COMBIPATCH Dosage & Rx Info | Uses, Side Effects

Combipatch Generic Name & Formulations

Legal Class

General Description

Estradiol, norethindrone acetate; 0.05mg/0.14mg, 0.05mg/0.25mg; per day; transdermal system.

Pharmacological Class

Estrogen + progestin.

How Supplied

Patches—8

Manufacturer

Noven Therapeutics

Generic Availability

Mechanism of Action

Endogenous estrogens are largely responsible for the development and maintenance of the female reproductive system and secondary sexual characteristics. Estrogens act through binding to nuclear receptors in estrogen-responsive tissues. Circulating estrogens modulate the pituitary secretion of the gonadotropins, luteinizing hormone (LH), and follicle stimulating hormone (FSH) through a negative feedback mechanism. Estrogens act to reduce the elevated levels of these hormones seen in postmenopausal women.

Combipatch Indications

Indications

In women with an intact uterus: moderate to severe vasomotor symptoms, and vulvar and vaginal atrophy due to menopause; hypoestrogenism due to hypogonadism, castration, or primary ovarian failure.

Combipatch Dosage and Administration

Adult

Use lowest effective dose for shortest duration. Apply to smooth, clean, dry area of lower abdomen (avoid breasts, waistline). Continuous combined regimen: 1 CombiPatch twice weekly for 28-day cycle; repeat. Continuous sequential regimen (use with 0.05mg/day estrogen patch): Use estrogen-only patch for first 14 days of cycle, then 1 CombiPatch twice-weekly for second 14 days of 28-day cycle; repeat. Rotate application site. Reevaluate at 3–6 month intervals to assess need.

Children

Not applicable.

Combipatch Contraindications

Contraindications

Undiagnosed abnormal genital bleeding. Known, suspected or history of breast cancer. Known or suspected estrogen-dependent neoplasia. Active DVT, PE or history of. Active arterial thromboembolic disease or history of. Known hepatic impairment. Known protein C, protein S, or antithrombin deficiency or other known thrombophilic disorders. Pregnancy.

Combipatch Boxed Warnings

Boxed Warning

Cardiovascular disorders. Endometrial and breast cancer. Probable dementia.

Combipatch Warnings/Precautions

Warnings/Precautions

Not for prevention of cardiovascular disease or dementia. Increased risk of cardiovascular disorders (eg, stroke, MI, PE, DVT); discontinue if occurs or suspected. Manage risk factors for cardiovascular disease and venous thromboembolism appropriately. Discontinue at least 4–6 weeks before surgery type associated with increased risk of thromboembolism or during prolonged immobilization. Endometrial, breast, or ovarian cancer. Risk of probable dementia in women ≥65yrs of age. Gallbladder disease. Bone disease associated with hypercalcemia. Visual abnormalities. Permanently discontinue if papilledema or retinal vascular lesions reveals on exam. History of hypertriglyceridemia. Discontinue if cholestatic jaundice, pancreatitis, or hypercalcemia occurs. Monitor thyroid function. Conditions aggravated by fluid retention. Hypoparathyroidism. Endometriosis. Hereditary angioedema. Asthma. Diabetes. Epilepsy. Migraine. Porphyria. SLE. Hepatic hemangiomas. Do initial complete physical and repeat yearly (include Pap smear, mammogram, BP). Reevaluate periodically. Nursing mothers: not recommended.

Combipatch Pharmacokinetics

Absorption

Steady-state serum concentrations: 45–50 pg/mL (estradiol); 489–840 pg/mL (norethindrone). Steady-state serum concentrations are obtained within 12–24 hours.

Distribution

Estrogens are widely distributed in the body and largely bound to SHBG and albumin. Norethindrone is ~90% bound to SHBG and albumin.

Metabolism

Hepatic.

Elimination

Renal. Half-life: 2–3 hours (estradiol); 6–8 hours (norethindrone).

Combipatch Interactions

Interactions

May be potentiated by CYP3A4 inhibitors (eg, erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir, grapefruit juice). May be antagonized CYP3A4 inducers (eg, phenobarbital, carbamazepine, rifampin, St. John's wort). Concomitant thyroid replacement; may need to increase thyroid dose. May interfere with lab tests (eg, thyroid, PT, coagulation factors, glucose tolerance, HDL/LDL, triglycerides, hormone concentrations, other binding or plasma proteins).

Combipatch Adverse Reactions

Adverse Reactions

See full labeling. Headache, breast pain, dysmenorrhea, menstrual disorder, back pain, asthenia, respiratory disorders, application site reactions; elevated BP, hypercalcemia, thromboembolic disorders, gallbladder disease.

Combipatch Clinical Trials

See Literature

Combipatch Note

Not Applicable

Combipatch Patient Counseling