The tablet contains 1500 microgram of levonorgestrel

For excipients see 6.1

Tablet

The tablet is round and white.

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

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.

Levonelle 1500 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 barrier method (e.g. condom, diaphragm or cap) until the next menstrual period starts. The use of Levonelle 1500 does not contraindicate the continuation of regular hormonal contraception.

Children: Levonelle 1500 is not recommended in children.

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

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

Levonelle 1500 is not recommended in patients with severe hepatic dysfunction.

Severe malabsorption syndromes, such as Crohn's disease, might impair the efficacy of Levonelle 1500.

Levonelle 1500 contains 142.5 mg lactose. This should be taken into account in women with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.

After Levonelle 1500 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 Levonelle 1500 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.

Levonelle 1500 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.

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 containing medication 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 cyclosporin toxicity due to possible inhibition of cyclosporin metabolism.

Pregnancy

Levonelle 1500 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.).

Lactation

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 following Levonelle 1500 administration.

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

The most commonly reported undesirable effect was nausea. The following undesirable effects were observed in two different studies ^{1, 2}.

¹ Task Force on post-ovulatory Methods of Fertility Regulation. Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception. Lancet, 1998; 352:428-433

(n=977; data on 0.75 mg levonorgestrel tablet taken as two doses with a 12-hour interval)

² Hertzen et al. Low dose mifepristone and two regimens of levonorgestrel for emergency contraception: a WHO multicentre randomised trial. Lancet. 2002; 360:1803-1810

(n=1,359; data on Levonelle 1500 taken as a single dose of 1.5 mg)

^* n=1,011 out of 1,359

^** n=1,334 out of 1,359

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.

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.

PROGESTOGENS

G03AC03

The precise mode of action of Levonelle 1500 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. It may also cause endometrial changes that discourage implantation. Levonelle 1500 is not effective once the process of implantation has begun.

Efficacy. It was estimated from the results of an earlier clinical study (Lancet, 1998; 352: 428-433), that levonorgestrel, taken as two 750 microgram doses with a 12 hour interval, prevents 85% of expected pregnancies. Efficacy appears to decline with time of start of treatment after intercourse (95% within 24 hours, 85% 24-48 hours, 58% if started between 48 and 72 hours)

Results from a recent clinical study (Lancet 2002; 360: 1803-1810) showed that a 1500 microgram single dose of Levonelle 1500 (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).

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

Levonorgestrel: orally administered levonorgestrel is rapidly and almost completely absorbed.

The results of a pharmacokinetic study carried out with 15 healthy women showed that following ingestion of one tablet of Levonelle 1500 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.

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.

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

Potato starch, maize starch, colloidal silica anhydrous, magnesium stearate, talc, lactose monohydrate.

Not applicable.

4 years.

Store in original container.

The folded carton of Levonelle 1500 contains one blister of one tablet. The blister is made of aluminium/PVC.

No special requirements.

Medimpex UK Limited

127 Shirland Road

London W9 2EP

United Kingdom

PL05276/0019

14^th June 2004

9 February 2007