Contraceptives, Transdermal Patch (Combination Product)

Pronunciation: kon-tra-SEP-tiv
Class: Hormonal contraceptive

Trade Names

Ortho Evra
- Patch, transdermal norelgestromin 6 mg/ethinyl estradiol 0.75 mg

Pharmacology

Inhibits ovulation by suppressing gonadotropins; alters cervical mucus, which increases the difficulty of sperm entry into the uterus; and alters the endometrium, which reduces the likelihood of implantation.

Indications and Usage

Prevention of pregnancy.

Contraindications

Thrombophlebitis; thromboembolic disorders; history of deep vein thrombophlebitis or thromboembolic disorders; known thrombophilic conditions; cerebral vascular disease; coronary artery disease; valvular heart disease with complications; severe hypertension (at least 160 mg Hg systolic or at least 100 mg Hg diastolic); diabetes with vascular involvement; headaches with focal neurological symptoms; major surgery with prolonged immobilization; known or suspected carcinoma of the breast or history of breast cancer; carcinoma of the endometrium; estrogen-dependent neoplasia; undiagnosed abnormal genital bleeding; cholestatic jaundice of pregnancy; jaundice with prior hormonal contraceptive use; acute or chronic hepatocellular disease with abnormal liver function; hepatic adenomas or carcinomas; pregnancy; hypersensitivity to any component of the product.

Dosage and Administration

Adults and Adolescents who have reached menarche

Transdermal Apply 1 patch each week for 3 wk (21 days). Apply every new patch on the same day of each week (patch change day). Week 4 is patch-free and withdrawal bleeding is expected at this time. On the day after week 4 ends, a new 4-wk cycle is started by applying a new patch. There should not be more than a 7-day patch-free interval between dosing cycles.

General Advice

  • The patch should not be cut, damaged, or altered in any way.
  • For the first day start method, the patch should be applied during the first 24 h of the menstrual cycle. A nonhormonal backup contraceptive (eg, condom) should be used concurrently for the first 7 consecutive days of the first treatment cycle if therapy is started after day 1 of the menstrual cycle.
  • For the Sunday start method, the first patch should be applied on the first Sunday after the start of the menstrual cycle. Backup contraception must be used for the first week of the first cycle. If the menstrual period begins on a Sunday, the first patch should be applied on that day and no backup contraception is needed.
  • The patch should be applied to clean, dry, intact, healthy skin on the buttock, abdomen, upper outer arm, or upper torso, in a place where it will not be rubbed by tight clothing. Do not apply patch to skin that is red, irritated, or cut, or on the breasts. Each patch should be applied to a new spot on the skin to help avoid irritation, although they may be kept in the same anatomic area.
  • No makeup, creams, lotions, powders, or other topical products should be applied to the skin area where the patch is or will be placed.
  • If the patch is partially or completely detached for less than 1 day, the woman should try to reapply it to the same place or replace it with a new patch immediately. No backup contraception is needed and the patch change day will remain the same.
  • A patch should not be reapplied if it is no longer sticky, if it has become stuck to itself or another surface, if it has other material stuck to it, or if it has previously become loose or fallen off. If a patch cannot be reapplied, a new patch should be applied immediately. Supplemental adhesives or wraps should not be used to hold the patch in place.
  • If the patch is partially or completely detached for more than 1 day or if the woman is unsure how long it has been detached, she should stop the current contraceptive cycle and start a new one immediately by applying a new patch. There is now a new Day 1 and new patch change day. Backup contraception must be used for the first week of the new cycle.
  • If a woman forgets to change her patch at the start of any patch cycle, she should apply the first patch of her new cycle as soon as she remembers. There is now a new Day 1 and new patch change day. Backup contraception must be used for the first week of the new cycle.
  • If a woman forgets to change her patch in the middle of the patch cycle (Wk 2/Day 8 or Wk 3/Day 15) for 1 or 2 days, she should apply a new patch immediately. The next patch should be applied on the usual patch change day. No backup contraception is needed. If it has been more than 2 days, she should stop the current contraceptive cycle and start a new one immediately by applying a new patch. There is now a new Day 1 and new patch change day. Backup contraception must be used for the first week of the new cycle.
  • There should not be more than a 7-day patch-free interval. If this occurs, the woman may not be protected from pregnancy and backup contraception (eg, condoms) must be used for 7 days.

Storage/Stability

Store at 59° to 86°F. Store patches in their protective pouches. Apply immediately upon removal from the protective pouch. Do not store in the refrigerator or freezer. Used patches should not be flushed down the toilet.

Drug Interactions

ACE inhibitors, aldosterone antagonists, angiotensin II receptor antagonists, heparin, NSAIDs, potassium-sparing diuretics

Use with caution with products containing drospirenone.

Acetaminophen

Acetaminophen concentration may be decreased, reducing the therapeutic effect. The effect on acetaminophen is not likely to be clinically important.

Acetaminophen, ascorbic acid, grapefruit, HMG-CoA reductase inhibitors (eg, atorvastatin, rosuvastatin), voriconazole

May increase ethinyl estradiol plasma concentrations. If estrogen-related adverse effects occur, consider acetaminophen, ascorbic acid, grapefruit, the HMG-CoA reductase inhibitor, or voriconazole as a possible cause.

Aprepitant, azole antifungal agents (eg, itraconazole), barbiturates (eg, phenobarbital), bosentan, carbamazepine, efavirenz, felbamate, griseofulvin, hydantoins (eg, phenytoin), modafinil, nevirapine, oxcarbazine, rifamycins (rifampin), rufinamide, St. John's wort, topiramate

The metabolism of norelgestromin/ethinyl estradiol may be increased, decreasing the effectiveness or increasing breakthrough bleeding. Women should be advised to use additional contraception or a different (nonhormonal) method of contraception.

Benzodiazepines

Plasma concentrations of benzodiazepines that undergo glucuronidation (eg, lorazepam, oxazepam, temazepam) may be reduced, decreasing the pharmacologic effect. Plasma concentrations of benzodiazepines that undergo oxidation (eg, diazepam, midazolam, triazolam) may be increased and their effect prolonged. Monitor the patients response to the benzodiazepine and adjust the benzodiazepine dose as needed.

Beta-blockers (eg, metoprolol, propranolol), corticosteroids, cyclosporine, theophylline

Effects may be increased by hormonal contraceptives, increasing the risk of toxicity. Monitor the response of the patient and adjust therapy as needed.

Clofibric acid, morphine, salicylic acid

Plasma concentrations of these agents may be reduced, decreasing the pharmacologic effects. Monitor the patient response and adjust the dose of these agents as needed.

Lamotrigine, valproic acid

Lamotrigine or valproic acid plasma concentrations may be decreased, increasing the risk of seizures. Monitor lamotrigine and valproic acid concentrations and the patient's clinical response. Adjust the lamotrigine or valproic acid dose as needed.

Protease inhibitors (eg, indinavir, ritonavir)

Plasma concentrations of estrogen and progestin may be increased or decreased. Women should be advised to use additional contraception or a different (nonhormonal) method of contraception.

Smoking

Cigarette smoking increases the risk of serious CV adverse effects from norelgestromin/ethinyl estradiol use. The risk increases with age and heavy smoking (15 or more cigarettes/day). Advise women who use norelgestromin/ethinyl estradiol to avoid smoking.

Laboratory Test Interactions

May cause increases in prothrombin and factors VII, VIII, IX, and X; norepinephrine-induced platelet aggregability; thyroid-binding globulin (TBG), leading to increased circulating total thyroid hormone, as measured by protein-bound iodine, T4 by column or by radioimmunoassay; binding proteins; sex hormone–binding globulins; and triglycerides. May cause decrease in antithrombin 3; free T3 resin uptake, reflecting elevated TBG; glucose tolerance; and serum folate levels.

Adverse Reactions

Cardiovascular

BP increased; arterial thrombosis, cerebrovascular accident, deep vein thrombosis, hypertension, hypertensive crisis, MI, thrombosis (postmarketing).

CNS

Headache (21%); mood, affect, and anxiety disorders (6%); dizziness, fatigue, migraine (3%); cerebral hemorrhage, cerebral thrombosis, insomnia, intracranial hemorrhage, libido decreased, libido increased, malaise (less than 3%); anger, dysgeusia, emotional disorder, frustration, irritability, migraine with aura (postmarketing).

Dermatologic

Acne, pruritus (3%); chloasma, dermatitis contact, erythema, skin irritation (less than 3%); alopecia, eczema, erythema multiforme, erythema nodosum, photosensitivity reaction, pruritus generalized, rash, seborrheic dermatitis, skin reaction, urticaria (postmarketing).

GI

Nausea (17%); abdominal pain (8%); vomiting (5%); diarrhea (4%); weight increased (3%); abdominal distention (less than 3%); colitis (postmarketing).

Genitourinary

Breast symptoms (22%); dysmenorrhea (8%); vaginal bleeding and menstrual disorders (6%); vaginal yeast infections (4%); galactorrhea, genital discharge, premenstrual syndrome, uterine spasm, vaginal discharge, vulvovaginal dryness (less than 3%); breast cancer, breast mass, cervical dysplasia, cervix carcinoma, fibroadenoma of breast, suppressed lactation, uterine leiomyoma (postmarketing).

Hepatic

Cholecystitis (less than 3%); blood cholesterol abnormal, cholelithiasis, cholestasis, hepatic adenoma, hepatic lesion, hepatic neoplasm, jaundice cholestatic, LDL increased (postmarketing).

Local

Application-site disorder (17%); application-site reaction, edema (postmarketing).

Metabolic

Fluid retention, lipid disorders (less than 3%); blood glucose abnormal, blood glucose decreased, hyperglycemia, insulin resistance (postmarketing).

Respiratory

Pulmonary embolism (less than 3%).

Miscellaneous

Muscle spasms (less than 3%); allergic reaction, contact lens intolerance or complication (postmarketing).

Precautions

Warnings

Smoking

Cigarette smoking increases the risk of serious CV adverse reactions. The risk increases with age (older than 35 y of age) and smoking at least 15 cigarettes/day. Women using hormonal contraceptives should not smoke.


Monitor

Monitor blood glucose in women with diabetes. Perform routine annual medical evaluation, including physical examination and relevant laboratory tests. Closely monitor women being treated for hyperlipidemia, women with a history of depression, and women with a family history of breast cancer or who have breast nodules. Carefully monitor women with conditions that may be aggravated by fluid retention.


Pregnancy

Category X .

Lactation

Undetermined; however, contraceptive steroids are excreted in breast milk.

Children

Safety and efficacy are expected to be the same for postpubertal adolescents younger than 16 y of age and for patients 16 y of age and older. Use before menarche is not indicated.

Elderly

Not indicated in elderly patients.

Hepatic Function

Estrogens may be poorly metabolized in patients with impaired liver function. Discontinue use if jaundice develops.

Bleeding irregularities

Breakthrough bleeding and spotting may occur.

BP

Encourage women with hypertension or hypertension-related diseases to use another nonhormonal method of contraception.

Body weight

Clinical trials suggest that norelgestromin/ethinyl estradiol transdermal may be less effective in women weighing 90 kg (198 lb) or more than in lower-weight women.

Breast cancer

Risk of breast cancer may be slightly increased but decreases over time after oral contraception discontinuation, and the increased risk disappears by 10 y after cessation of use.

Carbohydrate and lipid metabolism

Changes in serum triglycerides and lipoprotein levels have been reported. Some progestins may elevate LDL levels and interfere with control of hyperlipidemia.

Cerebrovascular disease

Increase in the relative and attributable risk of cerebrovascular events (eg, thrombotic and hemorrhagic strokes) has been reported. The risk is greatest among hypertensive women who are older than 35 y of age and who smoke.

Contact lenses

Contact lens wearers who develop visual changes or changes in lens tolerance should be assessed by an ophthalmologist.

CV disease

Increased risk of MI has been attributed to hormonal contraceptive use, primarily in smokers or women with underlying risk factors for coronary artery disease (eg, diabetes, hypertension, obesity). Increased risk of thrombotic disease associated with hormonal contraceptive use is well-established. Use with caution in women with CV disease risk factors (eg, hyperlipidemia).

Depression

Use with caution in women with a history of depression.

Ectopic pregnancy

Ectopic or intrauterine pregnancy may occur in contraceptive failure.

Fluid retention

May occur. Use with caution in women with conditions that may be aggravated by fluid retention.

Gallbladder disease

Existing gallbladder disease may be worsened or development may be accelerated in previously asymptomatic women.

Glucose tolerance

Glucose tolerance may be decreased.

Headache

Discontinue the contraceptive patch if there is exacerbation of migraine or development of headache with a new pattern that is recurrent, persistent, or severe.

Hepatic neoplasm

Benign hepatic adenomas, which may cause death through intra-abdominal hemorrhage, have been associated with hormonal contraceptive use.

Hormone exposure

The pharmacokinetic profile for the contraceptive patch is different from that of oral contraceptives in that it has higher steady-state concentrations and lower peak concentrations. Increased estrogen exposure may increase the risk of adverse reactions, including venous thromboembolism.

Immobilization

Discontinue during and following prolonged immobilization.

Surgery

Discontinue at least 4 wk prior and for 2 wk after elective surgery of a type associated with an increase in risk of thromboembolism.

Vascular disease

A positive association has been seen between amount of estrogen and progestin in hormonal contraceptives and risk of vascular disease. Many progestational agents have been reported to decrease HDL, which is associated with an increased incidence of ischemic heart disease.

Visual abnormalities

Retinal vascular thrombosis may occur, leading to loss of vision, sudden onset of proptosis, diplopia, or migraine.

Overdosage

Symptoms

Menstrual irregularities, nausea, vaginal bleeding, vomiting from acute oral ingestion of oral contraceptives.

Patient Information

  • Advise women that this product does not protect against HIV infection or other STDs.
  • Advise women to contact health care provider if they experience any of the following symptoms: breast lumps; coughing blood; crushing chest pain or heaviness in the chest; dark-colored urine or light-colored bowel movements; difficulty sleeping, weakness, lack of energy, fatigue, or a change in mood; dizziness or fainting; irregular vaginal bleeding or spotting that happens in more than 1 menstrual cycle or lasts for more than a few days; loss of appetite; pain in calf; problems with vision or speech; sharp chest pain; severe pain, swelling, or tenderness in the abdomen; sudden fever, vomiting, diarrhea, dizziness, fainting, or sunburn-like rash on the face or body; sudden shortness of breath; weakness or numbness in arm or leg; sudden partial or complete loss of vision; sudden, severe headache or vomiting; swelling of the fingers or ankles; tiredness; yellowing of the skin or whites of the eyes, especially with fever.
  • Instruct women that every new patch should be applied on the same day of each week and that only 1 patch should be worn at a time.
  • Instruct women to apply the patch to clean, dry, intact healthy skin on the buttock, abdomen, upper outer arm, or upper torso. The patch should not be placed on skin that is red, irritated, or cut, or on the breasts. To avoid irritation, apply each new patch to a different place on the skin. Creams, oils, powders, or makeup should not be applied to skin where the patch is or will be placed.
  • Advise women that the patch should not be cut, damaged, or altered in any way.
  • Advise women that they should never have the patch off for more than 7 days in a row. This may leave them unprotected against pregnancy. If a woman is not sure what to do about mistakes with a patch, instruct her to use a backup method of contraception (eg, condoms, diaphragm) every time she has intercourse and to contact her health care provider for instructions.
  • Advise women that if they miss 2 menstrual periods in a row to contact their health care provider because they may be pregnant.
  • Advise women who wear contact lenses that if they develop vision changes or changes in lens tolerance to be assessed by an ophthalmologist.
  • Advise women that the used patches still contain some active hormones. The sticky sides of the patch should be folded together and the folded patch placed in a sturdy container (preferably with a child-resistant cap) and the container thrown in the trash. Used patches should never be flushed down the toilet.
  • Advise postpartum women who elect not to breast-feed to start hormonal contraceptive no earlier than 4 wk after delivery.

Copyright © 2009 Wolters Kluwer Health.

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