Evra

/ Trima

This product should be applied to clean, dry, hairless, 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. this product should not be placed on the breasts or on skin that is red, irritated or cut. Each consecutive patch should be applied to a different place on the skin to help avoid potential irritation, although they may be kept within the same anatomic site. The patch should be pressed down firmly until the edges stick well. To prevent interference with the adhesive properties of this product, no make-up, creams, lotions, powders or other topical products should be applied to the skin area where the patch is currently placed or will be applied shortly. It is recommended that users visually check their patch daily to ensure continued proper adhesion. The patch should not be cut, damaged or altered in any way. If the patch is cut, damaged or altered in size, contraceptive efficacy may be impaired.
Switching from an oral contraceptive: Treatment with this product should begin on the first day of withdrawal bleeding. If there is no withdrawal bleeding within 5 days of the last active (hormone containing) tablet, pregnancy must be ruled out prior to start of treatment with this product. If therapy starts after the first day of withdrawal bleeding, a non-hormonal contraceptive must be used concurrently for 7 days. If more than 7 days elapse after taking the last active oral contraceptive tablet, the patient may have ovulated . The patient should be instructed to consult a physician before initiating treatment with this product. If coital exposure has occurred during such an extended patch-free interval, the possibility of pregnancy should be considered.
Use after Childbirth: Users who elect not to breast-feed should start contraceptive therapy with this product no sooner than 4 weeks after child-birth.
Use after Abortion or Miscarriage: After an abortion or miscarriage that occurs before 20 weeks gestation, this product may be started immediately. An additional method of contraception is not needed if this product is started immediately. Be advised that ovulation may occur within 10 days of an abortion or miscarriage. After an abortion or miscarriage that occurs at or after 20 weeks gestation, this product may be started either on Day 21 post-abortion or on the first day of the first spontaneous menstruation, whichever comes first. The incidence of ovulation on Day 21 post abortion (at 20 weeks gestation) is not known.
Breakthrough Bleeding or Spotting: In the event of breakthrough bleeding or spotting (bleeding that occurs during usage), treatment should be continued. This type of bleeding usually disappears after the first few cycles. If breakthrough bleeding persists, a cause other than this product should be considered. The incidence of breakthrough bleeding and spotting with this product is statistically and clinically comparable to that seen with oral contraceptives containing 20 – 40 mcg of EE. In the event of no withdrawal bleeding (bleeding that should occur during the patch-free week), treatment should be continued on the next scheduled Change Day. If this product has been used correctly, the absence of withdrawal bleeding is not necessarily an indication of pregnancy. Nevertheless, the possibility of pregnancy should be ruled out if absence of withdrawal bleeding occurs in 2 consecutive cycles.
For full details see prescribing information.

Female contraception. Evra is intended for women of fertile age.

Hypersensitivity to the active substances or to any of the exciCombined hormonal contraceptives (CHCs) should not be used in the following conditions. If one of these disorders occurs during the use of EVRA, EVRA must be discontinued immediately.
• Presence or risk of venous thromboembolism (VTE)
• Venous thromboembolism – current VTE (on anticoagulants) or history of (e.g. deep venous thrombosis [DVT] or pulmonary embolism [PE]);
• Known hereditary or acquired predisposition for venous thromboembolism, such as: APC-resistance, (including Factor V Leiden), antithrombin-III-deficiency, protein C deficiency, protein S deficiency;
• Major surgery with prolonged immobilisation .
• A high risk of venous thromboembolism due to the presence of multiple risk factors.
• Presence or risk of arterial thromboembolism (ATE)
• Arterial thromboembolism – current arterial thromboembolism, history of arterial thromboembolism (e.g. myocardial infarction) or prodromal condition (e.g. angina pectoris);
• Cerebrovascular disease – current stroke, history of stroke or prodromal condition (e.g. transient ischaemic attack, TIA);
• Known hereditary or acquired predisposition for arterial thromboembolism, such as hyperhomocysteinaemia and antiphospholipid-antibodies (anticardiolipin-antibodies, lupus anticoagulant);
• History of migraine with focal neurological symptoms;
• A high risk of arterial thromboembolism due to multiple risk factors or to the presence of one serious risk factor such as:
– diabetes mellitus with vascular symptoms
– severe hypertension
– severe dyslipoproteinaemia
• Known or suspected carcinoma of the breast
• Carcinoma of the endometrium or other known or suspected oestrogen-dependent neoplasia.
• Abnormal liver function related to acute or chronic hepatocellular disease.
• Hepatic adenomas or carcinomas
• Undiagnosed abnormal genital bleeding
• Concomitant use with the medicinal products containing ombitasvir/paritaprevir/ritonavir and dasabuvir.

Smoking and Age: Cigarette smoking increases the risk of serious cardiovascular from hormonal contraceptive use. This risk increases with age, particularly in women over 35 years of age, and with the number of cigarettes smoked. For this reason, hormonal contraceptives, including this product, should not be used by women who are over 35 years of age and smoke
Body Weight ≥ 90 kg: Analyses of phase III data suggest that this product may be less effective in users with body weight ≥ 90 kg than in users with lower body weights. Below 90 kg there was no association between body weight and pregnancy.
General: In case of undiagnosed, persistent or recurrent abnormal vaginal bleeding, appropriate measures should be taken to rule out malignancy.13,25 When this product was used correctly in clinical trials, the chance of becoming pregnant was less than 1% in the first year of use. The chance of becoming pregnant increases with dosing errors.
Pre-Existing Conditions: When weighing the risks/benefits of hormonal contraceptive use, the physician should be familiar with the following conditions that may increase the risk of complications associated with hormonal contraceptive use: Conditions which increase the risk of developing venous thromboembolic complications, e.g., prolonged immobilisation or major surgery, leg surgery or a leg cast, obesity, or family history of thromboembolic disease. Risk factors for arterial disease, e.g., smoking, hyperlipidaemia, hypertension (persistent blood pressure values ≥ 140 mm Hg systolic or ≥ 90 mm Hg diastolic), or obesity. Severe migraine without aura. Diabetes mellitus. Severe depression or a history of this condition. Presence or history of cholelithiasis. Chronic Idiopathic Jaundice. Family history of cholestatic jaundice (e.g., Rotor, Dubin-Johnson Syndrome)
Thromboembolic and Other Vascular Disorders: An increased risk of thromboembolic and thrombotic disease that could lead to permanent disability or death has been associated with the use of hormonal contraceptives and is well established. Case control studies have found the relative risk of users compared to non-users to be 3 for the first episode of superficial venous thrombosis, 4 to 11 for deep vein thrombosis or pulmonary embolism, and 1.5 to 6 for users with predisposing conditions for venous thromboembolic disease. Studies have shown the relative risk to be somewhat lower, about 3 for new cases and about 4.5 for new cases requiring hospitalisation. The risk of thromboembolic disease associated with hormonal contraceptives is not related to length of use and disappears after the hormonal contraceptive use is stopped. Epidemiologic, case-control studies were conducted in the U.S. using healthcare claims data to evaluate the risk of venous thromboembolism (VTE) among women aged 15–44 who used ORTHO EVRA (a transdermal patch bioequivalent to this product) compared to women who used oral contraceptives containing 30-35 mcg of ethinyl estradiol (EE) and either norgestimate (NGM) or levonorgestrel (LNG). NGM is the prodrug for norelgestromin, the progestin in ORTHO EVRA. These studies used slightly different designs and reported odds ratios ranging from 0.9 (indicating no increase in risk) to 2.5 (indicating an approximate doubling of risk). One study (i3 Ingenix) included patient chart review to confirm the VTE occurrence. Two studies using different databases were conducted by the Boston Collaborative Drug Surveillance Program (BCDSP) with LNG-containing oral contraceptives as the comparator.
For full details see prescribing information.

Changes in Contraceptive Effectiveness Associated With Co-administration of Other Drugs: If a woman on hormonal contraceptives takes a drug or herbal product that induces enzymes, including CYP3A4, that metabolize contraceptive hormones, she should be counseled to use additional contraception or a different method of contraception. Drugs or herbal products that induce such enzymes may decrease the plasma concentrations of contraceptive hormones, and may decrease the effectiveness of hormonal contraceptives or increase breakthrough bleeding. Some drugs or herbal products that may decrease the effectiveness of hormonal contraceptives include: Some anti-epileptics (e.g. carbamazepine, eslicarbazepine acetate, felbamate, oxcarbazepine, phenytoin, rufinamide, topiramate) (fos) aprepitant, barbiturates, bosentan, griseofulvin some (combinations of) HIV protease inhibitors (e.g. nelfinavir, ritonavir, ritonavir-boosted protease inhibitors) modafinil, some non-nucleoside reverse transcriptase inhibitors (e.g. nevirapine), rifampin and rifabutin, St. John’s wort.
Antibiotics: There have been reports of pregnancy while taking hormonal contraceptives and antibiotics, but clinical pharmacokinetic studies have not shown consistent effects of antibiotics on plasma concentrations of synthetic steroids. In a pharmacokinetic drug interaction study, oral administration of tetracycline HCl, 500 mg q.i.d. for 3 days prior to and 7 days during wear of this product did not significantly affect the pharmacokinetics of norelgestromin or EE.
For full details see prescribing information.

Pregnancy: EVRA is contraindicated for use in pregnancy.
Epidemiological studies indicate no increased risk of birth defects in children born to women who used hormonal contraceptives prior to pregnancy. The majority of recent studies also do not indicate a teratogenic effect, particularly insofar as cardiac anomalies and limb reduction defects are concerned, when hormonal contraceptives are used inadvertently during early pregnancy.
Lactation: A small amount of the contraceptive steroids and/or their metabolites may be excreted with the milk. Small amounts of combination hormonal contraceptive steroids have been identified in the milk of nursing mothers and a few adverse effects on the child have been reported, including jaundice and breast enlargement. In addition, combination hormonal contraceptives given in the postpartum period may interfere with lactation by decreasing the quantity and quality of breast milk. If possible, the nursing mother should be advised not to use this product or other combination hormonal contraceptives but to use other forms of contraception until the child is fully weaned.

Serious ill effects have not been reported following accidental ingestion of large doses of oral contraceptives. Overdose may cause nausea or vomiting. Vaginal bleeding may occur in some females. In cases of suspected overdose, all transdermal contraceptive systems should be removed and symptomatic treatment given.