The Clinical Guide to Supportive and Palliative Care for HIV/AIDS

A Clinical Guide to Supportive and Palliative Care for HIV/AIDS • Chapter 27: Pharmacologic Interactions of Clinical SignificanceMeasures to increase gastric acidity for azole bioavailability: Administration of acidic beveragessuch as 240 ml of orange juice, tomato juice, ginger ale, grapefruit juice or cola drinks in thepresence of achlorhydria of advanced HIV disease will enhance azole biovailability, especiallyfor ketoconazole. When hypochlorhydria is severe, each 200 mg of ketoconazole should be dissolvedin 4 ml of 0.2N hydrochloric acid. A straw should be used to avoid contact with teeth.PIs and NNRTIs with azoles: As a general rule, use of ketoconazole with PIs and NNRTIs is notadvised due to a large number of potentially significant drug-drug interactions. Fluconazole(Diflucan) is preferred. (See Tables 27-2 and 27-3.)• Indinavir:Levels are increased 68%; reduce indinavir dose to 600 mg q 8 h; SQV levels increasedthree-fold, no dose change required.• Ritonavir:Levels are increased more than three-fold; use less than 200 mg ketoconazole/day.• Amprenavir:Levels are increased 31% and ketoconazole levels increased 44%; dose implications notclear.• Nelfinavir:No dosage change.• Nevirapine:Levels are increased 15% to 30% and ketoconazole levels decreased by 60%; combinationis not recommended.• Efavirenz:Interactions between ketoconazole and efavirenz have not been studied; no recommendationscan be made at present.Ketoconazole and other drugs: Rifampin decreases activity of both drugs; INH decreases effectof ketoconazole; terfenadine and cisapride (both now removed from the market) lead to ventriculararrhythmias and concurrent use should be avoided.Didanosine: Didanosine buffered formulations usually cause problems of absorption for medicationswhose absorption are pH-sensitive. Didanosine can decrease absorption of itraconazole,ketoconazole, dapsone and delavirdine (Rescriptor) because of increased gastric pH. It can alsodecrease absorption of the quinolones and tetracyclines by chelation of these antibiotics withthe calcium and magnesium ions contained in the buffer.Oral fluoroquinolones: With oral fluoroquinolones, patients should avoid dairy products, elementalminerals and heavy nutritional supplements; take fluoroquinolones two hours before orsix hours after these items.554U.S. Department of Health and Human Services • Health Resources and Services Administration • HIV/AIDS Bureau