Osphena (Ospemifene) is a selective estrogen receptor modulator. It activates estrogen receptors in certain tissues while simultaneously blocks estrogen receptors in other tissues. It has been approved for the treatment of vaginal atrophy manifesting primarily as painful sexual intercourse and vaginal dryness.

Osphena (Ospemifene) Uses:

• Dyspareunia:

  • Used for treatment of moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy (VVA), due to menopause

• Vaginal dryness:

  • Used for treatment of moderate to severe vaginal dryness, symptoms of VVA, associated with menopause

Note:

• The International Society for the Study of Women’s Sexual Health and The North American Menopause Society has endorsed the term genitourinary syndrome of menopause (GSM) as new terminology for vulvovaginal atrophy.
• The term GSM encompasses all genital and urinary signs and symptoms associated with a loss of estrogen due to menopause (Portman 2014).

Osphena (Ospemifene) Dose in Adults

Osphena (Ospemifene) General dosing guidelines:

• When treating symptoms of menopause, therapy should be evaluated routinely for appropriate dose, duration, and route of administration for each individual patient based on treatment goals and changes in benefits, risks, and health over time.

Osphena (Ospemifene) Dose in the treatment of moderate to severe dyspareunia:

Postmenopausal females:

• Oral: 60 mg OD

Osphena (Ospemifene) dose in the treatment of moderate to severe Vaginal dryness:

Postmenopausal females:

• Oral: 60 mg OD

Osphena (Ospemifene) Dose in Childrens

Not recommended for use in children.

Osphena Pregnancy Risk Category: X

• Contraindicated for women who may be pregnant.
• Ospemifene can only be used by postmenopausal women.

Ospemifene use during breastfeeding:

• It is unknown if breast milk contains ospemifene.
• Manufacturers do not recommend breastfeeding.

Osphena Dose in Kidney Disease:

• Dosage adjustment not necessary.

Osphena Dose in Liver Disease:

• Mild or moderate impairment (Child-Pugh class A or B):

  • Dosage adjustment not necessary.

• Severe impairment (Child-Pugh class C):

  • No dosage adjustment provided in the manufacturer's labeling (has not been studied). Use is not recommended.

Common Side Effects of Osphena (Ospemifene):

• Endocrine & metabolic:

  • Hot flash

Less Common Side Effects of Osphena (Ospemifene):

• Central Nervous System:

  • Headache

• Dermatologic:

  • Hyperhidrosis
  • Night Sweats

• Genitourinary:

  • Endometrial Hyperplasia
  • Vaginal Discharge
  • Endometrial Polyps
  • Vaginal Hemorrhage

• Neuromuscular & Skeletal:

  • Muscle Spasm

Contraindication to Osphena (Ospemifene):

• Hypersensitivity to ospemifene and any component of the formulation (eg, angioedema or urticaria, skin rash, pruritus, etc.)
• Atypical genital bleeding that is not diagnosed
• DVT or PE (current and/or historical of)
• Current or past arterial thromboembolic diseases (eg stroke, MI)
• A known or suspected estrogen-dependent tumor
• Women who may or are pregnant

Warnings and precautions

• Breast cancer

  • Breast cancer patients who have not been adequately treated with Ospemifene have not had their concerns addressed.
  • It is not recommended to use estrogen-dependent breast cancer in women.

• Endometrial Cancer: [US Boxed Warn]

  • Ospemifene, an estrogen agonist/antagonist that has tissue-selective properties, is known as Ospemifene.
  • Ospemifene is an estrogen-agonistic agent in the endometrium.
  • A woman who has a uterus that uses unopposed estrogens may be at greater risk for endometrial carcinoma.
  • Take appropriate diagnostic measures, including random and directed endometrial sampling, when indicated to rule out malignancy.
  • Endometrial cancer risk for women who have an intact uterus and are taking estrogen without a progestin is dependent on the dose and duration of treatment.
  • Clinical studies of ospemifene did not show endometrial cancer (duration =52 week) and the use of progestins were not evaluated.
  • There are no data that recommends the addition of a progestin or ospemifene to ospemifene treatment in women with a female uterus. Current warnings are based upon safety data for systemic hormonal therapy with unopposed estrogen; appropriate evaluation should be done if there is any postmenopausal bleeding.

• Cardiovascular disease: [US-Boxed Warning]

  • These were the results of clinical trials involving ospemifene lasting less than 15 months:
    • Thromboembolic stroke 1.13/1,000 women'years (placebo 3.15/1,000 woman-years);
    • Hemorrhagic stroke 3.39/1,000 Women-years (placebo 0./1,000 Women-years);
    • DVT 2.26/1,000 women-years (placebo 3.15/1,000 women-years).
  • It is important to manage risk factors for cardiovascular diseases, arterial vascular disorders, venous embolism (VTE), and other conditions.
  • Risk factors include diabetes, hypercholesterolemia, hypertension, SLE, obesity, tobacco use, and/or history of VTE.
  • If you suspect a VTE, hemorhagic stroke, thromboembolic or thromboembolic event, immediately discontinue use.
  • Contraindicated for women with active DVT, PE or a history thereof, and women with an active or recently diagnosed arterial thromboembolic disorder (stroke and MI), or a history thereof.

• Hepatic dysfunction

  • It has not been tested in patients with severe hepatic impairment.
  • It is not advised.

Ospemifene: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring Parameters:

• Evaluate baseline risk for breast cancer and CVD prior to therapy.
• Efficacy and side effects beginning 1 to 3 months after starting therapy, then every 6 to 12 months as appropriate
• Age-appropriate breast and pelvic exams
• Blood pressure
• Unscheduled bleeding lasting more than 6 months for endometrial pathology (sooner in patients who are obese, diabetic, or have a history of endometrial cancer).
• The duration of treatment should be evaluated at least annually.

How to administer Osphena (Ospemifene)?

• Administer with food.

Mechanism of action of Ospemifene (Osphena):

• Ospemifene is a selective estrogen receptor modulator (SERM)
• It activates estrogen pathways and blocks estrogen pathways within certain tissues. Additionally, it has agonistic effects upon the endometrium.
• After 12 weeks of treatment, VVA-afflicted women were shown to experience vaginal changes due to the decline in natural estrogen production.
• Ospemifene significantly reduced vaginal dryness and dyspareunia, and improved vaginal maturation.

The onset of action:

• A significant decrease in vaginal dryness & dyspareunia were observed after 12 weeks of therapy.

Protein binding:

• more than 99% bound to serum proteins

Metabolism:

• Hepatic via CYP3A4, 2C9, and 2C19; forms a metabolite (4-hydroxyospemifene)

Bioavailability:

• Increased approximately two- to threefold by food

Half-life elimination:

• ~26 hours

Time to peak:

• ~2 hours (range: 1-8 hours)

Excretion:

• Feces (75%)
• urine (7%; <0.2% as unchanged drug)

International Brands of Ospemifene:

• Osphena

Ospemifene Brand Names in Pakistan:

No Brands Available in Pakistan.