- 1. Name of the medicinal product
- 2. Qualitative and quantitative composition
- 3. Pharmaceutical form
- 4. Clinical particulars
- 4.1 Therapeutic indications
- 4.2 Posology and method of administration
- 4.3 Contraindications
- 4.4 Special warnings and precautions for use
- 4.5 Interaction with other medicinal products and other forms of interaction
- 4.6 Fertility, pregnancy and lactation
- 4.7 Effects on ability to drive and use machines
- 4.8 Undesirable effects
- 4.9 Overdose
- 5. Pharmacological properties
- 5.1 Pharmacodynamic properties
- 5.2 Pharmacokinetic properties
- 5.3 Preclinical safety data
- 6. Pharmaceutical particulars
- 6.1 List of excipients
- 6.2 Incompatibilities
- 6.3 Shelf life
- 6.4 Special precautions for storage
- 6.5 Nature and contents of container
- 6.6 Special precautions for disposal and other handling
- 7. Marketing authorisation holder
- 8. Marketing authorisation number(s)
- 9. Date of first authorisation/renewal of the authorisation
- 10. Date of revision of the text
PosologyTablets 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 Cerelle
No preceding hormonal contraceptive use [in 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 abortionAfter 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 abortionContraceptive treatment with Cerelle 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 Cerelle when changing from other contraceptive methods
Changing from a combined hormonal contraceptive (combined oral contraceptive (COC), vaginal ring, or transdermal patch)The woman should start Cerelle 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.The woman may also start at the latest on the day following the usual tablet-free, patch-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 (mini pill, injection, implant) or from a progestogen-releasing intrauterine system (IUS)The woman may switch any day from 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 tabletContraceptive 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 disturbancesIn case of severe gastro-intestinal 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 subsection Management of missed tablet is applicable.
Treatment surveillanceBefore 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 Cerelle is taken regularly, bleeding disturbances may occur. If 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 Cerelle does not protect against HIV (AIDS) and other sexually transmitted diseases.
Paediatric populationThe safety and efficacy of desogestrel in adolescents below 18 years has not yet been established. No data are available.
|Age group||Expected cases combined OC-users||Expected cases non- users|
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, Cerelle should be discontinued in the event of a thrombosis.Discontinuation of Cerelle 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 a sustained hypertension develops during the use of Cerelle, or if a significant increase in blood pressure does not adequately respond to antihypertensive therapy, the discontinuation of Cerelle should be considered.Treatment with Cerelle 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 progestogen-only pills. Despite the fact that Cerelle 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 Cerelle.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 gestationis; otosclerosis-related hearing loss; (hereditary) angioedema.Cerelle contains lactose (52.34 mg) and therefore should not be administered to . patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Laboratory testsData obtained with COCs have 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 the normal range. To what extent this also applies to progestogen-only contraceptives is not known.
|System Organ Class (MedDRA)*||Frequency of adverse reactions|
|Common ≥ 1/100 to <1/10||Uncommon ≥1/1,000 to <1/100||Rare ≥1/10,000 to <1/1,000|
|Infections and infestations||Vaginal infection|
|Psychiatric disorders||Mood altered Libido decreased Depressed mood|
|Nervous system disorders||Headache|
|Eye disorders||Contact lens intolerance|
|Skin and subcutaneous tissue disorders||Acne||Alopecia||Rash, Urticaria, Erythema nodosum|
|Reproductive system and breast disorders||Breast pain, Menstruation irregular, Amenorrhoea||Dysmenorrhoea, Ovarian cyst|
|General disorders and administration site condition||Fatigue|
Mechanism of actionLike other progestogen-only pills, Cerelle 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 Cerelle 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 intention-to-treat group (user and method failures). Ovulation inhibition was achieved from the first cycle of use. In this study, when desogestrel 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 intention-to-treat Pearl-Index found for desogestrel was 0.4 (95% confidence interval 0.09 - 1.20), compared to 1.6 (95% confidence interval 0.42 - 3.96) for 30 μg levonorgestrel.The Pearl-Index for desogestrel is comparable to the one historically found for COCs in the general OC-using population.Treatment with desogestrel 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 populationNo clinical data on efficacy and safety are available in adolescents below 18 years.
AbsorptionAfter oral dosing of desogestrel is rapidly absorbed and converted into etonorgestrel. Under steady- state conditions, peak serum levels are reached 1.8 hours after tablet-intake and the absolute bioavailability of etonorgestrel is approximately 70%.
DistributionEtonorgestrel is 95.5-99% bound to serum proteins, predominantly to albumin and to a lesser extent to sex hormone binding globuline(SHBG).
BiotransformationDesogestrel is metabolised via hydroxylation and dehydrogenation to the active metabolite etonorgestrel. Etonorgestrel is metabolised via sulphate and glucuronide conjugation.
EliminationEtonorgestrel 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 i.v. administration of etonorgestrel is approximately 10 l per hour. Excretion of etonorgestrel and its metabolites either as free steroid or as conjugates, is with urine and faeces (ratio 1.5:1). In lactating women, etonorgestrel 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 etonorgestrel maybe ingested by the infant.
Tablet core:Lactose monohydrate, Potato starch, Povidone K-30,Silica, colloidal anhydrous, Stearic acid,all-rac-α-tocopherolTablet coat: Poly[vinyl alcohol], Titanium dioxide (E171), Macrogol 3000,Talc
Consilient Health Ltd
No. 1 Church Road, Richmond upon Thames, Surrey, TW9 2QE, UK
+44(0)20 3751 1889
+44(0) 20 3751 1888