Dehydrospirorenone

Uses

Dehydrospirorenone is used for oral contraception.

Dehydrospirorenone 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 Contraceptives

How Dehydrospirorenone works

Dehydrospirorenone 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.

Dehydrospirorenone 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. Dehydrospirorenone may also decrease the level of edema in sebaceous follicle during the second half of the menstrual cycle, when acne often appears.

Dosage

Dehydrospirorenone dosage

Dehydrospirorenone (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.

Precaution

Before you take Dehydrospirorenone, 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 Dehydrospirorenone 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 Dehydrospirorenone or increase breakthrough bleeding. Counsel patients to use a back-up or alternative method of contraception when enzyme inducers are used with Dehydrospirorenone.

Food Interaction

• Avoid St. John's Wort.
• Take at the same time every day.
• Take with or without food.

Dehydrospirorenone Drug Interaction

Moderate: sulfamethoxazole / trimethoprim, sulfamethoxazole / trimethoprimUnknown: isotretinoin, charcoal, amphetamine / dextroamphetamine, erenumab, lorazepam, ubiquinone, methylphenidate, bupropion / naltrexone, copper gluconate, glucose, diltiazem, escitalopram, metoprolol, metoprolol, cyanocobalamin, pyridoxine, cholecalciferol, zinc sulfate

Dehydrospirorenone Disease Interaction

Major: hyperkalemiaModerate: retinal thrombosis

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.

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%.

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.

Clearance

Dehydrospirorenone 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. Dehydrospirorenone 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.

Contraindication

• Renal impairment
• Adrenal insufficiency
• Presence or history of progestin sensitive cancers
• Liver tumors, benign or malignant, or hepatic impairment
• Undiagnosed abnormal uterine bleeding

Storage Condition

Store below 30°C and dry place. Keep away from light. Keep out of the reach of children.

Innovators Monograph

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