COMPOSITION Each tablet contains 1,50 mg of levonorgestrel.
PHARMACOLOGICAL CLASSIFICATION A. 21.8.2 Progesterones with or without oestrogens
Pharmacodynamics The precise mode of action of levonorgestrel is not known. Emergency hormonal contraception is thought to work mainly by preventing fertilisation by altering tubal transport of sperm and/or ova. It may also cause endometrial changes that discourage implantation. Efficacy: It has been estimated that levonorgestrel prevents 84% of expected pregnancies. At the recommended regimen, levonorgestrel is not expected to induce significant modification of blood clotting factors, and lipid and carbohydrate metabolism. Pharmacokinetics Orally administered levonorgestrel is rapidly and almost completely absorbed.
The results of a pharmacokinetic study carried out with 16 healthy women showed that following ingestion of one tablet of levonorgestrel, maximum drug serum level of 18,5 ng/mL was found at 2 hours. The mean value of area under the levonorgestrel concentration-time curve (0-infinity) was calculated as 310,2 ng.h/mL. After reaching maximum serum levels, concentration of levonorgestrel decreased with 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 presented as free steroid, but 65% are specifically bound to SHBG.
Following ingestion of one tablet of levonorgestrel the mean value of SHBG was about 40 nmol/L. Serum levels of SHBG tend to stay at these levels (or slightly increased) up to 24 hours, and then gradually decrease to reach levels of approximately 30 nmol/L at 192 hours.
The absolute bioavailability of levonorgestrel was determined to be almost 100% of the dose administered.
INDICATIONS Emergency contraception within 72 hours of unprotected sexual intercourse or failure of a contraceptive method.
Hypersensitivity to the active substance levonorgestrel or to any of the excipients.
Severe hepatic insufficiency.
Pregnancy or suspected pregnancy (see Pregnancy and Lactation).
WARNINGS Emergency contraception is an occasional method to be used in an emergency situation only. It should in no instance replace a regular contraceptive method. ESCAPELLE 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 ESCAPELLE 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 investigated. If pregnancy occurs with treatment with ESCAPELLE, the possibility of an ectopic pregnancy should be considered, especially in those women who present with abdominal/pelvic pain or collapse and those with a history of ectopic pregnancy, fallopian tube surgery or pelvic inflammatory disease.
INTERACTIONS The metabolism of ESCAPELLE is enhanced by concomitant use of liver enzyme inducers. Medicines 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. Johns Wort), rifampicin, ritonavir, rifabutin, griseofulvin, ampicillin and other antibiotics, including medicines used to treat tuberculosis, cyclosporine (see below).
The requirement for oral antidiabetics and insulin can change as a result of an effect on glucose tolerance.
Medicines containing levonorgestrel as in ESCAPELLE may increase the risk of cyclosporine toxicity due to possible inhibition of cyclosporine metabolism.
PREGNANCY AND LACTATION
Pregnancy ESCAPELLE should not be given to pregnant women and will not interrupt the pregnancy. In case of failure of this emergency contraception with developing pregnancy, epidemiological studies indicate no adverse effects of progestogens on the foetus.
In case of unprotected coitus more than 72 hours earlier, the patient may be pregnant. In these cases, pregnancy should be investigated. Lactation About 0,1% of the maternal ESCAPELLE dose can be transferred via milk to the nursed infant. Potential exposure of an infant to ESCAPELLE can be reduced if the breast-feeding woman takes the tablet immediately after feeding and avoids nursing following ESCAPELLE administration.
DOSAGE AND DIRECTIONS FOR USE For oral administration. The tablet should be taken no later than 72 hours after unprotected intercourse. If the patient vomits within three to four hours of taking the tablet, another tablet should be taken immediately. ESCAPELLE 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) until the next menstrual period starts. The use of ESCAPELLE does not contraindicate the continuation of regular hormonal contraception. Children: ESCAPELLE is not recommended in children.
Very limited data are available in women under 16 years of age.
SIDE EFFECTS AND SPECIAL PRECAUTIONS
Side Effects Nervous system disorders Very common (>1/10): Headache. Common (>1/100, <1/10): Dizziness. Gastrointestinal disorders Very common (>1/10): Nausea, lower abdominal pain. Common (>1/100, <1/10): Diarrhoea, vomiting. Reproductive system and breast disorders Very common (>1/10): Bleeding disturbances. Common (>1/100, <1/10): Breast tenderness, delay of menses more than 7 days.
Bleeding patterns may be temporarily disturbed. 78% of women will have their next menstrual period within 5 days of expected time.
If the next menstrual period is more than 5 days overdue pregnancy should be investigated. General disorders Very common (>1/10): Fatigue. Special precautions ESCAPELLE is not recommended in patients with severe hepatic dysfunction.
Severe malabsorption syndromes, such as Crohns disease, might impair the efficacy of ESCAPELLE.
After ESCAPELLE 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. It is recommended to make a medical appointment 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 ESCAPELLE 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.
ESCAPELLE 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.
KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT 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 and supportive.
IDENTIFICATION Almost white, flat, rimmed tablet of about 8 mm diameter, with an impression mark of G00 on one side.
PRESENTATION The folded carton of ESCAPELLE contains one aluminium/PVC blister of one tablet.
STORAGE INSTRUCTIONS Store below 25ºC. Protect from light.
Store in the original container until required for use.
KEEP OUT OF REACH OF CHILDREN.
REGISTRATION NUMBER 41/21.8.2/0021
NAME AND BUSINESS ADDRESS OF THE HOLDER OF THE CERTIFICATE OF REGISTRATION Pharmaplan (Pty) Ltd
106 16th Road
DATE OF PUBLICATION OF THE PACKAGE INSERT 5 July 2007
Updated on this site: May 2014 Source: Pharmaceutical Industry