These include, but are not limited to, thromboembolism, allergic reactions, fatigue, and headache, and others could occur. There are other additional adverse effects. Ospemifene is a selective estrogen receptor modulator. As such, many of the effects produced by estrogens are produced by ospemifene. The boxed warning of the medication indicates ospemifene may thicken the endometrium, which could lead to unusual bleeding and endometrial cancer. For women taking estrogens, concurrently taking a type of drug called a progestin has been shown to decrease the occurrence of endometrial hyperplasia. In theory, progestins may be expected to attenuate ospemifenes effects on endometrial thickening. However clinical trials confirming this have not been conducted. Like estrogens, ospemifene also may increase the risk for cardiovascular events, including "stroke, coronary heart disease, venous thromboembolism," and others. The risk of thrombotic and hemorrhagic strokes is given as 0.72 and 1.45 per 1,000 women, while that of deep vein thrombosis is estimated to be 1.45 per 1,000 women. The risks of these adverse events in women taking ospemifene are lower than those in women taking estrogen alone in the form of oral conjugated estrogens. Studies have not documented the relative risk compared with women taking estrogen/progestin therapy. Pharmacology
Pharmacodynamics
Ospemifene is "an estrogen agonist/antagonist that makes vaginal tissue thicker and less fragile resulting in a reduction in the amount of pain women experience with sexual intercourse." This medication should be used for the shortest amount of time possible due to associated adverse effects.
Ospemifene might not have an adverse influence on coagulation, in contrast to estrogens and other SERMs like tamoxifen and raloxifene.A binding assay was also performed to measure the affinity of ospemifene for the estrogen receptor (ERα and ERβ). The study showed that ospemifene bound ERα and ERβ with similar affinity. Ospemifene bound the estrogen receptors with a lower affinity than estradiol. Ospemifene was shown to be an antagonist of "ERE-mediated transactivation on MCF-7 cells," which the authors concluded indicates "anti-estrogenic activity in breast cancer cells." Pharmacokinetics
The pharmacokinetics of ospemifene were dose-dependent over a dose range of 10 to 800 mg/day. History
Approval process
Hormos Medical Ltd., which is a part of QuatRx Pharmaceuticals, filed a patent on January 19, 2005, for a solid dosage form of ospemifene. In March 2010, QuatRX Pharmaceuticals licensed ospemifene to Shionogi & Co., Ltd. for clinical development and marketing. A New Drug Application (NDA) was submitted to the FDA on April 26, 2012. Amendments to the NDA were submitted in June, July, August, October, and November 2012, and January and February 2013. It was ultimately approved by the FDA on February 26, 2013. Ospemifene (under the brand name Senshio) was subsequently approved by the European Commission for marketing in the EU in January 2015. Preclinial and clinical trials
Preclinical trials were performed in ovariectomized rats to model menopause. Oral ospemifene was compared with raloxifene (another SERM), its metabolites 4-hydroxy ospemifene and 4-hydroxy ospemifene, estradiol, and ospemifene administered as an intravaginal suppository.