Escapelle^® (Tablets) Instructions for Use

Marketing Authorization Holder

Gedeon Richter, Plc. (Hungary)

Contact Information

GEDEON RICHTER JSC (Hungary)

ATC Code

G03AD01 (Levonorgestrel)

Active Substance

Levonorgestrel (Rec.INN registered by WHO)

Dosage Form

Escapelle®

Tablets 1.5 mg: 1 pc.

Dosage Form, Packaging, and Composition

Tablets white or almost white, flat, round, with a bevel and with the engraving “G00” on one side.

Excipients: colloidal silicon dioxide, potato starch, magnesium stearate, talc, corn starch, lactose monohydrate.

1 pc. – blisters (1) cardboard packs^×.

^× a flat cardboard case for storing the blister is placed in the cardboard pack.

Clinical-Pharmacological Group

Postcoital contraceptive. Gestagen

Pharmacotherapeutic Group

Emergency contraceptive

Pharmacological Action

Levonorgestrel is a synthetic gestagen with contraceptive action, pronounced gestagenic and antiestrogenic properties.

The main mechanism of action is the inhibition and/or delay of ovulation as a result of suppression of the luteinizing hormone peak. At the recommended dosage regimen, Levonorgestrel suppresses ovulation and fertilization if sexual intercourse occurred in the preovulatory phase, when the possibility of fertilization is greatest. Levonorgestrel is not effective if implantation of a fertilized egg has already occurred.

Clinical efficacy and safety

According to the results of a previously conducted clinical study, taking two doses of levonorgestrel 0.75 mg with an interval of 12 hours prevents pregnancy in 85% of cases.

The effectiveness of the drug decreases with time after sexual intercourse (95% – when used within 24 hours, 85% – in the interval from 24 to 48 hours, 58% – from 48 to 72 hours).

The results of another clinical study showed that a single dose of levonorgestrel at a dose of 1.5 mg (within 72 hours after unprotected sexual intercourse) prevents pregnancy in 84% of cases.

There is limited data, requiring further confirmation, on the effect of excess body weight/high BMI on contraceptive efficacy.

In two clinical studies, a decrease in the effectiveness of levonorgestrel and an increase in the frequency of pregnancy in women with BMI ≥30 kg/m² compared to women with normal BMI (5.19% and 0.96%, respectively) were identified. However, in other clinical studies, a decrease in the contraceptive efficacy of levonorgestrel was not confirmed (the frequency of pregnancy was 1.17% in women with obesity and 0.99% in women with normal BMI).

At the recommended dosage regimen, Levonorgestrel does not have a significant effect on blood clotting factors, lipid and carbohydrate metabolism.

Adolescent girls under 18 years

A prospective observational study showed that out of 305 cases of using levonorgestrel as an emergency contraceptive, pregnancy occurred in 7 cases.

Thus, the overall failure rate was 2.3%. The failure rate in adolescent girls under 18 years of age (2.6% or 4/153) was comparable to the failure rate in women 18 years and older (2.0% or 3/152).

Pharmacokinetics

Absorption

When taken orally, Levonorgestrel is rapidly and almost completely absorbed.

After taking levonorgestrel at a dose of 1.5 mg, C_max in blood plasma is 18.5 ng/ml and is reached in 2 hours. After reaching maximum values, the concentration of levonorgestrel decreases. The absolute bioavailability is 100%.

Distribution

Levonorgestrel binds to blood plasma albumin and sex hormone-binding globulin (SHBG).

Only 1.5% of the total dose is in free form, 65% is bound to SHBG. Penetrates into breast milk.

Metabolism

The metabolism of levonorgestrel corresponds to the metabolism of sex hormones.

Levonorgestrel is hydroxylated in the liver and metabolites are excreted in the form of conjugated glucuronides. Pharmacologically active metabolites of levonorgestrel are unknown.

Excretion

It is excreted exclusively in the form of metabolites, approximately equally by the kidneys and through the intestines.

T_1/2 is about 26 hours.

Pharmacokinetics in special groups of patients

Patients with renal and hepatic impairment the pharmacokinetics of levonorgestrel in patients with hepatic or renal impairment has not been studied.

Patients with obesity: a pharmacokinetic study showed that levonorgestrel concentrations are significantly reduced in women with obesity (BMI ≥30 kg/m²) (approximately 50% decrease in C_max and AUC_0-24 was observed) compared to similar indicators in women with normal BMI (<25 kg/m²).

Another study also reported an approximately 50% decrease in C_max of levonorgestrel in women with obesity compared to the same indicator in women with normal BMI, while doubling the dose of levonorgestrel to 3 mg in women with obesity 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.

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

Indications

For women aged 16 years and older

• Emergency (postcoital) contraception within 72 hours after unprotected sexual intercourse or in case of unreliability of the contraceptive method used.

ICD codes

Dosage Regimen

Orally. The tablets should be taken with a small amount of water.

The drug can be used at any period of the menstrual cycle. In case of an irregular menstrual cycle, pregnancy must be preliminarily excluded.

To achieve a more reliable contraceptive effect, 1 tablet of the drug Escapelle^® should be taken as soon as possible, preferably within the first 12 hours (but no later than 72 hours after unprotected sexual intercourse).

If vomiting occurs within 3 hours after taking the tablet, another 1 tablet of the drug Escapelle^® should be taken.

After taking the drug Escapelle^® until the onset of the next menstruation, non-hormonal methods of contraception (condom, spermicide + cervical cap, diaphragm or contraceptive sponge) should be used.

The use of levonorgestrel is not a contraindication for continuing planned hormonal contraception.

The use of the drug for repeated unprotected sexual intercourse within one menstrual cycle is not recommended due to an increased risk of cycle disorders.

Data on the use of levonorgestrel in patients with hepatic impairment are not available. The use of the drug in patients with severe hepatic impairment is contraindicated.

Data on the use of levonorgestrel in patients with impaired renal function are not available.

The use of the drug Escapelle^® in children and adolescents under 16 years of age is contraindicated (due to limited data on the safety and efficacy of levonorgestrel in this age group).

Adverse Reactions

When using levonorgestrel, the most frequent adverse reaction was nausea.

Adverse reactions are presented by system-organ classes in accordance with the MedDRA classification and with the frequency of occurrence: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1000, <1/100), rare (≥1/10000, <1/1000), very rare (<1/10000), including individual reports. Within each group, adverse reactions are distributed in order of decreasing their significance.

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

If the onset of the next menstruation is delayed by more than 5 days, pregnancy should be excluded.

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

Contraindications

• Hypersensitivity to levonorgestrel or to any of the excipients included in the drug;
• Severe hepatic impairment;
• Age under 16 years (due to limited data on the safety and efficacy of levonorgestrel in this age group);
• Known or suspected pregnancy;
• Breastfeeding for at least 8 hours after taking the drug;
• Lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome.

With caution

Liver diseases (mild and moderate severity) or biliary tract diseases; jaundice (including in history); severe malabsorption syndromes, for example, Crohn’s disease; presence of hereditary or acquired predisposition to thrombosis.

Use in Pregnancy and Lactation

Pregnancy

Taking the drug during known or suspected pregnancy is contraindicated.

Based on available data, no adverse effects on the fetus were identified in case of pregnancy continuation against the background of the use of levonorgestrel-containing drugs for emergency contraception.

Breastfeeding period

Levonorgestrel penetrates into breast milk.

The potential impact of levonorgestrel on the child can be reduced if the woman takes the drug directly after feeding. After taking the drug, breastfeeding should be discontinued for at least 8 hours.

Fertility

Levonorgestrel increases the risk of menstrual cycle disorders, which in some cases can lead to earlier or later ovulation.

These changes may affect fertility, but there are no data on the effect of levonorgestrel on fertility with long-term use.

Use in Hepatic Impairment

The use of the drug is contraindicated in severe hepatic impairment.

With caution liver diseases (mild and moderate severity) or biliary tract diseases.

Use in Renal Impairment

Data on the use of levonorgestrel in patients with impaired renal function are not available.

Pediatric Use

The use of the drug is contraindicated under the age of 16 years.

Special Precautions

Emergency contraception is a method that can be used episodically. It should not replace planned contraception methods.

Emergency contraception does not prevent pregnancy in all cases.

If there is doubt about the time of unprotected sexual intercourse, or if unprotected intercourse occurred more than 72 hours ago within the same menstrual cycle, then there is a possibility that conception has already occurred.

In this regard, the use of the drug Escapelle^® for the second sexual intercourse may be ineffective in preventing pregnancy. If menstrual bleeding is delayed by more than 5 days and its character changes (scanty or heavy bloody discharge), pregnancy must be excluded.

If pregnancy occurs after using the drug Escapelle^®, the possibility of an ectopic pregnancy must be considered.

The appearance of pain in the lower abdomen, fainting may indicate an ectopic (ectopic) pregnancy. The absolute risk of ectopic pregnancy is apparently low, since Levonorgestrel prevents ovulation and fertilization. An ectopic pregnancy can develop despite the appearance of uterine bleeding. In this regard, the use of the drug Escapelle^® is not recommended in women at risk of developing an ectopic pregnancy (history of salpingitis or ectopic pregnancy).

The use of the drug Escapelle^® is not recommended in patients with severe liver dysfunction.

Severe malabsorption syndromes, for example, Crohn’s disease, may reduce the effectiveness of levonorgestrel.

After taking the drug Escapelle^®, the menstrual cycle, as a rule, does not change and menstrual bleeding occurs on time.

Sometimes menstrual bleeding may begin a few days earlier or later. In this case, you should consult a gynecologist to select and start using one of the planned contraception methods. If the drug Escapelle^® was taken during regular hormonal contraception, but the expected “withdrawal” bleeding in the next 7-day “pill-free” period did not occur, pregnancy should be excluded.

Repeated use of the drug within one menstrual cycle is not recommended due to the possibility of cycle disruption.

There is limited data, requiring further confirmation, that the contraceptive efficacy of the drug Escapelle^® may decrease with increasing body weight or BMI.

All women, regardless of their body weight and BMI, should take emergency contraceptives after unprotected sexual intercourse as early as possible.

The drug Escapelle^® is not effective as a permanent method of contraception and can only be used as an emergency measure.

Levonorgestrel at a dose of 1.5 mg should be used exclusively for emergency contraception.

Women who seek repeated courses of emergency contraception should be advised to use planned contraception methods.

The use of emergency contraception does not replace the necessary precautions related to protection against sexually transmitted diseases or the human immunodeficiency virus.

Cases of thromboembolic complications after taking levonorgestrel at a dose of 1.5 mg have been reported.

In this regard, in women with existing risk factors (hereditary or acquired predisposition to arterial or venous thrombosis, presence of thrombosis/thromboembolism in family history), the possibility of such complications should be considered.

Use in pediatrics

The use of the drug in adolescent girls under 16 years of age is possible only in exceptional cases (including rape) and only after consultation with a gynecologist.

After emergency contraception, a consultation with a gynecologist is recommended.

Effect on the ability to drive vehicles and mechanisms

The effect of the drug on the ability to drive vehicles and work with mechanisms has not been studied.

Overdose

No serious adverse reactions with acute overdose of large doses of oral contraceptives have been reported.

Symptoms nausea, vomiting and “withdrawal” bleeding.

Treatment symptomatic. There is no specific antidote.

Drug Interactions

With simultaneous use with drugs that induce liver microsomal enzymes (mainly inducers of the CYP3A4 isoenzyme), the metabolism of levonorgestrel is accelerated.

Concomitant use of efavirenz reduces the concentration of levonorgestrel in blood plasma by approximately 50%.

The following liver enzyme-inducing drugs may reduce the effectiveness of levonorgestrel: barbiturates and other drugs for the treatment of epilepsy (for example, primidone, phenytoin and carbamazepine), drugs used for the treatment of tuberculosis (for example, rifampicin, rifabutin), drugs for the treatment of HIV infection (for example, ritonavir, efavirenz), drugs for the treatment of fungal infections (griseofulvin), herbal preparations containing St. John’s wort (Hypericum perforatum).

Drugs containing Levonorgestrel may increase the risk of toxicity of cyclosporine, due to suppression of its metabolism.

Levonorgestrel may reduce the effectiveness of ulipristal acetate by competitive action on the progesterone receptor, in connection with which their simultaneous use is not recommended.

Storage Conditions

The drug should be stored out of the reach of children at a temperature not exceeding 30°C (86°F).

Shelf Life

The shelf life is 5 years. Do not use after the expiration date indicated on the package.

Dispensing Status

The drug is dispensed without a prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.