Avodel

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT AVODEL

Composition:

Active substance: levonorgestrel;

1 tablet contains 1.5 mg of levonorgestrel;

Excipients: microcrystalline cellulose, lactose monohydrate, poloxamer 188, sodium croscarmellose, magnesium stearate.

Pharmaceutical form. Tablets.

Main physicochemical properties: white, round, biconvex tablets with engraving «C» on one side and «1» 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 AVODEL is unknown. At recommended doses, levonorgestrel affects ovulation and fertilization when sexual intercourse occurs in 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.

Effectiveness: According to results from a previous clinical study, 750 mcg of levonorgestrel (as two 750 mcg doses taken 12 hours apart) prevents pregnancy in 85% of cases. The longer the time between sexual intercourse and taking the drug, the lower its effectiveness (95% within the first 24 hours, 85% between 24 and 48 hours, and 58% between 48 and 72 hours).

According to results from a previous 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 effect of excessive 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 decrease in efficacy with increasing body weight/BMI was observed (see Table 2). Both meta-analyses were conducted excluding cases where the drug was taken 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.

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. Biotransformation 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 serum 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.

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 drugs that are hepatic enzyme inducers, primarily inducers of the CYP3A4 enzyme system. A decrease in plasma levels of levonorgestrel (AUC) by approximately 50% has been observed when co-administered with efavirenz.

Medicinal products that may potentially reduce levonorgestrel plasma levels include barbiturates (including primidone), phenytoin, carbamazepine, herbal preparations containing St. John’s Wort (Hypericum perforatum), rifampicin, ritonavir, rifabutin, and griseofulvin.

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

Medicinal products containing levonorgestrel may increase cyclosporine toxicity due to a possible 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 AVODEL 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 conception 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 AVODEL tablet 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 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 uterine bleeding. If pregnancy occurs after taking AVODEL tablets, the possibility of ectopic pregnancy should be particularly considered in women presenting with abdominal/pelvic pain or collapse, especially those with a history of ectopic pregnancy, pelvic surgery, or pelvic inflammatory disease.

Therefore, levonorgestrel is not recommended for women who have a risk of ectopic pregnancy (such as a history of salpingitis or previous ectopic pregnancy).

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

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

The drug usually does not disrupt the regularity or normal nature of menstruation. However, menstruation may sometimes occur earlier or be delayed. After taking AVODEL, regular contraception should be ensured. If AVODEL 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.

There are limited data, requiring further confirmation, suggesting that the contraceptive efficacy of AVODEL may decrease with increasing body weight or body mass index (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 conventional regular contraceptive methods, AVODEL tablets are less effective. Women who frequently resort to 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 product contains lactose monohydrate. Patients with rare hereditary galactose intolerance, lactase deficiency, or glucose-galactose malabsorption syndrome should not take this medication.

Use during pregnancy or breastfeeding.

Pregnancy. Administration of AVODEL tablets during pregnancy is contraindicated. The drug does not cause termination of pregnancy. According to limited epidemiological data, no adverse effects on the fetus have been observed if pregnancy continues. However, there are no clinical data on the potential consequences of using doses exceeding 1.5 mg of levonorgestrel.

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

Fertility. Levonorgestrel may cause menstrual cycle disturbances, which in some cases may lead 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 influence reaction speed when driving or operating machinery.

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

Method of Administration and Dosage

The drug should be taken orally.

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

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

Women who have taken enzyme-inducing drugs during the past 4 weeks and require emergency contraception are recommended to use non-hormonal methods of emergency contraception, i.e. copper IUD, or to take a double dose of levonorgestrel (i.e. 2 tablets simultaneously) for women who cannot or do not wish to use a copper IUD (see section "Interaction with Other Medicinal Products and Other Forms of Interaction").

The drug AVODEL can be taken on any day of the menstrual cycle, provided there is no delayed menstruation.

After using emergency contraception, it is recommended to use a local barrier method (e.g. condom, diaphragm, spermicide, cervical cap) until the beginning of the next menstrual cycle. The use of levonorgestrel is not a contraindication for continuing regular hormonal contraception.

Children.

The use of AVODEL in children under 16 years of age is not recommended due to insufficient clinical experience.

Overdose.

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

Adverse reactions.

The most frequently reported adverse reaction was nausea.

The nature of bleeding may vary slightly; however, in most women, the next menstrual period begins within 5–7 days of the expected date.

If the next menstrual period is delayed by more than 5 days, pregnancy should be considered.

According to post-marketing surveillance data, the following additional adverse reactions have been reported:

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

Reproductive system and breast disorders: very rare (< 1/10,000): pelvic pain, dysmenorrhea (menstrual cycle disorder).

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

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

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after medicine authorization is important. It allows continued monitoring of the benefit/risk balance of the medicine. Healthcare professionals are asked to report any suspected adverse reactions.

Shelf life. 3 years.

Storage conditions.

No special storage conditions required. Keep out of reach and sight of children.

Packaging.

1 tablet in a blister, 1 blister in a cardboard box.

Prescription status.

Prescription only.

Manufacturer.

LABORATORIOS LEON FARMA, S.A.

Manufacturer's address and place of business.

C/ La Vallicna s/n, Polígono Industrial Navatejera, Villacilambre, León, 24193, Spain.