KYLEENA®

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

• Diarrhea
• Indigestion
• Nausea
• Traveler's diarrhea
• Gastrointestinal discomfort

Dosage

Children: Refer to the BNF for Children for specific pediatric dosing information.

Adults: Refer to the BNF for specific dosing guidelines.

Mechanism of action

Bismuth subsalicylate works by coating the stomach and intestinal lining, which protects it against irritation and inflammation. It has antibacterial properties that can reduce the growth of certain bacteria in the gastrointestinal tract. Additionally, it may reduce fluid secretion in the intestines, thereby decreasing diarrhea.

Pharmacodynamics

Bismuth subsalicylate exhibits antidiarrheal effects by decreasing bowel motility and increasing absorption of fluids and electrolytes from the intestinal tract. Its anti-inflammatory properties help alleviate symptoms associated with gastrointestinal irritation. The salicylate component also contributes to its anti-inflammatory effects.

Pharmacokinetics

Bismuth subsalicylate is minimally absorbed from the gastrointestinal tract. Most of the drug acts locally in the gut, with very little systemic absorption. The salicylate portion can be absorbed and metabolized, leading to potential systemic effects. The elimination half-life of salicylate is variable and can be influenced by renal function.

Interactions

• bismuth subsalicylate + drugs with anticoagulant effects: Unknown (increases risk of bleeding events)
• opioids + drugs that cause serotonin syndrome: Unknown (increases risk of serotonin syndrome)
• tapentadol + drugs that cause serotonin syndrome: Unknown (increases risk of serotonin syndrome)

Indications

• Enhanced absorption of poorly soluble drugs
• Improved therapeutic effectiveness of various medications

Dosage

Children: Refer to specific drug formulations for dosing information, as dosages can vary widely based on the active ingredient.

Adults: Refer to specific drug formulations for dosing information, as dosages can vary widely based on the active ingredient.

Mechanism of action

Micronization itself does not alter the pharmacological activity of the drug; rather, it enhances the drug's absorption characteristics. This is particularly significant for drugs that are poorly soluble, as increased absorption can lead to more effective therapeutic outcomes.

Pharmacodynamics

The pharmacodynamics of micronized drugs remain consistent with the pharmacological profile of the active ingredient. Micronized drugs often exhibit enhanced onset of action due to increased absorption rates, leading to quicker therapeutic effects. However, the specific effects will depend on the drug and its mechanism of action.

Pharmacokinetics

Micronization can significantly influence the pharmacokinetics of a drug by improving its absorption in the gastrointestinal tract. This may lead to increased peak plasma concentrations and altered time to peak effect. The elimination half-life and volume of distribution may remain unchanged, but the overall bioavailability may be improved.

Pregnancy

Micronized formulations should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Consultation with a healthcare provider is recommended.

Breast-feeding

Caution is advised when using micronized drugs while breastfeeding. The effects on the infant should be considered, and consultation with a healthcare provider is recommended.

Storage

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

Dosage

Children: Refer to specific substance guidelines for appropriate dosing in children, as paediatric dosages often require careful adjustment based on age, weight, and clinical condition.

Adults: Refer to specific substance guidelines for appropriate dosing, as dosages can vary widely based on medical indications and individual patient factors.

Mechanism of action

The mechanism of action of a substance varies significantly depending on its specific type. For example, some substances may act as agonists or antagonists at particular receptor sites, modulating physiological processes. Others may inhibit enzymes or block ion channels, leading to altered cellular function. Understanding the specific mechanism of action is critical for predicting therapeutic effects and potential side effects.

Pharmacodynamics

Pharmacodynamics refers to the effects of a substance on the body, specifically how it interacts with biological systems to produce therapeutic effects. This can include the drug's affinity for its target receptors, the dose-response relationship, and the duration of action. Different substances can exhibit various pharmacodynamic properties, such as potency, efficacy, and selectivity, which are crucial for their clinical application.

Pharmacokinetics

Pharmacokinetics involves the study of how a substance is absorbed, distributed, metabolized, and excreted in the body. Key parameters include the absorption rate, bioavailability, volume of distribution, half-life, and clearance. These factors influence the onset, intensity, and duration of the drug's effects. The pharmacokinetics of a substance can differ widely based on its chemical structure, formulation, and route of administration.

Pregnancy

Consult healthcare provider for risk assessment, as effects may vary based on substance.

Breast-feeding

Consult healthcare provider, as safety during breastfeeding is not well established.

Storage

Store in a cool, dry place away from direct sunlight, and 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.