Description

Drospirenone is a progestin and is indicated for use by females of reproductive potential to prevent pregnancy. It is an oral contraceptive that lowers the risk of becoming pregnant primarily by suppressing ovulation. Drospirenone is a spironolactone analogue with anti-mineralocorticoid activity. Absorption: The pharmacokinetics of oral Drospirenone is dose-proportional following single doses ranging from 1-10 mg. Maximum concentrations (Cmax) of Drospirenone in plasma of about 27 ng/ml are reached at about 2-6 hours after single ingestion of During a treatment cycle, maximum steady-state concentrations of Drospirenone in serum of about 41 ng/ml are reached after about 10 days of treatment. Concomitant ingestion of food has no influence on the extent of absorption of Drospirenone. Distribution: Drospirenone is 95% to 97% bound to serum albumin & does not bind to sex hormone binding globulin (SHBG) or corticosteroid-binding globulin (CBG). The apparent volume of distribution of Drospirenone is approximately 4 L/kg. Metabolism: Drospirenone is extensively metabolized after oral administration. The two main metabolites of found in human plasma were identified to be the acid form of generated by opening of the lactone ring and the 4,5-dihydro Drospirenone-3-sulfate, formed by reduction and subsequent sulfation. These metabolites were shown not to be pharmacologically active. Drospirenone is also subject to oxidative metabolism catalyzed by CYP3A4. Excretion: Drospirenone serum concentrations are characterized by a terminal disposition phase half-life of approximately 30 hours after both single and multiple dose regimens. Excretion of Drospirenone was nearly complete after ten days and amounts excreted were slightly higher in feces compared to urine. Drospirenone was extensively metabolized and only trace amounts of unchanged Drospirenone were excreted in urine and feces.

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

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. Adverse reactions: Acne Metrorrhagia Headache Breast pain Weight increased Dysmenorrhea Nausea Vaginal hemorrhage Libido decreased Breast tenderness Menstruation irregularity

Based on epidemiologic studies and meta-analyses, there is little or no increased risk of birth defects in the children of females who inadvertently use oral progestin during early pregnancy. Discontinue it if pregnancy occurs, because there is no reason to use hormonal contraceptives during pregnancy. Negligible amounts of Drospirenone are excreted in breast milk. Thus, at therapeutic doses of it, no effects on breastfed newborns/infants are anticipated. General, no adverse effects have been found on milk production or on the health growth, or development of the infant with use of POPs.

Hyperkalemia: Drospirenone, a progestin, which has anti-mineralocorticoid activity, including the potential for hyperkalemia in high-risk females, comparable to a 25 mg dose of spironolactone. Drospirenone is contraindicated in females with conditions that predispose to hyperkalemia (e.g. renal impairment, hepatic impairment, and adrenal insufficiency). Females receiving daily, long-term treatment for chronic conditions or diseases with medications that may increase serum potassium concentration should have their serum potassium concentration checked prior to starting treatment and during the first treatment cycle. Consider monitoring serum potassium concentration in females at increased risk for hyperkalemia i.e., those females who take a strong CYP3A4 inhibitor long-term and concomitantly with Drospirenone. Strong CYP3A4 inhibitors include azole antifungals (e.g. ketoconazole, itraconazole, voriconazole), HIV/HCV protease inhibitors (e.g., indinavir, boceprevir), and clarithromycin. Monitor females taking Drospirenone who later develop medical conditions  and/or begin medication that put them at an increased risk for hyperkalemia. Thromboembolic Disorders: Epidemiological studies have not indicated an association between progestin-only preparations and an increased risk of myocardial infarction, cerebral thromboembolism, or venous  thromboembolism. It is unknown whether the risk of VTE is increased with Drospirenone alone; however, if there is a risk, it is expected to be lower than that of Drospirenone in combination with ethinyl estradiol. When prescribing Drosperinone, consider the increased risk of thromboembolism inherent in the postpartum period and in females with a history of thromboembolism. Discontinue Drosperinone if arterial or venous thromboembolic events occur. Consider discontinuing Drospirenone, if feasible, in case of Drospirenone prolonged immobilization due to surgery or illness. Bone Loss: Treatment with Drospirenone leads to decreased estradiol serum levels. It is unknown if this may cause a clinically relevant loss of bone mineral density. Liver Disease: Discontinue Drospirenone if jaundice or acute or chronic disturbances of liver function develop. Do not resume use until markers of liver function return to normal and Drospirenone causation has been excluded. Drospirenone is contraindicated in females with liver tumors, benign or malignant, or hepatic impairment. Ectopic Pregnancy: Be alert to the possibility of ectopic pregnancy in females who become pregnant or complain of lower abdominal pain while on Drospirenone. Risk of Hyperglycemia in Patients with Diabetes: Some patients receiving progestins, including Drospirenone, may exhibit a decrease in insulin sensitivity. Therefore, patients with diabetes may be at greater risk of hyperglycemia and may require additional medication adjustments or monitoring. Bleeding Irregularities and Amenorrhea: Females using Drospirenone may experience unscheduled (breakthrough or intracyclic) bleeding and spotting, especially during the first three months of use. Bleeding irregularities may resolve over time or by changing to a different contraceptive product. If bleeding persists or occurs after previously regular cycles, evaluate for causes such as pregnancy or malignancy. If scheduled bleeding does not occur, consider the possibility of pregnancy. If the patient has not adhered to the prescribed dosing schedule (missed one or two active tablets or started taking them on a day later than she should have, consider the possibility of pregnancy at the time of the first missed period and perform appropriate diagnostic measures. If the patient has adhered to the prescribed dosing schedule and misses two consecutive periods, rule out pregnancy. Depression: Carefully observe females for a history of depression and discontinue Drospirenone if depression recurs to a serious degree. Data on the association of progestin-oacontraceptive products with onset of depression and exacerbation of depression are limited.

There have been no reports of serious deleterious effects from overdosage of Drospirenone. Symptoms that may occur include are nausea, vomiting, and vaginal bleeding. There are no antidotes and treatment should be to provide symptomatic support. Drospirenone is a spironolactone analogue which has antimineralocorticoid properties. Therefore, serum potassium and sodium, and evidence of metabolic acidosis, should be monitored in cases of overdose.

Oral Contraceptive preparations