Instructions Avodel tablets 1.5 mg blister No. 1
Composition
active ingredient: levonorgestrel;
1 tablet contains levonorgestrel 1.5 mg;
excipients: microcrystalline cellulose, lactose monohydrate, poloxamer 188, croscarmellose sodium, magnesium stearate.
Dosage form
Pills.
Main physicochemical properties: round biconvex white tablet engraved with “C” on one side and “1” on the other.
Pharmacotherapeutic group
Sex hormones and modulators of the reproductive system. Emergency contraceptives.
ATX code G03A D01.
Pharmacological properties
Pharmacodynamics.
The exact mechanism of action of AVODEL is unknown. At recommended doses, levonorgestrel affects ovulation and fertilization if intercourse occurs in the preovulatory phase of the menstrual cycle, i.e. when fertilization is most likely. The drug is not effective if implantation has already begun.
Efficacy: In a previously conducted clinical trial, 750 mcg of levonorgestrel (as two 750 mcg doses taken 12 hours apart) prevents pregnancy in 85% of cases. The longer the time between 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 the results of a previously conducted clinical study, 2 levonorgestrel 750 mcg tablets taken at the same time (within 72 hours after unprotected intercourse) prevent pregnancy in 84% of cases. There was no difference in pregnancy rates in women who took the drug on the third or fourth day after unprotected intercourse (p> 0.2).
There is limited evidence that requires further confirmation of the effect of overweight/high body mass index (BMI) on contraceptive efficacy. Three World Health Organization (WHO) studies showed no trend for reduced efficacy with increasing body weight/BMI (Table 1), while two other studies showed reduced efficacy with increasing body weight/BMI (Table 2). Both meta-analyses excluded cases of taking the pill later than 72 hours after unprotected intercourse (off-label use) and women who had unprotected intercourse after taking the pill.
Table 1
| BMI (kg/m2) | Women with low body weight 0−18.5 | Women with a normal body weight 18.5−25 | Overweight women 25−30 | Obese women ≥ 30 |
| Total number | 600 | 3952 | 1051 | 256 |
| Number of pregnancies | 11 | 3952 | 6 | 3 |
| Pregnancy rate | 1.83% | 0.99% | 0.57% | 1.17% |
| Confidence interval | 0.92–3.26 | 0.70–1.35 | 0.21–1.24 | 0.24–3.39 |
Table 2
| BMI (kg/m2) | Women with low body weight 0−18.5 | Women with a normal body weight 18.5−25 | Overweight women 25−30 | Obese women ≥ 30 |
| Total number | 64 | 933 | 339 | 212 |
| Number of pregnancies | 1 | 9 | 8 | 11 |
| Pregnancy rate | 1.56% | 0.96% | 2.36% | 5.19% |
| Confidence interval | 0.04–8.40 | 0.44–1.82 | 1.02–4.60 | 2.62–9.09 |
Recommended doses of levonorgestrel do not significantly affect blood clotting factors, fat and carbohydrate metabolism.
Pharmacokinetics.
When taken orally, levonorgestrel is rapidly and almost completely absorbed.
According to a study of 16 patients, 2 hours after a single dose of levonorgestrel 1.5 mg Cmax is 18.5 ng/ml.
After reaching maximum concentration, the level of levonorgestrel in the blood decreases, the average half-life is approximately 26 hours.
It is excreted in the form of metabolites with urine and feces in equal proportions. Biotransformation of levonorgestrel is carried out by a metabolic pathway characteristic of steroids. In the liver, levonorgestrel is hydroxylated and excreted from the body in the form of glucuronide conjugates. Pharmacologically active metabolites of levonorgestrel are unknown.
Levonorgestrel binds to serum albumin and sex hormone binding globulin (SHBG). 1.5% of the total amount in plasma is in the form of free steroid, 65% is specifically bound to SHBG.
Absolute bioavailability is 100% of the administered dose.
0.1% of the dose of the drug taken enters the baby's body through breast milk.
Indication
For emergency oral contraception in the first 72 hours after sexual intercourse, during which no contraceptive methods were used, or the contraceptive method used was not sufficiently reliable.
Contraindication
Hypersensitivity to any of the components of the drug; severe hepatic insufficiency; pregnancy.
Interaction with other medicinal products and other types of interactions
The metabolism of levonorgestrel is increased by concomitant use of drugs that are inducers of hepatic enzymes, mainly inducers of the CYP3A4 enzyme system. Concomitant use with efavirenz has been shown to decrease levonorgestrel plasma levels (AUC) by approximately 50%.
Drugs that are likely to decrease levonorgestrel plasma levels include barbiturates (including primidone), phenytoin, carbamazepine, herbal preparations containing St. John's wort (Hypericum perforatum St. John's Wort), rifampicin, ritonavir, rifabutin and griseofulvin.
Women who have taken drugs that induce hepatic microsomal enzymes within the past 4 weeks should consider using nonhormonal 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 of 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 taking hepatic microsomal enzyme inducers) has not been studied.
Medicinal products containing levonorgestrel may increase the toxicity of cyclosporine due to possible inhibition of its metabolism.
Application features
Emergency contraception is intended for emergencies. It is not a substitute for regular contraception. Repeated use of AVODEL tablets during the same menstrual cycle should be avoided to avoid cycle disruption.
Emergency contraceptives do not prevent pregnancy in all cases. The probability of fertilization is high in cases where the exact time of sexual intercourse is unknown and when more than 72 hours have passed since the moment of unprotected sexual intercourse for the period of one menstrual cycle. In such cases, taking the AVODEL tablet after the second sexual intercourse will not bring the desired result. If menstruation is delayed for more than 5 days, as well as in the case when menstruation has come on time, but is unusual or there is a suspicion of pregnancy for any other reason, a gynecological examination should be performed to exclude the presence of pregnancy, including ectopic pregnancy. The absolute risk of ectopic pregnancy is likely to be low, since levonorgestrel prevents ovulation and fertilization. Ectopic pregnancy may continue despite the occurrence of uterine bleeding. If pregnancy occurs after use of AVODEL tablets, the possibility of ectopic pregnancy should be considered, especially in women presenting with abdominal/pelvic pain or collapse and with a history of ectopic pregnancy, pelvic surgery or inflammation.
Therefore, levonorgestrel is not recommended for use in women at risk of developing ectopic pregnancy (history of salpingitis or ectopic pregnancy).
In severe liver dysfunction, the use of AVODEL is contraindicated.
Severe malabsorption in the digestive tract (e.g. Crohn's disease) reduces the effectiveness of the contraceptive drug.
The use of the drug usually does not disrupt the regularity and normal nature of menstruation. However, sometimes premature onset of menstruation or its delay is possible. After using the AVODEEL tablet, it is recommended to ensure regular contraception in the future. If AVODEEL is used due to errors made in regular hormonal contraception, and menstruation does not begin within the corresponding seven-day break, pregnancy should be excluded.
There are limited data that require further confirmation that the contraceptive efficacy of AVODEL may decrease with increasing body weight or body mass index (BMI) (see section 5.1). In all women, regardless of their body weight and BMI, emergency contraception should be taken as soon as possible after unprotected intercourse.
Compared to regular contraceptives, AVODEL tablets are less effective. Women who frequently use emergency contraception should consult their doctor to choose a regular contraceptive method.
Emergency contraception does not replace the need for protection against sexually transmitted diseases.
The drug contains lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this drug.
Use during pregnancy or breastfeeding
Pregnancy. Taking AVODEL tablets during pregnancy is contraindicated. The drug does not cause abortion. In the event of continued pregnancy, according to limited epidemiological data, no adverse effects on the fetus are noted. At the same time, there is no clinical data on the possible consequences of using a dose of the drug exceeding 1.5 mg of levonorgestrel.
Fertility: Levonorgestrel increases the possibility of menstrual irregularities, which in some cases lead to earlier or later ovulation. These changes may affect the dates of the fertile period, but there are no data on fertility with long-term follow-up.
Ability to influence reaction speed when driving vehicles or other mechanisms
No studies have been conducted to study the possible effects on the ability to drive vehicles or use other mechanisms.
Method of administration and doses
The drug should be administered orally.
You should take 1 tablet as soon as possible, preferably within 12 hours and no later than 72 hours after unprotected sexual intercourse (see the "Pharmacodynamics" section).
If vomiting occurs within 3 hours of taking the tablet, another tablet should be taken immediately.
Women who have taken enzyme-inducing drugs within the last 4 weeks and who need emergency contraception are advised to use non-hormonal emergency contraception, i.e. the copper IUD, or to take a double dose of levonorgestrel (i.e. 2 tablets at the same time) for women who cannot or do not want to use the copper IUD (see section “Interaction with other medicinal products and other forms of interaction”).
AVODEL can be taken on any day of the menstrual cycle, as long as there is no delay in menstrual bleeding.
After using emergency contraception, it is recommended to use a local barrier method (e.g. condom, diaphragm, spermicide, cervical cap) until the start of the next menstrual cycle. The use of levonorgestrel is not a contraindication to continuing regular hormonal contraception.
Children.
AVODEL is not intended for use in prepubertal children for emergency contraception.
Overdose
There are no data on severe adverse reactions after taking large doses of the drug. Overdose may cause nausea and breakthrough bleeding. There is no specific antidote, treatment is symptomatic.
Side effects
The most commonly reported adverse reaction was nausea.
| Organ system class | Adverse reactions by frequency |
| Very common (≥ 10) | Common (≥ 1/100 to < 1/10) |
| From the nervous system | Headache | Dizziness |
| On the part of the digestive system | Nausea Lower abdominal pain | Diarrhea Vomiting |
| Reproductive system and breast disorders | Bleeding not related to menstruation | Delay of menstruation for more than 7 days Irregular bleeding (spotting) Swelling of the mammary glands |
| General violations | Increased fatigue | |
The pattern of bleeding may vary slightly, but in most women, the next period begins within 5–7 days of the expected date.
If the next menstruation is more than 5 days late, the possibility of pregnancy should be considered.
According to post-marketing surveillance, the following adverse reactions have additionally been reported:
Skin and subcutaneous tissue disorders: very rare (< 1/10,000): itching, urticaria, rash.
Reproductive system and breast disorders: very rare (<1/10,000): pelvic pain, dysmenorrhea (menstrual disorder).
Gastrointestinal disorders: very rare (<1/10,000): abdominal pain.
Systemic disorders: very rare (<1/10,000): facial edema.
Reporting of suspected adverse reactions
Reporting adverse reactions after the registration of a medicinal product is important. This allows monitoring of the benefit/risk ratio of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all cases of suspected adverse reactions and lack of efficacy of the medicinal product via the Automated Information System for Pharmacovigilance at the following link: https://aisf.dec.gov.ua
Expiration date
3 years.
Storage conditions
Does not require any special storage conditions. Keep out of the reach of children.
Packaging
1 tablet in a blister, 1 blister in a cardboard box.
Vacation category
According to the recipe.
Producer
LABORATORIOS LEON PHARMA, S.A.
Location of the manufacturer and address of its place of business.
C/La Vallina s/n, Polígono Industrial Navatechera, Villacuilambre, Leon, 24008, Spain.
