desogestrel/ethinylestradiol (Ortho-Cept, Desogen, Apri, Caziant, Cyclessa, Emoquette, Enskyce, Kariva, Mircette, Reclipsen, Solia, Velivet, Viorele, Azurette, Kimidess, Pimtrea)

Dosing and uses of Ortho Cept (desogestrel-ethinyl estradiol)

• Adult
• Pediatric

 

Adult dosage forms and strengths

desogestrel/ethinyl estradioL

tablet, monophasic

• 0.15mg/0.03mg

tablet, biphasic

• 0.15mg/0.02mg x 21 days, then inert tabs x 2 days, then 0mg/0.01mg x 5 days

tablet, triphasic

• 0.1mg/0.025mg (7 tabs), plus
• 0.125mg/0.025mg (7 tabs), plus
• 0.15mg/0.025mg (7 tabs)

 

Contraception

Monophasic (Apri, Cyred, Desogen, Emoquette, Enskyce, Juleber, Ortho-Cept, Reclipsen, Solia)

• 1 tablet PO qDay for 28 days, then start new pack
• Days 1-21: Each tablet contains desogestrel 0.15 mg/ethinyl estradiol (EE) 0.03 mg
• Days 22-28: Inactive tablets

Biphasic (Azurette, Kariva, Kimidess, Mircette, Pimtrea, Viorele)

• 1 tablet PO qDay for 28 days in order indicated on package, then start new pack
• Days 1-21, Each tablet contains 0.15 mg desogestrel/0.02 mg EE
• Days 22-23: Inactive tablets
• Days 24-28: Each tablet contains 0.01 mg ethinyl estradiol

Triphasic (Cyclessa, Velivet, Caziant)

• 1 tablet PO qDay for 28 days in order indicated on package, then start new pack Day 1-7, each tablet contains 0.025 mg ethinyl estradiol and 0.1 mg desogestrel
• Days 8-14, each tablet contains 0.025 mg ethinyl estradiol and 0.125 desogestrel
• Days 15-21, each tablet contains 0.025 mg ethinyl estradiol and 0.15 desogestrel
• Days 22-28: Inactive tablets

 

Other Indications & Uses

Off-label: Dysmenorrhea, dysfunctional uterine bleeding, endometriosis, polycystic ovarian syndrome, acne

 

Pediatric dosage forms and strengths

Premenarche: Not recommended

 

Ortho Cept (desogestrel-ethinyl estradiol) adverse (side) effects

Frequency not defined

Arterial/venous thromboembolism

Edema

Hypertension

MI

Cerebral hemorrhage

Headache

Migraine

Chloasma

Melasma

Breast swelling/tenderness

Menstrual cramps

Emotional lability

Abdominal pains

Appetite changes

Nausea

Weight changes

Application site rxn (if transdermal preparation)

Gallbladder disease

Hepatic adenomas

Optic neuritis

Vaginal candidiasis

 

Warnings

Black box warnings

Cigarette smoking & risk of cardiovascular disease

• Cigarette smoking increases risk of serious cardiovascular adverse effects from combination hormonal contraceptive use
• This risk increases with age (>35 yr) and with heavy smoking (15 or more cigarettes/day)
• Advise women who use hormonal oral contraceptives not to smoke

 

Contraindications

Documented hypersensitivity

Active or history of breast cancer

Arterial thromboembolic disease (stroke, MI), thrombophlebitis, DVT/PE, thrombogenic valvular disease

Estrogen-dependent neoplasia

Liver disease, liver tumors

Undiagnosed abnormal vaginal bleeding

Uncontrolled hypertension (ie, persistent BP values >160 mm Hg systolic or >100 mg Hg diastolic)

Diabetes mellitus with vascular involvement, jaundice with prior oral contraceptive use

 

Cautions

Family history of breast cancer and or DVT/PE, current/history of depression, endometriosis, DM, HTN, bone mineral density changes, renal/hepatic impairment, bone metabolic disease, SLE; conditions exacerbated by fluid retention (eg, migraine, asthma, epilepsy)

Women with a history of hypertension or hypertension-related diseases, or renal disease should be encouraged to use another method of contraception

Discontinue if the following develop jaundice, visual problems (may cause contact lens intolerance), any signs of VTE, migraine with unusual severity, significang blood pressure increase, severe depression, increased risk of thromboembolic complications after surgery

Discontinue 4 week before major surgery or prolonged immobilization

Patients on warfarin, oral anticoagulants (increase in anticoagulant dose may be warranted)

Some studies link OCP use with increased risk of breast cancer, whereas other studies have not shown a change in risk

Woman's risk depends on conditions where naturally high hormone levels persist for long periods of time including early onset menstruation before age 12, late onset menopause, after age 55, first child after age 30, nulliparity

Increased risk of cervical cancer with OCP use, however HPV remains as main risk factor for this cancer; evidence suggests long-term use of OCPs, 5 or more years, may be associated with increased risk

Increased risk of liver cancer with OCP use; risk increases with longer duration of OCP use

Risk of venous thromboembolism (VTE) is highest in first year of use and when a combination oral contraceptive is started or re-started after a break in use of four weeks or more

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 and lactation

Pregnancy category: X

Lactation: enters breast milk/not recommended (AAP Committee states "compatible with nursing")

 

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.

 

Pharmacology of Ortho Cept (desogestrel-ethinyl estradiol)

Mechanism of action

Ethinyl estradiol (EE): Reduces LHRH release from hypothalamus, reduces gonadotropin release from pituitary; increase synthesis of DNA, RNA, and various proteins in target tissues

Desogestrel: Progestin; inhibits gonadotropin secretion from pituitary; prevents follicular maturation & ovulation, stimulates growth of mammary tissues

 

Pharmacokinetics

Peak plasma time: Etonogestrel 1-1.5 hr; EE 1-1.5 hr

Peak plasma concentration: Etonogestrel 2100-3800 pg/mL (dose-dependent); EE 90 pg/mL

AUC: Etonogestrel 200-250 pg.hr/mL/mcg; EE 26-29 pg.hr/mL/mcg

Protein Bound: Etonogestrel 98% bound to SHBG; EE extensively bound to serum albumin

Desogestrel: Metabolized by hepatic P450 enzyme CYP2C9 to etonogestrel (active metabolite)

EE: Metabolized by hepatic CYP3A4 to estriol, estrone

Half-Life: Etonogestrel: 38 hr; EE: 28 hr

Excretion: Urine, feces

 

Administration

Instructions

When initially starting, use additional contraceptive method during first consecutive 7 days of administration

Start on 1st day of menstrual cycle or on Sunday immediately following onset of menses

Missed periods

• If 1 menstrual period is missed and all doses have been taken on schedule (ie, no missed tablets), continue with next dosing cycle (pack)
• If 2 consecutive menstrual periods are missed, a pregnancy test is required before beginning the next dosing cycle (pack)

Initiating after pregnancy

• Increased risk for venous thromboembolism (VTE) following delivery with combined hormonal contraceptives; risk declines rapidly after 21 days, but does not return to normal until 42 days after delivery
• CDC guidelines recommend waiting 3-6 weeks in postpartum women without additional VTE risks (MMWR July 7, 2011)
• Initiating after vaginal birth: Wait at least 3 weeks
• Initiating after caesarean section birth: Wait at least 6 weeks
• Women with other risk factors for VTE in addition to postpartum: Do not use combined hormonal contraceptives