Levonorgestrel 1.5 Mg Tablets
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Levonorgestrel 1.5 mg Tablet
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 1.5 mg of Levonorgestrel.
Excipients with known effects: each tablet contains 154 mg of lactose monohydrate. For the full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Tablet
Round, white to off-white, 8.00 mm, uncoated flat tablets debossed ‘145’ on one side and other side plain.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Emergency contraception within 72 hours after an unprotected sexual intercourse, or when a contraceptive method failed.
4.2 Posology and method of administration
For oral use.
The treatment requires taking a tablet. The sooner after unprotected intercourse treatment is started, the greater the efficacy of method. The tablet should be taken as soon as possible, preferably within 12 hours but not more than 72 hours (3 days) after unprotected intercourse.
Levonorgestrel 1.5 mg can be taken at any time during the menstrual cycle.
If vomiting occurs within 3 hours after tablet intake, an additional one tablet should be taken immediately.
After using emergency contraception, it is recommended to use a local contraceptive (condom, spermicide, cervical cap) until the next menstrual period begins. The use of
Levonorgestrel 1.5 mg is not a contraindication to the continued use of regular hormonal contraception.
Paediatric population:
Levonorgestrel is not recommended in children.
Very limited data are available in women under 16 years of age.
4.3 Contraindications
Hypersensitivity to the active substance levonorgestrel or any of the excipients.
4.4 Special warnings and precautions for use
Concomitant use of Levonorgestrel 1.5 mg and medicines containing ulipristal acetate is not recommended (see section 4.5).
Emergency contraception is an occasional method. It should in no instance replace a regular contraceptive method. Emergency contraception does not always prevent a pregnancy and especially if uncertainty about the timing of unprotected intercourse. In case of uncertainty (about menstrual bleeding is more than 5 days late or abnormal bleeding at the expected date of menstruation or symptoms suggestive of pregnancy), the pregnancy test should be performed to rule out pregnancy.
If the women is more than 72 hours earlier had unprotected intercourse in the same menstrual cycle, conception may have occurred. Treatment with Levonorgestrel 1.5 mg after the second act of intercourse therefore may not be effective to prevent pregnancy.
Limited and inconclusive data suggest that there may be reduced efficacy of <invented name> 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 Levonorgestrel 1.5 mg, the possibility of an ectopic pregnancy should be considered. The absolute risk of ectopic pregnancy is probably low because Levonorgestrel 1.5 mg prevents ovulation and fertilization. An ectopic pregnancy may continue, despite the occurrence of a uterine bleeding. Therefore, Levonorgestrel 1.5 mg Tablet is not recommended for patients who are at risk of an ectopic pregnancy (previous history of salpingitis or of ectopic pregnancy).
Levonorgestrel 1.5 mg Tablet is not recommended in patients with severe hepatic impairment. Severe malabsorption syndromes, such as Crohn's disease, may reduce the effect of Levonorgestrel1.5 mg Tablet.
Cases of thromboembolic events have been reported after Levonorgestrel 1.5 mg Tablet intake. The possibility of occurrence of thromboembolic event should be considered in women with other pre-existing thromboembolic risk factor(s), especially personal or family history suggesting thrombophilia.
After Levonorgestrel 1.5 mg Tablet 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 Levonorgestrel 1.5 mg Tablet after regular hormonal contraception, pregnancy should be ruled out.
Repeated administration within a menstrual cycle is not recommended due to the undesirable high amount of hormones that the patient receives and the possibility of severe disturbances of the cycle. Women who present for repeated courses of emergency contraception should advised to use a contraceptive method for the long term.
The use of emergency contraception does not replace the necessary precautions against sexually transmitted diseases.
This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
4.5 Interaction with other medicinal products and other forms of interaction
Combinations to be taken into account:
The metabolism of levonorgestrel is enhanced by the concomitant use of hepatic enzymes: anticonvulsant (phenobarbital, phenytoin, primidone, carbamazepine), rifabutin, rifampicin, griseofulvin, ritonavir, Hypericum perforatum (St. John's Wort). The efficacy of Levonorgestrel 1.5 mg may reduced in case of simultaneous intake of these drugs.
Ulipristal acetate is a progesterone receptor modulator that may interact with the progestational activity of levonorgestrel. Therefore the concomitant use of levonorgestrel and medicines containing ulipristal acetate is not recommended.
Medicines containing levonorgestrel may increase the risk of cyclosporin toxicity due to possible inhibition of cyclosporin metabolism.
4.6 Fertility, pregnancy and lactation
Pregnancy
This medicine may not interrupt an existing pregnancy.
In case of failure of this contraceptive with persisting pregnancy, epidemiological studies indicate no malformative effects of progestins on the foetus.
Nothing is known about the consequences for the child if doses higher than 1.5 mg of levonorgestrel be taken.
Breast-feeding
Levonorgestrel is excreted into breast milk. Therefore, it is suggested that to breastfeed before taking the Levonorgestrel 1.5 mg tablet and to skip nursing at least 8 hours following Levonorgestrel 1.5 mg Tablet administration.
Fertility
After treatment with Levonorgestrel 1.5 mg Tablet emergency contraception it is likely that you are fertile again soon, therefore another method of contraception should be continued or be initiated as soon as possible after using Levonorgestrel 1.5 mg Tablet for continuous protection against pregnancy care.
Clinical experience does not indicate any effects on fertility in humans after use of levonorgestrel. Also non-clinical studies show no evidence of harmful effects in animals
(See section 5.3).
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. Nevertheless, if women experience fatigue and dizziness after taking Levonorgestrel 1.5 mg Tablet, they should not drive or use machines.
4.8 Undesirable effects
The following table shows the incidence of adverse events reported in clinical trials* after administration of Levonorgestrel 1.5 mg Tablet.
|
Body System |
Frequency of adverse reactions | |
|
Very common (>1/10) |
Common (>1/100 to <1/10) | |
|
Nervous system disorders |
Dizziness Headache | |
|
Gastrointestinal disorders |
Nausea Low abdominal pain |
Diarrhoea1 |
|
Reproductive system and breast disorders |
Breast tenderness Delay of menses3 Heavy menses2 Bleeding1 |
Vomiting |
|
General disorders and administration site conditions |
Fatigue1 | |
* 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 intake of Levonorgestrel 1.5 mg Tablet. Breast tenderness, spotting and irregular bleeding are reported in up to 30 percent of the patients and can last until the next menstrual period which may be delayed.
Cutaneous hypersensitivity reactions have been reported after the intake of Levonorgestrel 1.5 mg Tablet.
Cases of thromboembolic events have been reported during the posmarketing period (see section 4.4).
Reporting side effects
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 side effects have not been reported following acute ingestion of large doses of oral contraception. Overdose may cause nausea and withdrawal bleeding may occur. There is no specific antidote and treatment should focus on the symptoms.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Emergency Contraceptive - G03AD01.
The primary mechanism of action is blockade and/or delay of ovulation via suppression of the luteinizing hormone (LH) peak. Levonorgestrel interferes with the ovulatory process only if it is administered before the onset of the LH surge. Levonorgestrel has no emergency contraceptive effect when administered later in the cycle.
In clinical trials, the proportion of pregnancies avoided after the use of levonorgestrel varied from 52% (Glasier, 2010) to 85% (Von Hertzen, 2002) of expected pregnancies. Efficacy appears to decline with time after intercourse.
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 |
1.83% |
0.99% |
0.57% |
1.17% |
|
rate | ||||
|
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 |
5.2 Pharmacokinetic properties
Absorption
Orally administered levonorgestrel is rapidly and almost completely absorbed.
Distribution
Following ingestion of one tablet of Levonorgestrel 1.5 mg Tablet maximum drug serum levels of levonorgestrel of 18.5ng/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 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.
Biotransformation
The biotransformation follows the known pathways of steroid metabolism; the levonorgestrel is hydroxylated in the liver.
No pharmacologically active metabolites are known.
Elimination
Levonorgestrel metabolites, as glucuronide conjugates, are excreted in about equal proportions with urine and faeces.
5.3 Preclinical safety data
Preclinical data reveal no special hazard for humans, beyond the information included in other sections of the SPC. Animal studies with levonorgestrel have shown masculinisation of female fetuses at high doses.
Preclinical studies in mice showed no effect on fertility in the offspring of treated females. Two studies of the effects on the development of preembryo before implantation showed that levonorgestrel had no adverse effects on reproduction or growth of mouse preembryo in vitro.
6.1 List of excipients
Lactose monohydrate,
Maize starch,
Povidone (E1201),
Silica, colloidal anhydrous (E551), Magnesium stearate (E572)
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
PVC/ PVDC Aluminum-blister containing one tablet. The blister is packed in a carton.
6.6 Special precautions for disposal
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help to protect the environment.
7 MARKETING AUTHORISATION HOLDER
Famy Care Europe Ltd.
One Wood Street,
London, EC2V 7WS United Kingdom
8
MARKETING AUTHORISATION NUMBER(S)
PL 32821/0053
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
29/08/2014
10 DATE OF REVISION OF THE TEXT
19/02/2015