Debunica 75 Microgram Film-Coated Tablets
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Debunica 75 microgram Film-coated Tablets
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Each film-coated tablet contains 75 microgram of desogestrel
Excipients with known effects: Lactose monohydrate 55 mg, soybean oil
(maximum 0.026 mg).
For a full list of excipients, see section 6.1.
[To be completed nationally]
3 PHARMACEUTICAL FORM
Film-coated tablet.
White, round.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Oral contraception
4.2 Posology and method of administration
Route of administration: oral use How to use <invented name>
Tablets must be taken every day at about the same time so that the interval between two tablets always is 24 hours. The first tablet should be taken on the first day of menstrual bleeding. Thereafter one tablet each day is to be taken continuously, without taking any notice on possible bleeding. A new blister is started directly the day after the previous one.
How to start <invented name>
No preceding hormonal contraceptive use Tin the past month]
Tablet taking has to start on day 1 of the woman’s natural cycle (day 1 is the first day of her menstrual bleeding).
Starting on days 2-5 is allowed, but during the first cycle a barrier method is recommended for the first 7 days of tablet-taking.
Following first-trimester abortion:
After first-trimester abortion it is recommended to start immediately. In that case there is no need to use an additional method of contraception.
Following delivery or second-trimester abortion:
Contraceptive treatment with <invented name> after delivery can be initiated before the menstruations have returned. If more than 21 days have elapsed pregnancy ought to be ruled out and an additional method of contraception should be used for the first week.
For additional information for breastfeeding women see Section 4.6.
How to start <invented name> when changing from other contraceptive methods
Changing from another combined oral contraceptive (combined hormonal contraceptive (COC), vaginal ring or transdermal patch)
The woman should start with <invented name> preferably on the day after the last active tablet (the last tablet containing the active substances) of her previous COC or on the day of removal of her vaginal ring or transdermal patch. In these cases, the use of an additional contraceptive is not necessary. Not all contraceptive methods may be available in all EU countries.
The woman may also start at the latest on the day following the usual tablet-free, patch-free, ring-free, or placebo tablet interval of her previous combined hormonal contraceptive, but during the first 7 days of tablet-taking an additional barrier method is recommended.
Changing from a progestogen-only method (minipill, injection, implant) or from a progestogen-releasing intrauterine system (IUS)
The woman may switch any day from the minipill (from an implant or the IUS on the day of its removal, from an injectable when the next injection would be due.
Management of missed tablets
Contraceptive protection may be reduced if more than 36 hours have elapsed between two tablets. If the user is less than 12 hours late in taking any tablet, the missed tablet should be taken as soon as it is remembered and the next tablet should be taken at the usual time. If she is more than 12 hours late, she should use an additional method of contraception for the next 7 days. If tablets were missed in the first week and intercourse took place in the week before the tablets were missed, the possibility of a pregnancy should be considered.
Advice in case of gastrointestinal disturbances
In case of severe gastrointestinal disturbance, absorption may not be complete and additional contraceptive measures should be taken. If vomiting occurs within 3-4 hours after tablet taking absorption may not be complete. In such an event the advice concerning missed tablets as given in section 4.2 is applicable
Treatment surveillance
Before prescription, a thorough case history should be taken and a thorough gynaecological examination is recommended to exclude pregnancy. Bleeding disturbances, such as oligomenorrhoea and amenorrhoea should be investigated before prescription. The interval between check-ups depends on the circumstances in each individual case. If the prescribed product may conceivably influence latent or manifest disease (see Section 4.4), the control examinations should be timed accordingly.
Despite the fact that <invented name> is taken regularly, bleeding disturbances may occur. If the bleeding is very frequent and irregular, another contraceptive method should be considered. If the symptoms persist, an organic cause should be ruled out.
Management of amenorrhoea during treatment depends on whether or not the tablets have been taken in accordance with the instructions and may include a pregnancy test.
The treatment should be stopped if a pregnancy occurs.
Women should be advised that <invented name> does not protect against HIV (AIDS) and other sexually transmitted diseases.
The safety and efficacy of desogestrel in adolescents below 18 years has not yet been established. No data are available.
4.3 Contraindications
■ Active venous thromboembolic disorder.
■ Presence or history of severe hepatic disease as long as liver function values have not returned to normal.
■ Known or suspected sex-steroid sensitive malignancies.
■ Undiagnosed vaginal bleeding.
■ Hypersensitivity to the active substance or to any of the excipients.
■ if you are allergic to peanut or soya.
4.4 Special warnings and precautions for use
If any of the conditions/risk factors mentioned below is present the benefits of progestogen use should be weighed against the possible risks for each individual woman and discussed with the woman before she decides to start Debunica. In the event of aggravation, exacerbation, or first appearance of any of these conditions, the woman should contact her physician. The physician should then decide on whether the use of Debunica should be discontinued.
The risk for breast cancer increases in general with increasing age. During the use of combined oral contraceptives (COCs) the risk for having breast cancer diagnosed is slightly increased. This increased risk disappears gradually within 10 years after discontinuation of COC use and is not related to the duration of use, but to the age of the woman when using the COC. The expected number of cases diagnosed per 10 000 women who use combined COCs (up to 10 years after stopping) relative to never users over the same period has been calculated for the respective age groups and is presented in the table below.
|
Age group |
Expected cases COC-users |
Expected cases nonusers |
|
16-19 years |
4.5 |
4 |
|
20-24 years |
17.5 |
16 |
|
25-29 years |
48.7 |
44 |
|
30-34 years |
110 |
100 |
|
35-39 years |
180 |
160 |
|
40-44 years |
260 |
230 |
The risk in users of progestogen-only contraceptives (POC), such as Debunica, is possibly of similar magnitude as that associated with COCs. However, for POCs the evidence is less conclusive. Compared to the risk of getting breast cancer even in life, the increased risk associated with COCs is low. The cases of breast cancer diagnosed in COC users tend to be less advanced than in those who have not used COCs. The increased risk in COC users may be due to an earlier diagnosis, biological effects of the pill or a combination of both.
Since a biological effect of progestogens on liver cancer cannot be excluded an individual benefit/risk assessment should be made in women with liver cancer.
When acute or chronic disturbances of liver function occur, the woman should be referred to a specialist for examination and advice.
Epidemiological investigations have associated the use of COCs with an increased incidence of venous thromboembolism (VTE, deep venous thrombosis and pulmonary embolism). Although the clinical relevance of this finding for desogestrel used as a contraceptive in the absence of an oestrogenic component is unknown, Debunica should be discontinued in the event of a thrombosis. Discontinuation of Debunica should also be considered in case of long-term immobilisation due to surgery or illness. Women with a history of thrombo-embolic disorders should be made aware of the possibility of a recurrence.
Although progestogens may have an effect on peripheral insulin resistance and glucose tolerance, there is no evidence for a need to alter the therapeutic regimen in diabetics using progestogen-only pills. However, diabetic patients should be carefully observed during the first months of use.
If sustained hypertension develops during the use of Debunica, or if a significant increase in blood pressure does not adequately respond to antihypertensive therapy, the discontinuation of Debunica should be considered.
Treatment with Debunica leads to decreased estradiol serum levels, to a level corresponding with the early follicular phase. It is as yet unknown whether the decrease has any clinically relevant effect on bone mineral density.
The protection with traditional progestogen-only pills against ectopic pregnancies is not as good as with combined oral contraceptives, which has been associated with the frequent occurrence of ovulations during the use of progestogenonly pills. Despite the fact that Debunica consistently inhibits ovulation, ectopic pregnancy should be taken into account in the differential diagnosis if the woman gets amenorrhoea or abdominal pain.
Chloasma may occasionally occur, especially in women with a history of chloasma gravidarum. Women with a tendency to chloasma should avoid exposure to the sun or ultraviolet radiation whilst taking Debunica.
The following conditions have been reported both during pregnancy and during sex steroid use, but an association with the use of progestogens has not been established: jaundice and/or pruritus related to cholestasis; gallstone formation; porphyria; systemic lupus erythematosus; haemolytic uraemic syndrome; Sydenham's chorea; herpes gestations; otosclerosis-related hearing loss; (hereditary) angioedema
Each tablet of this medicinal product contains 55.07 mg of lactose.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption not take this medicinal product.
4.5 Interaction with other medicinal products and other forms of interaction
Interactions between hormonal contraceptives and other medicinal products may lead to breakthrough bleeding and/or contraceptive failure. The following interactions have been reported in the literature (mainly with combined contraceptives but occasionally also with progestogen-only contraceptives).
Hepatic metabolism: Interactions can occur with medicinal products that induce microsomal enzymes, which can result in increased clearance of sex hormones (such as, hydantoins, (e.g. phenytoin), barbiturates (e.g. phenobarbital), primidone, carbamazepine, rifampicin, and possibly also for oxcarbazepine, topiramate, rifabutin, felbamate, ritonavir, nelfinavir, griseofulvin and products containing St. John's wort (Hypericum perforatum))
Maximal enzyme induction is not seen for 2-3 weeks, but may then be sustained for at least 4 weeks after cessation of drug therapy.
Women on treatment with any of these medicinal products should temporarily use a barrier method in addition to Debunica. With microsomal enzyme-inducing drugs, the barrier method should be used during the time of concomitant drug administration and for 28 days after discontinuation. For women on long-term treatment with hepatic enzyme inducers a non-hormonal method of contraception should be considered.
During the treatment with medical charcoal, the absorption of steroid in the tablet may be reduced and thereby the contraceptive efficacy. Under these circumstances the advice as given for missed pills in Section 4.2 is applicable.
Hormonal contraceptives may interfere with the metabolism of other drugs. Accordingly, plasma and tissue concentrations may either increase (e.g. cyclosporin) or decrease.
Note: The prescribing information of concomitant medications should be consulted to identify potential interactions.
Laboratory tests
Data obtained with COCs have been shown that contraceptive steroids may influence the results of certain laboratory tests, including biochemical parameters of liver, thyroid, adrenal and renal function, serum levels of (carrier) proteins, e.g. corticosteroid binding globulin and lipid/lipoprotein fractions, parameters of carbohydrate metabolism and parameters of coagulation and fibrinolysis. The changes generally remain within normal range. To what extent this also applies to progestogen-only contraceptives is not known.
4.6 Fertility, pregnancy and lactation
Pregnancy
Debunica is not indicated during pregnancy. When pregnancy occurs during treatment with Debunica, further intake should be stopped.
Animal studies have shown that very high doses of progestagenic substances might cause masculinisation of female foetuses.
Extensive epidemiological studies have revealed neither an increased risk of birth defects in children born to women who used COCs before pregnancy, nor a teratogenic effect when COCs were taken inadvertently during early pregnancy. Pharmacovigilance data collected with various desogestrel-containing combined COCs also do not indicate an increased risk.
Lactation
Debunica does not influence the production or the quality (protein, lactose, or fat concentrations) of breast milk. However, small amounts of etonogestrel are excreted in the breast milk. As a result, 0.01 - 0.05 microgram etonogestrel per kg body weight per day might be ingested by the child (based on an estimated milk ingestion of 150 ml/kg/day).
Limited long-term follow up data are available on children, whose mothers started using Debunica during the 4th to 8th weeks post-partum. They were breast-fed for 7 months and followed up to 1.5 uears (n=32) or to 2.5 years (n=14) of age. Evaluation of growth and physical and psychomotor development did not indicate any differences compared with nursing infants, whose mother used a copper IUD. Based on the available data Debunica may be used during lactation. The development and growth of a nursing infant, whose mother uses Debunica, should however, be carefully observed.
4.7 Effects on ability to drive and use machines
Debunica has no or negligible influence on the ability to drive and use machines.
4.8 Undesirable effects
The most commonly reported undesirable effect in the clinical trials is bleeding irregularity. Some kind of bleeding irregularity has been reported in up to 50% of women using Debunica. Since Debunica causes ovulation inhibition close to 100%, in contrast to other progestogen-only pills, irregular bleeding is more common than with other progestogen-only pills. In 20 - 30% of the women, bleeding may become more frequent, whereas in another 20% bleeding may become less frequent or totally absent. Vaginal bleeding may also be of longer duration. After a couple of months of treatment, bleedings tend to become less frequent. Information, counselling and a bleeding diary can improve the woman’s acceptance of the bleeding pattern.
The most commonly reported other side effects in the clinical trials with Debunica (>2.5%) were acne, mood changes, breast pain, nausea and weight increase. The side effects mentioned below have been judged by the investigators as having an established, probable or possible link to the treatment.
The adverse reactions are listed below classified by frequency according to the following criteria:
Very common: >1/10
Common: >1/100 to <1/10 Uncommon: >1/1,000 to <1/100 Rare: >1/10,000 to <1/1,000 Very rare: <1/10,000
Infections and infestations Uncommon: vaginal infection.
Psychiatric disorders
Common: mood altered, libido decreased
Nervous system disorders Common: headache
Eye disorders
Uncommon: contact lens intolerance
Gastrointestinal disorders Common: nausea Uncommon: vomiting
Skin and subcutaneous tissue disorders Common: acne.
Uncommon: alopecia.
Rare: rash, urticaria, erythema nodosum.
Reproductive system and breast disorders
Common: breast pain, menstruation irregular, amenorrhoea.
Uncommon: dysmenorrhoea, ovarian cyst
General disorders and administration site conditions Uncommon: fatigue
Investigations Common: weight increased
Breast discharge may occur during use of Debunica. On rare occasions, ectopic pregnancies have been reported (see Section 4.4).
In women using (combined) oral contraceptives a number of (serious) undesirable effects have been reported. These include venous thromboembolic disorders, arterial thromboembolic disorders, hormone-dependent tumours (e.g. liver tumours, breast cancer) and chloasma some of which are discussed in more detail in Section 4.4.
4.9 Overdose
There have been no reports of serious adverse effects from overdose. Symptoms that may be caused by overdose are nausea, vomiting and, in young girls, slight vaginal bleeding. There are no antidotes and the treatment is symptomatic.
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: hormonal contraceptives for systemic use,
ATC code: G03AC09.
<invented name> is a progestogen-only pill, which contains the progestogen desogestrel. Like other progestogen-only pills, <invented name> is best suited for use during breast feeding and for women who may not or do not want to use oestrogens. In contrast to traditional progestogen-only pills, the contraceptive effect of <invented name> is achieved primarily by inhibition of ovulation. Other effects include increased viscosity of the cervical mucus.
When studied for 2 cycles, using a definition of ovulation as a progesterone level greater than 16 nmol/L for 5 consecutive days, the ovulation incidence was found to be 1% (1/103) with a 95% confidence interval of 0.02% -5.29% in the ITT group (user and method failures). Ovulation inhibition was achieved from the first cycle of use. In this study, when <invented name> was discontinued after 2 cycles (56 continuous days) ovulation occurred on average after 17 days (range 7-30 days).
In a comparative efficacy trial (which allowed a maximum time of 3 hours for missed pills), the overall ITT Pearl-Index found for <invented name> was 0.4 (95% confidence interval 0.09% - 1.20%), compared to 1.6 (95% confidence interval 0.42% - 3.96%) for 30 pg levonorgestrel.
The Pearl-Index for <invented name> is comparable to the one historically found for COCs in the general COC-using population. Treatment with <invented name> leads to decreased estradiol levels, to a level corresponding to the early follicular phase. No clinically relevant effects on carbohydrate metabolism, lipid metabolism and haemostasis have been observed.
Paediatric population
No clinical data on efficacy and safety are available in adolescents below 18 years.
5.2 Pharmacokinetic properties
Absorption
After oral dosing of Debunica, desogestrel (DSG) is rapidly absorbed and converted into etonogestrel (ENG). Under steady-state conditions, peak serum levels are reached 1.8 hours after tablet-intake and the absolute bioavailability of ENG is approximately 70%.
Distribution
ENG is 95.5-99% bound to serum proteins, predominantly to albumin and to a lesser extent to SHBG.
Metabolism
DSG is metabolised via hydroxylation and dehydrogenation to the active metabolite ENG. ENG is metabolised via sulphate and glucuronide conjugation.
Elimination
ENG is eliminated with a mean half-life of approximately 30 hours, with no difference between single and multiple dosing. Steady-state levels in plasma are reached after 4-5 days. The serum clearance after IV administration of ENG is approximately 10 l per hour. Excretion of ENG and its metabolites either as free steroid or as conjugates, is with urine and faeces (ratio 1.5:1). In lactating women, ENG is excreted in breast milk with a milk/serum ratio of 0.37-0.55.
Based on these data and an estimated milk intake of 150 ml/kg/day, 0.01 - 0.05 microgram etonogestrel may be ingested by the infant.
5.3 Preclinical safety data
Toxicological studies did not reveal any effects other than those, that can be explained from the hormonal properties of desogestrel.
6.1 List of excipients Tablet core:
Lactose monohydrate Maize starch Povidone K30 d-a-Tocopherol Soybean oil
Silica, colloidal anhydrous Silica, colloidal hydrated Stearic acid Coating:
Hypromellose 2910 Polyethylene Glycol Titanium Dioxide (E 171)
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
Blisters of aluminium push-through foil and PVC/PVDC film.
Pack sizes:
1 x 28 film-coated tablets 3 x 28 film-coated tablets 6 x 28 film-coated tablets 13 x 28 film-coated tablets
Not all pack sizes may be marketed.
6.6 Special precautions for disposal
No special requirements.
7 MARKETING AUTHORISATION HOLDER
Effik
Batiment le Newton
9-11 Rue Jeanne Braconnier
Meudon la Foret
F-92366
France
MARKETING AUTHORISATION NUMBER(S)
8
PL 31625/0002
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
20/09/2012
10 DATE OF REVISION OF THE TEXT
26/07/2013