norgestrel/ethinylestradiol (Cryselle, Lo/Ovral, Lo/Ovral-28, LoFemanal, Low-Ogestrel, Elinest, Ogestrel)

Dosing and uses of Cryselle, Lo/Ovral (norgestrel-ethinyl-estradiol)

• Adult
• Pediatric

 

Adult dosage forms and strengths

norgestrel/ethinyl estradioL

tablet

• 0.3mg/30mcg (Cryselle, Elinest, Lo-Ogestrel, Lo/Ovral)
• 0.5mg/50mcg (Ogestrel)

 

Contraception

Follow Manufacturer's color-coding for active versus inert tabs

Start on day 1 of menstrual cycle or Sunday following start of cycle

1 hormonally active tablet PO for 21 days, then 7 tablet-free days (or inert tablets as supplied); repeat cycle

 

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

 

Renal Impairment

Use caution; monitor blood pressure

 

Hepatic Impairment

Do not administer

 

Pediatric dosage forms and strengths

Safety and efficacy not established

 

Cryselle, Lo/Ovral (norgestrel-ethinyl-estradiol) adverse (side) effects

>10%

Edema

Weakness

Amenorrhea

Breakthrough bleeding

Change in menstrual flow

Spotting

Anorexia

 

Frequency not defined

DVt

Thrombophlebitis

Depression

Dizziness

Headache

Nervousness

Somnolence

Breast tenderness

Galactorrhea

Abdominal pain

Nausea

Vomiting

Change in weight

Cholestatic jaundice

 

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

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)

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

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: small amounts of steroids are excreted in breast milk; estrogens may reduce quality/quantity of milk; may be prudent to use other forms of birth control until full weaning (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 Cryselle, Lo/Ovral (norgestrel-ethinyl-estradiol)

Mechanism of action

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

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

 

Pharmacokinetics

Half-Life: 28 hr (ethinyl estradiol)

Protein Bound: Extensively bound to serum albumin (ethinyl estradiol)

Metabolism: Hepatic CYP3A4 to estriol, estrone (ethinyl estradiol)

Excretion: Ethinyl estradiol: Urine as conjugates, most estrogens are also excreted in bile and undergo enterohepatic recycling