LEVOPLANT 150MG (75MG/ROD) IMPLANT

Indications

• Contraception
• Emergency contraception
• Menorrhagia management

Dosage

Children: For females of childbearing potential, the dosage for emergency contraception is the same as for adults, 1.5 mg as a single dose. For long-term contraception, consult the BNF

Adults: For emergency contraception, a single dose of 1.5 mg should be taken as soon as possible after unprotected intercourse, preferably within 12 hours but no later than 72 hours. For contraception, the recommended dose may vary based on the specific formulation and patient needs, refer to the BNF for specific guidelines.

Mechanism of action

Levonorgestrel suppresses gonadotropins, inhibiting ovulation by binding to progesterone and androgen receptors, and slowing the release of gonadotropin-releasing hormone (GnRH) from the hypothalamus. This leads to the suppression of the luteinizing hormone (LH) surge necessary for ovulation. Additionally, it increases the thickness of cervical mucus, hindering sperm movement and survival, and induces changes in the endometrium that prevent implantation of a fertilized egg.

Pharmacodynamics

Levonorgestrel effectively prevents pregnancy through multiple mechanisms: by interfering with ovulation, fertilization, and implantation. The emergency contraceptive tablet is approximately 89% effective when taken within 72 hours after unprotected intercourse, while IUDs releasing levonorgestrel demonstrate over 99% effectiveness. It also serves a therapeutic role in preventing endometrial carcinoma associated with unopposed estrogen therapy.

Pharmacokinetics

Levonorgestrel is rapidly absorbed after oral administration, with peak plasma concentrations typically achieved within 1 to 2 hours. It has a half-life of approximately 24 hours and is metabolized in the liver. The drug is primarily excreted via urine and feces, and its pharmacokinetic profile can be affected by certain enzyme-inducing medications.

Contra-indications

• Pregnancy
• Severe liver disease
• Known or suspected hormone-sensitive malignancies
• Undiagnosed vaginal bleeding

Adverse effects

• Nausea
• Vomiting
• Fatigue
• Headache
• Dizziness
• Breast tenderness
• Mood changes
• Abdominal pain
• Changes in menstrual bleeding

Interactions

• Antiepileptics (carbamazepine, eslicarbazepine, fosphenytoin, oxcarbazepine, perampanel, phenobarbital, phenytoin, primidone, rufinamide, topiramate) may decrease efficacy
• Bosentan may decrease efficacy
• Ritonavir may decrease efficacy
• Lamotrigine may decrease effects
• Modafinil may decrease efficacy
• St. John's Wort may decrease efficacy
• Rifamycins may decrease efficacy
• Ulipristal may decrease efficacy

Precautions

• Monitor for ectopic pregnancy in women with a history of ectopic pregnancy or pelvic inflammatory disease
• Consider alternative contraceptive methods in cases of severe obesity
• Use caution in women with a history of thromboembolic disorders
• Regular follow-up is necessary to monitor for side effects and efficacy

Pregnancy

Levonorgestrel is contraindicated in pregnancy. It is not effective once implantation has occurred.

Breast-feeding

Levonorgestrel is excreted in breast milk, but it is considered safe for use during breastfeeding. However, it is advisable to take the medication just after breastfeeding to minimize exposure to the infant.

Storage

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

Formulations

• Levonorgestrel 1.5 mg oral tablet for emergency contraception
• Levonorgestrel intrauterine device (IUD) releasing 20 micrograms per day

Indications

• Contraception
• Menstrual cycle regulation
• Management of endometriosis
• Reduction of menstrual bleeding in heavy menstrual disorders

Dosage

Children: Refer to the specific product guidelines for dosage and administration instructions.

Adults: Refer to the specific product guidelines for dosage and administration instructions.

Mechanism of action

Implants release progestins, which primarily inhibit ovulation by suppressing luteinizing hormone (LH) surge. They also thicken cervical mucus, making it difficult for sperm to penetrate and alter the endometrium, reducing the likelihood of implantation.

Pharmacodynamics

The pharmacodynamics of hormonal implants involve sustained release of progestins, resulting in prolonged contraceptive efficacy. The hormonal changes lead to a decrease in endometrial receptivity and anovulation. The onset of action is rapid following insertion, and their effects persist for the duration of the implant's lifespan.

Pharmacokinetics

After subcutaneous insertion, implants release hormones into the bloodstream at a steady rate. The pharmacokinetics can vary based on the type of progestin used. Generally, the bioavailability is nearly 100%, and the half-life of the hormones allows for long-term action, typically lasting between 3 to 5 years depending on the specific implant. The metabolism primarily occurs in the liver, with renal excretion of metabolites.

Contra-indications

• Hypersensitivity to the active substance or any of the excipients
• Uncontrolled hypertension
• Severe liver disease
• Active venous thromboembolism
• Known or suspected breast cancer
• Pregnancy

Adverse effects

• Irregular menstrual bleeding
• Headache
• Nausea
• Breast tenderness
• Mood changes
• Weight gain
• Acne
• Ovarian cysts

Interactions

• Anticonvulsants (e.g., phenytoin, carbamazepine)
• Rifampicin and other rifamycins
• St. John's Wort
• Certain HIV medications (e.g., efavirenz)

Precautions

• Monitor for signs of venous thromboembolism
• Assess for any history of liver disease
• Evaluate for potential interactions with other medications
• Consider individual patient risk factors for cardiovascular disease

Pregnancy

Not indicated during pregnancy; potential risks include teratogenic effects.

Breast-feeding

Generally considered safe during breastfeeding, but may affect milk production.

Storage

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

Formulations

• Subdermal implant
• Intrauterine device

Indications

• Medical implants
• Prosthetics
• Catheters
• Surgical instrument coatings

Dosage

Children: Silastic is not used as a drug in a typical sense; refer to specific medical guidelines for pediatric applications of silicone-based medical devices.

Adults: Silastic is not administered as a drug; therefore, specific dosing is not applicable. Its use is determined by the specific medical application and the device or implant's design.

Mechanism of action

Silastic does not have a pharmacological mechanism of action in the traditional sense, as it is a synthetic material rather than a drug. Its biocompatibility and inertness prevent adverse reactions in the body, allowing for the safe use of silicone implants and devices.

Pharmacodynamics

As a silicone-based material, Silastic does not exert pharmacological effects like drugs do. Its physical properties, such as flexibility, durability, and resistance to degradation, are key to its performance as a medical implant. The material does not interact biochemically with body systems but instead provides structural support and protection.

Pharmacokinetics

Silastic is not absorbed or metabolized in the body like conventional drugs. Instead, it remains in place at the implantation site, providing a permanent solution for various medical needs without systemic distribution or elimination.

Pregnancy

Silastic is a brand name for a silicone elastomer, which is generally considered safe for use in medical devices during pregnancy. However, specific safety data regarding its use in pregnant individuals are limited.

Breast-feeding

Silastic is not known to be excreted in human milk, and thus, it is generally considered safe for use during breastfeeding. However, specific studies on its effects during lactation are limited.

Storage

Store Silastic in a cool, dry place away from direct sunlight and keep it sealed in its original packaging to prevent contamination.

Formulations

• Silastic elastomers
• Silastic adhesives
• Silastic medical-grade silicone products

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.