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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