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OSPHENA (ospemifene) tablet-治疗女性性交疼痛
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OSPHENA (ospemifene) tablet, film coated
[Shionogi Inc.]
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use OSPHENA safely and effectively. See full prescribing information for OSPHENA.
OSPHENATM (ospemifene) tablets, for oral use
Initial U.S. Approval: 2013
WARNING: ENDOMETRIAL CANCER AND
CARDIOVASCULAR DISORDERS
See full prescribing information for complete boxed warning.
OSPHENA is an estrogen agonist/antagonist with tissue selective effects. In the endometrium, OSPHENA has estrogen agonistic effects. There is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens. Adding a progestin to estrogen therapy reduces the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer. [see Warnings and Precautions (5.2)].
Estrogen-alone therapy has an increased risk of stroke and deep vein thrombosis (DVT). OSPHENA 60 mg had cerebral thromboembolic and hemorrhagic stroke incidence rates of 0.72 and 1.45 per thousand women, respectively vs. 1.04 and 0 per thousand women, respectively in placebo. For deep vein thrombosis, the incidence rate for OSPHENA 60 mg is 1.45 per thousand women vs. 1.04 per thousand women in placebo [see Warnings and Precautions (5.1)].
INDICATIONS AND USAGE
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 (1
DOSAGE AND ADMINISTRATION
One tablet taken orally once daily with food (2.1)
DOSAGE FORMS AND STRENGTHS
Tablet: 60 mg (3)
CONTRAINDICATIONS
Undiagnosed abnormal genital bleeding (4)
Known or suspected estrogen-dependent neoplasia (4, 5.2)
Active DVT, pulmonary embolism (PE), or a history of these conditions (4, 5.1)
Active arterial thromboembolic disease (for example, stroke and myocardial infarction [MI]), or a history of these conditions (4, 5.1)
Known or suspected pregnancy (4, 8.1)
WARNINGS AND PRECAUTIONS
Venous Thromboembolism: Risk of DVT and pulmonary embolism (5.1)
Known, suspected, or history of breast cancer (5.2)
Severe Hepatic Impairment (5.3, 8.7, 12.3)
ADVERSE REACTIONS
Adverse reactions (≥1 percent) include: hot flush, vaginal discharge, muscle spasms, genital discharge, hyperhidrosis. (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Shionogi Inc. at 1-855-OSPHENA (1-855-677-4362) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
DRUG INTERACTIONS
Do not use estrogens or estrogen agonist/antagonist concomitantly with OSPHENA (7.1,12.3)
Do not use fluconazole concomitantly with OSPHENA. Fluconazole increases serum concentrations of OSPHENA (7.2, 12.3)
Do not use rifampin concomitantly with OSPHENA. Rifampin decreases serum concentration of OSPHENA (7.2, 12.3)
USE IN SPECIFIC POPULATIONS
Nursing Mothers: It is not known whether OSPHENA is excreted in human breast milk (8.3)
See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.
Revised: 02/2013
Back to Highlights and Tabs
FULL PRESCRIBING INFORMATION: CONTENTS*
WARNING: ENDOMETRIAL CANCER AND CARDIOVASCULAR DISORDERS
1. INDICATIONS AND USAGE
2. DOSAGE AND ADMINISTRATION
2.1 Treatment of Moderate to Severe Dyspareunia, a Symptom of Vulvar and Vaginal Atrophy, due to Menopause
3. DOSAGE FORMS AND STRENGTHS
4. CONTRAINDICATIONS
5. WARNINGS AND PRECAUTIONS
5.1 Cardiovascular Disorders
5.2 Malignant Neoplasms
5.3 Severe Hepatic Impairment
6. ADVERSE REACTIONS
6.1 Clinical Trials Experience
7. DRUG INTERACTIONS
7.1 Estrogens and estrogen agonist/antagonist
7.2 Fluconazole
7.3 Rifampin
7.4 Ketoconazole
7.5 Warfarin
7.6 Highly Protein-Bound Drugs
7.7 Multiple Enzyme Inhibition
8. USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
8.3 Nursing Mothers
8.4 Pediatric Use
8.5 Geriatric Use
8.6 Renal Impairment
8.7 Hepatic Impairment
10. OVERDOSAGE
11. DESCRIPTION
12. CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
12.3 Pharmacokinetics
13. NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
14. CLINICAL STUDIES
16. HOW SUPPLIED/STORAGE AND HANDLING
16.1 How Supplied
16.2 Storage and Handling
17. PATIENT COUNSELING INFORMATION
17.1 Hot Flashes or Flushes
17.2 Vaginal Bleeding
*
Sections or subsections omitted from the full prescribing information are not listed.
FULL PRESCRIBING INFORMATION
WARNING: ENDOMETRIAL CANCER AND CARDIOVASCULAR DISORDERS
Endometrial Cancer
OSPHENA is an estrogen agonist/antagonist with tissue selective effects. In the endometrium, OSPHENA has estrogen agonistic effects. There is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens. Adding a progestin to estrogen therapy reduces the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer. Adequate diagnostic measures, including directed and random endometrial sampling when indicated, should be undertaken to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding [see Warnings and Precautions (5.2)].
Cardiovascular Disorders
There is a reported increased risk of stroke and deep vein thrombosis (DVT) in postmenopausal women (50 to 79 years of age) who received daily oral conjugated estrogens (CE) [0.625 mg]-alone therapy over 7.1 years as part of the Women’s Health Initiative (WHI) [see Warnings and Precautions (5.1)].
In the clinical trials for OSPHENA (duration of treatment up to 15 months), the incidence rates of thromboembolic and hemorrhagic stroke were 0.72 and 1.45 per thousand women, respectively in OSPHENA 60 mg treatment group and 1.04 and 0 in placebo [see Warnings and Precautions (5.1)]. The incidence of DVT was 1.45 per thousand women in OSPHENA 60 mg treatment group and 1.04 per thousand women in placebo [see Warnings and Precautions (5.1)]. OSPHENA should be prescribed for the shortest duration consistent with treatment goals and risks for the individual woman.
1. INDICATIONS AND USAGE
OSPHENA is indicated for the treatment of moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy, due to menopause.
2. DOSAGE AND ADMINISTRATION
OSPHENA is an estrogen agonist/antagonist which has agonistic effects on the endometrium. Generally, when a product with estrogen agonistic effects on the endometrium is prescribed for a postmenopausal woman with a uterus, a progestin should be considered to reduce the risk of endometrial cancer. A woman without a uterus does not need a progestin [see Warnings and Precautions (5.2)].
Use of OSPHENA should be for the shortest duration consistent with treatment goals and risks for the individual woman. Postmenopausal women should be re-eva luated periodically as clinically appropriate to determine if treatment is still necessary.
2.1 Treatment of Moderate to Severe Dyspareunia, a Symptom of Vulvar and Vaginal Atrophy, due to Menopause
Take one 60 mg tablet with food once daily.
3. DOSAGE FORMS AND STRENGTHS
OSPHENA tablets are white to off-white, oval, biconvex, film coated tablets containing 60 mg of ospemifene and engraved with “60” on one side.
4. CONTRAINDICATIONS
OSPHENA is contraindicated in women with any of the following conditions:
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Undiagnosed abnormal genital bleeding
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Known or suspected estrogen-dependent neoplasia
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Active DVT, pulmonary embolism (PE), or a history of these conditions
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Active arterial thromboembolic disease [for example, stroke and myocardial infarctions (MI)], or a history of these conditions
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OSPHENA is contraindicated in women who are or may become pregnant. OSPHENA may cause fetal harm when administered to a pregnant woman. Ospemifene was embryo-fetal lethal with labor difficulties and increased pup deaths in rats at doses below clinical exposures, and embryo-fetal lethal in rabbits at 10 times the clinical exposure based on mg/m2. If this drug is used during pregnancy, or if a woman becomes pregnant while taking this drug, she should be apprised of the potential hazard to a fetus.
5. WARNINGS AND PRECAUTIONS
5.1 Cardiovascular Disorders
Risk factors for cardiovascular disorders, arterial vascular disease (for example, hypertension, diabetes mellitus, tobacco use, hypercholesterolemia, and obesity) and/or venous thromboembolism (VTE) (for example, personal history or family history of VTE, obesity, and systemic lupus erythematosus), should be managed appropriately.
Stroke
In the WHI estrogen-alone substudy, a statistically significant increased risk of stroke was reported in women 50 to 79 years of age receiving daily CE (0.625 mg)-alone compared to women in the same age group receiving placebo (45 versus 33 per ten thousand women-years). The increase in risk was demonstrated in year 1 and persisted.
In the clinical trials for OSPHENA (duration of treatment up to 15 months), the incidence rates of thromboembolic and hemorrhagic stroke were 0.72 and 1.45 per thousand women, respectively in OSPHENA 60 mg treatment group and 1.04 and 0 per thousand women in placebo.
Should thromboembolic or hemorrhagic stroke occur or be suspected, OSPHENA should be discontinued immediately.
Coronary Heart Disease
In the WHI estrogen-alone substudy, no overall effect on coronary heart disease (CHD) events (defined as nonfatal MI, silent MI, or CHD death) was reported in women receiving estrogen-alone compared to placebo. In the OSPHENA clinical trials, a single MI occurred in a woman receiving 60 mg of ospemifene.
Venous Thromboembolism
In the WHI estrogen-alone substudy, the risk of VTE (DVT and PE), was increased for women receiving daily CE (0.625 mg)-alone compared to placebo (30 versus 22 per ten thousand women-years), although only the increased risk of DVT reached statistical significance (23 versus 15 per ten thousand women-years). The increase in VTE risk was demonstrated during the first 2 years.
In the OSPHENA clinical trials, the incidence of DVT was 1.45 per thousand women in OSPHENA 60 mg treatment group and 1.04 per thousand women in placebo. Should a VTE occur or be suspected, OSPHENA should be discontinued immediately.
If feasible, OSPHENA should be discontinued at least 4 to 6 weeks before surgery of the type associated with an increased risk of thromboembolism, or during periods of prolonged immobilization.
5.2 Malignant Neoplasms
Endometrial Cancer
OSPHENA is an estrogen agonist/antagonist with tissue selective effects. In the endometrium, OSPHENA has agonistic effects. In the OSPHENA clinical trials (60 mg treatment group), no cases of endometrial cancer were seen with exposure up to 52 weeks. There was a single case of simple hyperplasia without atypia. Endometrial thickening equal to 5 mm or greater was seen in the OSPHENA treatment groups at a rate of 60.1 per thousand women vs. 21.2 per thousand women for placebo. The incidence of any type of proliferative (weakly plus active plus disordered) endometrium was 86.1 per thousand women in OSPHENA vs. 13.3 per thousand women for placebo. Uterine polyps occurred at an incidence of 5.9 per thousand women vs. 1.8 per thousand women for placebo.
An increased risk of endometrial cancer has been reported with the use of unopposed estrogen therapy in a woman with a uterus. The reported endometrial cancer risk among unopposed estrogen users is about 2 to 12 times greater than in non-users, and appears dependent on duration of treatment and on estrogen dose. Most studies show no significant increased risk associated with the use of estrogens for less than 1 year. The greatest risk appears to be associated with prolonged use, with increased risks of 15- to 24-fold for 5 to 10 years or more. This risk has been shown to persist for at least 8 to 15 years after estrogen therapy is discontinued. Adding a progestin to postmenopausal estrogen therapy has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer. There are, however, possible risks that may be associated with the use of progestins with estrogens compared to estrogen-alone regimens. These include an increased risk of breast cancer. The use of progestins with OSPHENA therapy was not eva luated in the clinical trials.
Clinical surveillance of all women using OSPHENA is important. Adequate diagnostic measures, including directed or random endometrial sampling when indicated, should be undertaken to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding.
Breast Cancer
OSPHENA 60 mg has not been adequately studied in women with breast cancer; therefore it should not be used in women with known or suspected breast cancer or with a history of breast cancer.
6. ADVERSE REACTIONS
The following serious adverse reactions are discussed elsewhere in the labeling:
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The safety of OSPHENA has been assessed in nine phase 2/3 trials (N=1892) with doses ranging from 5 to 90 mg per day. The duration of treatment in these studies ranged from 6 weeks to 15 months. Most women (N=1370) had a treatment period of at least 12 weeks, 409 had at least 52 weeks (1 year) of exposure.
The incidence rates of thromboembolic and hemorrhagic stroke were 0.72 per thousand women (1 reported case of thromboembolic stroke) and 1.45 per thousand women (2 reported cases of hemorrhagic stroke), respectively in OSPHENA 60 mg treatment group and 1.04 and 0 per thousand women, respectively in placebo. The incidence of deep vein thrombosis (DVT) was 1.45 per |
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