Expiration date: 02/2025

Structure and Composition: 

The transdermal therapeutic system (TTS) system. 1 system contains:

norelgestromin (NY) 6 mg

ethinyl estradiol (EE) 600 mcg

TTS comprises the following layers:

base: the outer layer - of pigmented low density polyethylene and an inner layer - polyester

middle layer: adhesive blend of polyisobutylene-polybutene, crospovidone, nonwoven polyester, lauryl lactate

a peelable protective layer: film - of polyethylene terephthalate coating - polydimethylsiloxane

in a bag of the composite material 1 pc., in a transparent bag of plastic film bag 3 in the paper cartons 1 or 3 packets of a polymer film (containing 3 or 9 TTS) with special stickers on a calendar to mark the period of use.

Description pharmaceutical form:

Square TTS beige matte substrate, rounded corners, colorless adhesive (adhesive) layer and a transparent protective film. On the substrate embossed inscription - «EVRA 150/20».

Characteristic:

Each TTC for 24 hr 150 allocates norelgestromina ug and 20 ug ethinyl estradiol.

Pharmacokinetics:

Absorption. Concentrations norelgestromina and ethinyl estradiol in the serum reaching steady-state values ??after 48 hours after application of the TTS Evra constitute 0.8 and 50 ng / ml, respectively.

With prolonged use, the TTS Evra equilibrium concentration (Css) and area under the curve "concentration-time» (AUC) increased somewhat. At different temperatures and physical stress no significant change in AUC and Css norelgestromina, a AUC of ethinyl estradiol increased somewhat during exercise, while Css remains unchanged.

Target values ??Css norelgestromina and ethinyl estradiol are supported for 10 days wearing TTC Evra, ie TTS clinical efficacy can be maintained, even if the woman will replacing the TTC for 2 full days after the scheduled 7-day period.

Distribution. Norelgestromin and norgestrel (norelgestromina serum metabolite) have a high degree (over 97%) binding to serum proteins. Norelgestromin bound to albumin, norgestrel - predominantly binding globulin sex hormones. Ethinyl estradiol has a high degree of binding to serum albumin.

Biotransformation. Norelgestromin metabolized in the liver to form metabolite norgestrel, and various hydroxylated and conjugated metabolites. Ethinyl estradiol is metabolized to various hydroxylated compounds and their glucuronide and sulfate conjugates. Progestogens and estrogens inhibit many cytochrome P450 enzymes (including CYP3A4, CYP2C19) in human liver microsomes.

Elimination. The average T1 / 2 norelgestromina and ethinyl estradiol is about 28 and 17 hours, respectively. Metabolites norelgestromina and ethinyl estradiol are eliminated in the urine and feces.

Influence of age, body weight and body surface area. Css and AUC values ??norelgestromina and ethinyl estradiol significantly reduced with the increase of these indicators.

Description of the pharmacological actions:

It inhibits gonadotropic pituitary function, inhibits follicular development and prevent ovulation process. The contraceptive effect is enhanced by increasing the viscosity of the cervical mucus and decrease endometrial receptivity to the blastocyst. Pearl Index - 0.90.

The pregnancy rate is not dependent on such factors as the age, race and is increased in women with a body weight of 90 kg.

Testimony:

Contraception for women.

Contraindications:

• Hypersensitivity to the drug
  
• venous thrombosis, including history, including deep vein thrombosis, pulmonary thromboembolism
  
• arterial thrombosis, including history, including acute cerebrovascular accident, myocardial infarction, thrombosis, retinal artery thrombosis or precursors (including angina pectoris or transient ischemic attack)
  
• presence of serious or multiple risk factors, arterial thrombosis (severe hypertension - blood pressure over 160/100 mm Hg, diabetes with vascular lesions of hereditary dislipoproteinemia..)
  
• hereditary predisposition for venous or arterial thrombosis, such as activated protein C resistance, antithrombin deficiency-III, protein C deficiency, protein deficiency of the S, hyperhomocysteinemia and the presence of antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant)
  
• Migraine with aura
  
• confirmed or suspected breast cancer
  
• endometrial cancer and confirmed or suspected estrogen-dependent tumors
  
• adenoma and carcinoma of the liver
  
• genital bleeding
  
• postmenopausal
  
• age 18 years
  
• postpartum period (4 weeks)
  
• lactation
  
• unacceptable to use breast region, as well as erythematous, damaged or irritated skin.
  

Carefully:

• venous or arterial thromboembolism in siblings or parents at a relatively young age
  
• prolonged immobilization
  
• obesity (body mass index over 30 kg / m2, which is calculated as the ratio of weight in kilograms to the square of the height in meters)
  
• thrombophlebitis of superficial veins and varicose veins
  
• dislipoproteinemia
  
• arterial hypertension
  
• valvular lesions
  
• atrial fibrillation
  
• diabetes
  
• systemic lupus erythematosus
  
• hemolytic uremic syndrome
  
• Crohn's disease
  
• ulcerative colitis
  
• liver function abnormalities
  
• hypertriglyceridemia, including family history
  
• acute liver dysfunction during previous pregnancy or previous use of sex hormones
  
• menstrual irregularities
  
• impairment of renal function.
  

Application of pregnancy and breastfeeding:

TTS Evra is contraindicated during pregnancy and lactation.

Side effect:

On the part of the central and peripheral nervous system: dizziness, headache, paresthesia, hypoesthesia, seizures, tremors, emotional lability, depression, anxiety, insomnia, somnolence.

Cardio-vascular system: increased blood pressure, palpitations, edema syndrome, varicose veins.

From the digestive system: gingivitis, anorexia or increased appetite, gastritis, gastroenteritis, dyspepsia, abdominal pain, vomiting, diarrhea, flatulence, constipation, hemorrhoids.

The respiratory system: upper respiratory tract infection, shortness of breath, asthma.

Reproductive system: pain during sexual intercourse (dyspareunia), vaginitis, dysmenorrhea, decreased libido, breast enlargement, menstrual disorders (including intermenstrual bleeding, hypermenorrhoea), change of vaginal secretions, cervical mucus changes, lactation, arising It is due to childbirth, a violation of ovarian function, mastitis, fibroadenoma of the breast, ovarian cysts.

From the urinary system: urinary tract infection.

From the musculoskeletal system: muscle cramps, myalgia, arthralgia, ostalgiya (including back pain, pain in the lower limbs), tendinosis (tendon change), muscle weakness.

Skin and appendages: pruritus, urticaria, skin rash, contact dermatitis, bullous rash, acne, discoloration of the skin, eczema, increased sweating, alopecia, photosensitivity, skin dryness.

Metabolic and Nutritional Disorders: weight gain, hypertriglyceridemia, hypercholesterolemia.

Other: flu-like symptoms, fatigue, allergic reactions, chest pain, asthenia syndrome, syncope, anemia, abscesses, lymphadenopathy, conjunctivitis, visual disturbances.

Rarely (with a frequency of 1/10 to 1/1, 000, 000) observed the following side effects: muscle hypertonicity or hypotonia, incoordination, dysphonia, hemiplegia, neuralgia, stupor, increased libido, depersonalization, apathy, paranoia, benign tumors of the mammary glands , cervical cancer in situ, pain in the perineum, ulceration of the genital atrophy of the mammary glands, lowering blood pressure, enanthema, dry mouth or increased salivation, colitis, pain when urinating, hyperprolactinemia, melasma, violation of skin pigmentation, chloasma, xerophthalmia, weight reduction body or obesity, inflammation of the subcutaneous fat, alcohol intolerance, cholecystitis, cholelithiasis, abnormal liver function, purpura, "tides" of blood to the face, thrombosis (including deep vein thrombosis, thrombosis, pulmonary embolism), thrombophlebitis of superficial veins, pain veins, pulmonary embolism.

Drug Interactions:

Hydantoins, barbiturates, primidone, carbamazepine and rifampicin and oxcarbazepine, topiramate, felbamate, ritonavir, griseofulvin, modafinil and phenylbutazone can cause accelerated metabolism of sex hormones which may cause intermenstrual bleeding or inefficiency of hormonal contraception, i.e. unintended pregnancy. The mechanism of the interaction of these drugs and active ingredients TTC Evra is based on the ability of these agents to induce hepatic enzymes that metabolize hormones. Maximal enzyme induction is generally achieved no sooner than 2-3 weeks and can be stored for at least 4 weeks after the lifting of the respective drug.

Receiving vegetable preparations containing St. John's wort (Hypericum perforatum), while using the TTS Evra can lead to loss of effectiveness. Women taking these herbal remedies can be observed intermenstrual bleeding and unwanted pregnancies occur. This is due to the fact that St. John's wort induces enzymes metabolizing hormones. The inducing effect may persist for 2 weeks after the cancellation of herbal preparation containing St. John's wort.

Loss contraceptive effect may cause antibiotics (including tetracycline and ampicillin). Examination of pharmacokinetic interaction showed that oral administration of tetracycline hydrochloride for 3 days before and during the 7 days while using TTS Evra, has no significant effect on the pharmacokinetics norelgestromina or ethinyl.

Dosage and administration:

Dosage. To achieve maximum contraceptive effect women have to use TTS Evra in strict accordance with the instructions. Instructions relating to the applicability of TTS Evra are given below in the section "How to start the use of TTS Evra." You can use only one TTC Evra.

Everyone to use TTC Evra is removed and immediately replaced with a new one the same day of the week ( "replacement day"), on the 8th and the 15th days of the menstrual cycle (2nd and 3rd week). TTC Evra can be changed at any time to replace the day. During the 4th week, from 22 th to 28 th day of the cycle, do not use TTS Evra. A new contraceptive cycle begins on the next day after the end of the 4th week following TTS Evra should stick, even if menstruation has not been or is not over.

Under no circumstances should a break in wearing TTC Evra should not be more than 7 days, otherwise it increases the risk of pregnancy. In such situations, for 7 days is necessary to simultaneously use a barrier method of contraception, since the risk of ovulation increases with each day of exceeding the recommended length of time, free from the use of TTS Evra. In the case of sexual intercourse during this period increased the probability of conception is very high.

Mode of application. Locally. TTC Evra should stick to a clean, dry, intact and healthy skin of the buttocks, abdomen, upper outer surface of the shoulder or upper part of the body with minimal body hair, in areas where it will not come into contact with a tight-fitting clothing.

To avoid possible irritation, each following TTS Evra must be pasted into another area of ??the skin, it can be done within the same anatomical region. TTC Evra should be tightly pressed to the edges well in contact with the skin. To avoid reducing the adhesive properties of the TTS Evra can not apply make-up, creams, lotions, powders and other local resources to those areas of the skin where it is glued or pasted.

A woman should daily inspect TTC Evra to be confident in its permanently attached.

Used TTS must be carefully disposed of in accordance with the instructions.

How to start the use of TTS Evra

If during the previous menstrual cycles a woman has not used a hormonal contraceptive, contraception using TTS Evra begin in the 1st day of menstruation. Glued to the skin of a TTS Evra and use it throughout the week (7 days). Day of bonding the first TTS Evra (1st day - the day of the beginning) specifies the following days replacement. replacing Day will fall on the same day each week (8 th and 15 th days of the cycle). On the 22 th day of the cycle TTS is removed, and from 22 th to 28 th day of the cycle woman is not using TTS Evra. The next day is the first day of a new contraceptive cycle. If a woman begins to use TTS Evra from the first day of the cycle, it is necessary to simultaneously use a barrier method of contraception during the first 7 days of the first contraceptive cycle.

If a woman goes to the use of combined oral contraceptive to use TTS Evra, it should stick to the skin on the first day of menstruation, which started after the discontinuation of the combined oral contraceptive. If your period does not start within 5 days after receiving the contraceptive pill, it is necessary to exclude pregnancy before you start using TTS Evra.

If you use TTS Evra starts later than the first day of menstruation, within 7 days you must simultaneously use barrier methods of contraception.

If, after taking the last contraceptive pill has been more than 7 days, then the woman may have ovulated and therefore she should consult a doctor before starting to use the TTC Evra. Sexual intercourse during this prolonged period, receiving free contraceptive pills can lead to pregnancy.

If a woman goes from the use of products containing progestogen only, to use TTS Evra, during the first 7 days of application TTS Evra should use a barrier method to enhance the contraceptive effect (on the day of implant removal, on the day when the next injection should be done).

After an abortion or miscarriage. After an abortion or miscarriage before the 20th week of pregnancy, you can immediately start using the TTS Evra. If a woman begins to use TTS Evra immediately after an abortion or miscarriage, to resort to an additional method of contraception is not required. A woman should know that ovulation may occur within 10 days after an abortion or miscarriage. After an abortion or miscarriage in the 20th week of pregnancy or later, use the TTC Evra can begin on the 21 th day after the abortion or miscarriage or on the first day of the first ensuing menstruation.

After childbirth. Women who do not breast-feeding should start using TTS Evra no sooner than 4 weeks after giving birth. If a woman begins to apply the TTC Evra later, during the first 7 days it must additionally use a barrier method of contraception. If there has been sexual intercourse, it is necessary to exclude pregnancy before starting the use of TTS Evra, or the woman should wait until the first menstrual period.

At full or partial peeling off TTC Evra in the blood to an insufficient number of its active ingredients.

Even with partial peeling off TTC Evra:

• Less than one day (24 hours) should be re-glued TTC Evra to the same place or immediately replace it with a new TTC Evra. Additional contraception is not required. The next TTC Evra need to stick to a regular "day replacing"
  
• More than during the day (24 hours or more), and if the woman does not know exactly when the TTC Evra partially or totally unstuck: possible pregnancy. The woman should immediately start a new cycle, a new gluing TTC Evra and consider this day the first day of contraceptive cycle. Barrier methods of contraception should be used at the same time only during the first 7 days of the new cycle.
  

Do not attempt to re-glue the TTC Evra, if it has lost its adhesive properties instead, you must immediately attach a new TTC Evra. You can not apply additional adhesive tape or bandage to hold in place TTC Evra.

If you skipped the next day replacement TTC Evra:

At the beginning of any contraceptive cycle (Week 1 / Day 1):

• With increased risk of pregnancy, a woman must first stick TTC Evra a new cycle immediately as soon as you remember about it. This day is considered the new "1st day" and counted the new "day of replacement." Non-hormonal contraceptive should be used concurrently for the first 7 days of the new cycle. In the case of sexual intercourse during this elongated period without using TTS Evra may occur conception. 
  

In the middle of the cycle (Week 2 / Day 8 or Week 3/15-Day):

• From the date of replacement have been one or two days (48 hours): the woman should immediately attach a new TTC Evra. The next TTC Evra need to stick to a regular "day of replacement." If during the 7 days preceding the first missed day of fixing the TTS Evra, a woman used correctly Evra transdermal, additional contraception is not required
  
• The date of replacement passed over two days (48 hours or more): there is an increased risk of pregnancy. Women should stop the current contraceptive cycle and immediately start a new 4-week cycle by gluing a new TTC Evra. This day is considered the new "1st day" and counted the new "day of replacement." Barrier contraception must be used simultaneously for the first 7 days of the new cycle
  
• At the end of the cycle (Week 4 / Day 22): If the TTC Evra is not removed at the beginning of the 4th week (22-day), then it must be removed as quickly as possible. The next cycle of contraception should begin in the usual "day replacement", which is the next day after the 28th day. Additional contraception is not required.
  

Change the "replacement of the day." To postpone menstruation for one cycle, the woman must attach a new TTC Evra at the beginning of the 4th week (22-day), thus omitting the period, free from the use of TTS Evra. You may experience intermenstrual bleeding or spotting. After 6 consecutive weeks of transdermal Evra must be the 7-day interval, free from the use of TTS Evra. After this interval, resume regular use of the drug.

If assigned to this day (during the week, free use of) the woman wants to change the "day replacement," it must finish the current cycle, removing the third TTS Evra. A woman may choose a new "day of replacement", the first gluing TTC Evra next cycle on the chosen day. Period, free from the use of TTS Evra, in any case should not exceed 7 days. The shorter the period, the greater the likelihood that a woman will not be the next menstruation, and during the next cycle contraceptive may arise intermenstrual bleeding or spotting.

Overdose:

Symptoms include nausea, vomiting, vaginal bleeding.

Treatment: removal of the TTS, symptomatic therapy. No specific antidote.

Special instructions:

There is no clinical evidence that transdermal contraceptive system on any aspect of the safety of oral contraceptives.

Before the start or resumption of the use of TTS Evra is necessary to collect detailed medical history (including family history) and to exclude pregnancy. It is necessary to measure blood pressure and a physical examination, taking into account contraindications and warnings.

If you suspect that a family history of venous thromboembolism (If venous thromboembolism occurred in a sibling or parent at a relatively young age), a woman should be referred to a specialist for consultation, before addressing the question of the use of hormonal contraception.

The risk of vascular complications is elevated in women with thrombophlebitis of superficial veins and varicose veins, as well as obesity (body mass index - more than 30 kg / m2).

When prolonged immobilization after major surgery of the lower limbs or severe injury it is recommended to stop using hormonal contraceptives (for elective surgery is to be done in 4 weeks prior to her), and hormonal contraception resume no earlier than 2 weeks after complete remobilization.

Some epidemiological studies have shown an increased risk of cervical cancer in women who have long been used combined oral contraceptives.

In women receiving combined oral contraceptives, a liver tumor can arise, which may cause life-threatening intraabdominal bleeding. In the case of women who use the TTC Evra, severe pain in the upper abdomen, liver enlargement or signs of intra-abdominal bleeding, you should make a differential diagnosis to rule out a possible tumor of the liver.

Women with hypertriglyceridemia, or this disease in family history may be at increased risk of pancreatitis when using combination hormonal contraceptives.

In the event of a pharmacologically uncontrolled hypertension in women during use of combined hormonal contraceptive medication should be discontinued. Using TTS Evra can be resumed after the normalization of blood pressure. It was reported that after oral administration of combined hormonal contraceptives may occur or worsen following the disease, but conclusive evidence of their connection with the use of combined oral contraceptives do not. These include: jaundice and / or pruritus related to cholestasis cholelithiasis porphyria systemic erythematosus hemolytic uremic syndrome, Sydenham's chorea gestational herpes, hearing loss associated with otosclerosis.

Hormonal contraceptives may affect some endocrine indicators, markers of liver function and blood components:

• Increased concentrations of prothrombin and coagulation factors VII, VIII, IX and X are reduced levels of antithrombin-III reduced Protein S levels are enhanced by norepinephrine-induced platelet aggregation
  
• Increases the concentration of thyroxine binding globulin, which causes an increase in the total concentration of thyroid hormone, which is measured by the iodine content associated with a protein content of T4 (determined by chromatography or radioimmunoassay). TK reduced binding of free ion exchange resin, as evidenced by an increased concentration of thyroxine binding globulin, free T4 concentration is not changed.
  

Concentration may be increased in other serum binding proteins.

Increased concentration of binding globulin sex hormones, which leads to an increase in total circulating concentrations of endogenous sex hormones. However, the concentration of free or biologically active sex steroids remain unchanged or reduced. For women using TTS Evra may slightly increase (X-HDL) cholesterol concentration of high density lipoprotein, total cholesterol, low density lipoprotein cholesterol (LDL-C) and triglycerides, while the ratio of LDL-C / X-HDL may remain unchanged. Hormonal contraceptives may cause a decrease in serum concentrations of folate. This could have a potentially clinically significant consequences if pregnancy occurs in a woman shortly after the abolition of the hormonal contraceptive. Currently, all women are advised to take folic acid during and after the end of hormonal contraception.

Combined hormonal contraceptives may affect the resistance of peripheral tissues to insulin and glucose tolerance, but there is no evidence of the need for regime change diabetes therapy during use of combined hormonal contraceptives. However, should closely monitor the state of health of women with diabetes, especially in the early stages of use TTS Evra.

It has been reported about the aggravation of endogenous depression, of epilepsy, of Crohn's disease and ulcerative colitis in women taking combined oral contraceptives.

Women who have had a hyperpigmentation of the skin during pregnancy, should avoid exposure to sunlight or artificial UV light while wearing TTC Evra. Often this hyperpigmentation is not fully reversible.

Women should be informed that hormonal contraceptives do not protect against HIV infection (AIDS) and other diseases, sexually transmitted diseases.

Women taking drugs that induce microsomal enzymes (hydantoins, barbiturates, primidone, carbamazepine, rifampicin, oxcarbazepine, topiramate, felbamate, ritonavir, griseofulvin, modafinil and phenylbutazone) and antibiotics (except tetracycline) should temporarily use a barrier method in addition to the use of the TTC Evra or choose another method of contraception. The barrier method should be used during the course of treatment the above drugs, as well as for 28 days after discontinuation of inducers of microsomal enzymes, and for 7 days after discontinuation of antibiotics. If the period of receiving concomitant medications than 3-week cycle use TTS Evra, the new contraceptive cycle should be started immediately after the previous one, ie, without customary period of free use of the TTS. Women receiving long-term therapy with drugs that induce hepatic enzymes, have to choose another method of contraception.

When concomitant administration with Evra transdermal drugs that are metabolized by cytochrome P450 enzyme system (including CYP3A4, CYP2C19), especially those with a narrow therapeutic index (such as cyclosporine), physicians should carefully examine the recommendations on the use of drugs, in order to eliminate the possibility occurrence of clinically significant interaction.

When using any combined hormonal contraceptives may be disrupted menstrual cycle (spotting or intermenstrual bleeding), especially during the first months of application of these funds. The duration of the adaptation period - about three cycles. If while using the TTC Evra in accordance with the recommendations of the observed persistence of intermenstrual bleeding or bleeding occurs after a previous regular cycles, it is necessary to take into account other reasons, in addition to the use of the TTC. It must be remembered about non-hormonal causes of menstrual irregularities and, if necessary, to carry out adequate diagnostic testing to rule out organic disease or pregnancy.

Some women in the period of free use of TTS Evra, menstruation can occur. If a woman violated the instructions for use in the period preceding the first failed menstruation, or if she did not have menstruation after two breaks of using TTS, it is necessary to exclude pregnancy before continuing the use of the TTC Evra.

In some women, the abolition of hormonal contraceptives may provoke the occurrence of amenorrhea or oligomenorrhea, especially when they are available before the start of hormonal contraception.

If the use of TTS Evra causes skin irritation, you can paste a new TTC Evra to another area of ??the skin and wear it to the next day replacement.

Women with 90 kg of body weight or more contraceptive efficacy may be reduced.

Abnormal liver function: in case of liver dysfunction symptoms of the use of combined hormonal contraceptives should be discontinued until normalization of liver function markers.

In case of recurrence associated with cholestasis pruritus, which occurred during a previous pregnancy or previous use of sex hormones, combined hormonal contraceptives should be abolished.

Safety and efficacy of transdermal Evra set only for women from 18 to 45 years.

Recommendations for use and disposal: immediately after removing from the bag TTC Evra should be firmly glued to the skin. After removal of the TTS still contained in it significant quantities of active ingredients. Residual hormones can harm the environment if they are falling into the water, and therefore should be carefully used TTS disposed. For this special adhesive film is separated from the outside of the bag. Place the used TTS in a bag so that its adhesive side facing the painted area on the bag, and lightly pressed for sealing. Sealed packet is discarded. Used TTS should not be thrown in the toilet or down the drain.