Usage
Gestodene is primarily used in combination with ethinylestradiol as a combined oral contraceptive (COC) to prevent pregnancy. It belongs to the pharmacological classification of progestins, specifically a third-generation synthetic progestogen. Gestodene, in combination with ethinylestradiol, primarily works by inhibiting ovulation. It also alters the cervical mucus, making it thicker and less penetrable by sperm, and changes the uterine lining, making implantation less likely.
Alternate Names
Gestodene is the generic name. Brand names vary depending on the specific formulation and country but may include Minesse®, Femodene®, Minulet®, Harmonet®, and Millinette®.
How It Works
Pharmacodynamics: Gestodene, in combination with ethinylestradiol, suppresses the hypothalamic-pituitary-ovarian axis, inhibiting the release of gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH). This prevents follicular development and ovulation. Gestodene also induces changes in the cervical mucus, increasing its viscosity, thus hindering sperm penetration. Additionally, it alters the endometrium, making it less receptive to implantation.
Pharmacokinetics:
- Absorption: Gestodene is rapidly and completely absorbed after oral administration. Peak plasma concentrations are reached in about 1 hour. The plasma concentrations are dependent on sex hormone-binding globulin (SHBG) levels, which are increased by ethinylestradiol.
- Distribution: Gestodene is highly bound to plasma proteins, primarily SHBG (50-70%) and albumin (30%). It has an apparent volume of distribution of about 1.4 L/kg.
- Metabolism: Gestodene is extensively metabolized in the liver via the steroid metabolic pathway, primarily by CYP3A4 enzymes. It undergoes hydroxylation and reduction reactions.
- Elimination: Gestodene metabolites are excreted primarily in the urine and to a lesser extent in the feces. Less than 1% is excreted unchanged in urine.
Mode of Action: Gestodene binds to and activates progesterone receptors. It has a high affinity for these receptors, making it a very potent progestin. Although it has weak androgenic, antimineralocorticoid, and glucocorticoid activity, these effects are generally not clinically significant at the doses used in COCs.
Dosage
The dosage of gestodene is always in combination with ethinylestradiol and is dependent on the specific formulation.
Standard Dosage
Adults:
The typical dose is one tablet containing 60 mcg gestodene and 15-30 mcg ethinylestradiol daily for 21 days, followed by a 7-day pill-free interval (during which withdrawal bleeding usually occurs), or 24 active pills followed by 4 placebo pills.
Children:
COCs containing gestodene are generally not indicated for use before menarche. After menarche, the dosage is the same as for adults.
Special Cases:
- Elderly Patients: COCs are generally not recommended for postmenopausal women.
- Patients with Renal Impairment: Data is limited, and caution should be exercised in these patients.
- Patients with Hepatic Dysfunction: COCs are contraindicated in women with severe hepatic impairment. Caution is advised in those with mild to moderate impairment.
- Patients with Comorbid Conditions: Caution is advised in patients with conditions such as hypertension, diabetes, hyperlipidemia, or a history of thromboembolic events.
Clinical Use Cases
Gestodene-containing COCs are not indicated for use in the clinical settings listed (intubation, surgical procedures, mechanical ventilation, ICU use, and emergency situations). Their sole indication is contraception.
Dosage Adjustments
Dosage adjustments may be necessary for patients with hepatic impairment, or those taking medications that interact with gestodene metabolism (e.g., enzyme inducers or inhibitors).
Side Effects
Common Side Effects:
Nausea, headache, breast tenderness, breakthrough bleeding, mood changes, weight changes, and fluid retention.
Rare but Serious Side Effects:
Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), arterial thromboembolism (ATE), such as myocardial infarction and stroke, hepatic adenoma, and gallbladder disease.
Long-Term Effects:
Increased risk of certain cancers (breast, cervical) with long-term use, although the overall risk remains low.
Adverse Drug Reactions (ADR):
Allergic reactions (rash, itching, swelling), cholestatic jaundice, and elevated liver enzymes.
Contraindications
Pregnancy, history of VTE or ATE, severe hepatic impairment, known or suspected breast cancer, undiagnosed abnormal vaginal bleeding, and hypersensitivity to gestodene or ethinylestradiol.
Drug Interactions
Enzyme-inducing drugs (e.g., rifampicin, carbamazepine, phenytoin, St. John’s Wort) can decrease the effectiveness of gestodene. Certain anti-HIV medications and antifungals can also interact. Gestodene can increase the levels of some medications, such as cyclosporine. Alcohol, grapefruit juice, and some foods high in fat may affect absorption.
Pregnancy and Breastfeeding
Gestodene-containing COCs are contraindicated during pregnancy. They are not recommended during breastfeeding as they may reduce milk production and pass into breast milk, although the effects on the infant are generally considered minimal.
Drug Profile Summary
- Mechanism of Action: Inhibits ovulation, thickens cervical mucus, alters endometrium.
- Side Effects: Nausea, headache, breast tenderness, breakthrough bleeding, VTE, ATE.
- Contraindications: Pregnancy, history of VTE/ATE, severe hepatic disease, breast cancer.
- Drug Interactions: Enzyme inducers, certain anti-HIV medications, antifungals.
- Pregnancy & Breastfeeding: Contraindicated in pregnancy, not recommended during breastfeeding.
- Dosage: One tablet daily, specific dose depending on formulation.
- Monitoring Parameters: Blood pressure, liver function tests, signs of VTE/ATE.
Popular Combinations
Gestodene is typically combined with ethinylestradiol in various COC formulations.
Precautions
Assess for risk factors for VTE, ATE, and liver disease. Monitor blood pressure and liver function. Counseling on lifestyle factors (smoking, obesity) is important.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Gestodene?
A: Gestodene is administered in combination with ethinylestradiol. Dosage varies with the specific formulation but typically involves one tablet daily for 21 days followed by a 7-day break or 24 active pills followed by 4 placebo pills.
Q2: How effective is Gestodene in preventing pregnancy?
A: With perfect use, gestodene-containing COCs are over 99% effective. Typical use effectiveness is around 91%.
Q3: What are the major contraindications to using Gestodene?
A: Pregnancy, history of VTE/ATE, severe hepatic disease, breast cancer, undiagnosed vaginal bleeding.
Q4: Can Gestodene be used during breastfeeding?
A: It’s not recommended as it may reduce milk production and can be passed to the infant through breast milk.
Q5: What are the most common side effects of Gestodene?
A: Nausea, headache, breast tenderness, breakthrough bleeding, mood changes.
Q6: How does Gestodene interact with other medications?
A: Enzyme-inducing drugs can decrease its effectiveness. It can increase levels of drugs like cyclosporine.
Q7: Are there any long-term risks associated with Gestodene use?
A: A slightly increased risk of certain cancers (breast, cervical) with prolonged use, although the absolute risk remains low.
Q8: What should patients be monitored for while taking Gestodene?
A: Blood pressure, signs and symptoms of VTE/ATE, and liver function.
Q9: What is the mechanism of action of Gestodene?
A: Primarily inhibits ovulation, also thickens cervical mucus and alters the endometrium.
This information is current as of February 16, 2025, and may change with future research and clinical trials.
