ESCAPEL

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT ESKAPEL (ESCAPELLE®)

Composition:

Active substance: levonorgestrel;

1 dispersible tablet in the oral cavity contains 1.5 mg of levonorgestrel;

Excipients: mannite (E 421), pregelatinized starch, low-substituted hydroxypropylcellulose, crospovidone type B, sodium stearyl fumarate, Opadry orange (hypromellose, titanium dioxide (E 171), yellow azo dye FCF (E 110), iron oxide yellow (E 172), indigocarmine (E 132)), colloidal anhydrous silicon dioxide, aspartame (E 951), orange flavor.

Pharmaceutical form. Dispersible tablets in the oral cavity.

Main physicochemical properties: pale orange with dark specks, round, biconvex tablets, 6 mm in diameter. One side is engraved with "GC3", the other side is unmarked. With a slight orange odor.

Pharmacotherapeutic group. Sex hormones and modulators of the genital system. Emergency contraceptives. ATC code G03A D01.

Pharmacological properties.

Pharmacodynamics.

The exact mechanism of action of Escapel is unknown. At recommended doses, levonorgestrel affects ovulation and fertilization if sexual intercourse occurred during the preovulatory phase of the menstrual cycle, i.e., at the time of highest probability of fertilization. The drug is not effective once implantation has begun.

Efficacy. According to results of a previously conducted clinical study, 750 mcg of levonorgestrel (as two doses of 750 mcg each, taken 12 hours apart) prevents pregnancy in 85% of cases. The longer the time between sexual intercourse and drug administration, the lower the efficacy (95% within the first 24 hours, 85% between 24 and 48 hours, and 58% between 48 and 72 hours).

According to results of another previously conducted clinical study, two tablets of levonorgestrel 750 mcg taken simultaneously (within 72 hours after unprotected sexual intercourse) prevent pregnancy in 84% of cases. There was no difference in the frequency of pregnancy among women who took the drug on the third or fourth day after unprotected sexual intercourse (p > 0.2).

There are limited data requiring further confirmation regarding the effect of excessive body weight/high body mass index (BMI) of the patient on the contraceptive efficacy of the drug. In three studies by the World Health Organization, no trend toward reduced efficacy with increasing body weight/BMI was observed (see Table 1), whereas in two other studies, a reduction in efficacy with increasing body weight/BMI was observed (see Table 2). Both meta-analyses did not include cases of drug administration more than 72 hours after unprotected sexual intercourse (off-label use) or cases in which unprotected sexual intercourse occurred after drug administration.

Table 1

Table 2

Recommended doses of levonorgestrel do not significantly affect blood coagulation factors, lipid and carbohydrate metabolism.

Pediatric population

A prospective observational study showed that out of 305 cases of using levonorgestrel tablets as emergency contraception, pregnancy occurred in seven women. Thus, the overall pregnancy rate was 2.3%. The pregnancy rate in women under 18 years of age (2.6%, or 4 out of 153) was comparable to that in women aged 18 years and older (2.0%, or 3 out of 152).

Pharmacokinetics.

After oral administration, levonorgestrel is rapidly and almost completely absorbed.

According to a study involving 16 patients, two hours after a single 1.5 mg dose of levonorgestrel, the Cmax value was 18.5 ng/mL.

After reaching peak concentration, the blood level of levonorgestrel declines, with a mean elimination half-life of approximately 26 hours.

Levonorgestrel is excreted in the form of metabolites in urine and feces in equal proportions. Biodegradation of levonorgestrel occurs via metabolic pathways typical for steroids. In the liver, levonorgestrel is hydroxylated and excreted from the body as glucuronide conjugates. Pharmacologically active metabolites of levonorgestrel are not known.

Levonorgestrel binds to albumin and sex hormone-binding globulin (SHBG). 1.5% of the total amount in plasma exists as free steroid, and 65% is specifically bound to SHBG.

Absolute bioavailability is 100% of the administered dose.

0.1% of the administered dose of the drug passes into the infant’s body through breast milk.

Clinical characteristics.

Indications.

For emergency oral contraception within the first 72 hours after unprotected sexual intercourse, when no contraceptive method was used or when the contraceptive method used was not sufficiently reliable.

Contraindications.

Hypersensitivity to any component of the drug; severe hepatic impairment; pregnancy.

Interaction with other medicinal products and other forms of interaction.

The metabolism of levonorgestrel is enhanced when co-administered with hepatic enzyme inducers, primarily inducers of the CYP3A4 enzyme system. When co-administered with efavirenz, the plasma concentration of levonorgestrel (AUC) decreased by approximately 50%.

Medicinal products containing the following active substances may reduce the plasma concentration of levonorgestrel: barbiturates (including primidone); phenytoin; carbamazepine; herbal preparations containing Hypericum perforatum (St. John's wort); rifampicin; ritonavir; rifabutin; griseofulvin.

Women who have taken hepatic enzyme-inducing drugs within the previous 4 weeks and who require emergency contraception should consider using non-hormonal emergency contraceptives (e.g., a copper intrauterine system). Taking a double dose of levonorgestrel (3000 mcg of levonorgestrel within 72 hours after unprotected sexual intercourse) is an alternative option for women who are unable or unwilling to use a copper intrauterine system, although this specific combination (double dose of levonorgestrel while taking microsomal liver enzyme inducers) has not been studied.

Medicinal products containing levonorgestrel may increase cyclosporine toxicity due to inhibition of its metabolism.

Special precautions for use.

Emergency contraception is intended for emergency situations only and under no circumstances should it replace regular contraception. Repeated use of Escapel tablets within the same menstrual cycle should be avoided to prevent menstrual cycle disturbances.

Emergency contraceptive drugs do not prevent pregnancy in all cases. The likelihood of fertilization is high when the timing of sexual intercourse is uncertain or when more than 72 hours have passed since unprotected intercourse within one menstrual cycle. In such cases, taking an Escapel tablet after a second act of intercourse will not achieve the desired effect. If menstruation is delayed by more than 5 days, or if menstruation occurs on time but is unusual in character, or if pregnancy is suspected for any other reason, a gynecological examination should be performed to exclude pregnancy, including ectopic pregnancy. The absolute risk of ectopic pregnancy is likely low, as levonorgestrel prevents ovulation and fertilization. However, ectopic pregnancy may persist despite the occurrence of uterine bleeding. If pregnancy occurs after taking Escapel tablets, the possibility of ectopic pregnancy should be particularly considered in women presenting with abdominal/pelvic pain or collapse, and in those with a history of ectopic pregnancy, pelvic surgery, or pelvic inflammatory disease.

Therefore, levonorgestrel is not recommended for women who are at risk of ectopic pregnancy (e.g., history of salpingitis or ectopic pregnancy).

The use of Escapel tablets is contraindicated in patients with severe liver function impairment.

Severe malabsorption disorders in the gastrointestinal tract (e.g., Crohn's disease) reduce the effectiveness of the contraceptive agent.

The use of the drug usually does not disrupt the regularity or normal nature of menstruation. However, menstruation may occasionally occur earlier than expected or be delayed. After taking Escapel tablets, it is recommended to consult a physician for selection or adjustment of regular contraception. If Escapel was taken due to errors in regular hormonal contraception and menstruation does not begin during the appropriate seven-day break, pregnancy should be excluded.

There are limited data suggesting that the contraceptive efficacy of Escapel may decrease with increasing body weight or body mass index (BMI) of the patient (see section "Pharmacodynamics"). Nevertheless, regardless of body weight or BMI, a woman should take emergency contraceptive measures as soon as possible after unprotected intercourse.

Compared to regular contraceptive methods, Escapel tablets are less effective. Women who frequently use emergency contraception should consult a physician to select an appropriate method of regular contraception.

Emergency contraception does not replace the need for protection against sexually transmitted infections.

This medicinal product contains the colorant sunset yellow FCF (E 110), which may cause allergic reactions.

This medicinal product contains 0.8 mg of aspartame (E 951) in each tablet dispersible in the oral cavity. After oral administration, aspartame is hydrolyzed in the gastrointestinal tract. One of the main hydrolysis products is phenylalanine, which may be harmful to individuals with phenylketonuria (PKU).

This medicinal product contains less than 1 mmol (23 mg) of sodium per dispersible tablet, i.e., it is practically sodium-free.

Use during pregnancy or breastfeeding.

Pregnancy. The use of Escapel tablets during pregnancy is contraindicated. The drug does not cause termination of pregnancy. Epidemiological data indicate that if pregnancy occurs despite the use of emergency contraception, the drug does not have adverse effects on the fetus. However, there are no clinical data on the potential consequences of taking levonorgestrel in doses exceeding 1.5 mg.

Breastfeeding. Levonorgestrel passes into breast milk. The potential impact of levonorgestrel on the infant can be minimized by taking the drug immediately after breastfeeding or by avoiding breastfeeding for 8 hours after drug administration.

Fertility. Levonorgestrel may increase the likelihood of menstrual cycle disturbances, which in some cases may lead to earlier or later ovulation. These changes may affect the timing of the fertile period; however, there is no information on fertility following long-term observation.

Ability to affect reaction speed when driving or operating machinery.

No studies on the potential effect on the ability to drive or operate machinery have been conducted.

Method of Administration and Dosage

Method of Administration

For oral use.

The orodispersible tablet should be pressed out of the blister with dry hands and placed on the tongue, where it will dissolve and can then be swallowed with saliva.

The orodispersible tablet may be used even in situations where liquid is not available.

Dosage

One tablet should be taken as soon as possible after unprotected sexual intercourse, preferably within the first 12 hours and no later than 72 hours (see section "Pharmacodynamics").

Women who have been taking hepatic enzyme-inducing drugs during the previous 4 weeks and who require emergency contraception are advised to use non-hormonal contraceptives (e.g. a copper-containing intrauterine device). If a woman is unable or unwilling to use a copper-containing intrauterine device, a double dose of levonorgestrel (2 tablets as a single dose) is recommended (see section "Interaction with other medicinal products and other forms of interaction").

If vomiting occurs within 3 hours after taking the tablet, another tablet should be taken.

Escapelle, orodispersible tablet, may be taken on any day of the menstrual cycle provided that the previous menstruation was normal.

After using emergency contraception, it is recommended to use a local barrier method (e.g. condoms, diaphragms, spermicides, cervical caps) until the next menstrual period begins. The use of Escapelle orodispersible tablets does not contraindicate the continuation of regular oral hormonal contraceptive use.

Children

Escapelle orodispersible tablet is not intended for use in prepubertal children for emergency contraception.

Overdose

There are no data on severe adverse reactions following ingestion of large doses of the drug. Overdose may cause nausea and withdrawal bleeding. There is no specific antidote; treatment is symptomatic.

Adverse reactions.

The most common adverse effect observed during the use of Escapel was nausea.

Table 3

Possible temporary changes in the nature of menstruation may occur. In most women, menstrual cycle disturbances occur within 5 days. If menstruation is delayed by more than 5 days, pregnancy should be ruled out.

Additional adverse reactions reported during post-marketing surveillance include:

Gastrointestinal disorders:

Rare (< 1/10000): abdominal pain;

Skin and subcutaneous tissue disorders:

Rare (< 1/10000): rash, urticaria, pruritus;

Reproductive system and breast disorders:

Rare (< 1/10000): pelvic pain, dysmenorrhea;

General disorders:

Rare (< 1/10000): facial swelling.

Reporting of suspected adverse reactions

Reporting of suspected adverse reactions after medicinal product registration is important. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and patients, or their legal representatives, should report all suspected adverse reactions and lack of efficacy via the automated pharmacovigilance information system at the following link: https://aisf.dec.gov.ua/.

Shelf life. 3 years.

Storage conditions. Store in the original packaging to protect from moisture. Keep the medicinal product out of the reach of children.

Packaging. 1 tablet per blister. 1 blister per pouch made of laminated aluminum foil; 1 pouch per cardboard box.

Prescription category. Prescription only.

Manufacturer. JSC "Gedeon Richter".

Manufacturer's address and location of its operational site.

H-1103 Budapest, 19-21 Demréti Street, Hungary.