Lupinor

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT Lupinor (Lupinor)

Composition:

Active substance: levonorgestrel;

1 tablet contains 1.5 mg of levonorgestrel;

Excipients: lactose monohydrate, corn starch, povidone, colloidal anhydrous silicon dioxide, magnesium stearate.

Pharmaceutical form. Tablets.

Main physicochemical properties: round tablets of white to almost white color, with engraving «LV1» on one side and smooth on the other.

Pharmacotherapeutic group.

Sex hormones and modulators of the genital system, emergency contraception agents.

ATC code G03A D01.

Pharmacological properties.

Pharmacodynamics.

The exact mechanism of action of the drug is unknown. At recommended doses, levonorgestrel affects ovulation and fertilization if sexual intercourse occurred in the preovulatory phase of the menstrual cycle, i.e., at the time of highest probability of fertilization. In addition, endometrial changes induced by the drug interfere with the implantation of a fertilized egg. The drug is not effective once implantation has begun.

Effectiveness: prevents pregnancy in 85% of cases. Recommended doses of levonorgestrel do not significantly affect blood coagulation factors, lipid and carbohydrate metabolism.

Pharmacokinetics.

After oral administration, levonorgestrel is rapidly and almost completely absorbed. According to study data, two hours after administration of levonorgestrel, maximum concentration (Cmax) reaches 18.5 ng/mL. After reaching Cmax, the level of levonorgestrel in the blood decreases, with an average 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 for steroids. In the liver, levonorgestrel is hydroxylated and excreted from the body as glucuronide conjugates. Pharmacologically active metabolites of levonorgestrel are unknown.

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

Absolute bioavailability is 100%.

0.1% of the administered dose of the drug is excreted into an infant's body via breast milk.

Clinical characteristics.

Indications.

Emergency (post-coital) contraception within the first 72 hours after unprotected sexual intercourse, during which no contraceptive method was used or 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.

Metabolism of levonorgestrel is enhanced when co-administered with hepatic enzyme inducers, primarily those inducing 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 levonorgestrel plasma concentrations: barbiturates (including primidone), phenytoin, carbamazepine, St. John's wort (Hypericum perforatum), rifampicin, ritonavir, rifabutin, griseofulvin.

Women who have used hepatic enzyme-inducing drugs within the previous 4 weeks and 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 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 using microsomal hepatic enzyme inducers) has not been studied.

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

Special precautions for use.

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

Emergency contraceptive drugs do not prevent conception in all cases. The likelihood of conception is higher 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 tablets after the 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 appears unusual, or if there is any suspicion of pregnancy for other reasons, a gynecological examination should be performed to exclude pregnancy.

Pregnancy occurring during use of levonorgestrel tablets may be ectopic, particularly in women with lower abdominal pain, syncope, history of ectopic pregnancy, pelvic surgery, or pelvic inflammatory disease. The absolute risk of ectopic pregnancy is likely low, as levonorgestrel prevents ovulation and fertilization. However, ectopic pregnancy may persist despite uterine bleeding. Therefore, levonorgestrel is not recommended for women who have a risk of ectopic pregnancy (e.g., history of salpingitis or ectopic pregnancy).

The use of levonorgestrel tablets is contraindicated in cases of severe hepatic 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 character of menstruation. However, menstruation may occasionally occur earlier or be delayed (approximately ± 2 days). After using levonorgestrel, it is recommended to consult a physician for selection or adjustment of regular contraception. If levonorgestrel is used due to errors in regular hormonal contraception and menstruation does not occur during the appropriate seven-day break, pregnancy should be excluded.

Repeated use of tablets within the same menstrual cycle should be avoided to prevent menstrual cycle disturbances.

There are limited data suggesting that contraceptive efficacy may decrease with increasing body weight or body mass index (BMI), which require further confirmation (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, levonorgestrel tablets are less effective. Women who frequently use emergency contraception should be offered alternative methods of regular contraception.

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

The drug contains lactose monohydrate. The product should not be used by patients with rare hereditary galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption syndrome.

Use during pregnancy or breastfeeding.

Pregnancy

Administration of the drug during pregnancy is contraindicated. The drug does not cause termination of pregnancy. According to epidemiological data, if pregnancy occurs despite use of emergency contraception, the drug has no adverse effect on the fetus. However, clinical data on the potential consequences of using levonorgestrel in doses exceeding 1.5 mg are lacking.

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 refraining from breastfeeding for at least 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, data on fertility following long-term observation are lacking.

Ability to influence reaction speed when driving or operating machinery.

Studies on the potential effect on the ability to drive or operate machinery have not been conducted.

Method of Administration and Dosage.

Dosing. 1 tablet should be taken as soon as possible after unprotected sexual intercourse, preferably within the first 12 hours and no later than 72 hours.

If vomiting occurs within 3 hours after taking the tablet, another 1 tablet should be taken.

Women who have been taking enzyme-inducing drugs of the liver during the previous 4 weeks and who require emergency contraception are recommended 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, administration of a double dose of levonorgestrel (2 tablets as a single dose) is recommended (see section "Special Instructions").

The tablets can 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, such as a condom, should be used until the next menstruation. Use of the drug does not contraindicate continuation of regular oral hormonal contraceptive intake.

Children.

The drug is not intended for use in prepubertal children for emergency contraception indications.

Overdose.

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

Adverse reactions.

The most common adverse effect observed during treatment with the drug was nausea.

Possible adverse reactions and their frequencies are presented in Table 1.

Table 1

Possible temporary changes in the nature of menstruation. In most women, menstrual cycle disturbances are within 5 days.

If menstruation is delayed by more than 5 days, pregnancy should be excluded.

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

Gastrointestinal disorders: abdominal pain – very rare (<1/10,000);

Skin and subcutaneous tissue disorders: rash, urticaria, pruritus – very rare (<1/10,000);

Reproductive system and breast disorders: pelvic pain, dysmenorrhea – very rare (<1/10,000);

General disorders: facial swelling – very rare (<1/10,000).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after marketing authorization is very important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are required to report any suspected adverse reactions.

Shelf life. 2 years.

Storage conditions.

Store at temperatures not exceeding 25 °C in the original packaging.

Keep out of the reach of children.

Packaging.

1 tablet in a blister. 1 blister in a cardboard package.

Prescription status.

Prescription only.

Manufacturer.

Lupin Limited.

Manufacturer's address and place of business.

Unit-1, Plot No. 2, Special Economic Zone Phase II, Midsayam Zone, Apparel Park, Pithampur, District Dhar, Madhya Pradesh, IN 454775, India.

Marketing Authorization Holder.

Sky Pharma VZ LLC.

Address of the Marketing Authorization Holder.

Premises No. 708S, 7th Floor, Dubai Science Park (DSP), South Tower, Dubai Science Park, Dubai, United Arab Emirates.