Ritonavir (as stand alone agent) + Diltiazem = Precautionary

Effect on Concentration

Ritonavir (as stand alone agent)
No change
Applies within class?
No
Diltiazem
Increase
Applies within class?
No

Pharmacologic Effects

Ritonavir (as stand alone agent)
Effect
N/A
Applies within class?
No
Diltiazem
Effect
N/A
Applies within class?
No

Interaction History

N/A

Last Updated 27-Jun-2018

Summary

Sources

Pharmacokinetic interactions between indinavir plus ritonavir and calcium channel blockers. ^

Study Design

Healthy HIV‐ seronegative subjects received 120 mg diltiazem daily or 5 mg amlodipine daily for days 1 to 7 and 20 to 26. All subjects received 100 mg ritonavir and 800 mg indinavir every 12 hours on days 8 to 26. Twenty‐four‐hour pharmacokinetic collection was performed on days 7 and 26, with 12‐hour collection on day 19.

Study Results

Indinavir plus ritonavir increased the median amlodipine area under the curve from 0 to 24 hours (AUC) by 89.8%, from 122 to 230 ng · h/mL (n = 18, P < .0001), and increased the median diltiazem AUC by 26.5%, from 800 to 1060 ng · h/mL (n = 13, P = .06). Of 13 subjects, 2 (15%) had greater than 4‐fold increases in diltiazem AUC. Desacetyldiltiazem AUC increased by 102.2% (P = .001), and desmethyldiltiazem AUC decreased by 27.4% (P= .01). Neither amlodipine nor diltiazem affected steady‐state AUCs of the protease inhibitors. No serious cardiovascular adverse effects were observed.

Study Conclusions

Indinavir plus ritonavir increases the AUCs of both amlodipine and diltiazem, which may result in an increased response. If coadministration is indicated, amlodipine or diltiazem should be initiated at low doses with careful titration to response and side effects.

References

Glesby MJ, Aberg JA, Kendall MA, Fichtenbaum CJ, Hafner R, Hall S, Gerber, JG. Pharmacokinetic interactions between indinavir plus ritonavir and calcium channel blockers. Clinical Pharmacology And Therapeutics. 2005; 2: 143-153.