EMILY 52MG INTRAUTERINE DEVICE

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
• Heavy menstrual bleeding
• Endometrial protection in women with risk factors for endometrial hyperplasia
• Management of dysmenorrhea
• Emergency contraception (specific types)

Dosage

Children: The use of intrauterine devices in adolescents should be guided by clinical assessment and specific recommendations from healthcare providers, refer to the BNF for Children for appropriate dosing information.

Adults: Refer to specific product guidelines and the BNF for appropriate dosing instructions based on the type of intrauterine device and clinical indication.

Mechanism of action

The mechanism of action of intrauterine devices, particularly hormonal IUDs, involves the release of hormones such as levonorgestrel, which thickens cervical mucus, inhibits sperm motility, and alters the endometrial lining to prevent implantation. Copper IUDs release copper ions that are toxic to sperm and create a local inflammatory response that is hostile to sperm and eggs.

Pharmacodynamics

The pharmacodynamics of intrauterine devices involve the localized effects within the uterine cavity. Hormonal IUDs lead to changes in the endometrium, making it less receptive to implantation. The local release of hormones also reduces menstrual bleeding and dysmenorrhea. Copper IUDs primarily act by preventing fertilization through their impact on sperm viability and motility.

Pharmacokinetics

Pharmacokinetics varies between hormonal and copper IUDs. Hormonal IUDs release a steady dose of hormone locally, with minimal systemic absorption. The half-life of levonorgestrel in the systemic circulation is about 30 hours. Copper IUDs do not release systemic hormones and their effects are localized. The lifespan of copper IUDs can extend up to ten years, while hormonal IUDs may last for three to five years depending on the specific product.

Contra-indications

• Pregnancy
• Unexplained vaginal bleeding
• Pelvic inflammatory disease
• Uterine or cervical cancer
• Certain uterine abnormalities

Adverse effects

• Menstrual changes
• Pelvic pain
• Expulsion of the device
• Infection
• Uterine perforation

Precautions

• Ensure proper placement by a healthcare professional
• Monitor for signs of infection
• Consider potential for heavy menstrual bleeding
• Assess for risk factors for pelvic inflammatory disease

Pregnancy

Contraindicated during pregnancy. Should not be used if pregnancy is confirmed or suspected.

Breast-feeding

Generally considered safe, but consult a healthcare provider for individual circumstances.

Storage

Store at room temperature, away from moisture and direct sunlight. Follow specific storage instructions provided by the manufacturer.

Formulations

• Copper intrauterine device (IUD)
• Levonorgestrel-releasing intrauterine system (IUS)

Indications

• Attention Deficit Hyperactivity Disorder (ADHD)
• Depressive Disorders
• Anxiety Disorders
• Chronic Fatigue Syndrome
• Certain types of pain syndromes

Dosage

Children: Refer to specific paediatric guidelines for dosing information, as it varies by agent and condition treated.

Adults: Refer to specific prescribing guidelines for dosing information, as it varies by agent and condition treated.

Mechanism of action

Releasing agents often work by increasing the availability of neurotransmitters, such as dopamine, norepinephrine, and serotonin, in the synaptic cleft. This may occur through mechanisms such as promoting vesicular release, inhibiting reuptake transporters, or blocking autoreceptors that dampen neurotransmitter release. The precise mechanism can vary depending on the specific agent and its target neurotransmitter system.

Pharmacodynamics

The pharmacodynamics of releasing agents involve their effects on neurotransmitter levels and receptor activation. By increasing the concentration of neurotransmitters in the synaptic cleft, these drugs enhance receptor activation, leading to improved synaptic transmission. This can result in various clinical effects, including mood elevation, increased alertness, and improved cognitive function. The therapeutic window and the risk of side effects can vary significantly based on the specific agent and the dosage used.

Pharmacokinetics

The pharmacokinetics of releasing agents depend on the specific compound. Generally, these drugs are absorbed after administration, with peak plasma concentrations occurring within a few hours. They may undergo metabolism in the liver and are typically eliminated through renal excretion. The half-life varies widely, influencing the dosing schedule and potential for accumulation with repeated use.

Pregnancy

Consult healthcare provider. Safety during pregnancy depends on the specific releasing agent.

Breast-feeding

Consult healthcare provider. Safety during breastfeeding varies based on specific releasing agent.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Dosage

Children: Refer to specific drug information for appropriate dosing.

Adults: Refer to specific drug information for appropriate dosing.

Mechanism of action

Systemic medications typically work by entering the bloodstream and interacting with specific receptors or enzymes in various tissues, leading to a therapeutic effect. For example, antibiotics may inhibit bacterial cell wall synthesis, while analgesics may block pain receptors in the central nervous system.

Pharmacodynamics

The pharmacodynamics of systemic drugs depend on their specific class and mechanism of action. Generally, systemic drugs are intended to provide widespread effects across the body, which can lead to both therapeutic effects and potential side effects. The efficacy of these drugs is often measured by their ability to achieve desired plasma concentrations that correlate with clinical outcomes.

Pharmacokinetics

Pharmacokinetics of systemic medications involves absorption, distribution, metabolism, and excretion (ADME). After administration, systemic drugs are absorbed into the bloodstream, distributed to various tissues, metabolized by the liver or other organs, and then excreted, primarily through the kidneys. The half-life and clearance rates can vary significantly depending on the drug's chemical properties and the patient's physiology.

Pregnancy

Consult with a healthcare professional before use, as safety in pregnancy has not been established for all drugs.

Breast-feeding

Consult with a healthcare professional before use, as some drugs may pass into breast milk.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

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.