Ulipristal acetate for emergency contraception.

OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and safety of data of ulipristal acetate, a new emergency contraceptive approved for use up to 120 hours after unprotected intercourse. DATA SOURCES: Articles pertaining to the topic were identified and reviewed through searches of PubMed (1994-March 2011) and clinicaltrials.gov, using the key terms ulipristal and CDB-2914. Ella approval documents were obtained and reviewed from Drugs@FDA on the Food and Drug Administration (FDA) Web site. STUDY SELECTION AND DATA EXTRACTION: All published data and FDA approval documents examining pharmacologic, pharmacokinetic, and clinical studies related to ulipristal acetate as an emergency contraceptive were evaluated. Selected studies included 3 randomized trials and 1 meta-analysis. DATA SYNTHESIS: Ulipristal acetate is a progesterone agonist/antagonist emergency contraceptive approved for the prevention of pregnancy to be taken as soon as possible, within 120 hours after unprotected intercourse or a known or suspected contraceptive failure. Based upon results of the Phase 3 clinical trials used to obtain approval, ulipristal acetate administration was at least as effective as levonorgestrel in the reduction of pregnancy rate when studied alone after unprotected intercourse and when taken up to 120 hours after unprotected intercourse. Commonly reported adverse effects associated with ulipristal acetate in trials included headache, breast tenderness, nausea, and abdominal pain. CONCLUSIONS: Ulipristal acetate is effective as an emergency contraceptive for up to 120 hours after unprotected intercourse. Because ulipristal is available only via prescription, it may be covered by insurance. However, the additional factors of travel expenses and time to make and attend a physician appointment must be taken into account when considering use of ulipristal as an emergency contraceptive. Due to the similarity of its structure to mifepristone, controversy regarding ulipristal's mechanism of action has arisen.

Rivaroxaban for thromboprophylaxis in patients undergoing major orthopedic surgery.

OBJECTIVE: To review the pharmacology, pharmacokinetics, and clinical efficacy/safety profile of rivaroxaban to inform health-care professionals of this new agent for the prevention of venous thromboembolism (VTE) in patients undergoing major orthopedic surgery. DATA SOURCES: A literature search was performed in PubMed/MEDLINE (1966-March 2010), International Pharmaceutical Abstracts (1970-March 2010), and EMBASE (1990-March 2010), limited to publications in English, using the search terms BAY 59-7939, rivaroxaban, factor Xa inhibitor, hip replacement, and/or knee replacement to identify literature sources. References from retrieved articles were evaluated to identify relevant literature. Unpublished Phase 3 clinical trials in progress (using www.clinicaltrials.gov) were also reviewed. The Food and Drug Administration, European Medicines Agency, and Health Canada Web sites were used to retrieve product monographs, regulatory guidance, and advisory committee briefing packets. STUDY SELECTION AND DATA EXTRACTION: All available studies relevant to the pharmacology, pharmacokinetics, and clinical safety/efficacy of rivaroxaban for the prevention of VTE in patients undergoing major orthopedic surgery were included, with preference for clinical data. DATA SYNTHESIS: Rivaroxaban use was significantly more effective for thromboprophylaxis in patients undergoing total knee replacement (TKR) or total hip replacement (THR), compared to enoxaparin for the composite incidence of deep vein thrombosis, nonfatal pulmonary embolism, all-cause mortality, and the rate of major VTE; bleeding events occurred at statistically similar rates. In Phase 3 studies, rivaroxaban 10 mg was administered orally 6-8 hours post-surgery and post-hemostasis. Thereafter, administration was once daily for 35 days in THR and 10-14 days in TKR. CONCLUSIONS: Rivaroxaban has demonstrated comparable safety and superior efficacy to the commonly used low-molecular-weight heparin, enoxaparin. Ongoing and future clinical trials will allow clinicians to further assess the efficacy, safety, and pharmacoeconomics of rivaroxaban.