Document: spc-doc_PL 35507-0126 change

• spc-doc_PL 32821-0053
• spc-doc_PL 35507-0126

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SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Levonorgestrel 1.5mg Tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 1.5mg of levonorgestrel Excipient(s) with known effect:

Each tablet contains 140.10 mg of lactose monohydrate.

For a full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Tablet.

White to off-white round shaped tablets, debossed with “LV1” on one side and plain on the other side.

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

Emergency contraception within 72 hours of unprotected sexual intercourse or failure of a contraceptive method.

Levonorgestrel 1.5mg tablets are not recommended for use by young women under 16 years of age without medical supervision.

4.2 Posology and method of administration

For oral administration:

One tablet should be taken as soon as possible, preferably within 12 hours, and no later than 72 hours after unprotected intercourse (see section 5.1).

If vomiting occurs within three hours of taking the tablet, another tablet should be taken immediately.

Levonorgestrel 1.5mg tablets can be used at any time during the menstrual cycle unless menstrual bleeding is overdue.

After using emergency contraception it is recommended to use a local barrier method (e.g. condom, diaphragm, spermicide, cervical cap) until the next menstrual period starts. The use of levonorgestrel does not contraindicate the continuation of regular hormonal contraception.

Paediatric population

Levonorgestrel 1.5mg tablets are not recommended in children.

Very limited data are available in women under 16 years of age.

There is no relevant use of levonorgestrel for children of prepubertal age in the indication emergency contraception.

Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

4.4 Special warnings and precautions for use

Emergency contraception is an occasional method. It should in no instance replace a regular contraceptive method.

Emergency contraception does not prevent a pregnancy in every instance. If there is uncertainty about the timing of the unprotected intercourse or if the woman has had unprotected intercourse more than 72 hours earlier in the same menstrual cycle, conception may have occurred. Treatment with levonorgestrel following the second act of intercourse may therefore be ineffective in preventing pregnancy. If menstrual periods are delayed by more than 5 days or abnormal bleeding occurs at the expected date of menstrual periods or pregnancy is suspected for any other reason, pregnancy should be excluded.

If pregnancy occurs after treatment with levonorgestrel, the possibility of an ectopic pregnancy should be considered. The absolute risk of ectopic pregnancy is likely to be low, as levonorgestrel prevents ovulation and fertilisation. Ectopic pregnancy may continue, despite the occurrence of uterine bleeding.

Therefore, levonorgestrel is not recommended for patients who are at risk of ectopic pregnancy (previous history of salpingitis or of ectopic pregnancy).

Levonorgestrel is not recommended in patients with severe hepatic dysfunction.

Severe malabsorption syndromes, such as Crohn's disease, might impair the efficacy of levonorgestrel.

This medicinal product contains lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

After levonorgestrel intake, menstrual periods are usually normal and occur at the expected date. They can sometimes occur earlier or later than expected by a few days. Women should be advised to make a medical appointment to initiate or adopt a method of regular contraception. If no withdrawal bleed occurs in the next pill-free period following the use of levonorgestrel after regular hormonal contraception, pregnancy should be ruled out.

Repeated administration within a menstrual cycle is not advisable because of the possibility of disturbance of the cycle.

Levonorgestrel is not as effective as a conventional regular method of contraception and is suitable only as an emergency measure. Women who present for repeated courses of emergency contraception should be advised to consider long-term methods of contraception.

Use of emergency contraception does not replace the necessary precautions against sexually transmitted diseases.

4.5 Interaction with other medicinal products and other forms of interaction

The metabolism of levonorgestrel is enhanced by concomitant use of liver enzyme inducers.

Drugs suspected of having the capacity to reduce the efficacy of levonorgestrel include barbiturates (including primidone), phenytoin, carbamazepine, herbal medicines containing Hypericum perforatum (St.John’s Wort), rifampicin, ritonavir, rifabutin, griseofulvin.

Medicines containing levonorgestrel may increase the risk of cyclosporine toxicity due to possible inhibition of cyclosporin metabolism.

4.6 Fertility, pregnancy and lactation

Pregnancy

Levonorgestrel should not be given to pregnant women. It will not interrupt a pregnancy. In the case of continued pregnancy, limited epidemiological data indicate no adverse effects on the fetus but there are no clinical data on the potential consequences if doses greater than 1.5 mg of levonorgestrel are taken (see section 5.3.).

Breast-feeding

Levonorgestrel is secreted into breast milk. Potential exposure of an infant to levonorgestrel can be reduced if the breast-feeding woman takes the tablet immediately after feeding and avoids nursing at least 8 hours following Levonorgestrel administration.

Fertility

Levonorgestrel increases the possibility of cycle disturbances which can sometimes lead to earlier or later ovulation date. These changes can result in modified fertility date, however, there are no fertility data in the long term.

4.7 Effects on ability to drive and use machines

No studies on the effect on the ability to drive and use machines have been performed.

4.8 Undesirable effects

The most commonly reported undesirable effect was nausea.

All adverse drug reactions are listed by system, organ class and frequency.

Frequencies are defined as Very common (> 1/10), Common (> 1/100 to <1/10), Uncommon (> 1/1,000 to <1/100), Rare ( 1/10,000 to <1/1,000) and Very rare (<1/10,000), not known (cannot be estimated from the available data).

System Organ Class	Frequency of adverse reactions
MedDRA14.1
	Very common (> 10%)	Common (> 1% to <10%)
Nervous system disorders	Headache	Dizziness
Gastrointestinal disorders	Nausea Lower abdominal pain	Diarrhoea Vomiting
Reproductive system and breast disorders	Bleeding not related to menses*	Delay of menses more than 7 days **
		Irregular menstruation
		Breast tenderness
General disorders and administration site conditions	Fatigue

* Bleeding patterns may be temporarily disturbed, but most women will have their next menstrual period within 7 days of the expected time.

** If the next menstrual period is more than 5 days overdue, pregnancy should be excluded.

From Post-marketing surveillance additionally, the following adverse events have been reported:

Gastrointestinal disorders

Very rare (<1/10,000): abdominal pain

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

Reproductive system and breast disorders Very rare (<1/10,000): pelvic pain, dysmenorrhoea

General disorders and administration site conditions Very rare (<1/10,000): face oedema

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

4.9 Overdose

Serious undesirable effects have not been reported following acute ingestion of large doses of oral contraceptives. Overdose may cause nausea, and withdrawal bleeding may occur. There are no specific antidotes and treatment should be symptomatic.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Sex hormones and modulators of the genital system, emergency contraceptives, ATC code: G03AD01

The precise mode of action of levonorgestrel as an emergency contraceptive is not known. At the recommended regimen, levonorgestrel is thought to work mainly by preventing ovulation and fertilisation if intercourse has taken place in the preovulatory phase, when the likelihood of fertilisation is the highest. Levonorgestrel is not effective once the process of implantation has begun.

Clinical efficacy and safety

Results from a randomised, double-blind clinical study conducted in 2001 (Lancet 2002; 360: 1803-1810) showed that a 1500 microgram single dose of levonorgestrel (taken within 72 hours of unprotected sex) prevented 84% of expected pregnancies (compared with 79% when the two 750 microgram tablets were taken 12 hours apart).

There was no difference between pregnancy rates in case of women who were treated on the third or the fourth day after the unprotected act of intercourse (p>0.2).

Another study conducted in 1997 (Lancet 1998; 352: 428-33) showed that two 750 microgram doses taken 12 hours apart prevents 85% of expected pregnancies

At the recommended regimen, levonorgestrel is not expected to induce significant modification of blood clotting factors, and lipid and carbohydrate metabolism.

Paediatric population

A prospective observational study showed that out of 305 treatments with levonorgestrel emergency contraceptive tablets, seven women became pregnant resulting in an overall failure rate of 2.3%. The failure rate in women under 18 years (2.6% or 4/153) was comparable to the failure rate in women 18 years and over (2.0% or 3/152).

5.2 Pharmacokinetic properties

Absorption

Orally administered levonorgestrel is rapidly and almost completely absorbed.

Distribution

The results of a pharmacokinetic study carried out with 16 healthy women showed that following ingestion of single dose of 1.5 mg levonorgestrel maximum drug serum levels of levonorgestrel of 18.5 ng/ml were found at 2 hours. After reaching maximum serum levels, the concentration of levonorgestrel decreased with a mean elimination half-life of about 26 hours.

Biotransformation

Levonorgestrel is not excreted in unchanged form but as metabolites.

Levonorgestrel metabolites are excreted in about equal proportions with urine and faeces. The biotransformation follows the known pathways of steroid metabolism, the levonorgestrel is hydroxylated in the liver and the metabolites are excreted as glucuronide conjugates.

No pharmacologically active metabolites are known.

Levonorgestrel is bound to serum albumin and sex hormone binding globulin (SHBG). Only about 1.5% of the total serum levels are present as free steroid, but 65% are specifically bound to SHBG.

The absolute bioavailability of levonorgestrel was determined to be almost 100% of the dose administered.

About 0.1% of the maternal dose can be transferred via milk to the nursed infant.

5.3 Preclinical safety data

Animal experiments with levonorgestrel have shown virilisation of female fetuses at high doses.

Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeat-dose toxicity, genotoxicity and carcinogenicity potential, beyond the information included in other sections of the SmPC.

6    PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Lactose monohydrate

Maize starch Povidone K30 Silica, colloidal anhydrous Magnesium stearate

6.2    Incompatibilities

Not applicable.

10 DATE OF REVISION OF THE TEXT

30/09/2016