Design Features of Drug–Drug Interaction Trials Between Antivirals and Oral Contraceptives

Abstract

The aim of this work was to explore the major design features of drug-drug interaction trials between antiviral medications (AVs) and oral contraceptives (OCs). Information on these trials (n = 27) was collected from approved drug labels and clinical pharmacology reviews conducted by the U.S. Food and Drug Administration. The primary objective of all trials was to evaluate changes in OC exposure following the coadministration of AVs. In addition, an evaluation of potential pharmacodynamic interaction was performed in 10 of these trials. Twenty-two trials were open label with a fixed-sequence design, and 5 trials used a double-blind crossover design. The trials were conducted using one, two, or three 28-day ovulatory cycles in 10, 8, and 9 trials, respectively. Only 1 trial enrolled HIV-infected women. The median number of women in a trial was 20 (range, 12 to 52). Norethindrone/ethinyl estradiol (EE) combination was the most commonly used OC (n = 16, 59%) followed by norgestimate/EE (n = 9, 33%). Labeling recommendations were based on exposure changes in 25 cases and on safety observations in the trial in 2 cases. In conclusion, a wide variety of trial designs was used, and there is no preferred design. The answer to the exposure question can be achieved using multiple designs.

Drug‐Drug Interaction Studies With Oral Contraceptives: Pharmacokinetic/Pharmacodynamic and Study Design Considerations

“…7 Some of them have reviewed the design aspects of COC DDI studies. 8,9 There are also health authority guideline documents that outline the general recommendations for the evaluation of the potential for DDIs. The FDA guidance for labeling for COCs provides a section on drug interactions with information on drugs for which data on drug interactions with COCs are available.…”

“…Over the years, a few reviews on the drug interactions of COCs with certain classes of drugs such as antibiotics, antivirals, antifungals, and antiepileptics have been published 7 . Some of them have reviewed the design aspects of COC DDI studies 8,9 . There are also health authority guideline documents that outline the general recommendations for the evaluation of the potential for DDIs.…”

Interactive Design of Online Oral Training in University English Teaching

“…Multimedia computer combines sounds, images and words organically to form an integrated textbook, transforming the monotonous and boring traditional textbooks into vivid, intuitive and concrete modern online teaching contents, and establishing the teaching mode of "watching, listening and speaking" for students in English class. Writing comprehensive training has been strengthened, humanistic education ideas have been penetrated, and it is possible to make full use of modern network teaching methods to create a good language environment (Ayala et al, 2016). The Internet age not only brings new challenges to oral English teaching, but also provides a new way of thinking and means.…”

Confirmation of the Drug–drug Interaction Potential between Cobicistat-boosted Antiretroviral Regimens and Hormonal Contraceptives

“…Their disposition may also be influenced by efflux transporters such as P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) [6]. Drug–drug interactions (DDIs) between hormonal contraceptives and ARVs are well documented in the literature [7–12] and are of significance for certain agents, including ritonavir (RTV)-boosted protease inhibitors (PIs) and some non-nucleoside reverse transcriptase inhibitors (NNRTIs) as many are inhibitors or inducers of these metabolic and/or transport pathways [13,14].…”