indication

For the prevention of pregnancy in women who elect to use this product as a method of contraception.

pharmacology

Desogestrel is used as a female contraceptive. Desogestrel is a progestin or a synthetic form of the naturally occurring female sex hormone, progesterone. In a woman's normal menstrual cycle, an egg matures and is released from the ovaries (ovulation). The ovary then produces progesterone, preventing the release of further eggs and priming the lining of the womb for a possible pregnancy. If pregnancy occurs, progesterone levels in the body remain high, maintaining the womb lining. If pregnancy does not occur, progesterone levels in the body fall, resulting in a menstrual period. Desogestrel tricks the body processes into thinking that ovulation has already occurred, by maintaining high levels of the synthetic progesterone. This prevents the release of eggs from the ovaries.

mechanism of action

Binds to the progesterone and estrogen receptors. Target cells include the female reproductive tract, the mammary gland, the hypothalamus, and the pituitary. Once bound to the receptor, progestins like desogestrel will slow the frequency of release of gonadotropin releasing hormone (GnRH) from the hypothalamus and blunt the pre-ovulatory LH (luteinizing hormone) surge.

toxicity

Symptoms of overdose include nausea and vaginal bleeding.

biotransformation

Desogestrel is rapidly and completely metabolized by hydroxylation in the intestinal mucosa and on first pass through the liver. It is primarily metabolized to 3α-hydroxydesogestrel with small amounts of 3β-hydroxydesogestrel being formed. Both of these metabolites are then rapidly oxidized to its active metabolite, etonogestrel (3-ketodesogestrel). Other metabolites (e.g. 2-hydroxydesogestrel) with no pharmacologic action have also been identified. Desogestrel and some of its metabolites (e.g. 3β-hydroxydesogestrel, 15β-hydroxydesogestrel) may also undergo glucuronide and sulfate conjugation. Early in vitro studies demonstrated that CYP2C9 and possibly CYP2C19 were involved in the conversion of desogestrel to 3α-hydroxydesogestrel and 3β-hydroxydesogestrel (PMID 9864282); however, later clinical studies conducted in humans refuted this result (PMID 15963096). The latter study indicates that CYP3A4 plays an important role in metabolizing etonogestrel. Thus, strong CYP3A4 inhibitors or inducers could result in increased side effects or therapeutic failure, respectively.

absorption

Following oral administration, the relative bioavailability of desogestrel, as measured by serum levels of etonogestrel, is approximately 84%. The absolute oral bioavailability is about 76%.

half life

27.8±7.2 hours

drug interactions

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

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

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.

Lamotrigine: The oral contraceptive decreases the effect of lamotrigine

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

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

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