norelgestromin/ethinylestradiol (Ortho Evra, Xulane)

Dosing and uses of Ortho Evra, Xulane (norelgestromin-ethinyl-estradiol)

• Adult
• Pediatric

 

Adult dosage forms and strengths

norelgestromin/ethinyl estradioL

transdermal patch

• Delivers (150mcg/35mcg)/24 hr

 

Contraception

One patch applied to skin each week x 3 weeks (days 1, 8, & 15), then off for 1 week (days 22-28); repeat cycle

Initial treatment: Apply patch on 1st day of menstruation (day 1); if applied after 1st day, use additional form of contraception for 7 days

Switching from OC: Apply on 1st day of withdrawal bleeding; if applied after 1st day, use additional form of contraception for 7 days

After 1st trimester abortion: Begin treatment immediately; if not started within 5 days, use additional form of contraception for 7 days

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

 

If Patient Forgets to Change Patch

At start of patch cycle: Apply new patch immediately, count as "day 1" of cycle, use additional form of contraception for 7 days

In middle of patch cycle

• <48 hours: Apply new patch immediately, then next patch on usual "Patch Change Day"
• >48 hours: Apply new patch immediately, count as "day 1" of cycle, use additional form of contraception for 7 days

 

If Patch Partially or Completely Detached

<24 hours: Reapply to same place, or replace with new patch immediately

>24 hours: Apply new patch immediately, count as "day 1" of cycle

>1 week: Rule out pregnancy before restarting treatment; use additional form of contraception for 7 days

 

Renal Impairment

Use caution; monitor blood pressure

 

Hepatic Impairment

Do not administer

 

Other Information

At end of patch cycle (day 22): Take off patch immediately; apply next patch on usual start of next cycle

 

Pediatric dosage forms and strengths

Not recommended

 

Ortho Evra, Xulane (norelgestromin-ethinyl-estradiol) adverse (side) effects

Frequency not defined

Emotional liability

Headache

Abdominal pains

Nausea

Breast symptoms

Menstrual cramps

Applicaiton site reaction

Arterial/venous thromboembolism

Hypertension

Myocardial infarct

Cerebral hemorrhage

Gallbladder dz

Hepatic adenomas

 

Postmarketing Reports

Dysgeusia

Also see Estradiol combos for details; similar to oral contraceptives

 

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 w/ age (>35 yr) & w/ heavy smoking (15 or more cigarettes/day)
• For this reason, hormonal contraceptives, including Ortho Evra patch, should not be used by women who smoke and are 35 years or older

Thromboembolism

• Risk of venous thromboembolism (VTE) among women aged 15-44 who used the Ortho Evra patch compared to women who used oral contraceptives containing 30-35 mcg of ethinyl estradiol (EE) and either levonorgestrel or norgestimate was assessed in 4 U.S. case-control studies using electronic healthcare claims data
• The odds ratios ranged from 1.2-2.2
• One of the studies found a statistically significant increased risk of VTE for current users of Ortho Evra

 

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

Risk of venous thromboembolism (VTE) highest in first year of use; risk may increase when combined hormonal contraceptive re-started after a break in use of 4 weeks or longer

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 Ortho Evra, Xulane (norelgestromin-ethinyl-estradiol)

Mechanism of action

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

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

 

Pharmacokinetics

Half-Life: 17 hr (ethinyl estradiol); 28 hr (norelgestromin)

Metabolism: Norgestrel is primary metabolite of norelgestromin

Excretion: Urine, feces

Bioavailability: 60% (ethinyl estradiol)

Protein bound

• Ethinyl estradiol: Extensively bound to serum albumin
• Norelgestromin: Highly bound (>97%) to serum; also bound to albumin but not to SHBG