ACTIVELLE Tablets/Film-coated

What is ACTIVELLE

ACTIVELLE is a hormone replacement therapy (HRT) designed for postmenopausal women who are experiencing symptoms related to estrogen deficiency. Each film-coated tablet contains a combination of two active ingredients: Estradiol (as hemihydrate), a naturally occurring estrogen, and Norethisterone acetate, a synthetic progestogen. The product is packaged in a 28-tablet calendar dial pack to support daily and consistent use.

• Estradiol: Replaces the estrogen that naturally declines during menopause, helping alleviate symptoms such as hot flashes, night sweats, and vaginal dryness.
• Norethisterone: Prevents estrogen-induced endometrial hyperplasia, which could develop into cancer in women with an intact uterus if unopposed by a progestogen.
• Indicated for:
  • Relief of moderate to severe vasomotor symptoms of menopause.
  • Prevention of postmenopausal osteoporosis in high-risk women who are not candidates for other medications.
• Continuous combined regimen: Taken daily without interruption, allowing for a steady hormone level and avoiding withdrawal bleeding in most users.

ACTIVELLE is a well-established option for managing menopause-related hormonal imbalances and protecting long-term bone health when used appropriately under medical supervision.

How to use ACTIVELLE

ACTIVELLE should be used exactly as prescribed by a healthcare provider. It follows a continuous combined regimen with no breaks between packs.

• Dosage form: One film-coated tablet per day, taken orally at the same time each day.
• Calendar dial pack: The 28-day blister pack is labeled with the days of the week, which helps ensure consistent daily intake and adherence to the therapy.
• With or without food: Tablets can be taken with or without meals, but taking it with food may reduce the chance of gastrointestinal upset.
• Missed dose: If a dose is missed, it should be taken as soon as remembered. If more than 12 hours have passed, skip the missed dose and continue with the next tablet. Do not take two tablets at once.
• Start timing: For women transitioning from another HRT, the switch can be made directly. For first-time users, therapy should start based on the doctor’s advice, preferably shortly after the last natural menstruation.
• Follow-up: Periodic re-evaluation by the prescribing physician is essential to assess the need for continued therapy.

Adherence to the prescribed regimen ensures optimal control of menopausal symptoms and protection of the endometrium.

Mode of Action ACTIVELLE

ACTIVELLE combines two hormones to replicate the physiological hormonal environment of premenopausal women, aiming to relieve menopausal symptoms and reduce long-term risks of estrogen deficiency.

• Estradiol (as hemihydrate):
  • A form of 17β-estradiol, the principal endogenous estrogen.
  • Acts by binding to estrogen receptors (ERα and ERβ) in various tissues such as the brain, bone, and urogenital tract.
  • Reduces vasomotor symptoms (e.g., hot flashes), maintains bone density, and improves vaginal tissue health.
• Norethisterone acetate:
  • A synthetic progestin that converts to norethisterone in the body.
  • Acts by opposing the proliferative effects of estradiol on the endometrium, thereby reducing the risk of endometrial hyperplasia and carcinoma in women with a uterus.
  • Modulates estrogen receptor activity and regulates menstrual-like bleeding.
• Combined effect: Maintains hormonal balance by restoring estrogen levels while preventing estrogen-induced endometrial complications.

Through this dual mechanism, ACTIVELLE provides comprehensive symptom relief and endometrial protection for postmenopausal women.

ACTIVELLE Interactions ACTIVELLE

Several drugs may interact with ACTIVELLE, altering its effects or increasing the risk of side effects. It is crucial to inform your doctor about all medications being used.

• Enzyme-inducing drugs:
  • Rifampicin, rifabutin (antibiotics)
  • Carbamazepine, phenytoin, phenobarbital (antiepileptics)
  • St. John’s Wort (herbal remedy)
  • These can lower estradiol and norethisterone levels by increasing hepatic metabolism, reducing efficacy.
• Protease inhibitors and antifungals:
  • Ritonavir, ketoconazole, itraconazole may inhibit hormone metabolism and increase blood levels of ACTIVELLE.
• Anticoagulants:
  • Estrogens may reduce the efficacy of anticoagulants like warfarin; monitoring is advised.
• Thyroid medications:
  • ACTIVELLE may alter the need for thyroid hormone replacement (e.g., levothyroxine) due to protein binding interactions.
• Glucose-lowering agents:
  • May affect insulin sensitivity, potentially impacting diabetes control.

Patients should not start, stop, or change dosages of any medication without consulting their healthcare provider while on ACTIVELLE.

Dosage of ACTIVELLE

The standard dosage of ACTIVELLE is one tablet daily, which contains:

• Estradiol (as hemihydrate): 1 mg
• Norethisterone acetate: 0.5 mg

This fixed-dose combination is intended for continuous use without breaks between cycles, providing a steady hormone level.

• Administration: One tablet is taken orally at the same time each day.
• Calendar pack: The 28-day pack is designed for convenience and to enhance compliance, with each tablet marked by day of the week.
• Special populations:
  • Not recommended in children or adolescents.
  • In elderly women, treatment should be individualized and closely monitored.
• Missed dose: If a tablet is missed and more than 12 hours have passed, the missed dose should be skipped to avoid doubling up.
• Starting treatment: Should begin under medical guidance, often initiated immediately after menopause or transitioning from another HRT.

Dosing must be reassessed periodically by a healthcare provider to ensure continued need and adjust therapy based on individual response.

Possible side effects of ACTIVELLE

As with any hormone-based therapy, ACTIVELLE may cause side effects. While not everyone experiences them, some effects can be serious and warrant immediate attention.

• Common side effects:
  • Breast tenderness or pain
  • Headache or migraine
  • Nausea
  • Vaginal bleeding or spotting
  • Abdominal pain or bloating
• Less common or rare side effects:
  • Weight changes (gain or loss)
  • Mood swings or depression
  • Skin rash or itching
  • Increased blood pressure
• Serious side effects (seek immediate medical help):
  • Signs of a blood clot: sudden leg pain, swelling, chest pain, or difficulty breathing
  • Unusual vaginal bleeding
  • Yellowing of the skin or eyes (jaundice)
  • Vision or speech changes

Side effects should be discussed with a doctor, and therapy should be adjusted or discontinued if risks outweigh benefits.

ACTIVELLE Contraindications ACTIVELLE

ACTIVELLE should not be used in certain medical conditions due to the increased risk of severe complications.

• Absolute contraindications:
  • Known, suspected, or history of breast cancer
  • Estrogen- or progestogen-dependent malignancies
  • Undiagnosed vaginal bleeding
  • Active or history of venous thromboembolism (e.g., DVT, pulmonary embolism)
  • Arterial thromboembolic disorders (e.g., stroke, myocardial infarction)
  • Severe liver disease or liver tumors
  • Known hypersensitivity to estradiol, norethisterone, or any excipients
• Relative contraindications (use with caution):
  • History of endometriosis or fibroids
  • Hypertension
  • Diabetes with vascular involvement
  • Gallbladder disease

Before initiating ACTIVELLE, a thorough medical history and physical examination are essential to rule out contraindications.

Storage of ACTIVELLE

Proper storage of ACTIVELLE is essential to maintain its potency and safety:

• Temperature: Store below 25°C (77°F).
• Humidity: Keep tablets in the original blister pack to protect from moisture and light.
• Location: Store in a dry place out of reach of children and pets.
• Do not refrigerate or freeze.
• Expiration: Do not use after the expiry date printed on the pack. Safely discard any unused medicine as directed by your pharmacist.

Adhering to these storage conditions helps ensure that ACTIVELLE remains effective and safe throughout its shelf life.