Ez-van

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT EЗ-ВАН (EZ-ONE)

Composition:

Active substance: levonorgestrel;

1 tablet contains 1.5 mg of levonorgestrel;

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

Pharmaceutical form. Tablets.

Main physico-chemical properties: round, flat tablets with bevelled edges, white or almost white in colour, engraved with "J06" on one side and smooth on the other.

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 Escapelle is unknown. At recommended doses, levonorgestrel affects ovulation and fertilization if sexual intercourse occurs during the preovulatory phase of the menstrual cycle, i.e., at the time of highest probability of conception. 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 750 mcg doses taken 12 hours apart) prevents pregnancy in 85% of cases. It is assumed that the longer the time interval 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 a 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 were no differences in pregnancy rates 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 impact of increased body weight/high body mass index (BMI) on contraceptive efficacy. In three World Health Organization (WHO) studies, 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 were conducted excluding cases of drug administration later than 72 hours after unprotected sexual intercourse (off-label use) and women who had unprotected sexual intercourse after taking the drug.

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 in 16 patients, two hours after a single 1.5 mg dose of levonorgestrel, Cmax was 18.5 ng/mL. After reaching peak concentration, levonorgestrel levels in blood decline, 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. Biologically, levonorgestrel is transformed via metabolic pathways typical of steroids. In the liver, levonorgestrel undergoes hydroxylation and is eliminated 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 passes into the infant’s body via breast milk.

Clinical characteristics.

Indications.

Emergency oral contraception within the first 72 hours after unprotected sexual intercourse, when no contraceptive methods were 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, plasma levels of levonorgestrel (AUC) were reduced 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 enzyme-inducing drugs during the previous 4 weeks and who require emergency contraception should consider using non-hormonal emergency contraceptives (e.g., a copper-containing intrauterine device). Taking a double dose of levonorgestrel (3000 mcg levonorgestrel within 72 hours after unprotected sexual intercourse) is an alternative option for women who are unable or unwilling to use a copper-containing intrauterine device, although this specific combination (double dose of levonorgestrel while taking microsomal liver enzyme inducers) has not been studied.

Levonorgestrel-containing preparations may increase the toxicity of cyclosporine due to inhibition of its metabolism.

Special precautions.

Emergency contraception is intended for emergency situations only. It is in no way a substitute for regular contraception.

Repeated use of Es-Wan 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 Es-Wan tablet after the second act of intercourse will not produce the desired effect. If menstruation is delayed by more than 5 days, or if menstruation occurs on time but appears unusual, 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 Es-Wan tablets, the possibility of ectopic pregnancy should be particularly considered in women presenting with abdominal/pelvic pain or collapse, or in those with a history of ectopic pregnancy, pelvic surgery, or pelvic inflammatory disease. Therefore, levonorgestrel is not recommended for women at risk of ectopic pregnancy (e.g., history of salpingitis or ectopic pregnancy).

Es-Wan is contraindicated in patients with severe hepatic impairment.

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

The use of the drug generally does not disrupt the regularity or normal character of menstruation. However, early onset or delay of menstruation may occasionally occur. After taking Es-Wan tablets, it is recommended to consult a physician to select or adjust regular contraception. If Es-Wan is used due to errors in regular hormonal contraception and menstruation does not begin within the appropriate seven-day interval, pregnancy should be ruled out.

Limited data suggest that the contraceptive efficacy of Es-Wan may decrease with increasing body weight or BMI (see section "Pharmacodynamics"). In all women, regardless of body weight or BMI, emergency contraceptive methods should be used as soon as possible after unprotected intercourse.

Compared to regular contraceptive methods, Es-Wan 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.

The drug contains lactose monohydrate. Patients with rare hereditary disorders of galactose intolerance, lactase deficiency, or glucose-galactose malabsorption should not take this medication.

Use during pregnancy or breastfeeding.

Pregnancy. The use of the drug during pregnancy is contraindicated. The drug does not induce abortion. Epidemiological data indicate that if pregnancy occurs despite the use of emergency contraception, progestogen does not exert 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 period. 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 cause menstrual cycle disturbances, leading in some cases to earlier or delayed ovulation. These changes may affect the timing of the fertile period; however, there are no long-term observational data on fertility.

Ability to affect reaction speed when driving or operating machinery.

No studies have been conducted on the potential impact of the drug on the ability to drive or operate machinery.

Dosage and Administration.

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

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

Women who have used enzyme-inducing drugs of the liver during the past 4 weeks and require emergency contraception are advised to use non-hormonal contraceptives (e.g., a copper-containing intrauterine system). If a woman is unable or unwilling to use a copper-containing intrauterine system, a double dose of levonorgestrel (2 tablets as a single dose) is recommended (see section "Special instructions").

Es-Wan tablets may be taken on any day of the menstrual cycle provided that the previous menstruation occurred normally.

After using the emergency contraceptive, local barrier contraceptive methods (condom, diaphragm, spermicides, cervical cap) should be used until the onset of the next menstruation. Taking Es-Wan tablet does not contraindicate continuing regular use of oral hormonal contraceptives.

Administration method. Tablets for oral use.

Children.

Es-Wan is not intended for use in prepubertal children for emergency contraception indications.

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 Es-Van was nausea.

Possible temporary changes in menstrual character may occur. In most women, menstrual irregularities occur within a 5-day period. If menstruation is delayed by more than 5 days, pregnancy should be ruled out.

During post-marketing surveillance, the following additional adverse reactions have been reported:

Gastrointestinal disorders:

Rare (<1/10,000): abdominal pain;

Skin and subcutaneous tissue disorders:

Rare (<1/10,000): rash, urticaria, pruritus;

Reproductive system and breast disorders:

Rare (<1/10,000): pelvic pain, dysmenorrhea;

General disorders:

Rare (<1/10,000): facial swelling.

Reporting of suspected adverse reactions

Reporting of suspected adverse reactions during post-marketing surveillance is very important. It allows ongoing monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are required to report any suspected adverse reactions.

Shelf life. 3 years.

Storage conditions.

Store out of reach of children at a temperature not exceeding 30 °C.

Packaging.

1 tablet in a blister, 1 blister in a carton.

Prescription status. Prescription only.

Manufacturer.

Naari Pharma Private Limited.

Manufacturer's address and location of operations.

Plot No. 14-16 & 55-57, Sector-5, IIE, Pantnagar, Rudrapur, Dist. Udham Singh Nagar, Uttarakhand, 263153, India.

Marketing Authorization Holder.

Naari B.V.

Address of the Marketing Authorization Holder.

Rietveldenweg 102, 5222AS 's-Hertogenbosch, Netherlands.