Etonogestrel - instructions for use, dose, side effects, contraindications

Clinical and pharmacological group: & nbsp

"Estrogens, gestagens, their homologues and antagonists"

Included in the formulation

Implanone NKST®

implant PC

Organon, N.V. Netherlands

АТХ:

G.03.A..08 Etonogestrel

Pharmacodynamics:

Gestagen. Etonogestrel is a biologically active metabolite of desogestrel - gestagen, widely used as an oral contraceptive hormone. Structurally, it is a derivative of 19-nortestosterone and binds to the receptors of progesterone in the target organs with high affinity. The contraceptive effect of etonogestrel is mainly achieved by suppressing ovulation. Ovulation was not observed during the first 2 years of use, and only rarely occurred during the third year. In addition to suppressing ovulation etonogestrel also causes an increase in the viscosity of the secretion of the cervix, which prevents the passage of spermatozoa. Clinical studies were conducted in women aged 18-40 years.

The contraceptive effect of etonogestrel is reversible. Although etonogestrel suppresses ovulation, ovarian activity is not completely suppressed.

Etonogestrel does not affect the change in bone mineral density and lipid metabolism.

Pharmacokinetics:

Etonogestrel is characterized by a high degree of binding to plasma proteins: about 32% - with globulin binding the sex hormones, and 66% - with albumin.Metabolized with the participation of the isoenzyme CYP3A4. It is excreted in urine and feces in the form of metabolites and unchanged substance. Half-lifeis 25-30 hours. Etonogestrel penetrates into breast milk.

Indications:

Hormonal contraception.

ICD-10

XXI.Z30-Z39.Z30.0 General advice and advice on contraception

XXI.Z30-Z39.Z30 Monitoring the use of contraceptives

Contraindications:

Pregnancy (including presumed); thrombosis (arterial and venous) and thromboembolism now or in the anamnesis (including thrombosis, deep vein thrombophlebitis, pulmonary embolism, myocardial infarction, ischemic or hemorrhagic cerebrovascular disorders); the presence of antibodies to phospholipids; migraine with focal neurological symptoms; breast cancer (including history); established or suspected malignant hormone-dependent tumors; benign or malignant liver tumors at present or in the anamnesis; severe forms of liver disease (before normalization of functional liver tests), including jaundice; congenital hyperbilirubinemia (including in history); uncontrolled arterialhypertension; childhood; bleeding from the vagina of an unclear etiology; hypersensitivity to etonogestrel.

Carefully:

With caution and after careful evaluation in each specific case, the relationship between benefit and possible risk should be applied etonogestrel in the form of an implant in the presence of any of the following conditions or risk factors: prolonged immobilization caused by surgery or other causes; conditions preceding thrombosis (including transient ischemic attacks, angina pectoris, complicated heart valve disease, atrial fibrillation, extensive trauma); persistent arterial hypertension; Diabetes mellitus, including diabetes mellitus with diabetic angiopathy; hereditary or acquired predisposition to arterial thrombosis, including deficiency of protein C, deficiency of protein S, insufficiency of antithrombin III; liver diseases of mild and moderate severity with normal indicators of functional liver samples; therapy with anticoagulants; severe depression.

In case of acute or exacerbation of chronic liver diseases, a woman should consult a specialist for examination and counseling.

Pregnancy and lactation:

Contraindicated in pregnancy. Pre-clinical studies have found that very high doses of progestogen compounds can cause masculinization of female fetuses.

It is known that a small amount of etonogestrel is excreted in breast milk. Based on the available data, the use of etonogestrel in the form of an implant during breastfeeding is possible, but only under the supervision of the doctor for the development and growth of the infant.

Dosing and Administration:

It is used in the form of subcutaneous implants, as well as in a combination of hormonal contraceptives in the form of a vaginal ring.

The dose depends on the dosage form used.

Side effects:

The association of the following side effects with the use of etonogestrel in the form of an implant has not been confirmed, nor has it been refuted.

On the part of the reproductive system and mammary glands: changes in the nature of menstrual bleeding (including changes in frequency,intensity or duration of bleeding; very often (≥ 1/10) - soreness in the mammary glands, chest pain, irregular menstruation; often (≥ 1/100, <1/10) - dysmenorrhea, ovarian cyst; infrequent (≥ 1/1000, <1/100) - discomfort in the vulva and vagina, galactorrhea, enlargement of the mammary glands, itching in the vulva and vagina; separate messages - ectopic pregnancy.

Infections and infestations: very often (≥ 1/10) - vaginal infection (vulvovaginitis); infrequently (≥ 1/1000, <1/100) - pharyngitis, rhinitis, infection of the urinary tract (urethritis, cystitis).

From the nervous system: very often (≥ 1/10) - headache; often (≥ 1/100, <1/10) - dizziness; infrequently (≥ 1/1000, <1/100) - migraine, drowsiness.

From the psyche: often (≥ 1/100, <1/10) - emotional lability, depression, nervousness, decreased libido; infrequently (≥ 1/1000, <1/100) - anxiety, insomnia.

From the side of metabolism: very often (≥ 1/10) - weight gain; often (≥ 1/100, <1/10) - increased appetite, weight loss.

From the skin: very often (≥ 1/10) - acne; often (≥ 1/100, <1/10) - alopecia; infrequently (≥ 1/1000, <1/100) - hypertrichosis, rash, itching; rarely - seborrhea.

From the digestive system: often (≥ 1/100, <1/10) - abdominal pain, nausea, bloating; infrequently (≥ 1/1000, <1/100) - vomiting, constipation, diarrhea.

From the musculoskeletal system: infrequently (≥ 1/1000, <1/100) - back pain, arthralgia, myalgia, musculoskeletal pain.

From the side of the urinary system: infrequently (≥ 1/1000, <1/100) - dysuria.

Allergic reactions: it is possible - anaphylactic reactions, urticaria and angioedema (or its more severe course) and / or more severe course of hereditary angioedema.

General reactions: often (≥ 1/100, <1/10) - fatigue, flu-like condition, pain.

Other: often (≥ 1/100, <1/10) - tides; infrequently (≥ 1/1000, <1/100) - dysuria; rarely - a clinically significant increase in blood pressure.

Women who use contraceptive hormonal agents are possible: venous thromboembolism (deep vein thrombosis and pulmonary embolism); arterial thromboembolism; hormone-dependent tumors (liver tumors, breast cancer); Chloasma; jaundice and / or itching associated with cholestasis; cholelithiasis; porphyria; systemic lupus erythematosus; hemolytic-uremic syndrome; Sydenham's chorea; herpes during pregnancy; hearing loss associated with otosclerosis.

Overdose:

Data on the overdose of etonogestrel is not available. There are no reports of serious side effects due to an overdose of contraceptive hormonal drugs in general.

Interaction:

The interaction between hormonal contraceptives and other drugs can lead to breakthrough bleeding and / or a decrease in contraceptive effect. Special studies devoted to the study of the interaction with etonogestrel were not conducted.

Contraceptive hormonal agents can affect the metabolism of other drugs. Accordingly, concentrations of drugs in plasma and in tissues may increase (for example, ciclosporin) or decrease (for example, lamotrigine).

Drugs (for example, ketoconazole), inhibiting microsomal liver enzymes (such as CYP3A4), can increase plasma hormone concentrations.

Hepatic metabolism: interaction is possible with drugs - inducers of microsomal liver enzymes, especially cytochrome P450 isoenzymes (for example phenytoin, phenobarbital, primidon, bosentan, carbamazepine, rifampicin and, possibly, also with oxcarbazepine, topiramate, felbamate, griseofulvin, herbal preparations containing St. John's wort (Hypericum perforatum); HIV protease inhibitors (for example, ritonavir, nelfinavir); non-nucleoside reverse transcriptase inhibitors (for example, nevirapine, efavirenz) and combinations of the latter, which can lead to an increase in the clearance of sex hormones.

Special instructions:

In epidemiological studies, it was found that there is a link between the use of combined oral contraceptives and an increase in the incidence of venous thromboembolism (deep vein thrombosis and pulmonary embolism). Although the clinical significance of these results for etonogestrel (a biologically active metabolite of desogestrel) used as a contraceptive hormone is unknown in the absence of an estrogen component, in the case of thrombosis, the implant should be removed.

Although progestogens can influence the resistance of peripheral tissues to insulin and glucose tolerance, there is no evidence that there is a need to change the treatment regimen in diabetic patients using contraceptive hormones containing only progestogen. However, women with diabetes should be closely monitored throughout theperiod of use of contraceptive hormonal agents containing only progestogen.

It is necessary to conduct periodic examinations of women who are undergoing therapy for hyperlipidemia. Some progestogens can increase the level of LDL and worsen the control of hyperlipidemia.

Sometimes there may be a chloasma, especially in women with a history of pregnant women with chloasma. Women with a predisposition to chloasma should avoid exposure to sunlight or ultraviolet radiation during the application of etonogestrel.

Although etonogestrel suppresses ovulation, if a woman has amenorrhea or abdominal pain, differential diagnosis should take into account an ectopic pregnancy.

There are reports of the following conditions that occurred both with pregnancy and with the use of sex steroid hormones, but the connection with the use of progestogens has not been established: jaundice and / or pruritus associated with cholestasis; the formation of gallstones; porphyria; systemic lupus erythematosus; hemolytic-uremic syndrome; Sydenham's chorea; herpes during pregnancy; loss of hearing associated with otosclerosis and (hereditary) angioedema.

The use of etonogestrel is not indicated until the onset of menarche (the first menstruation).

Etonogestrel can cause dizziness. Therefore, a woman should be warned that when there is dizziness, do not drive vehicles or use complicated equipment.

The implant should always be removed before the introduction of a new one.

Instructions

Etonogestrel (Aetonogestrelum)