Vinelle

Document: Vinelle tablet ENG SmPC change

SummaryofProductCharacteristics

NAME OF THE MEDICINAL PRODUCT

Vinelle 75 microgram tablets.

QUALITATIVE AND QUANTITATIVE COMPOSITION

Onetablet contains 75 microgram desogestrel.

Excipients with known effect: 58.22 mg lactose(asLactose anhydrous).

Forthefull list ofexcipients, seesection 6.1.

PHARMACEUTICAL FORM

Tablet

The tablet is round, white to off-white, uncoated, biconvex , 5 mm in diameter, debossed ‘152’ on one side and other side plain.

CLINICAL PARTICULARS

4.1 TherapeuticIndications

Oral Contraception

4.2 Posologyandmethodofadministration

Posology

To achieve contraceptive effectiveness, Vinelle must be used as directed (see ‘How to take Vinelleand ‘How to start Vinelle’).

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 Vinelle 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 yet been established. No data are available.

Method of Administration

Vinelle mustbetakenevery day at about thesametimeso that theinterval between two tablets always is 24 hours. The first tablet should betaken on thefirst dayofmenstrual bleeding. Thereafteronetablet each day is to betaken continuously, without taking any noticeon possiblebleeding. Anew blisteris started directly theday aftertheprevious one.

Howto startVinelle

No preceding hormonalcontraceptiveuse[in thepast month]

Tablet-taking has to start on day 1 ofthewoman's natural cycle(day 1 is thefirst day ofhermenstrual bleeding). Starting on days 2-5 is allowed, but during thefirst cycleabarriermethod is recommended forthefirst 7 days oftablet-taking.

Following first-trimester abortion

Afterfirst-trimesterabortion it is recommended to start immediately. Inthat casethereis no need to usean additional method ofcontraception.

Following delivery or second-trimester abortion

The woman should be advised to start any day between day 21 to 28 after delivery or second-trimester abortion. 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 intercourse has already occurred, pregnancy should be excluded before the actual start of Cerazette use or the woman has to wait for her first menstrual period.

Foradditional information forbreastfeeding women seeSection 4.6.

Howto startVinelle whenchangingfromothercontraceptivemethods

Changing from a combined hormonal contraceptive (combined oral contraceptive (COC), vaginal ring, or transdermal patch)

Thewoman should startwithVinelle preferably on theday afterthelast activetablet (the last tablet containing the active substances)ofher previousCOCoron theday ofremoval of hervaginal ring ortransdermal patch. In these cases, theuseofan additional contraceptiveis not necessary. Not all contraceptive methods may be available in all EU countries.

Thewoman may also start at thelatest on theday following theusual tablet-free, patch-free, ring-free orplacebo tabletinterval ofherprevious combinedhormonal contraceptive, butduring thefirst 7 days oftablet-taking an additional barrier method is recommended.

Changing from a progestogen-only-method (minipill, injection, implantorfrom aprogestogen-releasing intrauterinesystem [IUS])

Thewoman may switch any day from theminipill (froman implant ortheIUSon theday ofits removal, from an injectablewhen thenext injection would bedue);

Management of missed tablet

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, the same procedure as above but 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.

Adviceincaseofgastrointestinaldisturbances

In caseofseveregastro-intestinal disturbance, absorption may not becompleteand additional contraceptivemeasures should betaken.

Ifvomiting occurs within 3-4 hours aftertablet-taking, absorption may not complete. The same advice is applicable as for a missed tablet.

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 Vinelle 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 Vinelle does not protect against HIV (AIDS) and other sexually transmitted diseases.

4.3 Contraindications

• Activevenous thromboembolicdisorder.

• Presenceorhistory ofseverehepaticdiseaseas long as liverfunction values havenot returned

to normal.

• Known orsuspected sex-steroid sensitivemalignancies.

• Undiagnosed vaginal bleeding.

• Hypersensitivity to activesubstanceorto any oftheexcipients listed in section 6.1

4.4 Specialwarningsandprecautionsforuse

Ifanyoftheconditions/risk factors mentioned belowis present, thebenefits ofprogesteroneuseshould beweighed against thepossiblerisks foreach individualwoman and discussed with thewoman beforeshedecides to start with Vinelle . In theevent ofaggravation, exacerbation, orfirst appearanceofany oftheseconditions, thewoman should contact herphysician. Thephysician should then decideon whethertheuseofVinelle should bediscontinued.

Therisk forbreastcancerincreases in general with increasing age. During theuseofcombined oralcontraceptives (COCs)therisk ofhaving breast cancerdiagnosed is slightly increased. This increased risk disappears gradually within 10 years after discontinuation ofCOCuseand is not related to thedurationofuse, but to theageofthewoman when using theCOC.

Theexpected numberofcases diagnosed per10 000 women whousecombined OCs (up to 10 yearsafterstopping) _re_l_a_tive_to
n_e_v_e_r_us_e_r_s
ov_e_r_t_he_s_a_me_p_e_r_iod
h_a_ve_b_e_e_n _ca_l_c_u_l_a_t_e_d _f_or_t_he_re_sp_e_c_tive_a_ge_g_r_{oups and is presented in
the table below.}

Age category combined	Expected cases _O_C_-u_s_e_r_s	Expected cases non- users
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

Therisk in users of progestogen-only contraceptives (POCs), such as Vinelle is possibly ofsimilarmagnitudeas thatassociated with combined OCs. However, forPOCs theevidenceis less conclusive. Compared totherisk ofgetting breast cancerever in life, theincreased risk associated with COCs is low. Thecases ofbreast cancerdiagnosed in COCusers tend to beless advanced than in thosewho havenotused COCs. Theincreased risk in COCusers may bedueto an earlierdiagnosis, biological effects ofthepill oracombination ofboth.

Sinceabiological effect ofprogestogens on livercancercannot beexcluded an individual benefit/risk assessment should bemadein woman with livercancer.

When acute or chronic disturbances of liver function occur the woman should be referred to a specialist for examination and advice.

Epidemiological investigations haveassociated theuseofcombined OCswith an increased incidenceofvenous thromboembolism (VTE, deepvenous thrombosis and pulmonary embolism). Although theclinical relevanceofthis finding fordesogestrel used as acontraceptivein theabsenceofan oestrogeniccomponent isunknown, Vinelle should bediscontinued in theevent ofathrombosis. Discontinuation of Vinelle should also be considered in case of long-term immobilisation due to surgery or illness. Women withahistory ofthrombo-embolicdisorders should be awareofthepossibility ofarecurrence.

Although progestogens mayhavean effect on peripheral insulin resistanceand glucosetolerance, thereis no evidence foraneed to alterthetherapeuticregimen in diabetics using progestogen-only pills. However, diabeticpatients should becarefully observed during thefirst months ofuse.

Ifasustained hypertensiondevelops during theuseofVinelle , orifasignificant increasein blood pressuredoes not adequately respond to antihypertensivetherapy, discontinuation ofVinelle tabletsshould beconsidered.

Treatmentwith Vinelle leads to decreased estradiol serum levels, to alevel corresponding with theearly follicular phase. Itis as yet unknown whetherthedecreasehas any clinicallyrelevant effect on bonemineral density.

Theprotection with traditional progestogen-only pills against ectopicpregnancies is not asgood as with combined oral contraceptives, which has been associated with thefrequent occurrenceofovulations during theuseofprogestogen-only pills. DespitethefactthatVinelle consistently inhibits ovulation, ectopicpregnancy should betaken into account in thedifferential diagnosis ifthewoman gets amenorrhoeaorabdominal pain.

Chloasmamay occasionally occur, especially in women with ahistory ofchloasmagravidarum. Women with a tendency to chloasmashould avoid exposureto thesun orultraviolet radiation whilst taking Vinelle.

Thefollowing conditions havebeenreported both during pregnancy and during sex steroid use, but an association with theuseofprogestogens has notbeen established: jaundiceand/orpruritus related to cholestasis; gallstoneformation; porphyria; systemiclupus erythematosus; haemolyticuraemicsyndrome;Sydenham’schorea; herpes gestationis; otosclerosis-related hearingloss; (hereditary)angioedema.

Vinelle contains 58.22 mg lactose(as LactoseAnhydrous)and thereforeshould not be administered to patients with rarehereditary problems ofgalactoseintolerance, theLapp lactasedeficiency, orglucose-galactosemalabsorption.

4.5 Interactionwithothermedicinalproductsandotherformsofinteraction

Interactions

Interactions between hormonal contraceptives and othermedicinal products may leadto breakthrough bleeding and/or contraceptivefailure. Thefollowing interactions havebeen reported in theliterature(mainly with combined contraceptives but occasionally also with progestogen-only contraceptives).

Hepaticmetabolism:Interactions can occurwith medicinal products thatinducemicrosomal enzymes, which can result in increased clearanceofsex hormones (such as hydantoins (e.g. phenytoin), barbiturates (e.g. phenobarbital), primidone, carbamazepine, rifampicin, and possibly also foroxcarbazepine, topiramate, rifabutin, felbamate, ritonavir, nelfinavir, griseofulvin and products containing St. John’swort(Hypericum perforatum)).

Maximal enzymeinductionis not seen for2-3 weeks,butmay then besustainedforatleast 4 weeks afterthecessation ofdrug therapy.Women on treatment with any ofthesemedicinalproducts should temporarily useabarriermethod in addition to Vinelle.With microsomal enzyme-inducing drugs, thebarriermethod should beused during thetimeofconcomitant drug administration and for28 days aftertheirdiscontinuation. Forwomen on long-term therapy with hepaticenzyme inducers anon-hormonal method contraception should beconsidered.

During treatment with medicinal charcoal, theabsorption ofthesteroid in thetablet may bereduced and thereby the contraceptiveefficacy. Underthesecircumstances, theadviceas given formissed tablets in section 4.2. is applicable.

Hormonal contraceptives may interferewith themetabolismofotherdrugs. Accordingly, plasmaand tissue concentrations may eitherincrease(e.g. cyclosporine)ordecrease.

Note: Theprescribing information ofconcomitant medications should beconsulted to identify potential interactions.

Laboratorytests

Dataobtained with COCs haveshown that contraceptivesteroids may influencetheresults ofcertain laboratory tests, including biochemical parameters ofliver, thyroid, adrenal and renal function,serum levels of(carrier)proteins, e.g. corticosteroid binding globulin and lipid/lipoprotein fractions, parameters ofcarbohydratemetabolism and parameters ofcoagulationand fibrinolysis. Thechanges generally remain within thenormalrange. To what extentthis also applies to progestogen-only contraceptives is not known.

4.6 Fertility, pregnancyandlactation

Pregnancy:

Vinelle is not indicated during pregnancy.When pregnancy occurs during treatment withVinelle, further intakeshould bestopped.

Animal studies haveshown thatvery high doses ofprogestogenicsubstances may causemasculinisation offemale foetuses.

Extensiveepidemiologicalstudies haverevealed neitheran increased risk ofbirth defects in children born to women who used OCs priorto pregnancy, norateratogeniceffectwhen OCs weretaken inadvertently during early pregnancy.

Pharmacovigilancedatacollected with various desogestrel-containing combined OCs also do not indicatean increased risk.

Breastfeeding

Vinelle does not influencetheproduction orthequality (protein, lactose, or fat concentrations) ofbreast milk. However, small amounts ofetonogestrel, (themetaboliteofdesogestrel)areexcretedwith themilk. As aresult, 0.01 -0.05 microgrametonogestrel perkg body weight perday may beingested by thechild (based on an estimated milk ingestion of150 ml/kg/day). Limited long-term follow-up data are available on children, whose mothers started using another desogestrel-only pill during the 4^thto 8^thweek 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 theavailabledata, Vinellemay beused during lactation. Thedevelopment and growth of thenursing infant, whose mother uses Vinelle,should, however, becarefully observed.

Fertility

Vinelle is indicated for the prevention of pregnancy. For information on return to fertility (ovulation), see section 5.1.

4.7 Effectsonabilityto driveandusemachines

Vinelle has no ornegligibleinfluenceon theability todriveand usemachines.

4.8 Undesirableeffects

Themost commonly reported undesirableeffect in theclinical trials is bleeding irregularity. Somekind ofbleeding irregularity has been reported in up to50%ofwomen using desogestrel. Sincedesogestrel causes ovulation inhibition closeto 100%, in contrast to otherprogestogen-only pills, irregularbleedingis morecommon than with other progestogen-only pills. In 20-30%ofthewomen, bleeding may becomemorefrequent, whereas in another20% bleeding may becomeless frequentortotally absent. Vaginal bleeding may also beoflongerduration.

Afteracoupleofmonthsoftreatment, bleedings tend to becomeless frequent. Information, counselling and ableeding diary can improvethewoman's acceptanceofthebleeding pattern.

Themost commonly reported otherundesirableeffects intheclinical trials with desogestrel (>2.5%)wereacne,mood changes, breastpain, nauseaand weight increase. Theundesirableeffects are mentioned in thetablebelow.

All ADRs are listed by system organ class and frequency; common (³1/100 to <1/10), uncommon (³1/1,000 to <1/100) and rare (³1/10,000 to <1/1,000).

System Organ Class (MedDRA)*	Frequency of adverse reactions
System Organ Class (MedDRA)*	Common ≥ 1/100	Uncommon <1/100, ≥1/1000	Rare <1/1000
Infections and infestations		Vaginal infection
Psychiatric disorders	Mood altered Libido decreased Depressed mood
Nervous system disorders	Headache
Eye disorders		Contact lens intolerance
Gastrointestinal disorders	Nausea	Vomiting
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
Investigations	Weight increased

*MedDRA version 12.1;

Breast discharge may occur during use of Vinelle . On rare occasions, ectopic pregnancies have been reported (see Section 4.4). 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.

Paediatric population

There is no relevant indication for the use of Vinellein children.

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 national reporting system listed in [To be completed nationally].

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, Progestogens.

ATC code: G03AC09

Vinelle is a progestogen-only pill, which contains the progestogen desogestrel. Like other progestogen-only pills,Vinelle is best for nursing mothers and women who are unable or unwilling to take estrogen.

Mechanism of action

Unlike traditional pills containing only progestogen, the contraceptive effect of Vinelleis achieved mainly by inhibiting 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 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 for 30 micrograms levonorgestrel (95% confidence interval 0.42 - 3.96).

The Pearl-Index for Vinelle is comparable to the one historically found for combined oral contraceptives in the general oral contraceptives-using population.

Treatment with Vinelle 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 is rapidly absorbed and converted into etonogestrel. Under steady-state conditions, peak serum levels are reached 1.8 hours after tablet-intake and the absolute bioavailability of etonogestrel is approximately 70%.

Distribution

Etonogestrel is 95.5-99% bound to serum proteins, predominantly to albumin and to a lesser extent to sex hormone binding globuline.

Biotransformation

Desogestrel is metabolised via hydroxylation and dehydrogenation to the active metabolite etonogestrel. Etonogestrel is metabolised via sulphate and glucuronide conjugation.

Elimination

Etonogestrel 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 etonogestrel is approximately 10 l per hour. Excretion of etonogestrel and its metabolites either as free steroid or as conjugates, is with urine and faeces (ratio 1.5:1). In lactating women, etonogestrel 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 maybe ingested by the infant.

Special populations

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

Effect of renal impairment

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

Effect of hepatic impairment

No studies were conducted to evaluate the effect of hepatic disease on the pharmacokinetics of desogestrel. 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.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Lactose anhydrous

Potato starch

Povidone

all-rac-α-tocopherol

Silica colloidal anhydrous

Stearic acid

6.2 Incompatibilities

Not applicable.

6.3 Shelf Life

3 years.

6.4 Special precautions for storage

This medicinal product does not require any special storage conditions.

6.5 Nature and contents of container

The blister consisting of PVC film coated with PVdC with counter-sealing foil made of aluminium with heat sealing coating. One blister to be packed in a tri-laminated pouch with or without silica gel bag.

Blister is presented as a calendar pack stating the week days on it.

Pack sizes: 1x28, 3x28, 6x28, 13x28 tablets.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

No special requirements.

Any unused product or waste material should be disposed of in accordance with local requirements.

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

5 October 2015