Transcript osphena
Osphena™ - Ospemifene Manufacturer: Shionogi INC FDA Approval Date: 02/26/13 Osphena™ - Ospemifene Clinical Application • Indications: • Treatment of moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy, due to menopause. • Place in therapy: • Monotherapy for those patients receiving no benefits using other estrogen therapies • Continue to have painful intercourse after menopause Osphena™ - Ospemifene Clinical Application • Contraindications: • Pregnancy • Active DVT • Pulmonary embolism • History of these conditions • Black Box warnings: None • Precautions: • Use of unopposed estrogen in women with an intact uterus is associated with an increased risk of endometrial cancer. • An increased risk of DVT and stroke reported with oral conjugated estrogens Osphena™ - Ospemifene Clinical Application • Pregnancy: • Category X • Lactation: • Excretion in breast milk unknown • Use is not recommended Osphena™ - Ospemifene Drug Facts • Pharmacology: • A selective estrogen receptor modulator (SERM) • Osphena has agonistic effects on the endometrium • Induces changes to the vaginal epithelium • Decreases vaginal pH Osphena™ - Ospemifene Drug Facts • Pharmacokinetics: • • • • A – Tmax 2h; absorption affected by food D – protein binding >99% bound to serum proteins M – Hepatic via CYP3A4, 2C9, and 2C19 E – Feces (75%); urine (7%; <0.2% as unchanged drug. Elimination t1/2 26 h Osphena™ - Ospemifene Drug Interactions • Drug Interactions – Object Drugs: • Fluconazole (2.7 fold • Ketoconazole (1.4 fold) • Rifampin (58%) Osphena™ - Ospemifene Drug Interactions • Drug Interactions – Precipitant Drugs: • Fluconazole (2.7 fold • Ketoconazole (1.4 fold) • Rifampin (58%) Osphena™ - Ospemifene Adverse Effects • Common Adverse Effects: • • • • Hot flushes (7.5%)[2.6%] Muscle spasm (3.2%)[0.9%] Vaginal discharge (3.8%)[0.3%] Hyperhidrosis (1.6%)[0.6%] • Serious Adverse Effects: • DVT • Hemorrhagic stroke • Thromboembolic stroke Osphena™ - Ospemifene Monitoring Parameters • Efficacy Monitoring: • None recommended • Toxicity Monitoring: • Signs of endometrial cancer in female patients with uterus. • Assess need for therapy at regular intervals. • Signs/symptoms of stroke and VTE Osphena™ - Ospemifene Prescription Information • Dosing: • 60mg orally once daily with food • Cost: $189 • Source: Medi-Span (via Lexi-comp online) • Accessed 03/31/2014 Osphena™ - Ospemifene Literature Review • A randomized, double-blind, parallel-group design to compare • The efficacy, safety, and tolerability of oral ospemifene 60 mg/day versus placebo Portman et al. Menopause 2013; 20(6):623-630 Osphena™ - Ospemifene Literature Review • Primary endpoints: • Change from baseline to week 12 of the following: • • • • Percentage of parabasal cells Percentage of superficial cells Vaginal pH Severity of the most bothersome symptom (MBS) • Secondary Endpoint: • Change in the severity of dyspareunia Portman et al. Menopause 2013; 20(6):623-630 Osphena™ - Ospemifene Literature Review • N = 605 • Inclusion criteria: • Postmenopausal women between 40-80 years • Negative Pap test result / lacked an intact cervix • Negative mammogram result < 9 months before randomization • Normal breast examination result at screening • Exclusion criteria: • BMI of >37 kg/m2 • Vaginal infection requiring medication • Strong CYP 3A4 inhibitors Portman et al. Menopause 2013; 20(6):623-630 Osphena™ - Ospemifene Literature Review Portman et al. Menopause 2013; 20(6):623-630 Osphena™ - Ospemifene Literature Review Portman et al. Menopause 2013; 20(6):623-630 Osphena™ - Ospemifene Literature Review Mean (SD) change from baseline to week 12/last observation carried forward in the percentage of parabasal cells in the ITT and PP populations. P < 0.0001 versus placebo Mean (SD) change from baseline to week 12/last observation carried forward in the vaginal pH of the ITT and PP populations. P < 0.0001 versus placebo. Portman et al. Menopause 2013; 20(6):623-630 Osphena™ - Ospemifene Literature Review Mean (SD) change from baseline to week 12/last observation carried forward in the percentage of superficial cells in the ITT and PP populations. P < 0.0001 versus placebo Mean (SD) change from baseline to week 12/last observation carried forward in the MBS severity scores of the ITT and PP populations. P = 0.0001 versus placebo. P = 0.0004 Portman et al. Menopause 2013; 20(6):623-630 Osphena™ - Ospemifene Literature Review • 12 weeks of treatment with ospemifene 60 mg/day induced statistically significant beneficial changes: • Parabasal cells decreased by 40.2% • Superficial cells increased by 12.3% • Compared with a 0% reduction and a 1.7% increase in the placebo group; P < 0.0001 • Vaginal pH decreased by -0.94 • Compared with -0.07 in the placebo group; P < 0.0001 • Self-reported MBS severity score of dyspareunia decreased by -1.5 • Compared with -1.2 in the placebo group; P = 0.0001 Portman et al. Menopause 2013; 20(6):623-630 Osphena™ - Ospemifene Literature Review • Study Conclusion: • Ospemifene 60 mg/day vs placebo effectively • Reduces the physiological signs of VVA and dyspareunia in postmenopausal women • Did not induce significant estrogenic effects on endometrial tissue • Reduction in nonhormonal lubricant use • The first oral alternative to vaginal estrogens for the treatment of dyspareunia associated with VVA Portman et al. Menopause 2013; 20(6):623-630 Osphena™ - Ospemifene Summary • Osphena is an estrogen agonist/antagonist indicated for the treatment of moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy, due to menopause • Osphena selectively binds to estrogen receptors, inducing changes to the vaginal epithelium and decreasing vaginal pH • There is an increased risk of endometrial cancer in women with a uterus who uses unopposed estrogens • The recommended daily dose is 60mg tablet taken orally once daily with food • The most common side effects include hot flushes, genital discharge, and muscle spasms • Osphena may be used as a monotherapy in those patients that have had no benefits using other estrogen therapies and continue to have painful intercourse after menopause Portman et al. Menopause 2013; 20(6):623-630 Osphena™ - Ospemifene References 1. http://www.osphena.com 2. Osphena package insert. Shionogi INC. Feb 2013. 3. Osphena. Lexicomp Drug Information. Accessed through UpToDate. Accessed on March 30, 2014 4. Portman DJ, Bachmann GA, Simon JA, et al. Ospemifene, a Novel Selective Estrogen Receptor Modulator for Treating Dyspareunia Associated with Postmenopausal Vulvar and Vaginal Atrophy. Menopause 2013; 20(6):623-630 5. Tan O, Bradshaw K, and Carr BR, "Management of Vulvovaginal Atrophy-Related Sexual Dysfunction in Postmenopausal Women: An Up-to-Date Review. Menopause 2012; 19(1):109-17