Desogestrel 75 microgram film-coated tablets – Summary of Product Characteristics (SmPC) for healthcare professionals

1 NAME OF THE MEDICINAL PRODUCT

Desogestrel 75 microgram film-coated tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each film-coated tablet contains 75 microgram of desogestrel

Excipients with known effect: Lactose monohydrate 55 mg, soybean oil (maximum 0.026 mg).

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Film-coated tablet.

White, round.

4.1 Therapeutic indications

Desogestrel is indicated as an oral contraceptive in women of childbearing age.

4.2 Posology and method of administration.

Posology

To prevent pregnancy, Desogestrel must be used as directed (see 'How to take Desogestrel ' and 'How to start Desogestrel ').

Special populations

Renal impairment

No clinical studies have been performed in patients with renal impairment.

Hepatic impairment

No clinical studies have been performed in patients with hepatic insufficiency. Since the metabolism of steroid hormones might be impaired in patients with severe hepatic disease, the use of Desogestrel in these women is not indicated as long as liver function values have not returned to normal (see section 4.3).

Paediatric population

The safety and efficacy of Desogestrel in adolescents below 18 years has not been established. No data are available.

Method of administration

Oral use.

How to take Desogestrel 75 microgram film-coated tablets

Desogestrel 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 Desogestrel 75 microgram film-coated tablets

The woman should have none of the contraindications listed in section 4.3 and should be advised to consult with her physician if in doubt.

Any pre-existing bleeding abnormalities such as oligomenorrhoea and amenorrhoea should be investigated by a physician before starting Desogestrel in order that any underlying pathology (see section 4.4) can be managed and followed-up appropriately.

No contraceptive use [in the past month]

It is preferable to start Tablet taking 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 then a barrier method is recommended for the first 7 days of tablet-taking.

Following miscarriage or abortion:

After miscarriage or abortion, it is recommended to start taking Desogestrel immediately or within 5 days. In that case there is no need to use an additional method of contraception.

Following childbirth

The woman should be advised to start any day between day 1 and day 21 after delivery When starting later, she should be advised to additionally use a

barrier method until completion of the first 7 days of tablet-taking. However, if unprotected intercourse has already occurred, the woman should take a pregnancy test or talk to her physician before the actual start of Desogestrel.

For additional information for breastfeeding women, see Section 4.6.

Starting or resuming Desogestrel after emergency contraception use If a woman wishes to start taking Desogestrel after using emergency hormonal contraception, it is advisable to start tablet-taking on day 1 of the woman’s natural cycle.

If it is considered necessary to start sooner, or if Desogestrel is being resumed after inconsistent use, the following advice should be noted:

Levonorgestrel

Desogestrel can be started or restarted on the same day as emergency contraception containing levonorgestrel. Additional contraceptive measures (abstinence or barrier methods) are required for the first 7 days of Desogestrel use.

Ulipristal acetate

Desogestrel should be started or restarted no sooner than 5 days (120 hours) after emergency contraception containing ulipristal acetate, because the effectiveness of ulipristal can be reduced (see section 4.5). Additional contraceptive measures (abstinence or barrier methods) are required during the 5 days delay before starting or restarting Desogestrel and for an additional 7 days after starting or restarting Desogestrel (12 days in total).

Ulipristal acetate may conversely reduce the effectiveness of Desogestrel. Concomitant use

is therefore not recommended (see section 4.5).

How to start Desogestrel 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 with Desogestrel 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, 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, or on the next day the contraceptive 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 even if it leads to taking two tablets in one day. If she is more than 12 hours late from her usual taking time, the woman should immediately take the forgotten tablet and take the next tablet at the usual time, even if it leads to taking two tablets in one day If more than one tablet has been missed, only one of the missed tablets should be taken immediately. In addition, she should use an additional barrier method of contraception for the next 7 days. Missed Desogestrel 75 microgram film-coated tablets at any time in the cycle can reduce the efficacy of Desogestrel and risk pregnancy but missing a tablet in the first week after initiation of Desogestrel is an especially vulnerable time. The need for emergency contraception must be considered for any missed pills.

Advice in case of gastrointestinal disturbances

If vomiting occurs within 3-4 hours of tablet-taking, then the pill should be considered ‘missed’ and the advice for a missed tablet should be followed.

In case of severe or persistent gastrointestinal disturbance (vomiting or diarrhoea), absorption of Desogestrel may not be complete and contraceptive efficacy may be reduced. Additional contraceptive measures should be taken for the duration of the illness and for the first 7 days of normal tablet taking.

Regular screening

Women should be advised to continue to have regular smear tests (cervical screening) while taking Desogestrel. Women aged 50 years and above should be advised to attend for regular breast screening while women below 50 years should be advised to report any lump or change in their breast to their physician.

Women should be advised that to go for a check-up at a sexual health clinic as soon as they can if they are worried they may have a Sexually Transmitted Infection (STI). Many STIs, including HIV (AIDS), have no symptoms at all. Women can only know for sure that they do not have an STI if they get tested.

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 listed in section 6.1.
• Known allergy to peanut or soya.
• Meningioma or history of meningioma (see section 4.4)

4.4 Special warnings and precautions for use

Excluding pregnancy

Excluding pregnancy before starting Desogestrel

The woman should use a reliable method of contraception (current contraceptive or a barrier method) until the first day of her next period before starting Desogestrel tablet. She should be advised that if her menstrual period is already late or does not come when she expects it, she may be pregnant and she should do a pregnancy test (at least 3 weeks after the last episode of unprotected sexual intercourse) or see a physician. Provided the pregnancy test is negative she can start Desogestrel on the first day of her next period. If, in the meantime, her menstrual period comes, she can start Desogestrel on the first day of her period.

Excluding pregnancy before starting a new pack of Desogestrel. Before starting a new pack of Desogestrel, a woman should be reasonably certain that she is not pregnant. If in doubt, particularly if she has not been using tablet correctly and consistently, she should be advised that there is a chance that she may be pregnant and she should do a pregnancy test at least 3 weeks after the last episode of unprotected intercourse. She should continue taking Desogestrel until the result of the pregnancy test is available but if it is positive she should stop immediately and see a physician.

Warnings

If any of the conditions/risk factors mentioned below is present the woman should be referred to her physician. 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 Desogestrel 75 microgram film-coated tablets. In the event of, 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 Desogestrel 75 microgram film-coated tablets should be discontinued.

Breast cancer

It is contraindicated in women who have breast cancer because it may increase the risk of recurrence (Section 4.3).

Women with a past history of breast cancer should be referred to a physician before taking Desogestrel.

The risk for breast cancer increases in general with increasing age.

The risk in users of progestogen-only contraceptives (POCs), is possibly of similar magnitude as that associated with combined oral contraceptives (COCs). However, for POCs the evidence is less conclusive. 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 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.

Compared to the risk of getting breast cancer ever 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.

Hepatic disorders and disturbances of liver function

Desogestrel is contraindicated in women who have, or have had, severe hepatic disease as long as liver function values have not returned to normal (Section 4.3).

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.

Hypertension

If sustained hypertension develops during the use of Desogestrel, or if a significant increase

in blood pressure does not adequately respond to antihypertensive therapy, a physician should decide whether this should be discontinued.

Thromboembolic disorders

Desogestrel is contraindicated in women who have an active venous thromboembolic disorder (Section 4.3)

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, Desogestrel 75 microgram film-coated tablets should be discontinued in the event of a thrombosis. Discontinuation of Desogestrel 75 microgram film-coated tablets 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.

Changes in bleeding patterns

It is contraindicated in women who have undiagnosed vaginal bleeding before they first start taking Desogestrel (Section 4.3).

Women taking Desogestrel will have bleeding patterns which differ from those associated with their natural cycle. If bleeding is not acceptable to the women (e.g. the frequency of the period is not acceptable), another contraceptive method should be considered.

If the bleeding disturbances persist after stopping Desogestrel, the women should be referred to her physician to rule out any pathological cause.

If the bleeding differs from that which would be expected with this medicine or is unusually heavy, she should be referred to her physician to rule out any underlying pathology.

Women who repeatedly have post-coital bleeding should be investigated for underlying gynecological pathology, especially cervical cancer. Other causes of postcoital bleeding include benign growths (endometrial and cervical polyps, cervical ectropion); infection (cervicitis, pelvic inflammatory disease, endometritis, vaginitis due to STIs); genital/vulvar lesions (Herpes simplex virus, genital warts); benign conditions usually occurring in postmenopausal women such as vaginal atrophy and uterine prolapse; endometriosis; vaginal and endometrial cancer; and trauma (sexual abuse, foreign bodies).

It is usual that some women may experience amenorrhea because Desogestrel primarily acts

by inhibiting ovulation. However, because amenorrhea may indicate pregnancy, if use of Desogestrel has been imperfect, women should be advised to do a pregnancy test. The

treatment should be stopped if pregnancy occurs.

Diabetes

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, in the case of any change in insulin requirements during the first months of use, diabetic patients should be referred to their physician.

Ectopic pregnancy

Desogestrel consistently inhibits ovulation and so reduces the risk of ectopic pregnancy (see section 5.1). However, as with all women of reproductive age, ectopic pregnancy should be considered in the

differential diagnosis if the woman has pelvic pain with either vaginal bleeding/spotting or with amenorrhoea, particularly if Desogestrel has been used inconsistently or incorrectly rendering pregnancy more likely.

Effect on bone mineral density

Treatment with Desogestrel 75 microgram film-coated tablets 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.

Chloasma

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 Desogestrel 75 microgram film-coated tablets or consider using another contraceptive.

Conditions reported during pregnancy or during sex steroid use

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.

Reduced efficacy

The efficacy of Desogestrel 75 microgram film-coated tablets may be reduced in the event of missed tablets (Section 4.2), gastro-intestinal disturbances (Section 4.2), or concomitant medications that decrease the plasma concentration of etonogestrel, the active metabolite of desogestrel (Section 4.5).

Psychiatric disorders

Depressed mood and depression are well-known undesirable effects of hormonal contraceptive use (see section 4.8). Depression can be serious and is a well-known risk factor for suicidal behaviour and suicide. Women should be advised to contact their physician in case of mood changes and depressive symptoms, including shortly after initiating the treatment.

Lactose intolerance

Each tablet of this medicinal product contains 55 mg of lactose.

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.

Sexually transmitted infections

Desogestrel Tablets does not protect against HIV (AIDS) and other sexually transmitted infections.

Meningioma

Current, prolonged use (≥1 year) of desogestrel has been associated with a small increased risk of meningioma (see sections 4.3 and 4.8). The risk increased with longer duration of treatment. The risk may be higher in women with previous exposure to progestogens associated with an increased risk of meningioma, which should be considered before initiating treatment. If a patient is diagnosed with meningioma, treatment with desogestrel must be discontinued. Available data suggest that the risk of meningioma may decrease after treatment discontinuation.

4.5 Interaction with other medicinal products and other forms of interaction

Interactions

Note: The prescribing information of concomitant medications should be consulted to identify potential interactions.

Effect of other medicinal products on Desogestrel 75 microgram film-coated tablets

Interactions can occur with medicinal products that induce microsomal enzymes, which can result in increased clearance of sex hormones and may lead to breakthrough bleeding and/or contraceptive failure.

Enzyme induction can occur after a few days of treatment. Maximum enzyme induction is generally observed within a few weeks. After drug therapy is discontinued, enzyme induction can last for about 4 weeks.

Short-term treatment

Women on treatment with hepatic enzyme-inducing medicinal or herbal products should be advised that the efficacy of Desogestrel 75 microgram film-coated tablets may be reduced. A barrier contraceptive method should be used in addition to Desogestrel 75 microgram film-coated tablets. The barrier method must be used during the whole time of concomitant drug therapy and for 28 days after discontinuation of the hepatic enzyme-inducing medicinal product.

Chronic and Long-term treatment

For women on long-term therapy with enzyme-inducing medicinal products, Desogestrel may not be the most appropriate method of contraception and the woman should be referred to her physician for further advice.

Substances increasing the clearance of contraceptive hormones (diminished contraceptive efficacy by enzyme induction) e.g.:

Barbiturates (e.g. phenobarbital), bosentan, carbamazepine, hydantoins (e.g. phenytoin), primidone, rifampicin, efavirenz and possibly also felbamate, griseofulvin, oxcarbazepine, topiramate, rifabutin and products containing the herbal remedy St. John's Wort (hypericum perforatum).

Substances with variable effects on the clearance of contraceptive hormones: When co-administered with hormonal contraceptives, many combinations of HIV protease inhibitors (e.g. ritonavir, nelfinavir) and non-nucleoside reverse transcriptase inhibitors (e.g. nevirapine) and/or combinations with Hepatitis C virus (HCV) medicinal products (e.g. boceprevir, telaprevir), can increase or decrease plasma concentrations of progestins. The net effect of these changes may be clinically relevant in some cases.

Therefore, the prescribing information of concomitant HIV/HCV medications should be consulted to identify potential interactions and any related recommendations. In case of any doubt, an additional barrier contraceptive method should be used by women on protease inhibitor or non-nucleoside reverse transcriptase inhibitor therapy.

Substances decreasing the clearance of contraceptive hormones (enzyme inhibitors):

Concomitant administration of strong (e.g. ketoconazole, itraconazole, clarithromycin) or moderate (e.g. fluconazole, diltiazem, erythromycin) CYP3A4 inhibitors may increase the serum concentrations of progestins, including etonogestrel, the active metabolite of desogestrel. The clinical relevance of potential interactions with enzyme inhibitors remains unknown.

Effects of Desogestrel on other medicinal products:

Hormonal contraceptives may interfere with the metabolism of other drugs. Accordingly, plasma and tissue concentrations of other active substances may either increase (e.g. ciclosporine) or decrease.

Desogestrel 75 microgram film-coated tablets and Emergency contraception containing ulipristal acetate:

Desogestrel and the emergency contraceptive containing ulipristal acetate both bind to the progesterone receptor. Concomitant use may result in reduced efficacy of both Desogestrel and ulipristal acetate and is therefore not recommended. Desogestrel should be started or restarted no sooner than 5 days (120 hours) after emergency contraception with

ulipristal acetate (see section 4.2)

Laboratory tests

Data 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.

4.6 Fertility, pregnancy and lactation

Pregnancy

Desogestrel 75 microgram film-coated tablets are not indicated during pregnancy. When pregnancy occurs during treatment with Desogestrel 75 microgram film-coated tablets, further intake should be stopped.

Animal studies have shown that very high doses of progestogenic substances may 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 prior to pregnancy, nor a teratogenic effect when COCs were taken inadvertently during early pregnancy. Pharmacovigilance data collected with various desogestrel-containing COCs also do not indicate an increased risk.

Breast-feeding

Based on clinical study data, Desogestrel 75 microgram film-coated tablets does not appear to influence the production or the quality (protein, lactose, or fat concentrations) of breast milk. However, there have been infrequent postmarketing reports of a decrease in breast milk production while using Desogestrel 75 microgram film-coated tablets. 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 may be ingested by the child (based on an estimated milk ingestion of 150 ml/kg/day). Like other progestogen-only pills, Desogestrel 75 microgram film-coated tablets can be used during breast feeding.

Limited long-term follow up data are available on children, whose mothers started using Desogestrel 75 microgram film-coated tablets during the 4th to 8th week post-partum. They were breast-fed for 7 months and followed up to 1.5 years (n=32) or to 2.5 years (n=14) of age. Evaluation of growth and physical and psychomotor development did not indicate any differences in comparison to nursing infants, whose mother used a copper IUD. Based on the available data Desogestrel 75 microgram film-coated tablets may be used during lactation. The development and growth of a nursing infant, whose mother uses Desogestrel 75 microgram film-coated tablets, should however, be carefully observed.

Fertility

Desogestrel 75 microgram film-coated tablets is indicated for the prevention of pregnancy. For information on return to fertility (ovulation), see section 5.1.

4.7 Effects on ability to drive and use machines

Desogestrel 75 microgram film-coated tablets has no or negligible influence on the ability to drive and use machines.

4.8 Contraindications

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 Desogestrel 75 microgram film-coated tablets. Since Desogestrel 75 microgram film-coated tablets 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 undesirable effects in the clinical trials with Desogestrel 75 microgram film-coated tablets (>2.5%) were acne, mood changes, breast pain, nausea and weight increase. The undesirable effects are mentioned in the table below.

All undesirable effects are listed by system organ class and frequency; common (≥1/100); uncommon (1/1,000 to <1/100), rare (<1/1,000) and not known (cannot be estimated from available data)

* MedDRA version 9.0

Meningioma

A case-control study found that current, prolonged use (≥1 year) of desogestrel 75 μg was associated with a small increased risk of intracranial meningioma requiring surgery (odds ratio, 1.3 [95% confidence interval (CI), 1.1 to 1.5]). The estimated number needed to harm was overall 67 300 women for one intracranial meningioma. The risk increased with longer duration (≥7 years) of treatment (odds ratio, 2.1 [95% CI, 1.5 to 2.9]). Excess risk was greater in women who had previously used a progestogen with a known association to meningioma (odds ratio 3.3 [95% CI 2.6 to 4.1]). The increased risk was no longer observed one year after discontinuation of desogestrel.

Breast discharge may occur during use of Desogestrel 75 microgram film-coated tablets. On rare occasions, ectopic pregnancies have been reported (see Section 4.4). Hypersensitivity reactions (including angioedema and anaphylaxis) have also been reported. In addition, aggravation of angioedema and/or aggravation of hereditary angioedema may occur (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.

Breakthrough bleeding and/or contraceptive failure may result from interactions of other drugs (enzyme inducers) with hormonal contraceptives (see section 4.5).

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 Yellow Card Scheme, website www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9 Overdose

There have been no reports of serious deleterious effects from overdose. Symptoms that may occur in this case are nausea, vomiting and, in young girls, slight vaginal bleeding. There are no antidotes and further treatment should be symptomatic.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: hormonal contraceptives for systemic use,

ATC code: G03AC09.

Mechanism of action

Desogestrel 75 microgram film-coated tablets is a progestogen-only pill, which contains the progestogen desogestrel. Like other progestogen-only pills, Desogestrel 75 microgram film-coated tablets can be used for women who may not or do not want to use oestrogens. In contrast to traditional progestogen-only pills, the contraceptive effect of Desogestrel 75 microgram film-coated tablets is achieved primarily by inhibition of ovulation. Other effects include increased viscosity of the cervical mucus.

Clinical efficacy and safety

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 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 ITT 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 COC-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 population

No clinical data on efficacy and safety are available in adolescents below 18 years.

5.2 Pharmacokinetic properties

Absorption

After oral dosing of Desogestrel 75 microgram film-coated tablets, 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.

Biotransformation

DSG is metabolised via hydroxylation and dehydrogenation to the active metabolite ENG. ENG is primarily metabolised by the cytochrome P450 3A (CYP3A) isoenzyme and subsequently conjugated with sulphate and glucuronide.

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 i.v. 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.

Special populations

Effect of renal impairment

No studies were performed to evaluate the effect of renal disease on the pharmacokinetics of DSG.

Effect of hepatic impairment

No studies were conducted to evaluate the effect of hepatic disease on the pharmacokinetics of DSG. However, steroid hormones may be poorly metabolized in women with impaired liver function.

Ethnic groups

No studies were performed to assess pharmacokinetics in ethnic groups.

5.3 Preclinical safety data

Toxicological studies did not reveal any effects other than those, which can be explained from the hormonal properties of desogestrel.

Environmental Risk Assessment (ERA)

The active substance etonogestrel shows an environmental risk to fish.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Tablet core:

Lactose monohydrate

Maize starch

Povidone K30

Soybean oil (d-Alpha-Tocopherol)

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

Store below 30ºC. Store in the original package.

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

Not all pack sizes may be marketed

6.6 Special precautions for disposal

The active substance etonogestrel shows an environmental risk to fish. Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

7 MARKETING AUTHORISATION HOLDER

Crescent Pharma Limited

Key House, Sarum Hill,

Basingstoke,

RG21 8SR

United Kingdom

8 MARKETING AUTHORISATION NUMBER(S)

PL 20416/0611

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE

AUTHORISATION

12/09/2024

10 DATE OF REVISION OF THE TEXT

28/09/2026