OVALEAP 300UI / 0.5ml injectible solution medication leaflet

Ovaleap 300 IU/0.5 mL solution for injection

Ovaleap 450 IU/0.75 mL solution for injection

Ovaleap 900 IU/1.5 mL solution for injection

Each mL of the solution contains 600 IU (equivalent to 44 micrograms) follitropin alfa*.

Ovaleap 300 IU/0.5 mL solution for injection

Each cartridge contains 300 IU (equivalent to 22 micrograms) follitropin alfa in 0.5 mL solution forinjection.

Ovaleap 450 IU/0.75 mL solution for injection

Each cartridge contains 450 IU (equivalent to 33 micrograms) follitropin alfa in 0.75 mL solution forinjection.

Ovaleap 900 IU/1.5 mL solution for injection

Each cartridge contains 900 IU (equivalent to 66 micrograms) follitropin alfa in 1.5 mL solution forinjection.

*Follitropin alfa (recombinant human follicle-stimulating hormone [r-hFSH]) is produced in Chinese

Hamster Ovary Cells (CHO DHFR-) by recombinant DNA technology.

Ovaleap contains 0.02 mg per mL of benzalkonium chloride

Ovaleap contains 10.0 mg per mL of benzyl alcohol

For the full list of excipients, see section 6.1.

Solution for injection (injection).

Clear, colourless solution.

The pH of the solution is 6.8 to 7.2.

In adult women

* Anovulation (including polycystic ovarian syndrome) in women who have been unresponsive totreatment with clomifene citrate.

* Stimulation of multifollicular development in women undergoing superovulation for assistedreproductive technologies (ART) such as in vitro fertilisation (IVF), gamete intra-fallopiantransfer and zygote intra-fallopian transfer.

* Ovaleap in association with a luteinising hormone (LH) preparation is indicated for thestimulation of follicular development in women with severe LH and FSH deficiency.

In adult men

* Ovaleap is indicated for the stimulation of spermatogenesis in men who have congenital oracquired hypogonadotropic hypogonadism with concomitant human Chorionic Gonadotropin(hCG) therapy.

Treatment with follitropin alfa should be initiated under the supervision of a physician experienced inthe treatment of fertility disorders.

Clinical assessment of follitropin alfa indicates that its daily doses, regimens of administration andtreatment monitoring procedures should be individualised to optimise follicular development and tominimise the risk of unwanted ovarian hyperstimulation. It is advised to adhere to the recommendedstarting doses indicated below.

Women with anovulation (including polycystic ovarian syndrome)

Follitropin alfa may be given as a course of daily injections. In menstruating women treatment shouldcommence within the first 7 days of the menstrual cycle.

In the registration trials, a commonly used regimen commenced at 75 to 150 IU FSH daily and wasincreased preferably by 37.5 or 75 IU at 7- or preferably 14-day intervals if necessary, to obtain anadequate, but not excessive, response.

In clinical practice, the starting dose is typically individualised based on the patient’s clinicalcharacteristics, such as markers of ovarian reserve, age, body mass index, and, if applicable, previousovarian response to ovarian stimulation.

The starting dose can be adjusted in a stepwise manner (a) lower than 75 IU per day if an excessiveovarian response in terms of number of follicles is anticipated based on the patient’s clinical profile(age, body mass index, ovarian reserve); or (b) higher than 75 up to a maximum of 150 IU per daymay be considered if a low ovarian response is anticipated.

The patient’s response should be closely monitored by measuring follicle size and number byultrasound and/or estrogen secretion.

If a patient fails to respond adequately (either low or excessive ovarian response), continuation of thattreatment cycle should be evaluated and managed according to the physician’s standard of care. Incases of low response, the daily dose should not exceed 225 IU FSH.

If an excessive ovarian response is obtained according to the physician’s assessment, treatment shouldbe stopped and hCG withheld (see section 4.4). Treatment should recommence in the next cycle at adose lower than that of the previous cycle.

Final follicular maturation

When an optimal response is obtained, a single injection of 250 micrograms recombinant humanchoriogonadotropin alfa (r-hCG) or 5 000 IU up to 10 000 IU hCG should be administered 24 to48 hours after the last follitropin alfa injection. The patient is recommended to have coitus on the dayof, and the day following, hCG administration. Alternatively intrauterine insemination may beperformed.

Women undergoing ovarian stimulation for multiple follicular development prior to in vitrofertilisation or other ART

In the registration trials, a commonly used regimen for superovulation involved the administration of150 to 225 IU of follitropin alfa daily, commencing on days 2 or 3 of the cycle.

In clinical practice, the starting dose is typically individualised based on the patient’s clinicalcharacteristics, such as markers of ovarian reserve, age, body mass index, and, if applicable, previousovarian response to ovarian stimulation.

If a low ovarian response is anticipated, the starting dose may be adjusted in a stepwise manner to nothigher than 450 IU daily. Conversely, if an excessive ovarian response is expected, the starting dosemay be decreased below 150 IU.

The patient’s response should continue to be closely monitored by measuring follicle size and numberby ultrasound and/or estrogen secretion until adequate follicular development has been achieved.

Follitropin alfa can be given either alone, or, to prevent premature luteinisation, in combination with agonadotropin-releasing hormone (GnRH) agonist or antagonist.

If a patient fails to respond adequately (either low or excessive ovarian response), continuation of thattreatment cycle should be evaluated and managed according to the physician’s standard of care. Incases of low response, the daily dose should not exceed 450 IU FSH.

Final follicular maturation

When an optimal ovarian response is obtained, a single injection of 250 micrograms r-hCG or 5000 IU up to 10 000 IU hCG is administered 24 to 48 hours after the last follitropin alfa injection toinduce final follicular maturation.

Women with severe LH and FSH deficiency

In LH and FSH deficient women, the objective of follitropin alfa therapy in association with aluteinising hormone (LH) preparation is to promote follicular development followed by finalmaturation after the administration of hCG. Follitropin alfa should be given as a course of dailyinjections simultaneously with lutropin alfa. If the patient is amenorrhoeic and has low endogenousestrogen secretion, treatment can commence at any time.

A recommended regimen commences at 75 IU of lutropin alfa daily with 75 to 150 IU FSH. Treatmentshould be tailored to the individual patient’s response as assessed by measuring follicle size byultrasound and estrogen response.

If an FSH dose increase is deemed appropriate, dose adaptation should preferably be after 7- to 14-dayintervals and preferably by 37.5 to 75 IU increments. It may be acceptable to extend the duration ofstimulation in any one cycle to up to 5 weeks.

When an optimal response is obtained, a single injection of 250 micrograms r-hCG or 5 000 IU up to10 000 IU hCG should be administered 24 to 48 hours after the last follitropin alfa and lutropin alfainjections. The patient is recommended to have coitus on the day of, and on the day following, hCGadministration. Alternatively, intrauterine insemination or another medically assisted reproductionprocedure may be performed based on the physician’s judgment of the clinical case.

Luteal phase support may be considered since lack of substances with luteotropic activity (LH/hCG)after ovulation may lead to premature failure of the corpus luteum.

If an excessive response is obtained, treatment should be stopped and hCG withheld. Treatment shouldrecommence in the next cycle at a dose of FSH lower than that of the previous cycle (see section 4.4).

Men with hypogonadotropic hypogonadism

Follitropin alfa should be given at a dose of 150 IU three times a week, concomitantly with hCG, for aminimum of 4 months. If after this period, the patient has not responded, the combination treatmentmay be continued; current clinical experience indicates that treatment for at least 18 months may benecessary to achieve spermatogenesis.

Special population

There is no relevant use of follitropin alfa in the elderly population. Safety and efficacy of follitropinalfa in elderly patients have not been established.

Safety, efficacy and pharmacokinetics of follitropin alfa in patients with renal or hepatic impairmenthave not been established.

There is no relevant use of follitropin alfa in the paediatric population.

Ovaleap is intended for subcutaneous use. The first injection should be performed under directmedical supervision. Self-administration should only be performed by patients who are wellmotivated, adequately trained and have access to expert advice.

As the multidose cartridge is intended for several injections, clear instructions should be provided tothe patients to avoid misuse of the medicine.

The Ovaleap cartridge is designed for use in conjunction with the Ovaleap Pen only, which isseparately available. For instructions on the administration with the Ovaleap Pen, see section 6.6.

* Hypersensitivity to the active substance follitropin alfa, FSH or to any of the excipients listed insection 6.1;

* tumours of the hypothalamus or pituitary gland;

* ovarian enlargement or ovarian cyst unrelated to polycystic ovarian disease and of unknownorigin;

* gynaecological haemorrhages of unknown origin;

* ovarian, uterine or mammary carcinoma.

Ovaleap must not be used when an effective response cannot be obtained, such as:

* primary ovarian failure;

* malformations of sexual organs incompatible with pregnancy;

* fibroid tumours of the uterus incompatible with pregnancy;

* primary testicular insufficiency.

In order to improve the traceability of biological medicinal products, the trade name and batch numberof the administered medicinal product should be clearly recorded in the patient file.

Follitropin alfa is a potent gonadotropic substance capable of causing mild to severe adverse reactionsand should only be used by physicians who are thoroughly familiar with infertility problems and theirmanagement.

Gonadotropin therapy requires a certain time commitment by physicians and supportive health careprofessionals, as well as the availability of appropriate monitoring facilities. In women, safe andeffective use of follitropin alfa calls for monitoring of ovarian response with ultrasound, alone orpreferably in combination with measurement of serum estradiol levels, on a regular basis. There maybe a degree of interpatient variability in response to FSH administration, with a poor response to FSHin some patients and exaggerated response in others. The lowest effective dose in relation to thetreatment objective should be used in both men and women.

Porphyria

Patients with porphyria or a family history of porphyria should be closely monitored during treatmentwith follitropin alfa. Deterioration or a first appearance of this condition may require cessation oftreatment.

Treatment in women

Before starting treatment, the couple’s infertility should be assessed as appropriate and putativecontraindications for pregnancy evaluated. In particular, patients should be evaluated forhypothyroidism, adrenocortical deficiency, hyperprolactinemia and appropriate specific treatmentgiven.

Patients undergoing stimulation of follicular growth, whether as treatment for anovulatory infertility or

ART procedures, may experience ovarian enlargement or develop hyperstimulation. Adherence torecommended follitropin alfa dose and regimen of administration and careful monitoring of therapywill minimise the incidence of such events. For accurate interpretation of the indices of follicledevelopment and maturation, the physician should be experienced in the interpretation of the relevanttests.

In clinical trials, an increase of the ovarian sensitivity to follitropin alfa was shown when administeredwith lutropin alfa. If an FSH dose increase is deemed appropriate, dose adaptation should preferablybe at 7 to 14 day intervals and preferably with 37.5 to 75 IU increments.

No direct comparison of follitropin alfa/LH versus human menopausal gonadotropin (hMG) has beenperformed. Comparison with historical data suggests that the ovulation rate obtained with follitropinalfa/LH is similar to that obtained with hMG.

Ovarian Hyperstimulation Syndrome (OHSS)

A certain degree of ovarian enlargement is an expected effect of controlled ovarian stimulation. It ismore commonly seen in women with polycystic ovarian syndrome and usually regresses withouttreatment.

In distinction to uncomplicated ovarian enlargement, OHSS is a condition that can manifest itself withincreasing degrees of severity. It comprises marked ovarian enlargement, high serum sex steroids andan increase in vascular permeability which can result in an accumulation of fluid in the peritoneal,pleural and, rarely, in the pericardial cavities.

The following symptomatology may be observed in severe cases of OHSS: abdominal pain, abdominaldistension, severe ovarian enlargement, weight gain, dyspnoea, oliguria and gastrointestinal symptomsincluding nausea, vomiting and diarrhoea. Clinical evaluation may reveal hypovolaemia,haemoconcentration, electrolyte imbalances, ascites, haemoperitoneum, pleural effusions,hydrothorax, or acute pulmonary distress. Very rarely, severe OHSS may be complicated by ovariantorsion or thromboembolic events such as pulmonary embolism, ischaemic stroke or myocardialinfarction.

Independent risk factors for developing OHSS include young age, lean body mass, polycystic ovariansyndrome, higher doses of exogenous gonadotropins, high absolute or rapidly rising serum estradiollevels and previous episodes of OHSS, large number of developing ovarian follicles and large numberof oocytes retrieved in assisted reproductive technology (ART) cycles.

Adherence to recommended follitropin alfa dose and regimen of administration can minimise the riskof ovarian hyperstimulation (see sections 4.2 and 4.8). Monitoring of stimulation cycles by ultrasoundscans as well as estradiol measurements are recommended to early identify risk factors.

There is evidence to suggest that hCG plays a key role in triggering OHSS and that the syndrome maybe more severe and more protracted if pregnancy occurs. Therefore, if signs of ovarianhyperstimulation occur, it is recommended that hCG be withheld and the patient be advised to refrainfrom coitus or to use barrier contraceptive methods for at least 4 days. OHSS may progress rapidly(within 24 hours) or over several days to become a serious medical event. It most often occurs afterhormonal treatment has been discontinued and reaches its maximum at about 7 to 10 days followingtreatment. Therefore, patients should be followed for at least 2 weeks after hCG administration.

In ART, aspiration of all follicles prior to ovulation may reduce the occurrence of hyperstimulation.

Mild or moderate OHSS usually resolves spontaneously. If severe OHSS occurs, it is recommendedthat gonadotropin treatment be stopped if still ongoing and that the patient be hospitalised andappropriate therapy be started.

Multiple pregnancy

In patients undergoing ovulation induction, the incidence of multiple pregnancy is increased comparedwith natural conception. The majority of multiple conceptions are twins. Multiple pregnancy,especially of high order, carries an increased risk of adverse maternal and perinatal outcomes.

To minimise the risk of multiple pregnancy, careful monitoring of ovarian response is recommended.

In patients undergoing ART procedures the risk of multiple pregnancy is related mainly to the numberof embryos replaced, their quality and the patient age.

The patients should be advised of the potential risk of multiple births before starting treatment.

Pregnancy loss

The incidence of pregnancy loss by miscarriage or abortion is higher in patients undergoingstimulation of follicular growth for ovulation induction or ART than following natural conception.

Ectopic pregnancy

Women with a history of tubal disease are at risk of ectopic pregnancy, whether the pregnancy isobtained by spontaneous conception or with fertility treatments. The prevalence of ectopic pregnancyafter ART, was reported to be higher than in the general population.

Reproductive system neoplasms

There have been reports of ovarian and other reproductive system neoplasms, both benign andmalignant, in women who have undergone multiple treatment regimens for infertility treatment. It isnot yet established whether or not treatment with gonadotropins increases the risk of these tumours ininfertile women.

Congenital malformation

The prevalence of congenital malformations after ART may be slightly higher than after spontaneousconceptions. This is thought to be due to differences in parental characteristics (e.g. maternal age,sperm characteristics) and multiple pregnancies.

In women with recent or ongoing thromboembolic disease or women with generally recognised riskfactors for thromboembolic events, such as personal or family history, treatment with gonadotropinsmay further increase the risk for aggravation or occurrence of such events. In these women, thebenefits of gonadotropin administration need to be weighed against the risks. It should be notedhowever that pregnancy itself as well as OHSS also carry an increased risk of thromboembolic events.

Treatment in men

Elevated endogenous FSH levels are indicative of primary testicular failure. Such patients areunresponsive to follitropin alfa/hCG therapy. Follitropin alfa should not be used when an effectiveresponse cannot be obtained.

Semen analysis is recommended 4 to 6 months after the beginning of treatment as part of theassessment of the response.

Benzalkonium chloride content

Ovaleap contains 0.02 mg/mL of benzalkonium chloride

Benzyl alcohol content

Ovaleap contains 10.0 mg per mL benzyl alcohol

Benzyl alcohol may cause allergic reactions.

High volumes should be used with caution and only if necessary, especially in subjects with liver orkidney impairment as well as in pregnant women or while breast-feeding, because of the risk ofaccumulation and toxicity (metabolic acidosis).

Ovaleap contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially “sodiumfree”.

Concomitant use of follitropin alfa with other medicinal products used to stimulate ovulation (e.g.hCG, clomifene citrate) may potentiate the follicular response, whereas concurrent use of a GnRHagonist or antagonist to induce pituitary desensitisation may increase the dose of follitropin alfaneeded to elicit an adequate ovarian response. No other clinically significant medicinal productinteraction has been reported during follitropin alfa therapy.

There is no indication for use of Ovaleap during pregnancy. Data on a limited number of exposedpregnancies (less than 300 pregnancy outcomes) indicate no malformative or foeto/neonatal toxicity offollitropin alfa.

No teratogenic effect has been observed in animal studies (see section 5.3). In case of exposure duringpregnancy, clinical data are not sufficient to exclude a teratogenic effect of follitropin alfa.

Ovaleap is not indicated during breast-feeding.

Ovaleap is indicated for use in infertility (see section 4.1).

Ovaleap has no or negligible influence on the ability to drive and use machines.

The most commonly reported adverse reactions are headache, ovarian cysts and local injection sitereactions (e.g. pain, erythema, haematoma, swelling and/or irritation at the site of injection).

Mild or moderate OHSS has been commonly reported and should be considered as an intrinsic risk ofthe stimulation procedure. Severe OHSS is uncommon (see section 4.4).

Thromboembolism may occur very rarely (see section 4.4).

The adverse reactions are ranked under heading of frequency using the following convention: verycommon (≥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) and not known (cannot be estimated from the available data). Withineach frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Treatment in women

Table 1: Adverse reactions in women

System organ class Frequency Adverse reaction

Immune system disorders Very rare Mild to severe hypersensitivityreactions, includinganaphylactic reactions andshock

Nervous system disorders Very common Headache

Vascular disorders Very rare Thromboembolism (both inassociation with and separatefrom OHSS)

Respiratory, thoracic and Very rare Exacerbation or aggravation ofmediastinal disorders asthma

Gastrointestinal disorders Common: Abdominal pain, abdominaldistension, abdominaldiscomfort, nausea, vomiting,diarrhoea

Reproductive system and breast Very common Ovarian cystsdisorders Common Mild or moderate OHSS(including associatedsymptomatology)

Uncommon Severe OHSS (includingassociated symptomatology)(see section 4.4)

Rare Complication of severe OHSS

General disorders and Very common Injection site reactions (e.g.administration site conditions pain, erythema, haematoma,swelling and/or irritation at thesite of injection)

Treatment in men

Table 2: Adverse reactions in men

System organ class Frequency Adverse reaction

Immune system disorders Very rare Mild to severe hypersensitivityreactions, includinganaphylactic reactions andshock

Respiratory, thoracic and Very rare Exacerbation or aggravation ofmediastinal disorders asthma

Skin and subcutaneous tissue Common: Acnedisorders

Reproductive system and breast Common Gynaecomastia, varicoceledisorders

General disorders and Very common Injection site reactions (e.g.administration site conditions pain, erythema, haematoma,swelling and/or irritation at thesite of injection)

Investigations Common Weight gain

Reporting suspected adverse reactions after authorisation of the medicinal product is important. Itallows continued monitoring of the benefit/risk balance of the medicinal product. Healthcareprofessionals are asked to report any suspected adverse reactions via the national reporting systemlisted in Appendix V.

The effects of an overdose of follitropin alfa are unknown, nevertheless, there is a possibility that

OHSS may occur (see section 4.4).

Pharmacotherapeutic group: Sex hormones and modulators of the genital systems, gonadotropins,

ATC code: G03GA05.

Ovaleap is a biosimilar medicinal product. Detailed information is available on the website of the

European Medicines Agency http://www.ema.europa.eu.

Follicle stimulating hormone (FSH) and luteinising hormone (LH) are secreted from the anteriorpituitary gland in response to GnRH and play a complementary role in follicle development andovulation. FSH stimulates the development of ovarian follicles, while LH action is involved in follicledevelopment, steroidogenesis and maturation.

Inhibin and estradiol (E2) levels are raised after administration of r-hFSH, with subsequent inductionof follicular development. Inhibin serum level increase is rapid and can be observed as early as thethird day of r-hFSH administration, while E2 levels take more time, and an increase is observed onlyfrom the fourth day of treatment. Total follicular volume starts to increase after 4 to 5 days of r-hFSHdaily dosing, and, depending on patient response, the maximum effect is reached after about 10 daysfrom the start of r-hFSH administration.

Clinical efficacy and safety in women

In clinical trials, patients with severe FSH and LH deficiency were defined by an endogenous serum

LH level < 1.2 IU/L as measured in a central laboratory. However, it should be taken into account thatthere are variations between LH measurements performed in different laboratories.

In clinical studies comparing r-hFSH (follitropin alfa) and urinary FSH in ART (see table 3 below)and in ovulation induction, follitropin alfa was more potent than urinary FSH in terms of a lower totaldose and a shorter treatment period needed to trigger follicular maturation.

In ART, follitropin alfa at a lower total dose and shorter treatment period than urinary FSH, resulted ina higher number of oocytes retrieved when compared to urinary FSH.

Table 3: Results of study GF 8407 (randomised parallel group study comparing efficacy and safety offollitropin alfa with urinary FSH in ART)follitropin alfa urinary FSH(n = 130) (n = 116)

Number of oocytes retrieved 11.0 ± 5.9 8.8 ± 4.8

Days of FSH stimulation required 11.7 ± 1.9 14.5 ± 3.3

Total dose of FSH required (number 27.6 ± 10.2 40.7 ± 13.6of FSH 75 IU ampoules)

Need to increase the dose (%) 56.2 85.3

Differences between the 2 groups were statistically significant (p < 0.05) for all criteria listed.

Clinical efficacy and safety in men

In men deficient in FSH, follitropin alfa administered concomitantly with hCG for at least 4 monthsinduces spermatogenesis.

There is no pharmacokinetic interaction between follitropin alfa and lutropin alfa when administeredsimultaneously.

Following intravenous administration, follitropin alfa is distributed to the extracellular fluid space withan initial half-life of around 2 hours and eliminated from the body with a terminal half-life of 14 to17 hours. The steady state volume of distribution is in the range of 9 to 11 L.

Following subcutaneous administration, the absolute bioavailability is 66% and the apparent terminalhalf-life is in the range of 24 to 59 hours. Dose proportionality after subcutaneous administration wasdemonstrated up to 900 IU. Following repeated administration, follitropin alfa accumulates 3-foldachieving a steady-state within 3 to 4 days.

Total clearance is 0.6 L/h and about 12% of the follitropin alfa dose is excreted in the urine.

Non-clinical data reveal no special hazard for humans based on conventional studies of single andrepeated dose toxicity and genotoxicity additional to that already stated in other sections of this SmPC.

Impaired fertility has been reported in rats exposed to pharmacological doses of follitropin alfa(≥ 40 IU/kg/day) for extended periods, through reduced fecundity.

Given in high doses (≥ 5 IU/kg/day) follitropin alfa caused a decrease in the number of viable foetuseswithout being a teratogen and dystocia similar to that observed with urinary menopausal gonadotropin(hMG). However, since Ovaleap is not indicated in pregnancy, these data are of limited clinicalrelevance.

Sodium dihydrogen phosphate dihydrate

Sodium hydroxide (2 M) (for pH adjustment)

Mannitol

Methionine

Polysorbate 20

Benzyl alcohol

Water for injections

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinalproducts.

3 years.

Shelf life and storage conditions after first opening

The cartridge in-use in the pen may be stored for a maximum of 28 days. Do not store above 25 °C.

The patient should write down in the patient diary provided with the Ovaleap Pen the date of first use.

The pen cap must be put back on the pen after each injection in order to protect from light.

Store in a refrigerator (2 °C - 8 °C).

Do not freeze.

Keep the cartridge in the outer carton in order to protect from light.

Before opening and within its shelf life, the medicinal product may be removed from the refrigerator,without being refrigerated again, for up to 3 months. Do not store above 25 °C. The medicinal productmust be discarded if it has not been used after 3 months.

For storage conditions after first opening of the medicinal product, see section 6.3.

Ovaleap 300 IU/0.5 mL solution for injection

Cartridge (type I glass) with a rubber piston (bromobutyl rubber) and a crimp-cap (aluminium) with aseptum (bromobutyl rubber), containing 0.5 mL of solution.

Injection needles (stainless steel; 0.33 mm x 12 mm, 29 G x ½')

Pack size of 1 cartridge and 10 injection needles.

Not all pack sizes may be marketed.

Ovaleap 450 IU/0.75 mL solution for injection

Cartridge (type I glass) with a rubber piston (bromobutyl rubber) and a crimp-cap (aluminium) with aseptum (bromobutyl rubber), containing 0.75 mL of solution..

Injection needles (stainless steel; 0.33 mm x 12 mm, 29 G x ½')

Pack size of 1 cartridge and 10 injection needles.

Not all pack sizes may be marketed.

Ovaleap 900 IU/1.5 mL solution for injection

Cartridge (type I glass) with a rubber piston (bromobutyl rubber) and a crimp-cap (aluminium) with aseptum (bromobutyl rubber), containing 1.5 mL of solution..

Injection needles (stainless steel; 0.33 mm x 12 mm, 29 G x ½')

Pack size of 1 cartridge and 20 injection needles.

Not all pack sizes may be marketed.

No special requirements for disposal.

The solution must not be used if it contains particles or if the solution is not clear.

Ovaleap is designed for use in conjunction with the Ovaleap Pen only. The instructions for use of thepen must be followed carefully.

Each cartridge must be used by a single patient only.

Empty cartridges must not be refilled. Ovaleap cartridges are not designed to allow any othermedicinal product to be mixed in the cartridges. Discard used needles immediately after injection.

Theramex Ireland Limited3rd Floor, Kilmore House,

Park Lane, Spencer Dock,

Dublin 1

D01 YE64

Ireland

Ovaleap 300 IU/0.5 mL solution for injection

EU/1/13/871/001

Ovaleap 450 IU/0.75 mL solution for injection

EU/1/13/871/002

Ovaleap 900 IU/1.5 mL solution for injection

EU/1/13/871/003

Date of first authorisation: 27 September 2013.

Date of latest renewal: 16 May 2018.

Detailed information on this medicinal product is available on the website of the European Medicines

Agency http://www.ema.europa.eu.