Darunavir Interactions with Lopinavir/Ritonavir, Contraceptives, and Erectile Dysfunction Drugs By Liz Highleyman The
novel non-peptide protease inhibitor
(PI) darunavir (Prezista; formerly TMC114) was approved
this past June as a component of antiretroviral therapy for heavily treatment-experienced
patients. Study 1 In the first study, researchers assessed the pharmacokinetic interactions between darunavir, with or without low-dose ritonavir (Norvir), and lopinavir/ritonavir (Kaletra). The study consist of panels of 16 subjects receiving different antiretroviral regimens in varying sequences (regimens included background agents in addition to the PIs):
On Day 14 of each treatment, 12-hour pharmacokinetic profiles of ritonavir, darunavir, and/or lopinavir were determined. Results
The
researchers concluded that, "The combination of lopinavir/ritonavir and darunavir
is not recommended, as exposure to darunavir is significantly decreased when combined
with lopinavir/ritonavir, which is expected to be clinically relevant." The second study investigated interactions between darunavir and birth control pills containing forms of estrogen (ethinyl estradiol) and progestin (norethindrone). The study included 18 healthy HIV negative women who had taken 0.035 mg ethinyl estradiol plus 1.0 mg norethindrone (components of the Ortho-Novum 1/35 pill) for at least 4 weeks. Subjects took Ortho-Novum for 21 days, then added darunavir/ritonavir 600/100 mg twice-daily. Results
"This pharmacokinetic interaction is considered to be clinically relevant since ethinyl estradiol concentrations are considerably reduced when darunavir/ritonavir is co-administered with Ortho-Novum," the researchers concluded. "Alternative or additional contraceptive measures should to be used when estrogen-based contraceptives are co-administered with darunavir/ritonavir." Study 3 Finally, researchers looked at interactions between darunavir and sildenafil (Viagra), a drug used to treat erectile dysfunction. The study assessed the effect of multiple doses of darunavir/ritonavir on the pharmacokinetics of sildenafil and its metabolite, N-desmethyl sildenafil. Sixteen healthy HIV negative volunteers received 2 treatments: a single 100 mg dose of sildenafil, and darunavir/ritonavir 400/100 mg twice-daily for 8 days with a single 25 mg dose of sildenafil co-administered on Day 7. Results
"Sildenafil exposure is increased in the presence of darunavir/ritonavir," the researchers concluded. "A dose adjustment for sildenafil is warranted; no more than 25 mg sildenafil is recommended over a 48-hour period when co-administered with darunavir/ritonavir." Similar types of interactions are expected with the related erectile dysfunction drugs vardenafil (Levitra) and tadalafil (Cialis). Taken together, these studies show that darunavir/ritonavir shares some of the same drug interactions seen with other PIs metabolized by the CYP3A4 enzyme. Patients should discuss potential drug-drug interactions with their physician, and tell their healthcare providers about all other drugs they are using (prescription, over-the-counter, recreational, or herbal). References V Sekar, E Lefebvre, G Boogaerts, and other. Pharmacokinetic interaction between the protease inhibitors TMC114 and lopinavir/ritonavir. 46th ICAAC. San Francisco, CA. September 27-30, 2006. Abstract A-367. V Sekar, E Lefebvre, E Felicione, and others. Pharmacokinetic interaction between ethinyl estradiol, norethindrone and TMC114, a new protease inhibitor. 46th ICAAC. Abstract A-368. V Sekar, E Lefebvre, T De Marez, and others. Pharmacokinetic interaction between TMC114, a new protease inhibitor, and sildenafil. 46th ICAAC. Abstract A-369.
|
| |
|
