinations: Effect on PI AUC
Antiretrovirals + MAC/TB Agents
Anticonvulsant Interactions: PI-Carbamazepine (CBZ)
St. John’s Wort + Indinavir
Drugs to Avoid/Use with Caution with Protease Inhibitors
Systematic Approach to Managing Drug Interactions
Systematic Approach to Managing Drug Interactions (2)
Evaluate Therapeutic Alternatives
Summary
Case Study Review
Case #1 - Ms. MC
Potential Interactions
Case #2 - Mr. JS
Potential Methadone Interaction?
Case #3 - Mr. GM
Three Weeks Later...
Case #4: Problem Solving
What If… Patient Wants to Take Zyban (bupropion)?
What If… Patient Requires a Sedative?
What If… Patient Requires MAC Prophylaxis?
What If…Patient Wants to Use Viagra?
Summary
Bibliography
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Author: dr. Alice Tseng
Email: Alice.Tseng@uhn.on.ca
Home Page: www.tthhivclinic.com
Production & publication of this slide kit was made possible through
an unrestricted educational grant from Agouron Pharmaceuticals Canada
Inc.
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