Ezinelle 1.5 Mg Tablet
Out of date information, search anotherSUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Ezinelle 1.5 mg tablet
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 1.5 mg of levonorgestrel.
Excipient with known effect:
Each tablet contains 154 mg lactose monohydrate For the full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Tablet
The tablet is a round, white to off-white, uncoated flat tablet debossed ‘145’ 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.
4.2 Posology and method of administration
Posology
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.
Ezinelle 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 Ezinelle does not contraindicate the continuation of regular hormonal contraception.
Paediatric population: Ezinelle is not recommended in children. Very limited data are available in women under 16 years of age.
Method of administration Ezinelle should be taken orally.
4.3 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 Ezinelle 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 Ezinelle, the possibility of an ectopic pregnancy should be considered. The absolute risk of ectopic pregnancy is likely to be low, as Ezinelle prevents ovulation and fertilisation. Ectopic pregnancy may continue, despite the occurrence of uterine bleeding.
Therefore, Ezinelle is not recommended for patients who are at risk of ectopic pregnancy (previous history of salpingitis or of ectopic pregnancy).
Ezinelle is not recommended in patients with severe hepatic dysfunction.
Severe malabsorption syndromes, such as Crohn's disease, might impair the efficacy of Ezinelle.
Ezinelle 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 Ezinelle 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 Ezinelle 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.
Limited and inconclusive data suggest that there may be reduced efficacy of Ezinelle 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.
Ezinelle 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 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 ciclosporin toxicity due to possible inhibition of ciclosporin metabolism.
4.6 Fertility, pregnancy and lactation
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^ however, there are no fertility data in the long term.
Pregnancy
Ezinelle 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 foetus 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 following Ezinelle administration.
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 reported.
4.8 Undesirable effects
The most commonly reported undesirable effect was nausea. The following undesirable effects were observed in two different studies.
Very common (> 1/10), Common (> 1/100, <1/10), Uncommon (> 1/1,000, <1/100), Rare (> 1/10,000, <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 | |
|
Very common (> 1/10) |
Common (> 1/100, <1/10) | |
|
Nervous system disorders |
Headache |
Dizziness |
|
Gastrointestinal disorders |
Nausea, abdominal pain |
Diarrhoea, vomiting |
|
Reproductive system and breast disorders |
Bleeding not related to menses1 |
Delay of menses more than 7 days2 Irregular menstruation Breast tenderness |
|
General disorders and administration site conditions |
Fatigue | |
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: Emergency contraceptives, ATC code: G03AD01
Mechanism of action
The precise mode of action of Ezinelle is not known.
Pharmacodynamic effects
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. Ezinelle is not effective once the process of implantation has begun.
Clinical efficacy and safety
Results from a recent clinical study (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).
At the recommended regimen, levonorgestrel is not expected to induce significant modification of blood clotting factors, and lipid and carbohydrate metabolism.
There is limited and inconclusive data on the effect of high body weight/high BMI on the contraceptive efficacy. In three WHO studies no trend for a reduced efficacy with increasing body weight/BMI was observed (Table 1), whereas in the two other studies (Creinin et al., 2006 and Glasier et al., 2010) a reduced contraceptive efficacy was observed with increasing body weight or BMI (Table 2). Both meta-analyses excluded intake later than 72 hours after unprotected intercourse (i.e. off-label use of levonorgestrel) and women who had further acts of unprotected intercourse.
Table 1: Meta-analysis on three WHO studies (Von Hertzen et al., 1998 and 2002; Dada et al., 2010)
|
BMI (kg/m2) |
Underweight 0 - 18.5 |
Normal 18.5 - 25 |
Overweight 25 - 30 |
Obese > 30 |
|
N total |
600 |
3952 |
1051 |
256 |
|
N pregnancies |
11 |
39 |
6 |
3 |
|
Pregnancy rate |
1.83% |
0.99% |
0.57% |
1.17% |
|
Confidence interval |
0.92 - 3.26 |
0.70 - 1.35 |
0.21 - 1.24 |
0.24 - 3.39 |
Table 2: Meta-analysis on studies of Creinin et al., 2006 and Glasier et al., 2010
|
BMI (kg/m2) |
Underweight 0 - 18.5 |
Normal 18.5 - 25 |
Overweight 25 - 30 |
Obese > 30 |
|
N total |
64 |
933 |
339 |
212 |
|
N pregnancies |
1 |
9 |
8 |
11 |
|
Pregnancy rate |
1.56% |
0.96% |
2.36% |
5.19% |
|
Confidence interval |
0.04 - 8.40 |
0.44 - 1.82 |
1.02 - 4.60 |
2.62 - 9.09 |
Pharmacokinetic properties
5.2
Levonorgestrel: orally administered levonorgestrel is rapidly and almost completely absorbed.
Following ingestion of one tablet of levonorgestrel 1.5 mg 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.
5.3 Preclinical safety data
Animal experiments with levonorgestrel have shown virilisation of female foetuses at high doses.
Preclinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeat dose toxicity, mutagenicity and carcinogenicity potential, beyond the information included in other sections of the SmPC.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Povidone K-25 Lactose monohydrate Maize starch
Silica, colloidal anhydrous Magnesium stearate
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
2 years
6.4 Special precautions for storage
This medicinal product does not require any special storage conditions.
6.5 Nature and contents of container
Blister composed of PVC film coated with PVDC and aluminium foil. Pack size: 1 tablet
6.6 Special precautions for disposal
No special requirements.
7 MARKETING AUTHORISATION HOLDER
Generics (UK) Ltd t/a Mylan
Station Close
Potters Bar
Hertfordshire
EN6 1TL
United Kingdom
MARKETING AUTHORISATION NUMBER(S)
8
PL 04569/1486
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
13/05/2015
10 DATE OF REVISION OF THE TEXT
13/05/2015
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.