Loperamide Ritonavir

PROTEASE INHIBITORS ANTIDIARRHOEAL DRUGS-LOPERAMIDE t risk of adverse effects when loperamide is co-ingested with ritonavir Ritonavir inhibits P-gp and CYP3A4 Monitor for clinical effect, and consider 1 dose if necessaiy. Stop if there are signs of abdominal distension in HIV patients as toxic megacolon has been reported... 

Fluorouracil Glucocorticoids Indinavir Loperamide Losartan Methotrexate Mitoxantrone Nelfinavir Paclitaxel Ritonavir Saquinavir Sirolimus Tacrolimus Topotecan Vinblastine Vincristine Vindesine Vinorelbine Verapamil ... 

Mukwaya, G., MacGregor, T., Hoelscher, D., Heming, T., Legg, D., Kavanaugh, K., Johnson, P., Sabo, J. P., and McCallister, S. (2005) Interaction of ritonavir-boosted tipranavir with loperamide does not result in loperamide-associated neurologic side effects in healthy volunteers. Antimicrob. Agents Chemother. 49, 4903-4910. 

Ritonavir increases the piasma levels of loperamide. Tipranavir, aione and combined with ritonavir, reduces the bioavailability and piasma ieveis of ioperamide and its metabolites. No central opioid adverse effects are seen when loperamide is given with ritonavir aione, tipranavir aione, or tipranavir/ritonavir. 

In a double-blind, placebo-controlled study, 12 healthy subjects were given a single 600-mg dose of ritonavir with either loperamide 16 mg or placebo. The loperamide AUC and maximum plasma level were increased threefold and 17%, respectively, by ritonavir, but no additional CNS adverse effects were seen. Anotiier study in 20 healthy subjects looked at the pharmacokinetics and pharmacodynamics of a single 16-mg dose of loperamide taken with either tipranavir 750 mg twice daily, ritonavir 200 mg twice daily or both drugs together. (Note that this dose of tipranavir is higher than tiie usual ritonavir-boosted dose of 500 mg twice daily.) Tipranavir alone reduced the maximum concentration and AUC of loperamide by 58% and 63%, respectively, whereas ritonavir increased these parameters by 83% and 121%, respectively. The combination of tipranavir/ritonavir, as is usual clinical practice, resulted in a net reduction in the maximum concentration and AUC of loperamide by 61% and 51%, respectively, similar to the effect seen with tipranavir alone. The maximum concentration and AUC of the metabolites of loperamide were also reduced. There were no clinically significant loperamide adverse effects on respiration or pupil contractility with either ritonavir alone, tipranavir alone, or the combination. ... 

Despite the increases seen in loperamide plasma levels seen in both studies with ritonavir alone, a lack of central opioid effects with loperamide (such as pupillary constriction, respiratory depression and also analgesic effects) was demonstrated. This suggests that the combination of loperamide with... 

The clinical relevance of the decrease in loperamide bioavailability with tipranavir alone or tipranavir/ritonavir is unknown. 

Tayrouz Y, Ganssmam B, Ding R, Klingm ann A, Adeijan R, Burhenne J, Haefeli WE, Mikus G. Ritonavir increases loperamide plasma concentrations wi ut evidence for P-glycoprotein involvement Clin Pharmacol Ther(2QO ) 70, 405-14. 

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