{"id":30007,"date":"2016-06-01T09:09:05","date_gmt":"2016-06-01T09:09:05","guid":{"rendered":"http:\/\/i-base.info\/htb\/?p=30007"},"modified":"2016-06-07T19:19:19","modified_gmt":"2016-06-07T19:19:19","slug":"doravirine-can-be-co-administered-with-oral-contraceptives","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/30007","title":{"rendered":"Doravirine can be co-administered with oral contraceptives"},"content":{"rendered":"

\"Women's<\/a>Polly Clayden, HIV i-Base<\/strong><\/p>\n

Multiple dosing with doravirine does not change the plasma pharmacokinetics (PK) of a single dose of ethinyl estradiol (EE) or levonorgestrel (LNG) to a clinically important extent, according to data shown at the 6th International Workshop on HIV and Women.<\/strong><\/p>\n

Doravirine is a novel non-nucleoside reverse transcriptase inhibitor with an anticipated once daily dose of 100 mg. This drug is primarily metabolised by CYP3A4 but shows no inhibitory or inductive potential on CYP3A4-mediated metabolism in clinical studies. Doravirine has shown no interaction with the enzymes responsible for the metabolism of either EE or LNG.<\/p>\n

Investigators from Merck conducted a study to assess the effect of doravirine on the plasma PK of an EE and LNG-containing oral contraceptive.<\/p>\n

The study was an open-label, two-period, fixed-sequence design with a seven-day washout between Periods 1 and 2, conducted in HIV negative women. In Period 1 participants received a single oral dose of 0.03 mg EE\/0.15 mg LNG. In Period 2 they received 100 mg doravirine once daily for 17 days, with a single dose of EE\/LNG co-administered with doravirine on day 14.<\/p>\n

The study enrolled 20 post menopausal or oophorectomised women aged 42-65 years. Plasma samples were taken for up to 96 hours post dose in each period.<\/p>\n

The investigators reported no serious adverse events (AEs) during the study. One participant discontinued due to a non-serious AE, not considered to be related to any study drug.<\/p>\n

Twelve participants reported 27 post dose clinical AEs: three were considered to be associated with study drugs, two doravine (mild erythematous rash, oral herpes) and one both doravirine and EE\/LNG (nervousness). One participant reported one laboratory AE associated with both doravirine and EE\/LNG (red blood cells in urine). All AEs were transient and judged to be mild or moderate.<\/p>\n

The geometric mean ratio (GMR) for EE, EE\/LNG + doravirine: EE\/LNG was: 0.98 (90% CI 0.94-1.03) for AUC0-inf and 0.83 (90% CI 0.80-0.87) for Cmax. GMR for LNG, EE\/LNG + doravirine: 1.21 (90% CI 1.14-1.28) for AUC0-inf and 0.96 (90% CI 0.88-1.05) for Cmax.<\/p>\n

Although the upper bound of the 90% CI for LNG AUC0-inf was outside the pre-specified bioequivalence interval (0.80-1.25), the investigators noted that the 90% CI for AUC0-last fell within the bounds: GMR 1.15 (90% CI 1.10-1.21). Although the upper bound of the 90% CI for LNG AUC0-inf slightly exceeded 1.25, this slight mean increase of 21% would not be expected to affect the efficacy of EE\/LNG.<\/p>\n

The investigators also reported that although bioequivalence criteria were met for Cmax of EE coadministered with doravirine, 8 out of 19 participants had individual GMR ratios below 0.80 – they suggested that this was unlikely to have a clinically significant effect on the contraceptive efficacy of OC\/LNG as this is dependent on the progesterone component of the combined pill. The investigators did not observe corresponding reduction in either AUC parameter.<\/p>\n

As a result of this PK evaluation there are no restrictions in the use of oral contraceptives in the phase 3 trials of doravirine.<\/p>\n

Reference:<\/p>\n

Anderson M et al. Effect of doravirine (MK-1439) on the pharmacokinetics of oral contraceptive (ethinyl estradiol [EE] and levonorgestrol [LNG]). 6th International Workshop on HIV & Women. 20-21 February 2016. Boston. Poster abstract 19.<\/p>\n\n","protected":false},"excerpt":{"rendered":"

Polly Clayden, HIV i-Base Multiple dosing with doravirine does not change the plasma pharmacokinetics (PK) of a single dose of ethinyl estradiol (EE) or levonorgestrel (LNG) to a clinically important extent, according to data shown at the 6th International Workshop …<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4,44],"tags":[220],"class_list":["post-30007","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-womens-health","tag-intl-workshop-on-hiv-and-women-6th-2016"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/30007","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\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/comments?post=30007"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/30007\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=30007"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=30007"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=30007"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}