norgestimate/ethinylestradiol (Mononessa, Ortho Cyclen-28, Ortho Tri-Cyclen, Ortho Tri-Cyclen Lo, Estarylla, Tri-Estarylla, Tri-Lo-Estarylla, Mili, Mono-Linyah, Tri-Linyah, Previfem, Sprintec 28, TriCyclen, Tri-Lo Sprintec, Tri-Mili, Trinessa, TriNessa Lo, TriPrevifem, TriSprintec)
Classes: Estrogens/Progestins; Contraceptives, Oral
Dosing and uses of Mononessa, Ortho Cyclen-28 (norgestimate/ethinylestradiol)
Adult dosage forms and strengths
norgestimate/ethinyl estradioL
tablet, monophasic (Estarylla, Mili, MonoNessa, Previfem, Sprintec)
- Days 1-21: 0.25mg/35mcg
- Days 22-28: Inert tablets
tablet, triphasic (Ortho Tri-Cyclen, Tri-Estarylla, Tri-Mili, Trinessa, Tri-Sprintec, Tri-Previfem)
- Days 1-7: 0.18mg/35mcg
- Days 8-14: 0.215mg/35mcg
- Days 15-21: 0.25mg/35mcg
- Days 22-28: Inert tablets
tablet, triphasic (Ortho Tri-Cyclen Lo, Tri-Lo-Estarylla)
- Days 1-7: 0.18mg/25mcg
- Days 8-14: 0.215mg/25mcg
- Days 15-21: 0.25mg/25mcg
- Days 22-28: Inert tablets
Contraception
Sunday starter: 1 hormonally active tablet daily for 21 days, then 1 inert tablet daily for 7 days; cycle repeated; start Sunday after onset of menstruation; if menstrual period occurs on Sunday, start that very same day; take additional method of contraception until after first 7 days of consecutive administration
Day 1 starter: Take first dose on the day of the menstrual cycle and continue to take 1 tablet daily
21-tablet package: Take 1 tablet for 21 days followed by 7 days off the medication
28-tablet package: Take 1 tablet daily without interruption
Missed dose monophasic
- One dose missed: Take dose as soon as remembered or take 2 tablets next day
- Two consecutive doses missed: Take 2 tablets as soon as remembered or 2 tablets next two days; use additional method of contraception for 7 days after missed dose
- Two consecutive doses missed in week three or three doses missed at any time: Use additional method of contraception for 7 days after missed dose
- Start a new pack if two doses missed in third week or three doses missed at any time as follows
- Sunday starter: Continue daily dose until Sunday, then discard the rest of the pack and start a new pack that same day
- Day 1 starter: Discard current pack and start a new pack that same day
Missed dose biphasic/triphasic formulations
- One dose missed: Take dose as soon as remembered or take 2 tablets next day
- Two consecutive doses missed in week 1 or 2 of the pack: Take 2 tablets as soon as remembered and 2 tablets the next day; continue taking 1 tablet daily until pack is empty; use additional method of contraception for 7 days after missed dose
- Two consecutive doses missed in week three of the pack: Use additional method of contraception for 7 days after missed dose
- Start a new pack if two doses missed in week 3 of the pack
- Sunday starter: Continue daily dose until Sunday, then discard the rest of the pack and start a new pack that same day
- Day 1 starter: Discard current pack and start a new pack that same day
Dosage modifications
Renal impairment: Use with caution; monitor blood pressure
Hepatic impairment: Do not administer
Dosing Considerations
Follow manufacturer's color-coding for sequence of administration (especially with triphasic formulations)
Pediatric dosage forms and strengths
Safety and efficacy not established
Mononessa, Ortho Cyclen-28 (norgestimate/ethinylestradiol) adverse (side) effects
Frequency not defined
Amenorrhea
Anorexia
Aterial thromboembolism
Cerebral hemorrhage
Crebral thrombosis
Retinal thrombosis
Breakthrough bleeding
Change in menstrual flow
Gallbladder disease
Edema
Spotting
Weakness
Abdominal pain
Breast tenderness
Cholestatic jaundice
Deep vein thrombosis (DVT)
Depression
Dizziness
Galactorrhea
Headache
Nausea
Nervousness
Somnolence
Thrombophlebitis
Varicose vein aggravation
Vomiting
Weight change
Warnings
Black box warnings
Cigarette smoking and risk of cardiovascular disease
- Cigarette smoking increases risk of serious cardiovascular adverse effects from use of combination hormonal contraceptives
- Risk increases with age (>35 years) and with heavy smoking (≥15 cigarettes/day)
- Women who use hormonal oral contraceptives are advised not to smoke
Contraindications
Documented hypersensitivity
Active or history of breast cancer
Arterial thromboembolic disease (stroke, myocardial infarction [MI]), thrombophlebitis, DVT/pulmonary embolism (PE), thrombogenic valvular disease
Estrogen-dependent neoplasia
Liver disease, liver tumors
Undiagnosed abnormal uterine bleeding
Uncontrolled hypertension (ie, persistent BP values >160 mm Hg systolic or >100 mg Hg diastolic)
Diabetes mellitus with vascular involvement
Jaundice with previous oral contraceptive use
Cautions
Use caution in family history of breast cancer and or DVT/PE, current or previous depression, endometriosis, diabetes mellitus, hypertension, bone mineral density changes, renal or hepatic impairment, bone metabolic disease, systemic lupus erythematosus (SLE), conditions exacerbated by fluid retention (eg, migraine, asthma, epilepsy)
Monitor prediabetic and diabetic women on therapy; consider alternate contraceptive method for women with uncontrolled dyslipidemia
Headache: Evaluate significant change in headaches and discontinue therapy if indicated
Women with a history of hypertension or hypertension-related diseases, or renal disease should be encouraged to use another method of contraception
Discontinue if any of the following develop: Jaundice, visual problems (may cause contact lens intolerance), signs of venous thromboembolism, migraine with unusual severity, significant blood pressure increase, severe depression, increased risk of thromboembolic complications after surgery
Discontinue 4 weeks before major surgery or prolonged immobilization
Patients on warfarin or oral anticoagulants: Increase in anticoagulant dosage may be warranted
Some studies link oral contraceptive use with increased risk of breast cancer, whereas others do not; risk depends on conditions where naturally high hormone levels persist for long periods, including early-onset menstruation (age <12 years), late-onset menopause (age >55 years), first child after age 30 years, nulliparity
Increased risk of cervical cancer with oral contraceptive use, however, human papillomavirus (HPV) remains primary risk factor for this cancer
Long-term (≥5years) use of oral contraceptives may be associated with increased risk
Increased risk of liver cancer with oral contraceptive use; risk increases with duration of use
Pregnancy and lactation
Pregnancy category: X
Lactation: Small amounts of steroids are excreted in breast milk; estrogens may reduce quality or quantity of milk; may be prudent to use other forms of birth control until full weaning (American Academy of Pediatrics committee states that agent is compatible with nursing); 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.
Pharmacology of Mononessa, Ortho Cyclen-28 (norgestimate/ethinylestradiol)
Mechanism of action
Ethinyl estradiol: Reduces release of luteinizing hormone-releasing hormone (LHRH) from hypothalamus; reduces release of gonadotropin from pituitary; increases synthesis of DNA, RNA, and various proteins in target tissues
Norgestimate: Inhibits secretion of gonadotropin from pituitary; prevents follicular maturation and ovulation; stimulates growth of mammary tissues
Absorption
Peak plasma time: 2 hr
Distribution
Protein bound: >97% (ethinyl estradiol)
Metabolism
Metabolized in liver by CYP3A4 to estriol, estrone (ethinyl estradiol)
Elimination
Half-life: Ethinyl estradiol, 10-16 hr; norgestimate, 18-25 hr; norgestrel, 38-45 hr
Excretion (ethinyl estradiol): Urine as conjugates; most estrogens are also excreted in bile and undergo enterohepatic recycling
Excretion (norgestimate): Urine (47%) and feces (37%) as metabolites
