Postinor, tablets 0,75 mg 2 pcs

Pharmacotherapeutic group: Medication for emergency contraception.
ATX code: G03AD01

Pharmacodynamics
Levonorgestrel is a synthetic progestagen with contraceptive action. It is used as an emergency contraceptive due to its pronounced gestagenic and anti-estrogenic effects. The main mechanism of action is inhibition and/or delay of ovulation as a result of suppression of peak luteinizing hormone. With the recommended dosing regimen, levonorgestrel suppresses ovulation and fertilization if sexual intercourse occurs in the pre-ovulatory phase, when the possibility of fertilization is greatest. Levonorgestrel is not effective if implantation of a fertilized egg has already occurred.

Efficacy: According to a previous clinical study, two doses of levonorgestrel 0.75 mg at 12-hour intervals prevented pregnancy in 85% of cases. Its efficacy decreases with time after sexual intercourse (95% if taken within 24 hours, 85% between 24 and 48 hours, and 58% between 48 and 72 hours).
The results of another clinical study showed that 2 0.75 mg tablets of levonorgestrel taken simultaneously (within 72 hours of unprotected intercourse) prevented pregnancy in 84% of cases.
There is limited data, requiring further confirmation, on the effect of excess body weight/high body mass index (BMI) on contraceptive efficacy. Two clinical trials (CIs) have shown decreased efficacy of levonorgestrel and increased pregnancy rates in women with BMI ≥30 kg/m2 compared with women with normal BMI (5.19% and 0.96%, respectively). However, no decrease in the contraceptive efficacy of levonorgestrel was demonstrated in other trials (pregnancy rates were 1.17% in women with
obesity and 0.99% in women with normal BMI).
With the recommended dosing regimen, levonorgestrel has no significant effect on clotting factors, lipid, and carbohydrate metabolism.
Adolescent girls under 18 years of age
In a prospective observational study, it was shown that of 305 cases of levonorgestrel as an emergency contraceptive, seven cases resulted in pregnancy. Thus, the overall failure rate was 2.3%.
The failure rate in adolescent girls younger than 18 years (2.6% or 4/153) was comparable to the failure rate in women 18 years and older (2.0% or 3/152).

Pharmacokinetics

Assimilation
Levonorgestrel is rapidly and almost completely absorbed when taken orally. After taking levonorgestrel at a dose of 1.5 mg, the maximum plasma concentration (Cmax) is 18.5 ng/ml and is reached after 2 hours. After reaching the maximum values, the concentration of levonorgestrel decreases. Absolute bioavailability is 100%.

Distribution
Levonorgestrel binds to plasma albumin and sex hormone-binding globulin (hGBS). Only 1.5% of the total dose is in free form; 65% is bound to hGH. Levonorgestrel penetrates into breast milk.

Metabolism
Metabolism of levonorgestrel corresponds to that of sex hormones. Levonorgestrel is hydroxylated in the liver and metabolites are excreted as conjugated glucuronides. Pharmacologically active metabolites of levonorgestrel are unknown.

Elimation
Excreted exclusively as metabolites, approximately equally by the kidneys and through the intestine. The elimination half-life (T1/2) is about 26 hours.

Pharmacokinetics in special groups of patients
In adolescent girls under 18 years

Studies of levonorgestrel pharmacokinetics were performed only in adult volunteers.

Patients with renal or hepatic impairment
Pharmacokinetics of levonorgestrel has not been studied in patients with hepatic or renal impairment.

Patients with obesity
A pharmacokinetics study showed that levonorgestrel concentrations were significantly reduced in obese women (BMI ≥30 kg/m²) (approximately 50% reduction in Cmax and AUC0-24 was observed) compared with those in women with normal BMI (< 25 kg/m²).
Another study also reported a reduction in levonorgestrel Cmax of approximately 50% in obese women compared with normal BMI women, while plasma concentrations of levonorgestrel after a 3 mg dose in obese women were comparable to plasma concentrations of levonorgestrel in women with normal BMI after a 1.5 mg dose. The clinical significance of these data is unclear.

Indications

Emergency (postcoital) contraception (after unprotected sexual intercourse or unreliability of the contraceptive method used).

Pharmacological effect

Pharmacotherapeutic group: emergency contraception.
ATX code: G03AD01

Pharmacodynamics
Levonorgestrel is a synthetic progestogen with a contraceptive effect. It is used as a means of emergency contraception due to its pronounced gestagenic and antiestrogenic effects. The main mechanism of action is inhibition and/or delay of ovulation as a result of suppression of the peak of luteinizing hormone. With the recommended dosing regimen, levonorgestrel suppresses ovulation and fertilization if sexual intercourse occurs in the preovulatory phase, when the possibility of fertilization is greatest. Levonorgestrel is not effective if implantation of a fertilized egg has already occurred.

Efficacy: According to the results of an earlier clinical study, taking two doses of levonorgestrel 0.75 mg every 12 hours prevented pregnancy in 85% of cases. The effectiveness of the drug decreases over time after sexual intercourse (95% when used within 24 hours, 85% when used within 24 to 48 hours, 58% when used within 48 to 72 hours).
Another clinical study showed that two 0.75 mg levonorgestrel tablets taken simultaneously (within 72 hours of unprotected intercourse) prevented pregnancy in 84% of cases.
There are limited data that require further confirmation on the impact of excess body weight/high body mass index (BMI) on contraceptive effectiveness. Two clinical studies (CTs) showed a decrease in the effectiveness of levonorgestrel and an increase in the pregnancy rate in women with a BMI ≥30 kg/m2 compared with women with a normal BMI (5.19% and 0.96%, respectively). However, in other clinical trials, a decrease in the contraceptive effectiveness of levonorgestrel was not demonstrated (pregnancy rate was 1.17% in women with
obese and 0.99% in women with normal BMI).
With the recommended dosage regimen, levonorgestrel does not have a significant effect on blood clotting factors, lipid and carbohydrate metabolism.
Teenage girls under 18
A prospective observational study showed that of 305 cases of levonorgestrel use as emergency contraception, pregnancy occurred in seven cases. Thus, the overall failure rate was 2.3%.
The failure rate for adolescent girls under 18 years of age (2.6% or 4/153) was comparable to the failure rate for women 18 years of age and older (2.0% or 3/152).

Pharmacokinetics

Suction
When taken orally, levonorgestrel is rapidly and almost completely absorbed. After taking levonorgestrel at a dose of 1.5 mg, the maximum concentration (Cmax) in blood plasma is 18.5 ng/ml and is achieved after 2 hours. After reaching maximum values, the concentration of levonorgestrel decreases. Absolute bioavailability is 100%.

Distribution
Levonorgestrel binds to plasma albumin and sex hormone binding globulin (SHBG). Only 1.5% of the total dose is in free form, 65% is associated with SHBG. Levonorgestrel passes 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.

Removal
It is excreted exclusively in the form of metabolites, approximately equally by the kidneys and through the intestines. The half-life (T1/2) is approximately 26 hours.

Pharmacokinetics in special groups of patients
For teenage girls under 18 years of age

Pharmacokinetic studies of levonorgestrel were conducted only in adult volunteers.

Patients with renal and liver failure
The pharmacokinetics of levonorgestrel in patients with hepatic or renal impairment have not been studied.

Obese patients
A pharmacokinetic study showed that levonorgestrel concentrations were significantly reduced in obese women (BMI ≥30 kg/m²) (approximately 50% reduction in Cmax and AUC0-24 was observed) compared with those in women with normal BMI (< 25 kg/m²).
Another study also reported a reduction in levonorgestrel Cmax of approximately 50% in obese women compared with those in women with a normal BMI, while plasma concentrations of levonorgestrel after a 3 mg dose in obese women were comparable to plasma levonorgestrel concentrations in women with a normal BMI after a 1.5 mg dose. The clinical significance of these data is unclear/

Special instructions

Levonorgestrel in a dose of 1.5 mg (2 tablets) should be used exclusively for emergency contraception! Emergency contraception is a method that can only be used occasionally. The drug Postinor® does not replace the use of methods of planned contraception.

Emergency contraception does not always prevent pregnancy.

Repeated use of the drug during one menstrual cycle is not recommended due to the possible risk of cycle disorders (the appearance of acyclic bleeding/spotting, delayed menstrual bleeding).

Postinor® should be taken as soon as possible, but no later than 72 hours after unprotected sexual intercourse. The effectiveness of emergency contraception with delayed use of the drug is significantly reduced.

In most cases, taking Postinor® in recommended doses does not affect the nature of the menstrual cycle. However, acyclic bleeding and a delay of menstruation for several days are possible. If menstruation is delayed by more than 5 days or the nature of the discharge changes (scanty or heavy bleeding), or if pregnancy is suspected for any other reason, pregnancy must be excluded. A woman should be recommended to consult a gynecologist to select and use one of the methods of planned contraception. If the drug Postinor® was taken against the background of regular hormonal contraception, but the expected “withdrawal” bleeding did not occur during the subsequent 7-day period of interruption in taking the contraceptive or during the period of taking placebo pills, pregnancy must be excluded.

If pregnancy occurs after taking Postinor®, the possibility of ectopic (ectopic) pregnancy should be considered. The appearance of pain in the lower abdomen and fainting may indicate an ectopic pregnancy. Because levonorgestrel suppresses ovulation, the absolute risk of ectopic pregnancy with its use is probably low. An ectopic pregnancy can develop despite the appearance of bleeding from the genital tract. In this connection, in women with a high risk of developing an ectopic pregnancy (the presence of inflammatory diseases of the fallopian tubes
or uterine appendages (salpingitis, salpingoophoritis) or a history of ectopic pregnancy) the use of levonorgestrel is not recommended.

The use of levonorgestrel in women with liver or biliary tract diseases requires precautions; in patients with severe liver failure it is contraindicated.

In diseases of the gastrointestinal tract (for example, Crohn’s disease), as well as in women with excess body weight, the contraceptive effectiveness of levonorgestrel may be reduced.

The use of Postinor® 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 second consultation with a gynecologist is recommended.

Emergency contraception does not protect against sexually transmitted diseases!

Cases of thromboembolic complications have been reported after taking levonorgestrel at a dose of 1.5 mg. In this regard, in women with existing risk factors (hereditary or acquired predisposition to arterial or venous thrombosis, the presence of thrombosis/thromboembolism in a family history), the possibility of such complications should be taken into account.

Effect on fertility
Levonorgestrel increases the risk of developing menstrual irregularities, which in some cases can lead to earlier or later ovulation. These changes may affect fertility, but there are no data on the effects of levonorgestrel on fertility with long-term use.

Impact on the ability to drive vehicles and machinery
The effect of using the drug Postinor® on the ability to drive vehicles and machines has not been studied/

Active ingredient

Levonorgestrel

Composition

1 tablet contains:

Active ingredient: levonorgestrel 0.75 mg.

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

Pregnancy

Pregnancy
Taking Postinor® during pregnancy is contraindicated. Based on the available data, no adverse effects on the fetus have been identified in the event of pregnancy using the emergency method of contraception with levonorgestrel.

Breastfeeding period
Levonorgestrel passes into breast milk. After taking Postinor®, breastfeeding should be stopped for at least 8 hours.

Contraindications

– Hypersensitivity to levonorgestrel and/or to any of the excipients in the drug.
– Age up to 16 years (due to limited data on the safety and effectiveness of levonorgestrel in this age group).
– Severe liver failure.
– Pregnancy, including intended.
– Breastfeeding for at least 8 hours after taking the drug.
– Lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome.

Taking Postinor® is not recommended for women with a high risk of ectopic pregnancy (with a history of ectopic pregnancy or inflammatory diseases of the fallopian tubes).

With caution
– Diseases of the liver (mild to moderate severity) or biliary tract.
– Jaundice (including history).
– Severe malabsorption syndromes, such as Crohn’s disease.
– The presence of a hereditary or acquired predisposition to thrombosis.

Side Effects

The most common adverse reaction with levonorgestrel was nausea.

Possible adverse reactions while taking levonorgestrel are distributed according to systemic organ classes, indicating the frequency of their occurrence according to WHO recommendations: very often (≥1/10), often (≥1/100, <1/10), infrequently (≥1/1000, <1/100), rarely (≥1/10000, <1/1000), very rarely (< 1/10000), including individual messages.

Nervous system disorders
Very common: headache.
Common: dizziness.

Gastrointestinal disorders
Very common: nausea, pain in the lower abdomen.
Common: diarrhea, vomiting.

Disorders of the genital organs and breast
Very common: bleeding not associated with menstruation.
Common: delay of menstruation by more than 7 days, irregular menstrual bleeding, engorgement of the mammary glands.

General disorders and disorders at the injection site
Very common: increased fatigue.

The nature of menstrual bleeding may vary slightly, but for most women, the next menstruation begins within 5 days of the expected due date.
If the onset of the next menstruation is delayed by more than 5 days, pregnancy should be excluded.

During the post-registration period of use of the drug Postinor®, the following adverse reactions were reported:

Gastrointestinal disorders
Very rare: abdominal pain.

Disorders of the skin and subcutaneous tissues
Very rare: skin rash, urticaria, itching.

Disorders of the genital organs and breast
Very rare: pelvic pain, dysmenorrhea.

General disorders and disorders at the injection site
Very rare: facial swelling.

Interaction

The metabolism of levonorgestrel is carried out with the active participation of the isoenzyme of the cytochrome P450 system – CYP3A4. When used simultaneously with drugs that induce microsomal liver enzymes (mainly inducers of the CYP3A4 isoenzyme), the metabolism of levonorgestrel is accelerated.

The following liver enzyme inducing drugs may reduce the effectiveness of levonorgestrel: barbiturates (including primidone), phenytoin and carbamazepine, drugs containing St. John’s wort (Hypericum perforatum), and rifampicin, ritonavir, rifabutin and griseofulvin.

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

Enzyme induction may continue for 4 weeks or more after discontinuation of such drugs. For women who received therapy with microsomal liver enzyme inducers in the last 4 weeks before unprotected sexual intercourse, another non-hormonal method of emergency contraception should be considered (for example, the installation of a copper-containing intrauterine contraceptive device).

Products containing levonorgestrel may increase the risk of cyclosporine toxicity due to inhibition of its metabolism.

Levonorgestrel may reduce the effectiveness of ulipristal by competitively acting on the progesterone receptor, and therefore their simultaneous use is not recommended.

Overdose

No serious adverse reactions have been reported after taking high doses of oral contraceptives.

Symptoms: nausea and withdrawal bleeding.

Treatment: symptomatic. There is no specific antidote.

Storage conditions

At a temperature not exceeding 30 °C.
Keep out of the reach of children.

Shelf life

5 years.
Do not use after the expiration date indicated on the package.

Manufacturer

Gedeon Richter, Hungary