Norgest

Approved Indications:

• Oral Contraception:
  Indicated for the prevention of pregnancy in women of reproductive age.
• Menstrual Cycle Regulation:
  Helps to establish regular monthly bleeding in women with irregular cycles.
• Treatment of Dysmenorrhea:
  Reduces the severity of menstrual cramps and pain.
• Moderate Acne Vulgaris:
  Indicated for women ≥14 years of age, who desire contraception and have achieved menarche.
• Heavy Menstrual Bleeding (Menorrhagia):
  Reduces excessive menstrual bleeding in women with no organic pathology.

Clinically Accepted Off-label Uses:

• Polycystic Ovary Syndrome (PCOS):
  Used to regulate menstrual cycles, reduce androgen levels (acne, hirsutism), and protect the endometrium from hyperplasia.
• Endometriosis Symptom Relief:
  May be used for reducing pelvic pain and suppressing ovulation in endometriosis management.
• Iron Supplementation:
  The ferrous fumarate in the placebo tablets helps prevent iron-deficiency anemia during menstruation.

Standard Dosage:

• Cycle Pack (28-day regimen):
• Days 1–21: One active tablet daily containing:
• Ethinyl Estradiol 0.03 mg
• Levonorgestrel 0.15 mg
• Days 22–28: One placebo tablet daily containing:
• Ferrous Fumarate 75 mg

Route of Administration: Oral

Administration Details:

• Tablets should be taken at the same time each day, preferably with food or at bedtime to reduce gastrointestinal discomfort.
• Begin on Day 1 of menstruation or the first Sunday after menstruation begins.

Missed Dose Instructions:

• One missed tablet: Take as soon as remembered.
• Two or more missed tablets: Follow package instructions and use backup contraception for 7 days.

Special Populations:

• Adolescents (post-menarche): Same dosage as adults.
• Elderly: Not indicated post-menopause.
• Hepatic Impairment: Contraindicated in severe hepatic dysfunction.
• Renal Impairment: Use with caution; no dosage adjustment specified but monitor closely.

Ethinyl Estradiol and Levonorgestrel work synergistically to inhibit ovulation. Ethinyl Estradiol suppresses the release of follicle-stimulating hormone (FSH), preventing follicular development, while Levonorgestrel suppresses luteinizing hormone (LH), inhibiting the mid-cycle LH surge required for ovulation. The combination also causes endometrial thinning, reducing implantation potential, and thickens cervical mucus, making it more difficult for sperm to enter the uterus. Ferrous Fumarate provides elemental iron supplementation during the placebo phase to help prevent iron loss associated with menstruation.

• Absorption:
• Ethinyl Estradiol: Rapid, with 40–50% bioavailability due to first-pass hepatic metabolism.
• Levonorgestrel: High bioavailability (~100%).
• Distribution:
• Ethinyl Estradiol: ~98% bound to plasma proteins (mainly albumin).
• Levonorgestrel: 97.5–99% bound to sex hormone-binding globulin (SHBG) and albumin.
• Metabolism:
• Both drugs are primarily metabolized in the liver by CYP3A4 enzymes.
• Ethinyl Estradiol undergoes glucuronidation and sulfation.
• Excretion:
• Ethinyl Estradiol: Half-life ~13–27 hours.
• Levonorgestrel: Half-life ~24 hours.
• Excreted via urine and feces.
• Ferrous Fumarate:
  Absorbed in the duodenum and upper jejunum; excess is excreted in feces.

• Pregnancy:
  Contraindicated. Should not be used during pregnancy. No benefit, and potential risks include hormonal effects on fetal development.
• Lactation:
  Use with caution.
• Ethinyl Estradiol can reduce the quantity and quality of breast milk.
• Small amounts of both hormones pass into breast milk; long-term effects on the infant are unknown.
• A progestin-only pill is generally preferred during the early months of breastfeeding.

• Class: Combined Oral Contraceptive (COC)
• Sub-class: Estrogen-Progestin combination
• Additional Component: Iron supplement (Ferrous Fumarate)
• Progestin Type: Second-generation progestin (Levonorgestrel)

• Hypersensitivity to Ethinyl Estradiol, Levonorgestrel, or Ferrous Fumarate
• Confirmed or suspected pregnancy
• Active or history of thromboembolic disorders (e.g., DVT, PE)
• History of stroke, ischemic heart disease, or myocardial infarction
• Known thrombophilia (e.g., protein C or S deficiency)
• Severe hepatic impairment or liver tumors
• Uncontrolled hypertension
• Breast cancer or estrogen/progestin-dependent tumors
• Migraine with aura
• Smokers aged ≥35 years

• Thromboembolic Risk: Elevated in smokers, obese patients, and those with clotting disorders.
• Cardiovascular Monitoring: Regular blood pressure checks recommended.
• Liver Function: Discontinue in case of liver enzyme abnormalities.
• Cancer Risks: Slight increased risk of breast and cervical cancer; routine screening recommended.
• Chloasma: May appear or worsen; advise sun protection.
• Depression and Mood Disorders: Monitor closely; discontinue if severe.

Seek Immediate Medical Attention If:

• Sudden chest pain or shortness of breath
• Severe headache or visual disturbances
• Leg swelling or pain (possible DVT)

Common Side Effects:

• Gastrointestinal: Nausea, vomiting, abdominal pain
• CNS: Headache, dizziness, mood changes
• Breasts: Tenderness, enlargement
• Menstrual: Breakthrough bleeding, spotting
• Dermatologic: Acne, melasma

Serious Side Effects:

• Thromboembolic events (DVT, PE, stroke)
• Myocardial infarction
• Liver dysfunction or tumors
• Depression and mood disturbances
• Vision changes due to retinal vascular events

Rare Side Effects:

• Gallbladder disease
• Anaphylaxis
• Hypertension crisis
• Pancreatitis

• Enzyme Inducers (↓ contraceptive efficacy):
• Rifampin, Phenytoin, Carbamazepine, Phenobarbital, St. John's Wort
• Enzyme Inhibitors (↑ hormone levels):
• Ketoconazole, Itraconazole, Ritonavir
• Antibiotics:
• Rifampin reduces efficacy significantly.
• Most antibiotics do not reduce COC effectiveness unless affecting gut flora significantly.
• Anticoagulants:
• Estrogens can antagonize anticoagulant effect (e.g., warfarin).
• Alcohol:
• Chronic use may impact metabolism and effectiveness.

Enzyme System:
Primarily metabolized via CYP3A4

• FDA and WHO: No recent changes specific to this formulation.
• EMA/NICE: Recommend continued risk assessment for thrombosis and cardiovascular risks in COC users.
• Clinical Updates:
• Support use of lower estrogen doses to reduce risks.
• Emphasis on individualized risk stratification before prescribing.

• Temperature: Store at 20°C to 25°C (68°F to 77°F)
• Allowable Range: 15°C to 30°C (59°F to 86°F)
• Humidity: Protect from moisture
• Light Protection: Store in original blister packaging
• Handling Instructions:
• Do not refrigerate
• Do not freeze
• Keep out of reach of children
• Dispose of unused tablets properly