{"id":2892,"date":"2006-12-06T23:03:55","date_gmt":"2006-12-06T22:03:55","guid":{"rendered":"http:\/\/moomango.co.uk\/htb\/?p=2892"},"modified":"2013-12-06T15:20:40","modified_gmt":"2013-12-06T15:20:40","slug":"drug-interactions-with-darunavir-tmc-114","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/2892","title":{"rendered":"Drug interactions with darunavir (TMC-114)"},"content":{"rendered":"

Simon Collins, HIV i-Base<\/strong><\/p>\n

An overview of clinical studies of drug interactions with the protease inhibitor darunavir (TMC-114), already approved in the US, was given in an oral presentation by David Back.<\/strong><\/p>\n

TMC114\/r was studied with atazanavir (ATV), indinavir (IDV), lopinavir\/r (LPV\/r), saquinavir\/r (SQV\/r), efavirenz (EFV), nevirapine (NVP), tenofovir disoproxil fumarate (TDF), atorvastatin (AVS), omeprazole (OME), ranitidine (RAN), sildenafil (SIL), clarithromycin (CLA), sertraline (SER), paroxetine (PAR), oral contraceptives (OC) and ketoconazole (KTZ).<\/p>\n

Results are summarised in Table 1 below. TMC114\/r increased exposure to EFV (21%), NVP (27%), TDF (22%), IDV (23%), LPV (37%), KTZ (212%), CLA (57%), AVS and SIL (4-fold), and decreased exposure to SER (49%), PAR (39%) and ethinyl estradiol (44%). There was no change in ATV or SQV. TMC114 exposure increased by 21%, 24% and 42%, respectively, when combined with TDF, IDV and KTZ, decreased by 13%, 13%, 26% and 53%, respectively, when combined with EFV, CLA, SQV\/r and LPV\/r, and was unchanged when combined with ATV, NVP, AVS, OME, RAN, SER and PAR.<\/p>\n

The study concluded that combining TMC114\/r with LPV\/r or SQV\/r is not recommended and that some co-administered drugs may require dose adjustments (SIL, AVS, KTZ and IDV). Additional contraception should be used when OC are combined with TMC114\/r.<\/p>\n

Table 1: Summary of drug interaction studies with darunavir (TMC-114)<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
<\/th>\nInteraction effect with TMC-114<\/th>\nRecommendation<\/th>\n<\/tr>\n
ARVs<\/th>\n<\/tr>\n
Efavirenz<\/td>\nEFV increased by 21%. TMC-144 decreased by 13%<\/td>\nNot clinically relevant<\/td>\n<\/tr>\n
Nevirapine<\/td>\nNVP increased by 27%. TMC-144 no change<\/td>\nNot clinically relevant<\/td>\n<\/tr>\n
Tenofovir<\/td>\nTDF increased by 22%. TMC-144 increased by 21%<\/td>\nNot clinically relevant<\/td>\n<\/tr>\n
Indinavir<\/td>\nIDV increased by 23%. TMC-144 increased by 24%<\/td>\nConsider TDM for IDV<\/td>\n<\/tr>\n
Lopinavir\/r<\/td>\nLPV increased by371%. TMC-144 decreased by 53%<\/td>\nDo no coadminister<\/td>\n<\/tr>\n
Saquinavir<\/td>\nSQV no change. TMC-144 decreased by 26%<\/td>\nDo no coadminister<\/td>\n<\/tr>\n
Atazanavir<\/td>\nATV no change. TMC-144 no change.<\/td>\nNo interaction<\/td>\n<\/tr>\n
Antibiotics<\/th>\n<\/tr>\n
Ketaconazole<\/td>\nKTZ increased by 212%. TMC-144 increased by 41%.<\/td>\nConsider reducing KTZ<\/td>\n<\/tr>\n
Clarithromycin<\/td>\nCLA increased by 57%. TMC-144 decreased by 13%.<\/td>\nOnly relevant with renal impairment<\/td>\n<\/tr>\n
SSRI’s<\/th>\n<\/tr>\n
SER<\/td>\nSER AUC decreased by 49%. TMC-144 no change.<\/td>\nMonitor clinically, titrate SSRI<\/td>\n<\/tr>\n
PAR<\/td>\nPAR AUC decreased by 39%. TMC-144 no change.<\/td>\nMonitor clinically, titrate SSRI<\/td>\n<\/tr>\n
Other<\/th>\n<\/tr>\n
Atorvastatin<\/td>\nAVS increased by 400%. TMC-144 no change.<\/td>\nStart with lowest AVS dose<\/td>\n<\/tr>\n
Pravastatin<\/td>\nPVS increased by 81% (23-166%).<\/td>\nStart with lowest PVS dose<\/td>\n<\/tr>\n
Sildenafil<\/td>\nSIL increased by 400%.<\/td>\nReduce SIL dose<\/td>\n<\/tr>\n
Ethinyl estradiol<\/td>\nEE exposure decreased by 44%.<\/td>\nUse other contraception<\/td>\n<\/tr>\n
Ranitedine<\/td>\nTMC-114 no change.<\/td>\nNo dosing change<\/td>\n<\/tr>\n
Omeprazole<\/td>\nTMC-114 no change.<\/td>\nNo dosing change<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Reference:<\/p>\n

D Back, V Sekar, E Lefebvre et al. Use of TMC114 in combination with other drugs: guidance from pharmacokinetic studies. 8th International Congress on Drug Therapy in HIV Infection, 12-16 November 2006, Glasgow. Oral abstract PL5.1.<\/p>\n","protected":false},"excerpt":{"rendered":"

Simon Collins, HIV i-Base An overview of clinical studies of drug interactions with the protease inhibitor darunavir (TMC-114), already approved in the US, was given in an oral presentation by David Back. TMC114\/r was studied with atazanavir (ATV), indinavir (IDV), …<\/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":[84],"class_list":["post-2892","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-pk-and-drug-interactions","tag-hiv-8-glasgow-2006"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/2892","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=2892"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/2892\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=2892"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=2892"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=2892"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}