indication

For the treatment of menopausal and postmenopausal disorders and alone or in combination with other hormones as an oral contraceptive.

pharmacology

Levonorgestrel 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. Levonorgestrel 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 levonorgestrel will slow the frequency of release of gonadotropin releasing hormone (GnRH) from the hypothalamus and blunt the pre-ovulatory LH (luteinizing hormone) surge.

toxicity

LD50 >5000 mg/kg (orally in rats)

biotransformation

Hepatic

absorption

Levonorgestrel is not subjected to a "first-pass" effect and is virtually 100% bioavailable.

route of elimination

About 45% of levonorgestrel and its metabolites are excreted in the urine and about 32% are excreted in feces, mostly as glucuronide conjugates.

drug interactions

Amobarbital: Phenobarbital decreases the effect of levonorgestrel

Aprobarbital: Phenobarbital decreases the effect of levonorgestrel

Artemether: Artemether may decrease the effectiveness of levonorgestrel 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 levonorgestrel, it is advised that women of childbearing potential use two forms of contraception (including at least one non-hormonal form).

Butabarbital: Phenobarbital decreases the effect of levonorgestrel

Butalbital: Phenobarbital decreases the effect of levonorgestrel

Butethal: Phenobarbital decreases the effect of levonorgestrel

Carbamazepine: Carbamazepine may decrease the contraceptive effect of levonorgestrel.

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.

Dihydroquinidine barbiturate: Phenobarbital decreases the effect of levonorgestrel

Ethotoin: Phenytoin decreases the contraceptive effect

Fosphenytoin: Phenytoin decreases the contraceptive effect

Heptabarbital: Phenobarbital decreases the effect of levonorgestrel

Hexobarbital: Phenobarbital decreases the effect of levonorgestrel

Mephenytoin: Phenytoin decreases the contraceptive effect

Methohexital: Phenobarbital decreases the effect of levonorgestrel

Methylphenobarbital: Phenobarbital decreases the effect of levonorgestrel

Pentobarbital: Phenobarbital decreases the effect of levonorgestrel

Phenobarbital: Phenobarbital decreases the effect of levonorgestrel

Phenytoin: Phenytoin decreases the contraceptive effect

Primidone: Phenobarbital decreases the effect of levonorgestrel

Quinidine barbiturate: Phenobarbital decreases the effect of levonorgestrel

Secobarbital: Phenobarbital decreases the effect of levonorgestrel

Talbutal: Phenobarbital decreases the effect of levonorgestrel

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

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

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