Indinavir Amlodipine

The pharmacokinetics of several drugs that are known P-gp substrates were not altered by GFJ in several clinical studies that investigated the effect of GFJ on the bioavailability of digoxin, amlodipine, and indinavir (27,75,99). Possible other unknown mechanisms and factors such as strength of the administered juices and length of consumption are relevant for the interactions of citrus with drugs (100). 

Symptomatic orthostasiisi occurred in a patient taking nelfinavir or ritonavir/indinavir and nifedipine. Another patient had similar symptoms when nelfinavir was added to felodipine therapy. Atazanavir markedly increased diltiazem bioavailability with an increase in cardiac effects in healthy subjects. Similarly, ritonavir/indinavir caused a modest to marked increase in diltiazem levels, and a 1.9-fold increase in amlodipine levels. Based on this evidence, raised calcium-channel blocker levels are predicted when any calcium-channel blocker is given with a protease inhibitor, especially ritonavir. Caution is required. 

Ritonavir/indinavir 100/800 mg twice daily given with amlodipine 5 mg... 

Although information is limited, these pharmacokinetic interactions are predictable, and potentially serious. To date, clinically relevant increases in calcium-channel blocker levels or effects have been shown for nelfinavir with nifedipine or felodipine, indinavir/ritonavir with amlodipine, diltiazem or nifedipine, and atazanavir with diltiazem. Caution would be required with any of these combinations, anticipating the need to use lower doses of the calcium-channel blocker. The manufacturers specifically recommend that if diltiazem is given with atazanavir the initial dose of diltiazem should be reduced by 50% with subsequent dose titration and ECG monitoring. They also note that verapamil levels may be raised and therefore advise caution. Similarly, the manufaeturers of nifedipine say that blood pressure monitoring is required and a reduction in nifedipine dose may be neeessary if it is given with HIV-protease inhibitors. However, some UK manufacturers (e.g. felodipine, lercanidipine, nimodipine ) recommend avoiding the concurrent use of ritonavir and other protease inhibitors if possible. 

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