{"id":289,"date":"2008-12-26T10:05:00","date_gmt":"2008-12-26T09:05:00","guid":{"rendered":"http:\/\/localhost\/new\/htb\/?p=289"},"modified":"2013-08-23T12:58:27","modified_gmt":"2013-08-23T12:58:27","slug":"drug-interaction-studies-with-approved-drugs","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/289","title":{"rendered":"Drug interaction studies with approved drugs"},"content":{"rendered":"

Marta Boffito, HIV-druginterations.org<\/strong><\/p>\n

The following summaries are selected from a longer report, available with hyperlinks to the conference abstracts, from www.hiv-druginteractions.org<\/a>.<\/strong><\/p>\n

Lopinavir\/r reduces gemfibrozil levels<\/h2>\n

The effect of lopinavir\/ritonavir (400\/100 mg twice daily) on a single dose of the lipid lowering drug gemfibrozil (600 mg) was studied in 15 HIV- subjects.<\/p>\n

Coadministration decreased gemfibrozil AUC by 41% and Cmax by 33%. There was no effect on half-life and clearance increased by 69%. The mechanism for this interaction is unclear, but it would appear that lopinavir\/ritonavir reduced absorption of gemfibrozil.<\/p>\n

Ref: Busse K, et al. Lopinavir\/ritonavir significantly decreases gemfibrozil plasma concentrations in healthy volunteers. 48th ICAAC, 25-28 October 2008. Washington. Abstract A-959.<\/p>\n

Darunavir\/r and raltegravir: rash seen in HIV-negative patients<\/h2>\n

Coadministration of raltegravir (400 mg twice daily) and darunavir\/ritonavir (600\/100 mg twice daily) was studied in 18 subjects.<\/p>\n

Contrary to clinical experience in HIV+ patients, eight subjects presented with a clinical adverse experience of rash, which progressed from mild\/moderate to serious in one subject. Only six subjects completed the study. Based on these limited pharmacokinetic data, raltegravir AUC decreased by 29%, Cmax decreased by 33% and Cmin increased by 38% (the latter parameter showing very marked variability). Darunavir pharmacokinetics were similar to historical data.<\/p>\n

Ref: Anderson MS, et al. Pharmacokinetic evaluation of darunavir\/ritonavir and raltegravir in healthy subjects. 48th ICAAC, 25-28 October 2008. Washington. Abstract A-962.<\/p>\n

Raltegravir may reduce efficacy of omeprazole<\/h2>\n

The effect of omeprazole (20 mg single dose) on the pharmacokinetics of raltegravir (400 mg once daily) was studied in HIV- subjects.<\/p>\n

Coadministration increased raltegravir AUC, Cmax and Cmin by 3.12-fold, 4.15-fold and 1.46-fold, respectively. There was no substantial effect on raltegravir Tmax or half-life. The mechanism for this interaction is likely a consequence of increased bioavailability secondary to increased gastric pH.<\/p>\n

Due to the high prevalence of achlorhydria in HIV+ subjects, the effect of omeprazole on raltegravir in the target population may be diminished relative to healthy subjects.<\/p>\n

Ref: Iwamoto M, et al. Omeprazole increases plasma levels of raltegravir in healthy subjects. 48th ICAAC, 25-28 October 2008. Washington. Abstract A-963.<\/p>\n

Interaction between raltegravir and rifampicin requires caution<\/h2>\n

Coadministration of raltegravir and rifampicin has been shown to decrease raltegravir trough concentration by ~60%. This study looked at whether increasing raltegravir to 800 mg twice daily when given with rifampicin (600 mg once daily) could overcome this effect.<\/p>\n

When compared to raltegravir alone (400 mg twice daily), coadministration of the higher dose with rifampicin decreased raltegravir trough concentrations by 53%, but increased AUC and Cmax by 27% and 62%, respectively. Therefore, doubling the dose of raltegravir does not overcome the effect of rifampicin on raltegravir trough concentrations.<\/p>\n

Although trough concentrations have not been shown to correlate with efficacy, caution should be exercised when raltegravir is given with rifampicin.<\/p>\n

Ref: Brainaird DM, et al. Doubling the dose of raltegravir does not increase trough levels in the presence of rifampin. 48th ICAAC, 25-28 October 2008. Washington. Abstract A-964.<\/p>\n

Quinine requires dose adjustment when used with ritonavir<\/h2>\n

This study looked at the effect of ritonavir (200 mg twice daily) on pharmacokinetics of quinine (600 mg single dose) in 10 HIV- subjects. Ritonavir increased both the AUC and Cmax of quinine by ~4-fold and increased half-life by 20%. The metabolism of quinine to its major metabolite, 3-hydroxyquinine, was markedly inhibited. Quinine had no significant effect on ritonavir pharmacokinetics.<\/p>\n

Dose adjustment of quinine is likely to be necessary when coadministered with ritonavir.<\/p>\n

Ref: Soyinka JO, et al. Pharmacokinetic interaction between ritonavir and quinine. 48th ICAAC, 25-28 October 2008. Washington. Abstract A-965.<\/p>\n

Tipranavir\/r interactions with buprenorphine\/naloxone<\/h2>\n

The effect of tipranavir\/ritonavir (500\/200 mg twice daily) on the pharmacokinetics of buprenorphine and naloxone was assessed in HIV- subjects stable on buprenorphine\/naloxone therapy. Coadministration had no effect (<6%) on buprenorphine AUC or Cmin, but decreased Cmax by 14%. The AUC, Cmax and Cmin of norbuprenorphine (the major metabolite) decreased by ~80%. The AUC, Cmax and Cmin of naloxone decreased by 44%, 36% and 20%, respectively. Despite these changes, there was no evidence of opioid withdrawal and no need to modify the dose of buprenorphine.<\/p>\n

When compared to historical data, there was no effect (<6%) on tipranavir Cmax, but AUC and Cmin decreased by 26% and 39%, respectively. Ritonavir Cmin was similar to historical data, but AUC decreased by 35% and Cmax decreased by 40-50%. The mechanism by which buprenorphine\/naloxone affects tipranavir and ritonavir is unclear.<\/p>\n

Caution should be used if coadministered as tipranavir may be less effective due to decreased concentrations.<\/p>\n

Ref: Bruce R, et al. Pharmacokinetic interactions between buprenorphine\/naloxone and tipranavir\/ritonavir in HIV-negative subjects chronically receiving buprenorphine\/naloxone. 48th ICAAC, 25-28 October 2008. Washington. Abstract A-967a.<\/p>\n

Dose reduction and monitoring needed when rifabutin levels given with darunavir\/r<\/h2>\n

Coadministration of darunavir\/ritonavir (600\/100 mg twice daily) and rifabutin (300 mg once daily alone or 150 mg every other day when coadministered) was studied in HIV- subjects. Rifabutin AUC was comparable when given at the standard dose alone or at the reduced dose in combination. The AUC of 25-O-desacetyl rifabutin increased by 881% when coadministered with darunavir\/ritonavir. Coadministration increased the AUC of darunavir by 57% and increased ritonavir AUC by 66%.<\/p>\n

A dose reduction of rifabutin by 75% (i.e., 150 mg every other day) and increased monitoring for rifabutin-related adverse events is warranted when coadministered with darunavir\/ritonavir.<\/p>\n

Ref: Sekar VJ, et al. Pharmacokinetic interaction between darunavir in combination with low-dose ritonavir and rifabutin. 48th ICAAC, 25-28 October 2008. Washington. Abstract H-4053.<\/p>\n

Maraviroc reduces raltegravir levels but no dose adjustment needed<\/h2>\n

The pharmacokinetics of raltegravir (400 mg twice daily) and maraviroc (300 mg twice daily) was assessed in 17 HIV- subjects. Coadministration decreased maraviroc AUC, Cmax and Cmin by 14%, 21% and 10%, respectively. Raltegravir AUC, Cmax and Cmin were decreased by 37%, 33% and 28%, respectively. In all subjects the maraviroc average concentration (AUC\/12) was greater than 100 ng\/ml, the apparent threshold for increased risk of virologic failure.<\/p>\n

The 28% decrease in raltegravir Cmin was not considered clinically relevant (only decreases above 60% are considered clinically relevant) and so no dose adjustments are recommended.<\/p>\n

Reference:<\/p>\n

Andrews E, et al. A pharmacokinetic study to evaluate an interaction between maraviroc and raltegravir in healthy adults. 48th ICAAC, 25-28 October 2008. Washington. Abstract H-4055.<\/p>\n","protected":false},"excerpt":{"rendered":"

Marta Boffito, HIV-druginterations.org The following summaries are selected from a longer report, available with hyperlinks to the conference abstracts, from www.hiv-druginteractions.org. Lopinavir\/r reduces gemfibrozil levels The effect of lopinavir\/ritonavir (400\/100 mg twice daily) on a single dose of the lipid …<\/p>\n","protected":false},"author":4,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4,34],"tags":[102],"class_list":["post-289","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-pk-and-drug-interactions","tag-icaac-48th-2008"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/289","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/users\/4"}],"replies":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/comments?post=289"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/289\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=289"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=289"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=289"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}