Remens

Approved Indications:

• Menstrual Disorders:
• Secondary amenorrhea
• Dysfunctional uterine bleeding (due to hormonal imbalance)
• Menorrhagia (heavy menstrual bleeding)
• Metrorrhagia (irregular uterine bleeding)
• Polymenorrhea or oligomenorrhea
• Endometriosis:
• Treatment of mild to moderate endometriosis symptoms (pain, dysmenorrhea, dyspareunia)
• Contraception (when combined with estrogen):
• As a component of combined oral contraceptives (COCs)
• Premenstrual Syndrome (PMS):
• For cyclic symptoms such as breast tenderness, irritability, bloating

Clinically Accepted Off-label Uses:

• Delay of Menstruation:
• In healthy women for personal or cultural reasons
• Fibroid-Related Bleeding:
• To reduce excessive uterine bleeding associated with uterine fibroids
• Hormone Replacement Therapy (HRT):
• In combination with estrogen to prevent endometrial hyperplasia

Adults:

• Secondary Amenorrhea:
• 2.5–10 mg orally once daily for 5–10 days
• Withdrawal bleeding usually occurs within 3–7 days after stopping
• Abnormal Uterine Bleeding:
• 2.5–10 mg once daily for 5–10 days during bleeding
• Bleeding should stop within days; withdrawal bleeding follows therapy
• Endometriosis:
• Start with 5 mg once daily for 2 weeks, then increase by 2.5 mg every 2 weeks up to 15 mg/day as tolerated
• Duration: Typically 6–9 months
• Menstrual Delay:
• 5 mg orally three times daily starting 3 days before expected menses
• Continue for up to 14 days; withdrawal bleeding starts 2–4 days after stopping

Elderly:

• Not recommended unless prescribed as part of hormone therapy; limited safety data in postmenopausal women

Pediatrics:

• Not approved for use in premenarcheal girls; use with caution in adolescents

Renal/Hepatic Impairment:

• Contraindicated in severe hepatic impairment
• Use cautiously in mild to moderate renal impairment

Route of Administration:

• Oral (with or without food)

Duration:

• Varies depending on indication; may be cyclic or continuous

Norethisterone acetate is a synthetic progestin that binds to intracellular progesterone receptors in the female reproductive tract, hypothalamus, and pituitary. It mimics the natural hormone progesterone, transforming the endometrium from a proliferative to a secretory state, stabilizing the uterine lining, and preventing irregular bleeding. It also inhibits the mid-cycle surge of luteinizing hormone (LH), thereby suppressing ovulation. Additionally, it thickens cervical mucus, which impedes sperm penetration, and alters the endometrial lining, reducing the likelihood of implantation. These combined effects underlie its use in menstrual regulation, endometriosis, and contraception.

• Absorption:
  Rapidly absorbed after oral administration
• Bioavailability:
  Approximately 50–65% due to first-pass hepatic metabolism
• Peak Plasma Concentration:
  Reached in 1–2 hours
• Distribution:
  Widely distributed; high plasma protein binding (~90–95%)
• Metabolism:
  Hepatic via reduction, hydroxylation, and conjugation; active metabolites include 5α-dihydro-norethisterone
• Half-life:
  Approximately 5–14 hours
• Elimination:
  Primarily in urine (as metabolites), some fecal excretion

• Pregnancy:
  Category X (US FDA) – Contraindicated
• Known to cause fetal harm, including virilization of female fetuses
• Do not use during pregnancy or if pregnancy is suspected
• Lactation:
• Excreted into breast milk in small amounts
• Generally considered safe during breastfeeding in low doses; however, may reduce milk production
• Monitor infant for adverse effects (e.g., hormonal disturbances)

• Primary Class: Hormonal Agent – Progestin
• Subclass: 19-nortestosterone derivative

• Known hypersensitivity to norethisterone or formulation components
• Pregnancy (Category X)
• Active or history of thromboembolic disorders (e.g., DVT, PE, stroke)
• Severe liver disease (active hepatic impairment or tumors)
• Undiagnosed vaginal bleeding
• Known or suspected breast or genital cancer sensitive to progestins
• Porphyria

• Thromboembolic Risk:
• Use cautiously in women with risk factors (e.g., smoking, obesity, immobility, family history)
• Avoid in patients with active or prior thrombotic disorders
• Liver Dysfunction:
• Monitor liver enzymes periodically; discontinue if hepatotoxicity occurs
• Depression:
• May exacerbate mood disorders; monitor for worsening psychiatric symptoms
• Breast Cancer Risk:
• Prolonged use may slightly increase the risk in some populations; use lowest effective dose
• Visual Disturbances:
• Report visual changes promptly; discontinue if optic neuropathy or retinal issues occur
• Diabetes:
• May affect glucose tolerance; monitor blood sugar in diabetic patients
• Clinical Monitoring:
• Periodic breast and pelvic exams, liver function tests, and assessment of thrombotic risk

Common (≥1%):

• Endocrine/Reproductive:
• Breakthrough bleeding
• Amenorrhea
• Breast tenderness
• Menstrual irregularities
• CNS:
• Headache
• Dizziness
• Mood changes (e.g., irritability, depression)
• GI:
• Nausea
• Bloating
• Skin:
• Acne
• Rash

Serious (Rare):

• Thromboembolism (DVT, PE, stroke)
• Hepatotoxicity
• Vision disturbances (retinopathy, optic neuritis)
• Severe depression or suicidal ideation
• Breast cancer (long-term risk)

Timing:

• Side effects may appear within days to weeks of initiation
• Dose-dependent and often reversible upon discontinuation

• Enzyme Inducers (CYP3A4):
• Rifampin, phenytoin, carbamazepine – may reduce effectiveness
• Antibiotics (e.g., ampicillin, tetracycline):
• Potential reduction in contraceptive efficacy due to GI flora disruption
• St. John's Wort:
• Induces CYP3A4 and may reduce efficacy
• Other Hormonal Agents:
• Combined use with estrogens may increase thrombotic risk
• Anticoagulants:
• Progestins may antagonize anticoagulant effects
• CYP450 System:
• Primarily metabolized by CYP3A4; interactions occur with inhibitors or inducers

• FIGO & WHO Guidelines:
• Recognize norethisterone as a useful option for endometriosis and menstrual disorders
• Emphasize limited long-term use due to thrombotic risk
• Recent Reviews (2024):
• Support short-term use for cycle regulation and delay of menstruation
• Preference shifting to newer progestins with better side effect profiles for long-term therapy
• EMA Safety Update (2023):
• Reaffirmed contraindication in pregnancy
• Updated labeling on depression and mood disorder risk

• Temperature:
  Store below 25°C (77°F)
• Humidity:
  Protect from moisture; store in a dry place
• Light Protection:
  Keep in original packaging to protect from light
• Handling:
  No special handling precautions required
• Shelf Life:
  Refer to expiry date on packaging; typically 3–5 years