Escapel, 1.5 mg tablets

Pharmacotherapeutic group:Emergency contraceptive.
ATX code: G03AD01

Pharmacodynamics
Levonorgestrel is a synthetic gestagen with contraceptive action, pronounced gestagenic and anti-estrogenic properties. The main mechanism of action is inhibition and/or delay of ovulation as a result of suppression of peak luteinizing hormone. Under the recommended dosing regimen, levonorgestrel suppresses ovulation and fertilization if sexual intercourse occurred in the pre-ovulatory phase, when
the possibility of fertilization is greatest. Levonorgestrel is not effective if implantation of a fertilized egg has already occurred.

Effectiveness: According to a previous clinical study, two doses of levonorgestrel 0.75 mg at 12-hour intervals prevented pregnancy in 85% of cases. Its efficacy decreases with time following intercourse (95% if used within 24 hours, 85% between 24 and 48 hours, and 58% between 48 and 72 hours).
The results of another clinical study showed that a single levonorgestrel dose of 1.5 mg (within 72 hours of unprotected intercourse) prevents pregnancy in 84% of cases.
There is limited data, requiring further confirmation, on the effect of excess body weight/high body mass index (BMI) on contraceptive efficacy. Two clinical trials (CIs) found decreased efficacy of levonorgestrel and increased pregnancy rates in women with BMI ≥30 kg/m2 compared with women with normal BMI (5.19% and 0.96%, respectively). However, no decrease in the contraceptive efficacy of levonorgestrel was confirmed in other studies (pregnancy rates were 1.17% in obese women and
0.99% in women with normal BMI).
With the recommended dosing regimen, levonorgestrel has no significant effect on clotting factors, lipid and carbohydrate metabolism.

Adolescent girls under 18 years
In a prospective observational study, it was shown that of 305 cases of levonorgestrel as an emergency contraceptive, seven resulted in pregnancy. Thus, the overall failure rate was 2.3%.
The failure rate in adolescent girls younger than 18 years (2.6% or 4/153) was comparable to the failure rate in women 18 years and older (2.0% or 3/152).

Pharmacokinetics

Assimilation
Levonorgestrel is rapidly and almost completely absorbed when taken orally. After taking levonorgestrel at a dose of 1.5 mg, the maximum plasma concentration (Cmax) is 18.5 ng/ml and is reached after 2 hours. After reaching the maximum values, the concentration of levonorgestrel decreases. Absolute bioavailability is 100%.

Distribution
Levonorgestrel binds to plasma albumin and sex hormone-binding globulin (hGBS). Only 1.5% of the total dose is in free form, 65% is bound to HSPH. Passes into breast milk.

Metabolism
Metabolism of levonorgestrel corresponds to that of sex hormones. Levonorgestrel is hydrolysed in the liver and the metabolites are excreted as conjugated glucuronides. Pharmacologically active metabolites of levonorgestrel are unknown.

Elimation
Excreted exclusively as metabolites, approximately equally by the kidneys and through the intestine. The elimination half-life (T1/2) is about 26 hours.

Pharmacokinetics in special groups of patients

Children and adolescents under 18 years:The pharmacokinetics of levonorgestrel have been studied exclusively in adult women; there are limited data on the use of levonorgestrel in adolescent girls under 16 years of age.

Patients with renal and hepatic impairment: Pharmacokinetics of levonorgestrel in patients with hepatic or renal impairment have not been studied.

Patients with obesity
. A pharmacokinetics study showed that levonorgestrel concentrations were significantly reduced in obese women (BMI ≥30 kg/m²) (approximately 50% reduction in Cmax and AUC0-24 was observed) compared with those in women with normal BMI (< 25 kg/m²).
Another study also reported a reduction in levonorgestrel Cmax of approximately 50% in obese women compared with that in women with normal BMI, while doubling the levonorgestrel dose to 3 mg in obese women provided plasma concentrations similar to those observed in women with normal BMI who received 1.5 mg of levonorgestrel. The clinical significance of these
data is unclear.

Indications

Emergency (postcoital) contraception (after unprotected intercourse or when the contraceptive method used is unreliable).

Active ingredient

Composition

How to take, the dosage

Ingestion.

The drug can be used at any time of the menstrual cycle. In case of irregular menstrual cycle it is necessary to exclude pregnancy in advance.

To obtain a stronger contraceptive effect, 1 tablet of Escapel® should be taken as soon as possible, preferably within 12 hours (but not later than 72 hours after unprotected intercourse). If within 3 hours after taking the tablet vomiting occurred, you should take 1 more tablet of Escapel®. After taking Escapel® until the next menstruation you should use non-hormonal methods of contraception (condom, spermicide + cervical cap, diaphragm or contraceptive sponge). The use of levonorgestrel is not a contraindication for continuation of planned hormonal contraception. The use of the drug in repeated unprotected intercourse within the same menstrual cycle is not recommended because of the increased risk of the development of cycle disorders.

Particular groups of patients

Children and adolescents under 16 years of age

The use of Escapel® is contraindicated before the age of 16 years (due to limited data on the safety and effectiveness of levonorgestrel in this age group).

Patients with renal impairment

There are no data on the use of levonorgestrel in patients with renal impairment.

Patients with hepatic impairment

There are no data on the use of levonorgestrel in patients with hepatic impairment. Its use in patients with severe hepatic impairment is contraindicated.

Interaction

Concomitant use with drugs inducers of microsomal liver enzymes (mainly inducers of CYP3A4 isoenzyme) accelerates the metabolism of levonorgestrel.

The concomitant use of efavirenz decreases plasma concentrations of levonorgestrel by approximately 50%.

The following liver enzyme-inducing drugs may decrease the effectiveness of levonorgestrel: barbiturates (including primidone), phenytoin and carbamazepine, preparations containing Hypericum perforatum, and rifampicin, ritonavir, rifabutin and griseofulvin.

The drugs containing levonorgestrel may increase the risk of cyclosporine toxicity by inhibiting its metabolism.

Levonorgestrel may decrease the efficacy of ulipristal acetate through competitive effects on the progesterone receptor, and therefore concomitant use is not recommended.

Special Instructions

Synopsis

Contraindications

Side effects

The most common adverse reaction (AR) with levonorgestrel was nausea.

HDs are presented by systemic organ class according to the MedDRA classification and with frequency of occurrence: very common (≥1/10), common (≥1/100, < 1/10), infrequent (≥1/1000, < 1/100), rare (≥1/10000, < 1/1000), very rare (< 1/10000), including individual reports. Within each group, HPs are distributed in decreasing order of importance.

Nervous system disorders

Very common: headache.

Often: dizziness.

Gastrointestinal tract disorders

Very common: nausea, pain in the lower abdomen.

Often: diarrhea, vomiting.

Genital and mammary disorders

Very common: bleeding not associated with menstruation.

Often: menstrual delays of more than 7 days, irregular menstrual bleeding, breast engorgement.

General disorders and disorders at the site of administration

Very common: increased fatigue.

The nature of menstrual bleeding may change slightly, but in most women the next menstruation begins within 5 days of the expected due date.

If your next period is more than 5 days late, pregnancy should be ruled out.

The following adverse events have been observed in clinical practice during the post-registration period:

Gastrointestinal disorders

Very rare: abdominal pain.

Skin and subcutaneous tissue disorders

Very rare: skin rash, urticaria, itching.

Gender and mammary gland disorders

Very rare: pelvic pain, dysmenorrhea.

General disorders and disorders at the site of administration

Very rare: facial swelling.

Overdose

Pregnancy use

Similarities