HRA Pharma UK and Ireland Limited

NORLEVO 1.5 mg tablet

Each tablet contains 1.5 mg levonorgestrel

Excipients: each tablet contains 90.90 mg lactose monohydrate.

For a full list of excipients, see section6.1.

Tablet

White, round biconvex tablet engraved with code NL 1.5 on one face.

• Emergency contraception within 72 hours after an unprotected sexual intercourse or in case of failure of a contraceptive method.

Oral use

The treatment necessitates the intake of one tablet. The efficacy of the method is higher the sooner after the unprotected intercourse the treatment is initiated. Therefore, the tablet must be taken as soon as possible, preferably within 12 hours after the unprotected intercourse, and no longer than 72 hours (3 days) after the intercourse.

Norlevo 1.5 mg can be taken at any moment during the menstrual cycle.

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

After using an emergency contraception, it is recommended to use a local contraceptive mean (condom, spermicide, cervical cap) until the next menstrual periods resume. The use of Norlevo 1.5 mg does not contraindicate the continuation of regular hormonal contraception.

Hypersensitivity to levonorgestrel or any of the excipients.

If the woman has had unprotected intercourse more than 72 hours earlier in the same menstrual cycle, conception may have occurred. Treatment with Norlevo 1.5 mg following the second act of intercourse may therefore be ineffective in preventing pregnancy.

If pregnancy occurs after treatment with Norlevo 1.5 mg, the possibility of an ectopic pregnancy should be considered. The absolute risk of ectopic pregnancy is likely to be low as Norlevo 1.5 mg prevents ovulation and fertilisation. Ectopic pregnancy may continue, despite the occurrence of uterine bleeding. Therefore, Norlevo 1.5 mg is not recommended for patients who are at risk of ectopic pregnancy (previous history of salpingitis or of ectopic pregnancy).

Norlevo 1.5 mg is not recommended in patients with severe hepatic dysfunction. Severe malabsorption syndromes, such as Crohn's disease, might impair the efficacy of Norlevo 1.5 mg.

Cases of thromboembolic events have been reported after Norlevo intake. The possibility of occurrence of a thromboembolic event should be considered in women with other pre-existing thromboembolic risk factor(s), especially personal or family history suggesting thrombophilia.

After Norlevo 1.5 mg intake, menstrual periods are usually of normal abundance and occur at the expected date. They can sometimes occur earlier or later than expected by a few days. It is recommended to have a medical visit to initiate or adapt a method of regular contraception. In case no menstrual period occurs in the next pill-free period following the use of Norlevo 1.5 mg after regular hormonal contraception, pregnancy should be ruled out.

Repeated administration within a menstrual cycle is not advisable, because of an undesirable high load of hormones for the patient and the possibility of severe disturbances of the cycle. Women who present for repeated courses of emergency contraception should be advised to consider long-term methods of contraception.

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

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.

Associations to be taken into consideration:

The metabolism of levonorgestrel is enhanced by the concomitant use of liver enzyme inducers: anticonvulsant (phenobarbital, phenytoin, primidone, carbamazepine); rifabutin; rifampicin; griseofulvin; ritonavir; Hypericum perforatum (St. John's wort). The efficacy of Norlevo 1.5 mg may be decreased in case of concomitant intake of these active substances.

Pregnancy

This medicinal product cannot interrupt an ongoing pregnancy.

In case of failure of this contraceptive mean with persisting pregnancy, epidemiological studies indicate no malformative effects of progestins on foetus.

Nothing is known on the consequences for the child if doses higher than 1.5 mg levonorgestrel are taken.

Breastfeeding

Levonorgestrel is excreted into breast milk. Therefore, it is suggested to breastfeed immediately before taking the Norlevo 1.5 mg, tablet and to skip nursing at least 8 hours following Norlevo 1.5 mg administration.

Fertility

A rapid return to fertility is likely following treatment with Norlevo for emergency contraception; therefore, regular contraception should be continued or initiated as soon as possible following the use of Norlevo to ensure ongoing prevention of pregnancy.

Clinical experience reveal no effect on fertility in humans after use of levonorgestrel. Similarly nonclinical studies show no evidence of adverse effects in animals (see section 5.3)

No studies on the effect on the ability to drive and use machines have been reported. Nevertheless, if women experience fatigue and dizziness after taking Norlevo, they should not drive or use machines.

The following table gives the frequency of undesirable effects after intake of 1.5 mg levonorgestrel reported in clinical trials*.

* Trial 1 (n=544): Contraception, 2002, 66, 269-273

* Trial 2 (n=1359): Lancet, 2002, 360:1803-10

¹ Not recorded in Trial 1

² Not recorded in Trial 2

³ Delay defined as more than 7 days.

These undesirable effects usually disappear within 48 hours after the intake of Norlevo 1.5 mg. Breast tenderness, spotting and irregular bleeding are reported in up to 30 percent of patients and can last until the next menstrual period which can be delayed.

Cutaneous hypersensitivity reactions have been reported after the intake of Norlevo.

Cases of thromboembolic events have been reported during the postmarketing period (see section 4.4).

Serious 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.

Pharmacotherapeutic group: EMERGENCY CONTRACEPTIVES - G03AD01

The precise mode of action of Norlevo 1.5 mg is not known. At the used regimen, levonorgestrel is believed to suppress ovulation thus preventing fertilization if the intercourse has taken place in the preovulatory phase when the likelihood of fertilization is the highest. It could also prevent implantation. It is not effective once the process of implantation has begun. In clinical trials, Norlevo 1.5 mg has been shown to prevent 85% of expected pregnancies. Efficacy appears to decline with time after intercourse (95% within 24 hours, 85 % 24-48 hours, 58% if used between 48 and 72 hours). Efficacy after 72 hours is unknown.

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

Bioavailability of oral levonorgestrel is approximately 100 percent. In the plasma, it is strongly bound to SHBG. Levonorgestrel is eliminated via kidney (60-80%) and liver (40-50%).

After oral administration of 1.5 mg levonorgestrel, the plasma terminal half-life of the product is estimated to 43 hours. The maximal plasma concentration of levonorgestrel (approximately 40 nmol/l) is reached within 3 hours. Levonorgestrel is hydroxylated in the liver and the metabolites are excreted as glucuronide conjugates.

Nonclinical data reveal no special hazard for humans, beyond the information included in other sections of the SPC. Animal experiments with levonorgestrel have shown virilization of female fetuses at high doses.

A preclinical study conducted in mice showed no effect on fertility in the progeny of treated dams. Two studies investigating the consequence of exposure to levonorgestrel on the development of pre-embryos before implantation, showed that levonorgestrel had no adverse effects on fertilisation and the in vitro growth of mouse pre-embryos.

Lactose monohydrate,

Maize starch,

Povidone,

Colloidal anhydrous silica,

Magnesium stearate.

Not applicable

3 years

Keep the blister in the outer carton in order to protect from light.

PVC/PE/PVDC/Aluminium blister of 1 tablet.

Pack sizes with 1 tablet and 5 10, 25 or 50 tablets as hospital packs only.

Not all pack sizes may be marketed.

No special requirements.

Laboratoire HRA Pharma

15, rue Béranger

75003 Paris

France

PA 1166/2/1

Date of first authorisation: 26 August 2005

Date of last renewal: 19 April 2009

July 2011