Drospirenone + Estetrol

Drospirenone + Estetrol Uses, Dosage, Side Effects, Food Interaction and all others data.

Drospirenone is a Progestin-only pill which is a synthetic form of progesterone. The hormonal component of Drospi inhibit ovulation by Suppressing gonadotropin release, Secondary mechanisms, which may contribute to the effectiveness of Drospi as a contraceptive, include changes in the cervical mucus (which increase the difficulty of sperm penetration) and changes in the endometrium (which reduce the likelihood of implantation). Drospirenone has antimineralocorticoid activity, counteracting oestrogen related sodium retention. Drospirenone exerts antiandrogenic activity.

Drospirenone inhibits the maturation of follicles and inhibits ovulation, preventing pregnancy. It has antiandrogen effects, improving acne and hirsutism. When combined with ethinyl estradiol, it has been shown to have favorable effects on the plasma lipid profile. Due to its similarity to naturally occurring progesterone, drospirenone is thought to be associated with a lower incidence of progesterone contraceptive related adverse effects, such as breast tenderness and mood swings.

A note on venous thromboembolism risk and antimineralcorticoid effects

As with other oral contraceptives, the risk of venous thromboembolism and cardiovascular events may be increased when drospirenone is taken. The risk is especially higher in smokers and women aged 35 and older. Women taking this drug should be advised not to smoke. In addition, drospirenone, due to its antimineralcorticoid effects, may increase the risk of hyperkalemia. Patients at high risk for hyperkalemia should not be administered this drug. Consult the official prescribing information for detailed and updated information on the cardiovascular and other risks associated with drospirenone use.

Naturally or synthetically produced steroid estrogens have a wide range of pharmaceutical uses ranging from hormonal contraception to the treatment of menopausal symptoms. Estetrol (E4) is a native estrogen occurring naturally during pregnancy, but can be synthesized from a plant source and used for contraception. It is more potent and is safer than the synthetic estrogen ethinylestradiol (EE2) found in 97% of oral contraceptive pills, reducing the environmental accumulation of unwanted endocrine disrupting chemicals (EDCs) that often lead to harmful epigenetic effects.

On April 15 2021, Mayne Pharma Group Limited and Mithra Pharmaceuticals were granted FDA approval for the oral contraceptive Estelle/Nextstellis, a combination of drospirenone and estetrol. Estetrol is the first new estrogen introduced to the USA in over 50 years and is the first approved estetrol product in the world. The combination of drospirenone and estetrol offers a new choice with a favourable safety profile for women seeking contraceptive therapy. In Canada, Nextstellis was approved for use in March 2021; it was developed by Mithra and is marketed by Searchlight Pharma.

Estetrol prevents pregnancy by suppressing ovulation.

Drospirenone + Estetrol
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	Drospirenone + Estetrol
Generic	Drospirenone + estetrol
Type
Therapeutic Class
Manufacturer
Available Country	Bangladesh
Last Updated:	September 24, 2024 at 5:38 am

Uses

Drospirenone is used for oral contraception.

Estetrol is an estrogen used in combination with drospirenone for oral contraception.

Estetrol is indicated in combination with drospirenone for the prevention of pregnancy.

Drospirenone + Estetrol is also used to associated treatment for these conditions: Abnormal Uterine Bleeding, Acne Vulgaris, Endometriosis, Hypermenorrhea, Idiopathic Hirsutism, Menstrual Distress (Dysmenorrhea), Menstrual Irregularities, Osteoporotic Fractures, Pregnant State, Premenstrual Dysphoric Disorder, Vasomotor Symptoms Associated With Menopause, Vulvovaginal Atrophy, Hypoestrogenism, Folate supplementation therapy, Hormone Replacement Therapy, Oral ContraceptivesOral Contraceptives

How Drospirenone + Estetrol works

Drospirenone and ethinyl estradiol in combination suppress the release of follicle stimulating hormone (FSH) and luteinizing hormone (LH), preventing ovulation. Other changes induced by this drug which may aid in the prevention of pregnancy include alterations in cervical mucus consistency, hindering sperm movement, and lowering the chance of embryo implantation.

Drospirenone is an analog of the diuretic spironolactone, which exerts anti-mineralocorticoid activity, blocking aldosterone receptors, which increases sodium and water excretion. Studies in animals have demonstrated that drospirenone administration leads to antiandrogenic activity. This activity helps to oppose the effects of naturally occurring androgens, inhibiting the binding of dihydrotestosterone (DHT) to its receptor, and preventing androgen synthesis in the ovaries, helping to treat acne and hirsutism. Drospirenone may also decrease the level of edema in sebaceous follicle during the second half of the menstrual cycle, when acne often appears.

Estetrol is a synthetic analogue of a naturally occurring estrogen present during pregnancy, demonstrating selectivity for both estrogen receptor-α (ER-α) and ER-β and suppressing ovulation. Estetrol binds with a low to moderate affinity human estrogen receptor alpha (ER alpha) and ER beta with a preference for ER alpha. Estetrol demonstrates a unique mechanism of action via tissue selective activity, showing estrogen receptor agonist activity on the vagina, the uterus and the endometrium, and negative estrogenic activity on breast tissue.

Dosage

Drospirenone + Estetrol dosage

Drospirenone (white active and light pink inert tablets) is swallowed whole once a day. Take one tablet daily for 28 consecutive days; one white active tablet daily during the first 24 days and one light pink inert tablet daily during the 4 following days. Tablets must be taken every day at about the same time of the day so that the interval between two tablets is always 24 hours.

Side Effects

The following clinically significant Side Effects are described elsewhere in other sections of the labeling:

Hyperkalemia
Bleeding Irregularities and Amenorrhea
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Toxicity

The oral LD50 of drospirenone in rats is >2000 mg/kg.

Overdose information An overdose of drospirenone, like other oral contraceptives, may lead to cause nausea or withdrawal bleeding. For drospirenone in particular, as an analog of spironolactone, may affect the levels of serum sodium and potassium. Their concentrations should be monitored in cases of overdose in addition to monitoring from metabolic acidosis and hyperkalemia, which may also result.

LD50 information for estetrol is not readily available in the literature. Subjects receiving a dose of 20 mg, 40 mg or 60 mg of estetrol per day over 12 weeks were tolerated without dose-limiting toxicity. Symptoms that may occur in association with overdose, based on existing information on overdosage with oral contraceptives include nausea, vomiting, and vaginal bleeding. In one clinical study, 1 of 32 healthy research subjects receiving a dose of 75 mg of estretol with 15 mg of drospirenone for 10 days experienced deep vein thrombosis of the lower right limb. There is no known antidote to an estretol overdose; conduct laboratory testing for electrolytes and evidence of metabolic acidosis and provide symptomatic treatment.

Precaution

Before you take Drospirenone, do not take this medicine and tell your doctor if you are already taking the following medicines: efavirenz, phenytoin, barbiturates, carbamazepine, bosentan, felbamate, griseofulvin, oxcarbazepine, rifampicin, rifabutin, rufinamide, aprepitant, products containing St. John's wort. Take special care while taking Drospirenone Hyperkalemia Thromboembolic Disorders, Bone Loss, Liver Disease Ectopic Pregnancy, Risk of Hyperglycemia in Patients with Diabetes, Bleeding Irregularities, and Amenorrhea, Depression.

Interaction

Drugs or herbal products that induce certain enzymes (for example, CYP3A4) may decrease the effectiveness of Drospirenone or increase breakthrough bleeding. Counsel patients to use a back-up or alternative method of contraception when enzyme inducers are used with Drospirenone.

Volume of Distribution

The volume of distribution of drospirenone is estimated to be 4 L/kg, according to the FDA label for Yaz. Prescribing information from a combination of estradiol and drospirenone estimates the volume of distribution to range from 3.7- 4.2 L/kg.

Limited distribution of estetrol into red blood cells has been demonstrated.

Elimination Route

The absolute bioavailability of drospirenone is approximately 76% due to first-pass effects. The maximum plasma concentration of drospirenone occurs within 1 to 2 hours after oral administration and is estimated to range between 60 and 87 ng/mL. A European prescribing monograph for the combination product of estradiol and drospirenone indicates that drospirenone is both completely and rapidly absorbed. It reports a Cmax of 21.9 ng/ml, achieved approximately 1-hour post-administration. The absolute bioavailability is reported to range between 76 to 85%.

Estetrol is rapidly absorbed from the gastrointestinal tract. The Cmax of estetrol is 18 ng/mL according to the results of a pharmacokinetic study, with an AUC of 36.4 ng•h/mL. When estetrol and drospirenone are taken in a single product, maximum serum concentrations of approximately 48.7 ng/mL are achieved within 1-3 h. Bioavailability of the combination ranges between 76 and 85%. The Tmax can range from 0.5 to 2 hours and time to steady state is approximately 4 days, according to the results of one clinical study.

Half Life

The serum half-life of drospirenone is estimated to be 30 hours. The half-life of drospirenone metabolite excretion in the urine and feces is approximately 40 hours.

The elimination half-life of estetrol is approximately 27 hours. Half-life may range between 19-40 hours.

Clearance

Drospirenone is rapidly cleared, typically within 2-3 days of administration of the last active tablet. The rate of clearance of drospirenone calculated in the serum ranges from 1.2-1.5 ml/min/kg, however, this value can vary by up to 25% according to the patient.

Elimination Route

Various metabolites of drospirenone are measured in the urine and feces. Drospirenone elimination from the body is almost after 10 days post-administration when negligible amounts of drospirenone are found unchanged in both the urine and feces. Between 38% to 47% of the metabolites are identified as glucuronide and sulfate conjugates in the urine. In the feces, approximately 17% to 20% of identifiable metabolites are found to be excreted as glucuronides and sulfates.

Estrogens are generally excreted as sulfated and glucuronidated derivatives. Approximately 69% of a dose of estetrol is excreted in the urine, and about 22% is excreted in the feces as unchanged drug.