Evra

Pharmacological means of Euras Medical is referred to the clinical and pharmacological group of hormonal contraceptive preparations for transdermal use.

[1],

Indications Evra

The considered pharmacological agent was initially developed only with one orientation - as a contraceptive. Therefore, direct evidence for the use of Evra - contraception for the fair sex.

[2]

Release form

On the modern pharmacological market this innovative preparation is represented by two varieties of proposed packages. The form of release is a plaster with a special hormonal composition applied to the inner surface.

Produced packaging:

1. Three contraceptive units that are sterile sealed, individually, in an individual case consisting of two layers: laminated paper and foil. Together, the three patches are packed in a bag of polymer material.
2. The second type of packaging offered is a case from nine contraceptive units that are packaged similarly to the first variant, but in one general package of polymer material there are three cases consisting of three individually packaged patches of Eur.

Plaster for female contraception - transdermal therapeutic system (TTS) - is a square with smoothly rounded corners. Layering is looked at: a matt pale beige hue pigmented LDPE substrate, on which the characters making up the word "EVRA" are applied. The inner layer is an adhesive layer of colorless glue, which includes a non-woven material made of polyester, crospovidone, lauryl lactate, polyisobutylene-polybutene. Directly the inner layer protecting the septicity of active substances and removed before use is a transparent film of polyethylene terephthalate (or polydimethylsiloxane).

[3]

Pharmacodynamics

This patch was designed as a contraceptive drug for transdermal use. Therefore, the pharmacodynamics of Evra is aimed at blocking or reducing the number of hormones produced by the ovaries and affecting the endometrium. The effect goes directly to the gonadotropic function of the pituitary gland. This is where the signal for oppression of the proliferation of the follicle comes from, which makes it impossible to fertilize the cell (the passage of the ovulation process).

Contraceptive properties of the drug increase with an increase in the viscosity of the secretion, produced by secrets located in the cervix (cervical mucus). It is still necessary to reduce the sensitivity of endometrial tissue to the blastocyst.

The effectiveness of the pharmacodynamics of the Euro by the Pearl Index can be estimated as 0.90.

It should be remembered that the quantitative indicator of passing inseminations is not related to the age of the woman (if she is still of childbearing age), and does not depend on the race of the potential mother.

[4], [5]

Pharmacokinetics

Since the attachment of the contraceptive patch to the skin of a woman passes a small amount of time (up to 48 hours), when hormones such as ethinylestradiol C _ss and norelgestromine begin to be detected in the blood serum. Their quantitative indices are respectively shown in figures of 0.8 ng / ml and 50 ng / ml.

When using this tool for a long time, the level of C _ss and AUC increases slightly. If the body of a woman is subjected to increased physical and emotional stress, or within certain limits, the temperature component changes, no significant fluctuations in the indices of these hormones are observed, especially in the case of AUC noregestromine and C _ss, AUC ethinyl estradiol may show a slight increase in concentration.

Therapeutic efficacy of the patch is maintained for ten days after the application of the transdermal therapeutic system. This fact allows you to maintain the necessary effectiveness of the drug, even if a woman, for some reason, delayed the replacement of the patch for a couple of days from seven recommended days.

Such metabolites of noregestromine as norgestrel and norelgestromine give high rates for interaction levels and compounds with plasma proteins. Primarily, pairs of compounds are observed: norgestrel - globulin and noregestromine - albumin, ethinyl estradiol - albumin. The indicator of binding sex hormones is high enough and is more than 97%. These indicators can significantly decrease with an increase in such parameters of the human body as the surface area and body weight of the patient, the adjustment can also make her age.

Metabolism of noregestromine occurs almost entirely in the liver, the result of this transformation is norgestrel, which is concomitant with other conjugated and hydroxylated metabolites. The end result of the metabolism of ethinyl estradiol (a transformation resulting from chemical reactions that occur in the living body to sustain life and development) are hydroxylated chemical compounds, sulfate and glucuronide conjugates.

Inhibit or slow down, the life process of most microsomal hepatic enzymes suppresses hormones such as estrogens and progestogens.

The average half-life of decay products (T _1/2 ), affecting the woman's body substances of ethinyl estradiol and norelgestromine, is approximately 17 and 28 hours, respectively. The main way of excretion of metabolic products is classical: through the urinary system with urine and through the intestine with calves.

[6], [7], [8], [9], [10], [11]

Dosing and administration

There are certain rules and recommendations that should not be ignored, only then you can achieve the desired result and minimize complications and the manifestation of secondary symptoms.

1. It is not recommended to use more than one contraceptive TTS in parallel.
2. Careful observance of all instructions.
3. The replacement of the patch of the TTS Eur is carried out strictly according to the schedule: on the first, the eighth and the 15th day of the menstrual cycle, which corresponds to the second and third seven-day menstrual block.
4. The application of the next plaster is possible during 24 hours of the day, which are selected by "shift day".
5. In the fourth week of the menstrual cycle (the twenty-second - twenty-eighth day of the physiocycle), the body rests from extraneous influence. Contraceptive is not prescribed.
6. The new contraceptive course starts on the second day after the end of the fourth seven-day period. There is a need to clarify: the applicator of the Eur is glued, in any case, even if there are no monthly blood releases at all or they are still passing.
7. Do not allow interruptions in the effect of the transdermal therapeutic system on the body of the fair sex for more than seven days. Otherwise, the therapeutic efficacy drops sharply and the likelihood of ovarian fertilization and pregnancy increases.
8. If it is necessary to prolong the break for more than a week, the probability of conception increases daily, for this period it is necessary to use the barrier method of contraception (non-hormonal methods and preparations).

In different life circumstances, the way of application and dose of the drug Evra somewhat vary.

If the previous menstrual cycle has passed without the use of hormonal contraceptives.

1. The plaster is applied to the skin in the first day of the physiological cycle. The application is held for a week. The name of the day of the week, when the first plaster of Eur is glued and will be basic, the subsequent patches will be changed on the same day ("replacement day"), but a week later (the 8th and 15th days of the cycle).
2. On the 22nd day, they remove Evra. The week, until the 28th day of the cycle, is rest.

If the previous menstrual cycle, the woman took combined oral contraceptives, and now transfers to the TTC of Eur.

1. The patch is glued on the first day of the menstrual cycle, which follows the completed course of oral intake of combined contraception.
2. If after the end of the procedure five days have passed and the monthly ones have not begun, it is better to take a pregnancy test. Only after receiving a negative result can you start using the TTC Evra.
3. If the patch was firstly applied later than the first day of the cycle, then barrier contraceptive methods should be introduced in parallel throughout the week.
4. If the last birth control pill has been drunk, and after that has passed more than a week, the female body can tolerate the ovulation of the egg. In this situation it is better to consult an obstetrician - a gynecologist and only with his permission to continue using the TTC Evra. Sexual relations during this period can lead to the fertilization of the cell and pregnancy.

If the previous menstrual cycle, the woman took medications, which are based only on progestogens, and now it goes to the TTC of Eur.

1. In this case, a woman can go to a transdermal therapeutic system any day after the reception of the contraceptive used before is completed.
2. It is necessary to fulfill one condition: the application of Evra should be introduced immediately after the rejection of the previous drug. And for the next seven days, it is necessary to carry out parallel barrier contraception. This will keep the necessary therapeutic effect.

Transition to TTS after abortion or miscarriage.

1. If an artificial or natural abortion occurred at a time when the pregnancy did not reach the twentieth week, the TTC of the Eur can be started immediately after this unpleasant procedure. In this case, it is not necessary to take supporting methods of contraception in parallel. A new conception can happen only after the expiration of ten days after miscarriage or abortion.
2. If the pregnancy was interrupted after the onset of the 20th week, the contraceptive patch may be administered from the 21st day after an unpleasant procedure, or on the first day of a new menstrual cycle.

Transition to Eur after delivery.

1. If a young mother does not feed a newborn baby with breast milk, then the TTC can be used four weeks after the significant day, the baby's birth.
2. If the input comes later than the agreed period, in parallel, during the week, additional contraception (the barrier method) is also applied.
3. If there was a sexual intercourse during this period, before starting to use a band-aid, it is necessary to make sure of the absence of pregnancy or to wait for the beginning of menstrual bloodshed.

If during the period of using the patch, partial or complete peeling was observed.

1. This situation indicates that the woman's body received a smaller number of necessary connections.
2. Even incomplete removal of the drug from the skin during the day (24 hours) can significantly spoil the expected result. Therefore, as early as possible, you need to replace the adhesive tape by gluing a new one (for this same place). There are no other supporting methods.
3. The subsequent change of Evra is carried out in the "replacement day" adopted earlier.
4. If a complete or partial impairment of contact has been observed for more than 24 hours, or there is no complete certainty in this time parameter, then the probability of the birth of a pregnancy is high enough.
5. In this situation, primarily, it is necessary to conduct a pregnancy test. If the result is negative, start taking the TTC Evra from scratch, considering this application as the first day of the contraceptive cycle and, accordingly, there is a change in the "replacement day".
6. For the first week, contraception of the barrier type is necessarily introduced in parallel.
7. If the adhesive has lost its stickiness, do not try to attach it again to the skin. Do not use an ordinary sticky tape or a bandage to improve the fixation.

Correction of the "replacement day".

If there was a need to shift menstrual bleeding for one cycle, it is necessary to use a new application, which is attached in the 22nd day. This will delay the break and, accordingly, stop the subsequent bleeding.

In this situation, there may be bloody discharge in the intervals between menstruations. Consistently it is not recommended to use the patch in a row for more than six weeks. There must be a break in the application of the TTS for a week (seven days). After maintaining this period, you can again start using Evra.

Change the "day of replacement" a woman can in the period free from the use of the drug, pasting the first application of the TTC Evra. At the same time, we should not forget that the period between the removal of the third applicator of the previous cycle and the imposition of a new one (with a change in the "replacement day") should not exceed seven days.

Use Evra during pregnancy

The transdermal therapeutic system (TTS) is a hormonal pharmacological product, and its effect on the body of the fair sex is on a more subtle level. Therefore, the use of Evra during pregnancy and during the period when a young mother feeds a newborn baby with breast milk is categorically contraindicated, since such an effect transforms many processes in the human body, which can have unpredictable consequences for the health and development of the future little man.

Contraindications

As it was said earlier, the plaster in question exerts its influence on the woman's organism at the level of its hormonal background. Proceeding from such force of influence, which is sufficiently significant, there are also numerous contraindications to the use of Eur.

• Individual intolerance to the components of the contraceptive component.
• Clogging of arterial blood vessels, including:
  • Ischemia of the heart muscle.
  • The acute phase of pathological malfunctions during blood through the vessels, which affects the nutrition and enrichment of the brain tissue with oxygen.
  • Occlusion of the blood capillaries of the ocular retina.
  • Precursors of blockage, for example, ischemic cardiac blockade of transitory nature or failure of rhythm.
• Lack of antithrombin-III.
• Predisposition of a hereditary character to the blockage of veins or blood vessels.
• Low level of resistance of activated protein C and S. Their deficiency in the body of a woman.
• Severe hypertension with arterial pressure values above 160/100 mm Hg. Art.
• Diabetes mellitus, affecting the integrity and changes in other indicators of the norm of blood vessels.
• Thrombosis of veins, including deep, including thromboembolism of the lungs.
• Hereditary dyslipoproteinemia (quantitative and qualitative violations of the composition of blood lipoproteins).
• Endometrial cancer.
• Migraine with aura is a headache felt paroxysmal and manifested by a stable localization in the fronto-temporal-ophthalmic region and covering half of the head that arises after previous neurological symptoms (aura).
• Hyperhomocysteinemia (increased concentration of amino acid hyperhomocysteine).
• The presence in the patient's body of antiphospholipid antibodies that work against cardiolipin is a lupus anticoagulant.
• Diagnosis or suspicion of a malignant neoplasm in the mammary gland of a woman.
• Estrogen-dependent tumors or suspicion of their presence.
• Bleeding from the genitals.
• Hepatic carcinoma and adenoma.
• The postmenopausal age of a woman.
• Less than four weeks after childbirth.
• Breastfeeding time.
• If a woman is under 18 years of age.
• You can not impose an application in the area of the mammary glands, hyperemic areas of the skin or where there is irritation or various kinds of damage to the epidermis.

With great care, the TTC of Eur should be applied if there are the following factors:

• The presence and development of thromboembolism arterial or venous localization in close relatives of a woman, at a fairly young age.
• Malfunction of the menstrual cycle.
• Continuous immobilization (immobility) of the whole organism or individual parts of the body.
• Excess body weight with an index exceeding 30 kg / m², which indicates significant obesity.
• Dysfunction of the liver and kidneys.
• Presence in the anamnesis of a woman of varicose veins or superficial thrombophlebitis of veins.
• Prolonged arterial hypertension.
• Kolit, burdened with ulcers.
• Atrial fibrillation is supraventricular tachyarrhythmia with chaotic electrical activity of the atria with a pulse frequency of 350-700 per minute.
• Heart valve flaw.
• Crohn's disease is a chronic inflammatory disease that affects the entire gastrointestinal tract: from the oral cavity to the anus.
• Hemolytic-uremic syndrome - microangiopathic hemolytic anemia, renal failure and thrombocytopenia.

[12], [13], [14]

Side effects Evra

The contraceptive adhesive plaster in question is considered to be a strong systemic drug. Hence the possible multiple side effects of the Euro.

• Reaction of peripheral and central nervous system:
  • Dizziness.
  • Headache.
  • Partial loss of sensitivity of the upper or lower extremities.
  • Tremor and convulsions.
  • Emotional stress: depressive states, irritability.
  • Problems with sleep.
• Response of the genitourinary system:
  • Urinary tract infection.
  • Dyspareunia is a painful coitus.
  • Vaginitis - inflammation of the vaginal mucosa, provoked by pathogenic microorganisms.
  • Mastitis is an inflammation of the tissues of the mammary glands.
  • Decreased level of sexual desire.
  • Dysmenorrhea is a pain symptomatology in the abdominal area associated with uterine spasms during menstruation.
  • Growth of breast volume.
  • Failure of the female menstrual cycle. There may be bloody discharge in the intervals between menstruation, hypermenorrhoea.
  • Fibroadenoma of the mammary glands.
  • Violation of the production of cervical mucus and breast milk, not associated with obstetric care.
  • Ovarian failure, polycystosis.
• The reaction of the gastrointestinal tract:
  • Gingivitis - inflammation of the mucous membrane of the gums.
  • Failure in the process of nutrition (increased appetite or, conversely, reluctance to eat).
  • Pain in the abdomen.
  • Gastritis and gastroenteritis (acute or chronic inflammation in the wall of the stomach and small intestine).
  • Dyspepsia is a digestive disorder that manifests itself as flatulence, diarrhea, or, conversely, constipation and vomiting.
  • Hemorrhoids - inflammation and enlargement, as well as bleeding and prolapse of internal venous nodes of the rectum plexus.
• Reaction of the respiratory system:
  • Attacks of asthma.
  • Appearance of shortness of breath.
  • The probability of infection with ENT organs.
• Cardiovascular system reaction:
  • Tachycardia.
  • Varicose veins.
  • Increased blood pressure.
  • Puffiness.
• Skin Reaction:
  • An allergic reaction, manifested by itching, rashes, hives.
  • Increased dryness of the skin.
  • Contact dermatitis.
  • Photosensitivity - increase the sensitivity of the body to the action of ultraviolet radiation.
  • Bullous or acne.
  • Changing the shade of the epidermis.
  • Appearance of a copy.
  • Increased sweating.
  • Alopecia is a pathological hair loss.
• Reaction of musculoskeletal tissues:
  • Tendonosis - changes in the parameters of tendons.
  • Arthralgia is pain in the affected joint.
  • Muscle cramps and a decrease in their tone.
  • Ostalgia is a pain symptomatology manifested in the spine and legs.
  • Myalgia - pain in the muscles.
• Metabolism:
  • Weight gain.
  • Hypercholesterolemia - increased cholesterol levels in the blood.
  • Hypertriglyceridemia - increased triglycerides (TG) in the blood plasma on an empty stomach.
• Other reactions:
  • Decreased general tone, a constant sense of fatigue.
  • Anemia.
  • Thrombophlebitis of superficial veins.
  • Pain symptomatology in the chest.
  • Flu-analgesic manifestations.
  • Asthenic syndrome is a condition in which the body works out of last strength.
  • Conjunctivitis, vision problems.
  • Fainting.
  • Lymphadenopathy is a condition manifested by an increase in the lymph nodes of the lymphatic system.
  • Abscesses.
  • Alcohol intolerance.
  • Embolism of the pulmonary artery.

[15], [16], [17]

Overdose

If you deviate from the recommendations in the use of the transdermal therapeutic system of Eur, an overdose of the constituent components of the plaster is possible. The woman's organism in such a situation is able to respond with nausea, at times quite strong and passing into vomiting. There may be bleeding from the vagina.

When this symptomatology appears, it is necessary to remove the plaster immediately and seek help and advice from the local gynecologist.

[18], [19]

Interactions with other drugs

It is necessary with special caution to apply a parallel intake of two or more drugs, because it is not always possible to predict the consequences of their mutual influence. Some results of the interaction of Eur with other drugs are known and are given below.

Provoke an increase in the activity of formation and functioning of sex hormones, which can lead to uterine bleeding in the interim period of the cycle and reduce the reliable operation of the hormonal contraceptive is able to share the use of TTC Eur with such pharmacological drugs and classes of drugs:

• Barbiturates and hydantoins.
• Oxcarbazepine.
• Carbamazepine.
• Ritonavir.
• Felbamat.
• Rifampicin.
• Griseofulvin.
• Primidone.
• Modafinil.
• Topiramate.
• Phenylbutazone.

Their admission with TTS can lead to an unwanted pregnancy. These drugs are quite capable of causing and accumulating liver enzymes, with the help of which the metabolism of these hormones occurs.

The maximum inductance of the hepatic enzyme is mainly observed two to three weeks after the joint administration and is able to stay about a month after their withdrawal.

The joint use of a patch with a number of herbal preparations can significantly reduce the contraceptive effectiveness of Eur. For example, such a result can be obtained by concurrent admission with drugs that include St. John's wort (Hypericum perforatum). In this situation, intermenstrual bleeding may appear. The mechanism of occurrence of such an effect is similar to the previous one. The inducing result is maintained for two weeks after the cessation of co-administration.

To lose the contraceptive ability of TTS Evra can and in case of application of medical therapy with use of antibiotics, including preparations of tetracycline and ampicillin groups. 

[20], [21]

Storage conditions

In many respects, the high therapeutic characteristics of the pharmacological product directly depend on the accuracy of the storage conditions of the Eur. In this case, it is necessary to maintain a temperature storage regime in the range of 15 to 25 degrees above zero. It is inadmissible to store TTC in the refrigerator or even more in the freezer. Before opening, the patch should be in the original packaging.

[22],

Special instructions

Note:

1. To date, there is no evidence base that would unequivocally call TTS safer than oral contraception.
2. Before starting the application of the patch of Evra, it is advisable to undergo a complete examination to collect an anamnesis and obtain a complete picture of the woman's health status. It is necessary to confirm the absence of pregnancy.
3. It should be noted that hormonal-based contraceptives are not a blocking factor in protecting a woman's body against infection with a sexually transmitted infection, including HIV.
4. In some women, after stopping the use of hormonal contraceptives, amenorrhea (absence of the menstrual cycle) or oligomenorrhoea may manifest, when bloody discharge is insignificant and can last from a few hours to a couple of days.
5. If the epidermis is noticeable on the application area, the next patch should be applied to the other surface of the skin.
6. If a woman weighs more than 90 kg, the effectiveness of the drug is reduced.
7. The expected effect and low probability of complications is quite appreciated only for women of the age range from 18 to 45.
8. The individual package must be opened immediately before use. After depressurization, the adhesive immediately adheres to the skin.
9. After the patch was used for the intended purpose, the applicator is removed, but a certain amount of the active substance is still included in its composition. If they get into the water, and with it into the ground - it threatens harmful negative effects on the natural environment. Therefore, there are certain rules for the disposal of the transdermal therapeutic system of Eur, as provided by the manufacturer. For this, a special outer layer of sticky film is removed from the packaging. The used plaster is placed in a bag so that the sticky side of the TTS is covered with a colored area on the package. The layers of the packet and adhesive patch are pressed against each other. Only after this, the TTC Eur can be thrown into the trash can. Dispose of in the toilet or through other sewage plums is strictly prohibited.

The drug Evra will be effective and safe for the woman's health only if all the recommendations sounded by the instruction accompanying the drug are observed and with the permission of the treating gynecologist who is really able to assess the woman's health at the time of the appointment of the TTC.

Shelf life

With the right approach and the fulfillment of all storage requirements, the shelf life of the pharmacological agent in question is two years. After the expiration of the storage period, use of this drug is not recommended.