dienogest/estradiol valerate (Rx)

>10%

Headache, including migraines (13.2%)

1-10%

Metrorrhagia and irregular menstruation (8%)

Breast pain, discomfort, or tenderness (6.6%)

Nausea or vomiting (6.5%)

Acne (3.9%)

Weight gain (2.85)

<1%

Venous thromboembolism

Jaundice or cholestasis

Gallbladder disease

Depression

Contraindications

Pregnancy

Hypersensitivity

Breast Cancer, or other estrogen- or progestin-sensitive cancer

A high risk of arterial or venous thromboembolic disorders

Undiagnosed uterine bleeding

Cautions

Poorly metabolized with hepatic impairment

Use caution in patients with history of migraine, seizure disorder,

Not recommended for women smokers >35 years

Oral contraceptives can reduce production of milk in breastfeeding mothers

Evaluate significant change in headaches and discontinue therapy if indicated

Women taking strong CYP3A4 inducers (for example, carbamazepine, phenytoin, rifampicin, and St. John’s wort) should choose an alternate oral contraceptive due to the possibility of decreased contraceptive efficacy

Discontinue therapy if jaundice occurs

Not for administration for women with uncontrolled hypertension or hypertension with vascular disease

Monitor prediabetic and diabetic women receiving therapy

Consider an alternate contraceptive method for women with uncontrolled dyslipidemia

Evaluate uterine bleeding or amenorrhea

Thromboembolic disease may occur; stop therapy for at least 4 weeks before and through 2 weeks after major surgery; initiate therapy no sooner than 4 weeks after delivery, in women who are not breastfeeding

Safety and efficacy not established for BMI >30 kg/m²

CDC guidelines recommend waiting at least 3 weeks following vaginal birth or 6 weeks after cesarean section to decrease risk for venous thromboembolism before initiating combined hormonal contraceptives; women with additional risk factors for VTE (besides postpartum) should not use combined hormonal contraceptives (MMWR July 7, 2011)

Pregnancy considerations: There is little or no increased risk of birth defects in women who inadvertently use combined oral contraceptives (COCs) during early pregnancy; epidemiologic studies and meta-analyses have not found increased risk of genital or non-genital birth defects following exposure to low dose COCs prior to conception or during early pregnancy; the administration of COCs to induce withdrawal bleeding should not be used as a test for pregnancy; COCs should not be used during pregnancy to treat threatened or habitual abortion; women who do not breastfeed may start COCs no earlier than four weeks postpartum.

Lactation: May decrease breast milk production; enters milk; not recommended

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Estrogen/progestin combined oral contraceptive; decreases risk of becoming pregnant primarily by suppressing ovulation May also cause cervical mucus changes that inhibit sperm penetration and endometrial changes that decrease ability for implantation

Pharmaockinetics

Bioavailability: 91% (dienogest)

Vd: 1.2 L/kg (estradiol IV)

Peak Plasma Time: 6 hr (17-beta estradiol); 11 hr (dienogest)

Peak Plasma Concentration: 73.3 pg/mL (17-beta estradiol); 91.7 ng/mL (dienogest)

Protein Bound: 60% (estradiol); 90% (dienogest)

Half-life elimination

• estradiol: 14 hr
• dienogest: 1 hr

Excretion

• estradiol and its metabolites: feces (10%), urine (90%)
• dienogest: predominantly via urine as metabolites and unchanged dienogest