Postinor

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

Composition:

Active substance: levonorgestrel;

1 tablet contains 0.75 mg of levonorgestrel;

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

Pharmaceutical form. Tablets.

Main physicochemical properties: flat tablets with bevel, almost white in color, approximately 6 mm in diameter, with engraving "INOR" on one side.

Pharmacotherapeutic group. Hormonal contraceptives for systemic use. Emergency contraceptives. Levonorgestrel. ATC code G03A D01.

Pharmacological properties.

Pharmacodynamics.

Mechanism of action

The exact mechanism of action of Postinor is unknown.

It is presumed that, at the recommended doses, levonorgestrel prevents ovulation and fertilization when sexual intercourse occurs in the preovulatory phase, when the likelihood of fertilization is highest. The drug is ineffective if implantation has already begun.

Effectiveness

According to results from a previously conducted clinical study, 750 mcg of levonorgestrel (administered as two doses of 750 mcg each, taken 12 hours apart) prevents approximately 85% of expected pregnancies. The efficacy of the drug likely decreases with increasing time elapsed after sexual intercourse (95% within 24 hours, 85% when used within 24 hours and no later than 48 hours, 58% when used within 48 hours and no later than 72 hours).

According to results from a previously conducted clinical study, two tablets of levonorgestrel 750 mcg taken simultaneously within 72 hours after unprotected sexual intercourse prevent 84% of expected pregnancy cases. There were no differences in the frequency of pregnancy occurrence among women who took the drug on the third or fourth day after unprotected sexual intercourse (p > 0.2).

Results from three studies conducted by WHO, and a meta-analysis, are summarized in Table 1.

Table 1. Meta-analysis of three studies conducted by WHO (Von Hertzen et al., 1998 and 2002; Dada et al., 2010)

* The expected pregnancy rate in the absence of emergency contraception is 8%.

There are limited data requiring further confirmation regarding the influence 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 2), whereas in two other studies (Creinin et al., 2006 and Glasier et al., 2010), a decrease in contraceptive efficacy with increasing body weight/BMI was observed (see Table 3). Both meta-analyses excluded cases where the drug was taken more than 72 hours after unprotected intercourse (off-label use) and cases where unprotected intercourse occurred after drug administration (for information on pharmacokinetic studies conducted in women with obesity, see below).

Table 2. Meta-analysis of three WHO studies (Von Hertzen et al., 1998 and 2002; Dada et al., 2010)

Table 3. Meta-analysis of studies (Creinin et al., 2006 and Glasier et al., 2010)

With the recommended dosing regimen, levonorgestrel has no significant effect on blood coagulation factors, lipid and carbohydrate metabolism.

Children

In a prospective non-experimental study, among 305 cases of using levonorgestrel tablets for emergency contraception, pregnancy occurred in 7 cases, resulting in an overall failure rate of 2.3%. The failure rate in women under 18 years of age (2.6% or 4/153) was comparable to that in women aged 18 years and older (2.0% or 3/152).

Pharmacokinetics.

After oral administration, levonorgestrel is rapidly and almost completely absorbed.

In a pharmacokinetic study in 16 healthy women following a single 1.5 mg dose of levonorgestrel, the maximum plasma concentration was 18.5 ng/mL, reached within 2 hours.

After peak levels are achieved, levonorgestrel concentrations decline with a mean elimination half-life of approximately 26 hours.

Levonorgestrel is excreted as metabolites and is not excreted unchanged. Metabolites of levonorgestrel are excreted in urine and feces in approximately equal amounts. Biotransformation occurs via well-known steroid metabolic pathways. Levonorgestrel is hydroxylated in the liver, and metabolites are excreted as conjugated glucuronides. Pharmacologically active metabolites are not known.

Levonorgestrel binds to serum albumin and sex hormone-binding globulin (SHBG). Approximately 1.5% of the total concentration in serum exists as free steroid, while 65% is specifically bound to SHBG. Absolute bioavailability of levonorgestrel is nearly 100%.

Approximately 0.1% of the administered dose is excreted in breast milk and thus transferred to the infant.

Pharmacokinetics in women with obesity

A pharmacokinetic study showed that levonorgestrel concentrations are reduced in women with obesity (BMI ≥ 30 kg/m²), with approximately 50% lower Cmax and AUC0–24, compared to women with normal BMI (< 25 kg/m²) (Praditpan et al., 2017). Another study also demonstrated approximately 50% lower Cmax of levonorgestrel in obese women compared to those with normal BMI, while administration of a double dose (3 mg) in women with obesity resulted in plasma concentrations similar to those observed in women with normal BMI receiving 1.5 mg levonorgestrel (Edelman et al., 2016). The clinical significance of these findings has not been established.

Clinical characteristics.

Indications.

Emergency contraception within 72 hours after unprotected sexual intercourse or when the contraceptive method used has failed or is suspected to be unreliable.

Contraindications.

Hypersensitivity to the active substance (levonorgestrel) or to any of the excipients.

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

Medicinal products that may 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 been taking drugs that are inducers of hepatic microsomal enzymes during the previous 4 weeks should consider using non-hormonal emergency contraceptives (e.g., copper IUD) when emergency contraception is needed. Taking a double dose of levonorgestrel (e.g., 3000 mcg of levonorgestrel within 72 hours after unprotected sexual 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 inducers of hepatic microsomal enzymes) 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 a method that can be used episodically. It should not replace regular contraception.

Emergency contraception does not in all cases prevent pregnancy.

If there is uncertainty regarding the timing of unprotected sexual intercourse or if more than 72 hours have passed since the unprotected intercourse within the same menstrual cycle, there is a possibility that conception has already occurred. Therefore, the use of Postinor after repeated sexual intercourse may be ineffective in preventing pregnancy. If menstruation is delayed by more than 5 days, or if unusual bleeding occurs on the expected day of menstruation, or if there are other reasons to suspect pregnancy, pregnancy must be ruled out.

If pregnancy occurs after taking Postinor, ectopic pregnancy should be considered. The absolute probability of ectopic pregnancy is likely low, as levonorgestrel prevents ovulation and fertilization.

Ectopic pregnancy may develop despite uterine bleeding. Therefore, levonorgestrel should be used with increased caution in patients at risk of ectopic pregnancy (e.g., history of salpingitis or previous ectopic pregnancy).

Postinor is not recommended for patients with severe hepatic impairment.

Severe malabsorption syndromes, such as Crohn's disease, may negatively affect the efficacy of Postinor. Women with such conditions should consult a physician when emergency contraception is needed.

After taking Postinor, the regularity and nature of menstruation are usually not disrupted. Occasionally, menstruation may start several days earlier or later than expected. Women should be advised to consult a physician to select and initiate a regular contraceptive method. If withdrawal bleeding does not occur in the following tablet-free period after using Postinor or after starting regular hormonal contraception, pregnancy must be excluded.

Repeated use of the drug within the same menstrual cycle is not recommended due to the risk of menstrual cycle disturbances.

There are limited data, requiring further confirmation, suggesting that the contraceptive efficacy of Postinor may decrease with increasing body weight or body mass index (BMI) (see sections "Pharmacodynamics" and "Pharmacokinetics"). All women, regardless of body weight or BMI, should take emergency contraception as soon as possible after unprotected sexual intercourse.

Postinor is less effective than regular contraceptive methods and should only be used as an emergency measure. Women seeking repeated emergency contraception should be advised to consider long-term contraceptive methods.

Emergency contraception does not replace necessary protective measures against sexually transmitted infections.

This medicinal product contains lactose. It should not be used in patients with rare hereditary problems of galactose intolerance, lactase deficiency, or glucose-galactose malabsorption syndrome.

Use during pregnancy or breastfeeding.

Pregnancy

Postinor should not be used during pregnancy. The drug does not interrupt an existing 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 administering doses exceeding 1.5 mg of levonorgestrel.

Lactation

Levonorgestrel is excreted in breast milk. The potential effect of levonorgestrel on infants can be minimized if the breastfeeding woman takes the tablet immediately after feeding and avoids breastfeeding for at least 8 hours after each dose of Postinor.

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 data on fertility following long-term observation.

Ability to drive or operate machinery.

The effect of the drug on the ability to drive or operate machinery has not been studied.

Administration method and dosage.

Dosage

Two tablets must be taken simultaneously.

If vomiting occurs within 3 hours after taking the tablets, 2 additional tablets should be taken immediately.

Women who have taken enzyme-inducing medications during the past 4 weeks and require emergency contraception are advised to use non-hormonal methods of emergency contraception, i.e., copper IUD, or to take a double dose of levonorgestrel (i.e., 4 tablets at once) 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").

Postinor may be used at any phase 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., condoms, diaphragms, spermicides, cervical caps) until the onset of the next menstruation. The use of Postinor is not a contraindication for continuing regular hormonal contraception.

For oral use.

Children.

Postinor is not intended for use in prepubertal children for the indication of emergency contraception.

Overdose.

Serious adverse effects following acute overdose with large doses of oral contraceptives have not been reported. In case of overdose, nausea and breakthrough bleeding may occur. There are no specific antidotes; treatment is symptomatic.

Adverse reactions.

The most common adverse effect was nausea.

Table 4

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

If the next menstruation 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 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 medicinal product authorization is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals and patients, as well as patients’ legal representatives, are encouraged to report all suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at: https://aisf.dec.gov.ua.

Shelf life.

5 years.

Storage conditions.

Store at temperatures not exceeding 25 °C.

Keep this medicine out of the reach of children!

Packaging.

2 tablets per blister; 1 blister in a cardboard package.

Prescription status.

Over-the-counter (without prescription).

Manufacturer.

JSC "Gedeon Richter".

Manufacturer's address and location of operations.

H-1103 Budapest, 19-21, Demrédi Street, Hungary.