Evra TTS 203 + 33.9mcg/24h #3

Evra TTS user manual

You can buy Evra TTS here

Composition

1 system contains: norelgestromin (NG) 6 mg, ethinyl estradiol (EE) 600 mcg;
The composition of the base TTS: outer layer of pigmented low density polyethylene and the inner layer of polyester.
The composition of the middle layer TTS: adhesive mixture of polyisobutylene-polybutene, crospovidone, non-woven material from polyester, lauryl lactate.
The composition of the removable protective layer TTS: a film of polyethylene terephthalate, a coating of polydimethylsiloxane.
Packaging
3 pcs

pharmachologic effect

Evra is a contraceptive for transdermal use. It inhibits the gonadotropic function of the pituitary gland, inhibits the development of the follicle and interferes with the process of ovulation. The contraceptive effect is enhanced by increasing the viscosity of cervical mucus and reducing the susceptibility of the endometrium to the blastocyte. Pearl Index - 0.90.
The frequency of pregnancy does not depend on such factors as age, race, and increases in women weighing more than 90 kg.

Pharmacokinetics

Suction and distribution

Css of norelgestromine and ethinyl estradiol in blood serum is reached 48 hours after the application of ETC's TTS and is 0.8 ng / ml and 50 pg / ml, respectively.
With long-term use of TTS Evra Css and AUC increase slightly. Under different temperature conditions and physical exertion, there were no significant changes in Css and AUC of norelgestromine, and the AUC of ethinyl estradiol slightly increased during exercise, while Css remained unchanged.
Target Css values ​​of norelgestromine and ethinyl estradiol are maintained for 10 days with TTS applications, i.e. The clinical efficacy of TTS can be maintained even if the woman conducts another replacement of TTS 2 full days later than the scheduled seven-day period.
Norelgestromin and norgestrel (serum metabolite of norelgestromin) have a high degree (more than 97%) of binding to serum proteins. Norelgestromin binds to albumin, norgestrel binds predominantly to the globulins that bind the sex hormones. Ethinyl estradiol has a high degree of binding to serum albumin.

Metabolism

Norelgestromin is metabolized in the liver, with the formation of the metabolite norgestrel, as well as various hydroxylated and conjugated metabolites. Ethinyl estradiol is metabolized to various hydroxylated compounds and their glucuronide and sulfate conjugates. Progestogens and estrogens inhibit many microsomal liver enzymes of the cytochrome P450 system (including CYP3A4, CYP2C19).

Removal

The average T1 / 2 of norelgestromine and ethinyl estradiol is about 28 hours and 17 hours, respectively. Metabolites of norelgestromine and ethinyl estradiol are excreted in the urine and feces.

Pharmacokinetics in special clinical situations

The Css and AUC values ​​of norelgestromine and ethinyl estradiol decrease slightly with increasing age, body weight, or body surface area.

Evra, indications for use

Contraception in women.

Contraindications

    hypersensitivity to the drug;
    venous thrombosis including history (including deep vein thrombosis, pulmonary thromboembolism);
    arterial thrombosis, including a history of (including acute cerebrovascular accident, myocardial infarction, retinal artery thrombosis) or precursors of thrombosis (including angina pectoris or a transient attack of ischemia);
    presence of serious or multiple risk factors for arterial thrombosis: severe arterial hypertension (more than 160/100 mm Hg), diabetes mellitus with vascular lesions;
    hereditary dyslipoproteinemia;
    genetic predisposition to venous or arterial thrombosis (for example, resistance of activated protein C, deficiency of antithrombin III, deficiency of protein C, deficiency of protein S, hyperhomocysteinemia and antiphospholipid antibodies - antibodies against cardiolipin, lupus anticoagulant);
    migraine with aura;
    confirmed or suspected breast cancer;
    endometrial cancer and confirmed or suspected estrogen-dependent tumors;
    liver adenoma and carcinoma;
    genital bleeding;
    postmenopausal period;
    age up to 18 years;
    postpartum period (4 weeks);
    lactation period.
Do not use on the area of ​​the mammary glands, as well as on hyperemic, irritated or damaged skin.
Caution should be used when giving a family history of venous or arterial thromboembolism in brothers, sisters or parents at a relatively young age; with prolonged immobilization; obesity (body mass index of more than 30 kg / m2, calculated as the ratio of body weight in kilograms to the square of height in meters); thrombophlebitis of superficial veins and varicose veins; dyslipoproteinemia; hypertension; lesions of the valvular apparatus of the heart; atrial fibrillation; diabetes; systemic lupus erythematosus; hemolytic-uremic syndrome; Crohn's disease; ulcerative colitis; abnormal liver function; hypertriglyceridemia (including in family history); acute liver dysfunction during a previous pregnancy or previous use of sex hormones; in violation of the menstrual cycle; impaired renal function.

Dosage and administration

The patient should be informed that in order to achieve the maximum contraceptive effect, it is necessary to strictly follow the instructions on the use of Evr TTS. Only one TTS can be used at a time.
Each used TTS is removed and immediately replaced with a new one on the same day of the week (“replacement day”) on the 8th and 15th days of the menstrual cycle (2nd and 3rd week). TTS can be changed at any time of the day of replacement. During the 4th week, from the 22nd to the 28th day of the cycle, TTS is not used. A new contraceptive cycle begins the day after the end of the 4th week; the following TTS should be stuck, even if the menstruation was not or it has not ended.
Under no circumstances should the break in the TTS Evra application be longer than 7 days, otherwise the risk of pregnancy is increased. In such situations, for 7 days it is necessary to simultaneously use a barrier method of contraception, since The risk of ovulation increases with each day that the recommended duration of the period, free from the use of TTS, is exceeded. In the case of sexual intercourse during such an extended period, the probability of conception is very high.

Start applying TTS Evra

If during the previous menstrual cycle a woman did not use a hormonal contraceptive
Contraception using TTS Evra begin on the first day of menstruation. One TTS Evra is glued to the skin and is used all week (7 days). The day of sticking the first TTS Evra (1st day / start day) determines the next days of replacement. The replacement day will be on the same day of each week (8th and 15th days of the cycle). On the 22nd day of the cycle, the TTS is removed, and from the 22nd to the 28th day of the cycle, the woman does not use the ETC TTS. The next day is considered the first day of the new contraceptive cycle. If a woman starts using TTS Evra not from the first day of the cycle, then barrier methods of contraception should be used simultaneously for the first 7 days of the first contraceptive cycle.

If a woman switches from using a combined oral contraceptive to TTS Evra

TTS Evra should be applied to the skin on the 1st day of menstruation, which began after discontinuation of the combined oral contraceptive. If menstruation does not begin within 5 days after taking the contraceptive pill, then it is necessary to exclude pregnancy before starting to use TTS Evra.
If the use of Evra begins after the 1st day of menstruation, then within 7 days it is necessary to simultaneously use barrier methods of contraception.
If more than 7 days have passed after taking the last contraceptive pill, then a woman may experience ovulation, and therefore she should consult a doctor before starting to use TTS Evra. Sexual intercourse during this extended period free from taking contraceptive pills can lead to pregnancy.

If a woman shifts from using progestogen-only products to using Evra's TTS

A woman can go on any day with a drug containing only progestogen (on the day the implant is removed, on the day when another injection should be given), but during the first 7 days of using ETC TTS, a barrier method should be used to enhance the contraceptive effect.

After abortion or miscarriage

After an abortion or miscarriage before the 20th week of pregnancy, you can immediately start applying TTS Evra. If a woman begins to apply TTS Evra immediately after an abortion or miscarriage, then additional methods of contraception are not required. A woman should know that ovulation can occur within 10 days after an abortion or miscarriage. After an abortion or miscarriage in the 20th week of pregnancy or later, the use of Evra TTS can be started on the 21st day after the abortion or miscarriage, or on the 1st day of the first menstruation.

After childbirth

Women who are not breastfeeding should start using TTS Evra no earlier than 4 weeks after delivery. If a woman begins to use TTS Evra later, then during the first 7 days she should additionally use a barrier method of contraception. If sexual intercourse has taken place, it is necessary to exclude pregnancy before starting using TTS Evra, or a woman should wait for the first menstruation.

With full or partial peeling off TTS Evra

If TTS Evra is completely or partially peeled off, then insufficient amount of its active ingredients enters the blood.
Even with a partial peeling off of the TTS Evra in less than a day (up to 24 hours): you should re-glue the TTS Evra in the same place or immediately replace it with a new TTS Evra. Additional contraceptives are not required. The next TTS Evra needs to be glued on a regular “replacement day”.
With a partial peeling off for more than a day (24 hours and longer), and also if a woman does not know exactly when TTS Evra is partially or completely peeled off - the onset of pregnancy is possible. A woman should immediately begin a new cycle, sticking a new TTS Evra and consider this day as the first day of the contraceptive cycle. Barrier contraceptive methods should be used at the same time only in the first 7 days of the new cycle.
You should not try to re-glue TTS Evra if she lost her adhesive properties; instead, you must immediately glue the new TTS Evra. Do not use additional adhesive tapes or dressings to keep TTS Evra in place.

If the next days of replacing TTS Evra are missed

At the beginning of any contraceptive cycle (1st week / 1st day): with an increased risk of pregnancy, a woman should stick the first TTS of Evra on a new cycle as soon as she remembers. This day is considered a new "1st day" and a new "replacement day" is being counted. Non-hormonal contraception should be simultaneously applied during the first 7 days of a new cycle. In the case of sexual intercourse during such an extended period, conception may occur without the use of Evra's TTS.
In the middle of the cycle (2nd week / 8th day or 3rd week / 15th day):
—If 1 day or 2 days have passed since the replacement (up to 48 hours): the woman should immediately paste the new TTS. The following TTS needs to be glued on a regular “replacement day”. If during the 7 days preceding the first missed day of TTS attachment, the use of TTS was correct, then additional contraception is not required;
—If more than 2 days have passed since the replacement date (48 hours or more): there is an increased risk of pregnancy. A woman should stop the current contraceptive cycle and immediately start a new 4-week cycle by pasting a new ETC TTS. This day is considered a new "1st day" and a new "replacement day" is being counted. Barrier contraception should be applied simultaneously during the first 7 days of the new cycle;
—At the end of the cycle (4th week / 22nd day): if the TTS is not deleted at the beginning of the 4th week (22nd day), then it should be removed as soon as possible. The next contraceptive cycle should begin on the usual “replacement day”, which is the day after the 28th day. Additional contraception is not required.

Change day replacement

In order to postpone menstruation for one cycle, a woman must glue a new TTS Evra at the beginning of the 4th week (22nd day), thereby skipping the period free from using the TTS Evra. There may be intermenstrual bleeding or spotting. After 6 consecutive weeks of TTS use, there should be a 7-day interval free from TTS use. After the end of this interval, regular use of the drug is resumed.
If a woman wants to change the day of replacement on the day appointed for this purpose during the week, she must complete the current cycle by removing the third TTS of Evra; A woman can choose a new replacement day by sticking the first TTS of Evra of the next cycle on the selected day. In no case should the period free from using TTS Evra be more than 7 days. The shorter this period, the higher the likelihood that a woman will not have another menstruation, and during the next contraceptive cycle, intermenstrual bleeding or spotting may occur.

Mode of application

TTS Evra should be glued on clean, dry, intact and healthy skin of the buttocks, abdomen, outer surface of the upper part of the shoulder or upper part of the body with minimal hair growth, in areas where it will not come into contact with tight clothing.
In order to avoid possible irritation, each following TTS of Evra should be glued to another area of ​​skin, this can be done within the same anatomical region.
TTS Evra must be pressed tightly so that its edges are in good contact with the skin. To prevent the adhesion of TTS Evra from decreasing, you should not apply make-up, creams, lotions, powders and other local products on the skin where it will be glued or glued.
A woman should inspect the TTS Evra on a daily basis in order to be confident in its firm attachment.
Used TTCs must be carefully disposed of in accordance with the instructions.

Use during pregnancy and lactation

The drug Evra is contraindicated during pregnancy and lactation.

Side effects of Evra

On the part of the central nervous system and peripheral nervous system: dizziness, migraine, paresthesia, hypesthesia, convulsions, tremor, emotional lability, depression, anxiety, insomnia, drowsiness.
Since the cardiovascular system: increased blood pressure, palpitations, edematous syndrome, varicose veins.
On the part of the digestive system: gingivitis, anorexia or increased appetite, gastritis, gastroenteritis, dyspepsia, abdominal pain, vomiting, diarrhea, flatulence, constipation, hemorrhoids.
On the part of the respiratory system: infections of the upper respiratory tract, shortness of breath, bronchial asthma.
Reproductive system: pain during sexual intercourse (dyspareunia), vaginitis, dysmenorrhea, decreased libido, increase in mammary glands, menstrual disorders (including intermenstrual bleeding, hypermenorrhea), changes in vaginal secretion, changes in cervical mucus, lactation that occurs not due to childbirth, ovarian dysfunction, mastitis, breast fibroadenomas, ovarian cysts.
On the part of the urinary system: urinary tract infections.
On the part of the musculoskeletal system: muscle cramps, myalgia, arthralgia, ostalgia (including back pain, pain in the lower extremities), tendinosis (tendon changes), muscle weakness.
Dermatological reactions: pruritus, urticaria, skin rash, contact dermatitis, bullous rash, acne, discoloration of the skin, eczema, increased sweating, alopecia, photosensitization, dry skin.
On the part of the organ of vision: conjunctivitis, visual impairment.
On the part of metabolism: weight gain, hypertriglyceridemia, hypercholesterolemia.
Other: flu-like syndrome, fatigue, allergic reactions, chest pain, asthenic syndrome, syncope, anemia, abscesses, lymphadenopathy.
Rarely (with a frequency of> 0.01% to less than 0.1%): hypertonicity or muscle hypotonia, incoordination, dysphonia, hemiplegia, neuralgia, stupor, increased libido, depersonalization, apathy, paranoia, benign breast tumors, cervical cancer in situ , perineal pain, ulceration of the genitals, atrophy of the mammary glands, lowering blood pressure, enanthema, dry mouth or increased salivation, colitis, pain during urination, hyperprolactinemia, melanosis, skin pigmentation disorders, chloasma, xerophthalmia, weight loss, or obesity subcutaneous tissue, alcohol intolerance, cholecystitis, cholelithiasis, abnormal liver function, purpura, blood flushes to the face, thrombosis (including deep vein thrombosis, pulmonary artery thrombosis), thrombophlebitis of superficial veins, vein pain, pulmonary embolism arteries.

special instructions

There is no clinical evidence that, in any aspect, the transdermal contraceptive system is safer than oral contraceptives.
Before starting or resuming the use of TTS Evra, a detailed medical history (including family history) must be collected and pregnancy should be excluded. It is necessary to measure blood pressure and conduct a physical examination, taking into account contraindications and warnings.
If hereditary predisposition to venous thromboembolism is suspected (if venous thromboembolism occurred in a brother, sister or parents at a relatively young age), a woman should be referred for consultation to a specialist before deciding on the use of hormonal contraception.
The risk of vascular complications is increased in women with thrombophlebitis of the superficial veins and varicose veins, as well as in obesity (body mass index of more than 30 kg / m2).
With prolonged immobilization, after extensive surgery on the lower limbs or severe injury, it is recommended to stop the use of hormonal contraceptives (during a planned operation, this should be done 4 weeks before it) and resume hormonal contraception no earlier than 2 weeks. after complete remobilization.
Some epidemiological studies have revealed an increased risk of cervical cancer in women who have been using combined oral contraceptives for a long time.
Women taking combined oral contraceptives may develop liver tumors, which can cause life-threatening intra-abdominal bleeding. In the case of women who use TTS Evra, severe pain in the upper abdomen, liver enlargement or symptoms of intra-abdominal bleeding, a differential diagnosis should be made to rule out a possible liver tumor.
In women with hypertriglyceridemia or this disease in the family history, the risk of pancreatitis in the case of the use of combined hormonal contraceptives may be increased.
If pharmacologically uncontrolled arterial hypertension occurs in women during the use of combined hormonal contraceptives, the drug should be discontinued. Application TTS Evra can be resumed after the normalization of blood pressure.
It was reported that oral administration of combined hormonal contraceptives may cause or worsen the diseases listed below, but there is no convincing evidence of their connection with the use of combined oral contraceptives. These include: jaundice and / or pruritus associated with cholestasis; cholelithiasis; porphyria; systemic erythematosus; hemolytic uremic syndrome; Chorea Sydenham; gestational herpes associated with otosclerosis hearing loss. Hormonal contraceptives can affect some endocrine parameters, liver function markers and blood components:
- increases the concentration of prothrombin and coagulation factors VII, VIII, IX and X; reduced levels of antithrombin III; decreases the level of protein S; increased norepinephrine platelet aggregation;
- increases the concentration of thyroxin-binding globulin, which causes an increase in the concentration of total thyroid hormone, which is measured by iodine content associated with protein, T4 content (determined using chromatography or radioimmunoassay); binding of free T3 to an ion-exchange resin decreases, as evidenced by an increase in the concentration of thyroxin-binding globulin, the concentration of free T4 does not change. Serum concentration of other binding proteins may be increased;
- increases the concentration of globulins that bind sex hormones, which leads to an increase in concentrations of total circulating endogenous sex hormones. However, concentrations of free or biologically active sex steroids are reduced or remain unchanged.
Women using TTS Evra may slightly increase concentrations of LDL-C, total cholesterol, LDL-C and TG, while the ratio of LD-C / LDL / C-HDL may remain unchanged.
Hormonal contraceptives may cause a decrease in serum folate concentrations. This can have potentially clinically significant consequences if a woman has a pregnancy shortly after withdrawing a hormonal contraceptive. Currently, all women are advised to take folic acid during and after hormonal contraception.
Combined hormonal contraceptives can affect peripheral insulin resistance and glucose tolerance, but there is no evidence of the need to change the regimen of diabetes mellitus while using combined hormonal contraceptives. At the same time, the condition of patients suffering from diabetes should be carefully monitored, especially at the early stage of the use of Evra TTS.
Exacerbation of endogenous depression, epilepsy, Crohn's disease and ulcerative colitis has been reported in women taking combined oral contraceptives.
Women who have experienced hyperpigmentation of their skin during pregnancy should avoid exposure to sunlight or artificial ultraviolet light while wearing TTS Evra. Often, such hyperpigmentation is not completely reversible.
Women should be informed that hormonal contraceptives do not protect against HIV infection (AIDS) and other sexually transmitted diseases.
Women taking medications that induce microsomal enzymes (hydantoins, barbiturates, primidone, carbamazephen, rifampicin, oxcarbazepine, topiramate, felbamate, ritonavir, griseofulvin, modafinil, and phenylbutazone) and antibiotics (for tetracyclists, except for tetracyclists, except for tetracyclists, except for tetracyclists, except for tetracyclists, except for tetracyclists, but for children, except tetracyclists,) TTS Evra or choose a different method of contraception. The barrier method should be applied during the course of treatment with the above preparations, as well as within 28 days after discontinuation of the inducers of microsomal enzymes and within 7 days after discontinuation of antibiotics. If the period for taking concomitant drugs exceeds the 3-week cycle of using Eur's TTS, then the new contraceptive cycle should be started immediately after the previous one, that is, without the usual period free from using TTS. Women who receive long-term therapy with drugs that induce liver enzymes should choose another method of contraception.
When prescribing Evra drugs that are metabolized by CYP3A4, CYP2C19 isoenzymes, especially those with a narrow therapeutic index (for example, cyclosporine), against the background of TTS use, the probability of a clinically significant interaction should be excluded.
When using any combined hormonal contraceptives, the menstrual cycle may be disturbed (spotting or intermenstrual bleeding), especially in the first months of using these remedies. The duration of the adaptation period is about three cycles.
If during the use of TTS Evra in accordance with the recommendations, persistence of intermenstrual bleeding is observed or such bleeding occurs after previous regular cycles, then other reasons besides the use of TTS should be taken into account. It should be borne in mind the possibility of non-hormonal causes of menstrual disorders and, if necessary, conduct an adequate diagnostic examination to exclude organic disease or pregnancy.
Some women in the period, free from the use of TTS Evra menstruation may not occur. If a woman violated the instructions for use in the period preceding the first failed menstruation, or if she did not have two menstruations after interruptions in the use of TTS, it is necessary to exclude pregnancy before continuing to use TTS Evra.
In some women, the abolition of hormonal contraceptives can provoke the occurrence of amenorrhea or oligomenorrhea, especially if they are present before the onset of hormonal contraception.
If the application of TTS Evra causes skin irritation, you can glue the new TTS to another area of ​​skin and wear it until the next day of replacement.
In women weighing 90 kg or more, the effectiveness of contraception can be reduced.
If symptoms of liver dysfunction occur, the use of combined hormonal contraceptives should be stopped until the normalization of liver function markers.
In the case of the relapse of pruritus associated with cholestasis, which occurred during a previous pregnancy or prior use of sex hormones, the combined hormonal contraceptives should be canceled.
The safety and effectiveness of TTS Evra are established only for women from 18 to 45 years.

Recycling Recommendations

Immediately after removing the TTS from the bag, it should be firmly glued to the skin. After removing TTS, it still contains significant amounts of active ingredients. Residual hormones can harm the environment if they enter the water, and therefore used TTS should be disposed of carefully. To do this, separate the special adhesive film from the outside of the bag. Place the used TTS in the bag in such a way that its sticky side faces the painted area on the bag, and lightly press it to seal it. The sealed bag is thrown away. Used TTS should not be thrown into the toilet or into the sewer.

Interaction

Hydantoins, barbiturates, primidone, carbamazepine and rifampicin, as well as oxcarbazepine, topiramate, felbamate, ritonavir, griseofulvin, modafinil, and phenylbutazone, can cause an acceleration of the metabolism of sex hormones, which can lead to interfunctional bleeding or failure, and ineffectiveness will not work. of pregnancy. The mechanism of interaction of these drugs and the active ingredients of TTS Evra is based on the ability of the above listed drugs to induce liver enzymes, with the participation of which the sex hormones are metabolized. The maximum induction of enzymes is usually achieved no earlier than 2-3 weeks, and can last for at least 4 weeks after discontinuation of the corresponding drug.
Acceptance of herbal preparations containing St. John's wort (Hypericum perforatum) concurrently with the use of Evra TTS may lead to a loss of contraceptive effect. Women who have taken these herbal remedies may experience intermenstrual bleeding and unwanted pregnancy. This is due to the fact that St. John's wort induces enzymes that metabolize sex hormones. Inducing effect may persist for 2 weeks. after the abolition of the herbal preparation containing St. John's wort.
The loss of the contraceptive effect may be caused by antibiotics (including ampicillin and tetracyclines). A study of the pharmacokinetic interaction showed that oral administration of tetracycline hydrochloride 3 days before and for 7 days while using TTS Evra does not have a significant effect on the pharmacokinetics of norelgestromin or ethinyl estradiol.

Overdose

Symptoms: nausea, vomiting, vaginal bleeding.
Treatment: there is no specific antidote. TTS should be removed and symptomatic therapy should be performed.
Shelf life - 2 years.

Indications for use

Z30 Supervision of contraceptive use

Storage conditions

The drug should be stored out of reach of children at a temperature of 15 ° to 25 ° C.

Terms of sell

You can buy Evra without a prescription.