NORLEVO Tablet Ref.[51098] Active ingredients: Levonorgestrel

Emergency contraception is an occasional method. It should in no instance replace a regular contraceptive method. Emergency contraception does not prevent a pregnancy to occur in every instance, especially if uncertainty about the timing of the unprotected intercourse. In case of doubt (menstrual periods delayed by more than five days or abnormal bleeding at the expected date of menstrual periods, symptoms of pregnancy), it is mandatory to check the absence of pregnancy by performing a pregnancy test.

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

Limited and inconclusive data suggest that there may be reduced efficacy of NorLevo with increasing body weight or body mass index (BMI) (see section 5.1). In all women, emergency contraception should be taken as soon as possible after unprotected intercourse, regardless of the woman’s body weight or BMI.

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

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

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 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 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.

Concomitant use of NorLevo and drugs containing ulipristal acetate is not recommended (see section 4.5).

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 concomitant use of liver enzyme inducers, mainly CYP3A4 enzyme inducers. Concomitant administration of efavirenz has been found to reduce plasma levels of levonorgestrel (AUC) by around 50%.

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

For women who have used enzyme-inducing drugs in the past 4 weeks and need emergency contraception, the use of non-hormonal emergency contraception (i.e. a Cu-IUD) should be considered. Taking a double dose of levonorgestrel (i.e. 3000 mcg within 72 hours after the unprotected intercourse) is an option for women who are unable or unwilling to use a Cu-IUD, although this specific combination (a double dose of levonorgestrel during concomitant use of an enzyme inducer) has not been studied.

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

Ulipristal acetate is a progesterone receptor modulator that may interact with the progestational activity of levonorgestrel. Therefore the concomitant use of levonorgestrel and drugs containing ulipristal acetate is not recommended.

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.

Breast-feeding

Levonorgestrel is excreted into breast milk. Therefore, it is suggested to breastfeed immediately before taking NorLevo and to skip nursing at least 8 hours following NorLevo 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
^* Trial 3 (n=1117): Lancet 2010; 375:555-62
^* Trial 4 (n=840): Obstetrics and Gynecology 2006; 108:1089-1097
¹ Not recorded in Trial 1.
² Not recorded in Trial 2.
³ Not reported in Trial 1 or 2.
⁴ Delay defined as more than 7 days.

These undesirable effects usually disappear within 48 hours after the intake of NorLevo. 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.

Hypersensitivity reactions such as pharyngeal/face oedema and cutaneous reactions have been reported after the intake of NorLevo.

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

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: HPRA Pharmacovigilance, Earlsfort Terrace, IRL – Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517; Website: www.hpra.ie; e-mail: medsafety@hpra.ie.

Not applicable.