OVRETTE 0.075MG TABLET

Indications

• Contraception
• Management of menstrual disorders
• Hormonal replacement therapy
• Prevention of endometrial carcinoma

Dosage

Adults: For contraception, the usual dosage is one tablet containing 0.3 mg of norgestrel taken orally once daily. For emergency contraception, norgestrel is typically administered as a single dose of 1.5

Mechanism of action

Norgestrel acts by binding to progesterone and androgen receptors, which suppresses gonadotropins and inhibits ovulation. It slows the release of gonadotropin-releasing hormone (GnRH) from the hypothalamus, thereby reducing the luteinizing hormone (LH) surge that is necessary for ovulation. Additionally, norgestrel increases the thickness of cervical mucus, making it more difficult for sperm to enter the uterus, and induces changes in the endometrium that prevent implantation of a fertilized egg.

Pharmacodynamics

Norgestrel effectively prevents pregnancy by interfering with ovulation, fertilization, and implantation. The oral contraceptive containing norgestrel is approximately 89% effective when used within 72 hours after unprotected intercourse. Long-acting forms such as intrauterine devices (IUDs) and implants that release norgestrel demonstrate over 99% efficacy in preventing pregnancy. Furthermore, norgestrel helps prevent endometrial carcinoma in women receiving unopposed estrogen therapy.

Pharmacokinetics

Following oral administration, norgestrel is rapidly absorbed, with peak plasma concentrations typically reached within 1 to 2 hours. It has a half-life of approximately 33 hours, allowing for once-daily dosing in contraceptive regimens. Norgestrel undergoes hepatic metabolism, primarily through the cytochrome P450 system, and is excreted in urine and feces. Its bioavailability can be influenced by factors such as food intake and individual metabolic variations.

Contra-indications

• Pregnancy
• Unexplained vaginal bleeding
• Active liver disease
• Thromboembolic disorders
• Known or suspected breast cancer

Adverse effects

• Nausea
• Vomiting
• Breast tenderness
• Headache
• Irregular menstrual bleeding
• Fatigue
• Dizziness

Interactions

• Antibiotics (e.g., rifampicin, rifabutin)
• Anticonvulsants (e.g., carbamazepine, phenytoin)
• HIV protease inhibitors (e.g., ritonavir)
• St. John's Wort

Precautions

• Use with caution in patients with a history of depression
• Monitor for signs of thromboembolic events
• Consider risks versus benefits in patients with cardiovascular disease
• Assess for potential drug interactions

Pregnancy

Levonorgestrel is contraindicated in pregnancy. It is not effective for terminating an existing pregnancy and should not be used as an abortifacient.

Breast-feeding

Levonorgestrel is excreted in breast milk. It is generally considered safe to use during breastfeeding, but monitoring of the infant for any potential effects is advisable.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Formulations

• Oral tablets (e.g., emergency contraceptive)
• Intrauterine device (IUD)
• Implantable contraceptive

Mechanism of action

**Mechanism of action on ovulation** Oral contraceptives containing levonorgestrel suppress gonadotropins, inhibiting ovulation. Specifically, levonorgestrel binds to progesterone and androgen receptors and slows the release of gonadotropin-releasing hormone (GnRH) from the hypothalamus. This process results in the suppression of the normal physiological luteinizing hormone (LH) surge that precedes ovulation. It inhibits the rupture of follicles and viable egg release from the ovaries. Levonorgestrel has been proven to be more effective when administered before ovulation. **Mechanism of action in cervical mucus changes** Similar to other levonorgestrel-containing contraceptives, the intrauterine (IUD) forms of levonorgestrel likely prevent pregnancy by increasing the thickness of cervical mucus, interfering with the movement and survival of sperm, and inducing changes in the endometrium, where a fertilized ovum is usually implanted. Levonorgestrel is reported to alter the consistency of mucus in the cervix, which interferes with sperm migration into the uterus for fertilization. Levonorgestrel is not effective after implantation has occurred. Interestingly, recent evidence has refuted the commonly believed notion that levonorgestrel changes the consistency of cervical mucus when it is taken over a short-term period, as in emergency contraception. Over a long-term period, however, levonorgestrel has been proven to thicken cervical mucus. The exact mechanism of action of levonorgestrel is not completely understood and remains a topic of controversy and ongoing investigation. *Effects on implantation** The effects of levonorgestrel on endometrial receptivity are unclear, and the relevance of this mechanism to the therapeutic efficacy of levonorgestrel is contentious. Prescribing information for levonorgestrel IUDs state that they exert local morphological changes to the endometrium (e.g. stromal pseudodecidualization, glandular atrophy) that may play a role in their contraceptive activity. **Mechanism of action in hormone therapy** When combined with estrogens for the treatment of menopausal symptoms and prevention of osteoporosis, levonorgestrel serves to lower the carcinogenic risk of unopposed estrogen therapy via the inhibition of endometrial proliferation. Unregulated endometrial proliferation sometimes leads to endometrial cancer after estrogen use. Norgestrel (and more specifically the active stereoisomer levonorgestrel) binds to the progesterone and estrogen receptors within the female reproductive tract, the mammary gland, the hypothalamus, and the pituitary. Once bound to the receptor, progestins like levonorgestrel will slow the frequency of release of gonadotropin releasing hormone (GnRH) from the hypothalamus and blunt the pre-ovulatory LH (luteinizing hormone) surge. Loss of the LH surge inhibits ovulation and thereby prevents pregnancy. Combination oral contraceptives act by suppression of gonadotrophins. Although the primary mechanism of this action is inhibition of ovulation, other alterations include changes in the cer-vical mucus (which increase the difficulty of sperm entry into the uterus) and the endometrium (which may reduce the likelihood of implantation). Progestins enter target cells by passive diffusion and bind to cytosolic (soluble) receptors that are loosely bound in the nucleus. The steroid receptor complex initiates transcription, resulting in an increase in protein synthesis. /Progestins/ Progestins are capable of affecting serum concentrations of other hormones, particularly estrogen. Estrogenic effects are modified by the progestins, either by reducing the availability or stability of the hormone receptor complex or by turning off specific hormone-responsive genes by direct interaction with the progestin receptor in the nucleus. In addition, estrogen priming is necessary to increase progestin effects by upregulating the number of progestin receptors and/or increasing progesterone product

Pharmacodynamics

Levonorgestrel prevents pregnancy by interfering with ovulation, fertilization, and implantation. The levonorgestrel-only containing emergency contraceptive tablet is 89% effective if it is used according to prescribing information within 72 hours after intercourse. The intrauterine and implantable devices releasing levonorgestrel are more than 99% in preventing pregnancy. Levonorgestrel utilized as a component of hormonal therapy helps to prevent endometrial carcinoma associated with unopposed estrogen administration.