indication

For the prevention of pregnancy in women who elect an oral contraceptive.

pharmacology

Drospirenone differs from other synthetic progestins in that its pharmacological profile in preclinical studies shows it to be closer to the natural progesterone. As such it has anti-mineralocorticoid properties, counteracts the estrogen-stimulated activity of the renin-angiotensin-aldosterone system, and is not androgenic.

mechanism of action

Progestins such as drospirenone diffuse freely into target cells in the female reproductive tract, mammary gland, hypothalamus, and the pituitary and bind to the progesterone receptor. Once bound to the receptor, progestins slow the frequency of release of gonadotropin releasing hormone (GnRH) from the hypothalamus and blunt the pre-ovulatory LH surge.

biotransformation

Extensively metabolized following oral or intravenous administration. The two major metabolites are inactive and are formed independent of the CYP450 enzyme system. The metabolites are the acid form of drospirenone formed by opening of the lactone ring and the 4,5-dihydro-drospirenone-3-sulfate.

absorption

Oral bioavailability is approximately 76%.

half life

30 hours

drug interactions

Artemether: Artemether may decrease the effectiveness of drospirinone by increasing its metabolism via CYP3A4. Consider an alternate non-hormonal means of contraception during artemether therapy.

Benazepril: Increased risk of hyperkalemia

Bexarotene: Bexarotene may decrease the serum concentration of Contraceptives (Progestins). Since bexarotene is teratogenic and can lower serum concentrations of drospirenone, it is advised that women of childbearing potential use two forms of contraception (including at least one non-hormonal form).

Candesartan: Increased risk of hyperkalemia

Captopril: Increased risk of hyperkalemia

Cilazapril: Increased risk of hyperkalemia

Colesevelam: Bile Acid Sequestrants may decrease the serum concentration of Contraceptives (Progestins). Administer oral progestin-containing contraceptives at least 1-4 hours prior to or 4-6 hours after administration of a bile acid sequestrant. Consider alternatives in order to avoid this combination when possible, due to the risk for impaired contraceptive effectiveness.

Enalapril: Increased risk of hyperkalemia

Eprosartan: Increased risk of hyperkalemia

Fosinopril: Increased risk of hyperkalemia

Heparin: Heparin can increase risk of hyperkalemia for patients on drospirenone

Irbesartan: Increased risk of hyperkalemia

Lisinopril: Increased risk of hyperkalemia

Losartan: Increased risk of hyperkalemia

Olmesartan: Increased risk of hyperkalemia

Perindopril: Increased risk of hyperkalemia

Potassium: Increased risk of hyperkalemia

Quinapril: Increased risk of hyperkalemia

Ramipril: Increased risk of hyperkalemia

Telmisartan: Telmisartan may increase the hyperkalemic effect of Drospirenone. Monitor for increased serum potassium concentrations during concomitant therapy.

Thiopental: Thiopental may decrease the effect of Drospirenone. Contraceptive failure may occur. Alternative nonhomomonal contraception should be used during concomitant therapy.

Trandolapril: Increased risk of hyperkalemia. Monitor serum potassium levels.

Treprostinil: Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use.

Tretinoin: Oral Tretinoin may decrease the effect of oral contraceptive, Drospirenone. An alternate form of contraception should be used during concomitant therapy.

Triamterene: Increased risk of hyperkalemia

Warfarin: Drospirenone may alter the anticoagulant effect of warfarin. Concomitant therapy should be avoided. Monitor for changes in coagulation status if drospirenone is initiated, discontinued or dose changed.