Evra

Doctors classify the pharmacological agent Evra as a clinical-pharmacological group of hormonal contraceptive drugs for transdermal use.

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Indications Evra

The pharmacological agent in question was initially developed with only one purpose – as a contraceptive. Therefore, direct indications for the use of Evra are contraception for the fair sex.

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Release form

On the modern pharmacological market, this innovative drug is presented in two types of offered packaging. The release form is a patch with a special hormonal composition applied to the inner surface.

Available packaging:

1. Three contraceptive units, sterilely sealed, each separately, in an individual case consisting of two layers: laminated paper and foil. Together, the three patches are packed in a polymer bag.
2. The second type of packaging offered is a case of nine contraceptive units, which are packed similarly to the first option, but in one common polymer package there are three cases consisting of three individually packed Evra patches.

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

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Pharmacodynamics

This patch was specifically developed as a contraceptive drug for transdermal use. Therefore, the pharmacodynamics of Evra is aimed at blocking or reducing the amount of hormones produced by the ovaries and affecting the endometrium. The effect is directly on the gonadotropic function of the pituitary gland. It is from there that the signal comes to suppress follicle proliferation, which makes cell fertilization impossible (the ovulation process).

The contraceptive properties of the drug increase with the growth of the viscosity index of the secretion produced by the secretions located in the cervix (cervical mucus). At the same time, it is also necessary to reduce the sensitivity of the endometrial tissue to the blastocyte.

The pharmacodynamic effectiveness of Evra according to the Pearl Index can be estimated as 0.90.

It is worth remembering that the quantitative indicator of fertilizations occurring is in no way connected with the woman’s age (if she is still of childbearing age), and does not depend on the race of the potential mother.

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Pharmacokinetics

From the moment the contraceptive patch is attached to the woman's skin, a short period of time (up to 48 hours) passes when hormones such as ethinyl estradiol C _ss and norelgestromin begin to be determined in the blood serum. Their quantitative indicators are shown by the figures 0.8 ng/ml and 50 ng/ml, respectively.

When using this product for a long time, the level of C _ss and AUC increases slightly. If the woman's body is subjected to increased physical and emotional stress, or the temperature component changes within certain limits, significant fluctuations in the indicators of these hormones are not observed, this is especially true for AUC norelgestromin and C _ss, AUC ethinyl estradiol may show a slight increase in the concentration level.

The therapeutic effectiveness of the patch is maintained for ten days from the moment of application of the transdermal therapeutic system. This fact allows maintaining the necessary effectiveness of the drug, even if the woman, for some reason, has missed the patch change by a couple of days from the recommended seven days.

Such metabolites of norelgestromin as norgestrel and norelgestromin give high rates of interaction and connection with plasma proteins. The following pairs of compounds are mainly observed: norgestrel - globulin and norelgestromin - albumin, ethinyl estradiol - albumin. The rate of binding sex hormones is quite high and is more than 97%. These rates 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 be made by her age.

The metabolism of norelgestromin occurs almost entirely in the liver, the result of this transformation is norgestrel, which is accompanied by other conjugated and hydroxylated metabolites. The end result of the metabolism of ethinyl estradiol (a transformation that is the result of chemical reactions that occur in a living organism to maintain life and development) are hydroxylated chemical compounds, sulfate and glucuronide conjugates.

Hormones such as estrogens and progestogens inhibit or slow down, suppress the vital process of most microsomal liver enzymes.

The average half-life of the breakdown products (T _1/2 ) of the substances ethinyl estradiol and norelgestromin affecting the female body is approximately 17 and 28 hours, respectively. The main route of excretion of metabolic products is classical: through the urinary system with urine and through the intestines with feces.

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Dosing and administration

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

1. It is not recommended to use more than one TTS contraceptive in parallel.
2. Careful adherence to all instructions.
3. The TTS Evra patch is replaced strictly according to the schedule: on the first, eighth and 15th days of the menstrual cycle, which correspond to the second and third seven-day period of the menstrual block.
4. The application of the next patch is possible during the 24 hours of the day that are chosen as the “change day”.
5. In the fourth week of the menstrual cycle (the twenty-second to twenty-eighth day of the physiocycle), the body rests from external influences. Contraceptives are not used.
6. A new course of contraception starts on the second day after the end of the fourth seven-day period. It is necessary to clarify: the Evra applicator is glued in any case, even if there was no monthly bleeding at all or it is still passing.
7. It is not recommended to allow interruptions in the effect of the transdermal therapeutic system on the body of a representative of the fair sex for more than seven days. Otherwise, the therapeutic effectiveness drops sharply and the probability of fertilization of the egg and pregnancy increases.
8. If it is necessary to extend the break for more than a week, the probability of conception increases daily, during this period it is necessary to use a barrier method of contraception (non-hormonal methods and drugs).

Under different life circumstances, the method of application and dosage of the drug Evra may vary slightly.

If the previous menstrual cycle occurred without the use of hormonal contraception.

1. The patch is applied to the skin on the first day of the physiological cycle. The application is kept for a week. The name of the day of the week when the first Evra patch is glued will be the base one, subsequent patches are changed on the same day ("replacement day"), but a week later (the 8th and 15th days of the cycle).
2. On the 22nd day, Evra is removed. A week, until the 28th day of the cycle, is rest.

If the woman has been taking combined oral contraceptives during the previous menstrual cycle and is now switching to Evra TTS.

1. The patch is applied on the first day of the menstrual cycle following the completed course of oral combined contraception.
2. If five days have passed since the end of the course and your period has not started, it is better to take a pregnancy test. Only after receiving a negative result can you start using TTS Evra.
3. If the patch was initially applied later than the first day of the cycle, then barrier contraceptive methods must be used in parallel for a week.
4. If the last contraceptive pill was taken and more than a week has passed since then, the female body may allow the egg to ovulate. In this situation, it is better to consult an obstetrician-gynecologist and only with his permission continue using TTS Evra. Sexual intercourse during this period can lead to fertilization of the cell and pregnancy.

If during the previous menstrual cycle a woman took drugs based only on progestogens, and now she switches to TTS Evra.

1. In this case, a woman can switch to a transdermal therapeutic system on any day after finishing the previously used contraceptive.
2. It is necessary to fulfill one condition: the Evra application must be administered immediately after stopping the previous drug. And during the next seven days, it is necessary to simultaneously use barrier contraception. This will allow maintaining the necessary therapeutic effect.

Transition to TTS after an abortion or miscarriage.

1. If an artificial or natural abortion occurred during the period when the pregnancy has not reached the twentieth week, then TTS Evra can be used immediately after this unpleasant procedure. In this case, there is no need to take supporting methods of contraception in parallel. A new conception can only occur after ten days have passed since the miscarriage or abortion.
2. If the pregnancy was terminated after the 20th week, it is possible to insert the contraceptive patch from the 21st day after the unpleasant procedure, or on the first day of the new menstrual cycle.

Transition to Evra after childbirth.

1. If a young mother does not breastfeed her newborn, then she can begin using TTS four weeks after the momentous day of the baby’s birth.
2. If the introduction occurs later than the agreed time, additional contraception (barrier method) is used in parallel for a week.
3. If there was sexual intercourse during this period, before starting to use the patch, you must make sure that you are not pregnant or wait until your menstrual bleeding begins.

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

1. This situation indicates that the woman’s body received fewer essential compounds.
2. Even partial removal of the preparation from the skin within 24 hours can significantly spoil the expected result. Therefore, it is necessary to replace the patch as soon as possible by gluing a new one (to the same place). No other supporting methods are needed.
3. The subsequent change of the Evra is carried out on the previously adopted "change day".
4. If a complete or partial disruption of contact was observed for more than 24 hours, or there is no complete certainty about this time parameter, then the probability of pregnancy is quite high.
5. In such a situation, first of all, it is necessary to conduct a pregnancy test. If the result is negative, start taking TTS Evra from scratch, considering this application as the first day of the contraceptive cycle and, accordingly, the "replacement day" is changed.
6. During the first week, barrier contraception must be introduced in parallel.
7. If the patch has lost its stickiness, do not try to reattach it to the skin. Do not use regular adhesive tape or bandage over Evra to improve fixation.

Adjusting the "replacement day".

If it is necessary to shift menstrual bleeding by one cycle, then it is necessary to use a new application, which is attached on the 22nd day. This will allow you to postpone the break and, accordingly, stop subsequent bleeding.

In this situation, bleeding may occur between periods. It is not recommended to use the patch for more than six weeks in a row. There must be a break in the use of TTS for a week (seven days). After this period, you can start using Evra again.

A woman can change the "replacement day" during a period free from using the drug by sticking on the first application of TTS Evra. It should not be forgotten that the period between removing the third applicator of the previous cycle and applying 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 occurs at a more subtle level. Therefore, the use of Evra during pregnancy and during the period when a young mother breastfeeds a newborn baby is strictly contraindicated, since such an effect transforms many processes in the human body, which can unpredictably affect the health and development of the future person.

Contraindications

As was said earlier, the patch in question has an effect on the woman's body at the level of her hormonal background. Based on such a force of influence, which is quite significant, contraindications to the use of Evra are also extensive.

• Individual intolerance to the components of the contraceptive composition.
• Occlusion of arterial blood vessels, including:
  • Ischemia of the heart muscle.
  • The acute phase of pathological disturbances in the flow of blood through the vessels, which affects the nutrition and oxygenation of the brain tissue.
  • Occlusion of the blood capillaries of the retina.
  • Precursors of blockage, such as transient ischemic heart block or rhythm disturbances.
• Antithrombin III deficiency.
• A hereditary predisposition to blockage of veins or blood arteries.
• Low level of resistance to activated protein C and S. Their deficiency in the woman's body.
• Severe hypertension with blood pressure readings above 160/100 mmHg.
• Diabetes mellitus, which affects the integrity and changes other normal parameters of blood vessels.
• Venous thrombosis, including deep vein thrombosis, including pulmonary thromboembolism.
• Hereditary dyslipoproteinemia (quantitative and qualitative disturbances in the composition of blood lipoproteins).
• Endometrial cancer.
• Migraine with aura is a headache that is felt in attacks and manifests itself as a stable localization in the frontal-temporal-orbital region and covers half of the head, which occurs after the preceding neurological symptoms (aura).
• Hyperhomocysteinemia (elevated concentration of the amino acid hyperhomocysteine).
• The presence in the patient's body of antiphospholipid antibodies that work against cardiolipin are a lupus anticoagulant.
• Diagnosis or suspicion of a malignant neoplasm in a woman's mammary gland.
• Estrogen-dependent tumors or suspicion of their presence.
• Bleeding from the genitals.
• Liver carcinoma and adenoma.
• Postmenopausal age of a woman.
• Less than four weeks after delivery.
• Time to breastfeed your baby.
• If the woman has not reached the age of 18.
• The application should not be applied to the mammary glands, hyperemic areas of the skin, or where there is irritation or various types of damage to the epidermis.

TTS Evra should be used with great caution if the following factors are present:

• The presence and development of thromboembolism of arterial or venous localization in close relatives of a woman, at a fairly young age.
• Menstrual cycle failure.
• Long-term immobilization (immobility) of the entire body or individual parts of the body.
• Excess body weight with an index exceeding 30 kg/m², which indicates significant obesity.
• Liver and kidney dysfunction.
• A history of varicose veins or superficial thrombophlebitis in the woman's medical history.
• Long-term arterial hypertension.
• Colitis aggravated by ulcers.
• Atrial fibrillation is a supraventricular tachyarrhythmia with chaotic electrical activity of the atria with a pulse rate of 350–700 per minute.
• Heart valve defect.
• Crohn's disease is a chronic inflammatory disease that affects the entire gastrointestinal tract: from the mouth to the anus.
• Hemolytic uremic syndrome - microangiopathic hemolytic anemia, renal failure and thrombocytopenia.

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Side effects Evra

The contraceptive adhesive plaster in question is classified as a strong systemic drug. This is where the possible multiple side effects of Evra come from.

• Peripheral and CNS reactions:
  • Dizziness.
  • Headaches.
  • Partial loss of sensation in the upper or lower extremities.
  • Tremors and convulsions.
  • Emotional stress: depressive states, irritability.
  • Problems with sleep.
• Reaction of the genitourinary system:
  • Urinary tract infection.
  • Dyspareunia is painful coitus.
  • Vaginitis is an inflammation of the vaginal mucosa caused by pathogenic microorganisms.
  • Mastitis is an inflammation of the breast tissue.
  • Decreased level of sexual desire.
  • Dysmenorrhea is a painful symptom in the abdominal area associated with uterine spasms during menstruation.
  • Increase in the volume of mammary glands.
  • Disruption of the female menstrual cycle. There may be bleeding between periods, hypermenorrhea.
  • Fibroadenoma of the mammary glands.
  • Disruption of cervical mucus and breast milk production not related to obstetrics.
  • Ovarian dysfunction, polycystic disease.
• Gastrointestinal reaction:
  • Gingivitis is an inflammation of the mucous membrane of the gums.
  • Disruption in the eating process (increased appetite or, conversely, unwillingness to eat).
  • Abdominal pain.
  • 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 are inflammation and enlargement, as well as bleeding and prolapse of the internal venous nodes of the rectal plexus.
• Respiratory response:
  • Asthma attacks.
  • The appearance of shortness of breath.
  • The probability of infection of ENT organs.
• Cardiovascular response:
  • Tachycardia.
  • Varicose veins.
  • Increased blood pressure.
  • Swelling.
• Skin reaction:
  • An allergic reaction manifested by itching, rashes, and hives.
  • Increased dryness of the skin.
  • Contact dermatitis.
  • Photosensitization is an increase in the body's sensitivity to the effects of ultraviolet radiation.
  • Bullous or acne rash.
  • Change in the shade of the epidermis.
  • The appearance of eczema.
  • Increased sweating.
  • Alopecia is a pathological hair loss.
• Musculoskeletal tissue reaction:
  • Tendinosis - changes in tendon parameters.
  • Arthralgia is pain in the affected joint.
  • Muscle cramps and decreased muscle tone.
  • Ostalgia is a painful symptom that manifests itself in the spine and legs.
  • Myalgia is a painful sensation in the muscles.
• Metabolism:
  • Weight gain.
  • Hypercholesterolemia is an increase in the level of cholesterol in the blood.
  • Hypertriglyceridemia is an elevated level of triglycerides (TG) in the blood plasma on an empty stomach.
• Other reactions:
  • Decreased overall tone, constant feeling of fatigue.
  • Anemia.
  • Thrombophlebitis of superficial veins.
  • Painful symptoms in the chest.
  • Flu-like manifestations.
  • Asthenic syndrome is a condition in which the body works with all its strength.
  • Conjunctivitis, vision problems.
  • Fainting.
  • Lymphadenopathy is a condition characterized by enlargement of the lymph nodes of the lymphatic system.
  • Abscesses.
  • Alcohol intolerance.
  • Pulmonary embolism.

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Overdose

If you do not follow the recommendations for using the Evra transdermal therapeutic system, you may overdose on the components of the patch. In such a situation, the woman's body may respond with nausea, sometimes quite severe and turning into vomiting. Vaginal bleeding is possible.

If these symptoms appear, you must immediately remove the patch and seek help and advice from your local gynecologist.

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Interactions with other drugs

It is necessary to be especially careful when taking two or more medications in parallel, because it is not always possible to predict the consequences of their mutual influence. Some results of the interaction of Evra with other drugs are known and are given below.

The combined use of TTS Evra with the following pharmacological drugs and classes of medications can provoke an increase in the activity of the formation and functioning of sex hormones, which can lead to uterine bleeding in the intermediate period of the cycle and a decrease in the reliable operation of the hormonal contraceptive:

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

Taking them together with TTS can lead to unwanted pregnancy. These drugs are quite active in causing and accumulating liver enzymes, which are used to metabolize these hormones.

The maximum induction of the liver enzyme is mainly observed two to three weeks after combined administration and can last for about a month after their withdrawal.

The combined use of the patch with a number of herbal preparations can significantly reduce the contraceptive effectiveness of Evra. For example, such a result can be obtained with parallel use with drugs that contain St. John's wort (Hypericum perforatum). In this situation, intermenstrual bleeding may occur. The mechanism of this effect is similar to the previous one. The inducing effect lasts for two weeks after the combined use is stopped.

TTS Evra may also lose its contraceptive ability in the case of treatment with antibiotics, including drugs of the tetracycline and ampicillin groups.

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Storage conditions

In many ways, the high therapeutic characteristics of the pharmacological product directly depend on the accuracy of the storage conditions of Evra. In this case, it is necessary to maintain the storage temperature in the range from 15 to 25 degrees above zero. It is unacceptable to store TTS in the refrigerator or, especially, in the freezer. Before opening, the patch must be in the original packaging.

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Special instructions

Note:

1. To date, there is no evidence base that would clearly indicate that TTS is safer than oral contraception.
2. Before starting to use the Evra patch, it is advisable to undergo a full examination to collect anamnesis and obtain a complete picture of the woman's health. It is necessary to confirm the absence of pregnancy.
3. It should be known that hormonal contraceptives are not a blocking factor in protecting a woman’s body from contracting sexually transmitted infections, including HIV.
4. Some women, after stopping the use of hormonal contraceptives, may experience amenorrhea (absence of a menstrual cycle) or oligomenorrhea, when bleeding is insignificant and can last from several hours to a couple of days.
5. If irritation of the epidermis is noticeable in the application area, it is better to apply the next patch to another surface of the skin.
6. If a woman weighs more than 90 kg, the effectiveness of the drug decreases.
7. The expected effect and low probability of complications are sufficiently assessed only for women aged 18 to 45.
8. The individual package must be opened immediately before use. After depressurization, the patch is immediately glued to the skin.
9. After the patch has been used for its intended purpose, the applicator is removed, but it still contains a certain amount of the active substance. If they get into the water, and with it into the soil, this threatens a harmful negative impact on the natural environment. Therefore, there are certain rules for the disposal of the transdermal therapeutic system Evra, provided by the manufacturer. To do this, a special outer layer of adhesive film is removed from the packaging. The used patch is placed in a bag so that the sticky side of the TTS is covered by the colored area on the package. The layers of the bag and the patch are pressed against each other. Only after this can the TTS Evra be thrown into the trash. Disposal in the toilet or through other sewer drains is strictly prohibited.

The drug Evra will be effective and safe for a woman’s health only if all the recommendations provided in the instructions attached to the drug are followed and with the permission of the attending gynecologist, who is really able to assess the woman’s health at the time of prescribing TTS.

Shelf life

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