- 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
PosologyThe maximum dose is 250 micrograms. The following dose regimen should be used:• Women undergoing superovulation prior to assisted reproductive techniques such as in vitro fertilisation (IVF): One prefilled syringe of Ovitrelle (250 micrograms) is administered 24 to 48 hours after the last administration of a follicle stimulating hormone (FSH) or human menopausal gonadotropin (hMG) preparation, i.e. when optimal stimulation of follicular growth is achieved.• Anovulatory or oligoovulatory women: One prefilled syringe of Ovitrelle (250 micrograms) is administered 24 to 48 hours after optimal stimulation of follicular growth is achieved. The patient is recommended to have coitus on the day of, and the day after, Ovitrelle injection.
Renal or hepatic impairmentSafety, efficacy and pharmacokinetics of Ovitrelle in patients with renal or hepatic impairment have not been established.
Paediatric populationThere is no relevant use of Ovitrelle in the paediatric population.
Method of administrationFor subcutaneous use. Selfadministration of Ovitrelle should only be performed by patients who are adequately trained and have access to expert advice.Ovitrelle is for single use only.
Ovarian Hyperstimulation Syndrome (OHSS)Patients undergoing ovarian stimulation are at an increased risk of developing OHSS due to multiple follicular development.Ovarian hyperstimulation syndrome may become a serious medical event characterised by large ovarian cysts, which are prone to rupture, weight gain, dyspnoea, oliguria or the presence of ascites within a clinical picture of circulatory dysfunction. Severe OHSS could be complicated in rare cases by haemoperitoneum, acute pulmonary distress, ovarian torsion, and thromboembolism. To minimise the risk of OHSS, ultrasonographic assessments of follicular development and/or determination of serum estradiol levels should be performed prior to treatment and at regular intervals during treatment. In anovulation, the risk of OHSS is increased by a serum estradiol level > 1500 pg/mL (5400 pmol/L) and more than 3 follicles of 14 mm or more in diameter. In assisted reproductive techniques, there is an increased risk of OHSS with a serum estradiol > 3,000 pg/mL (11,000 pmol/L) and 18 or more follicles of 11 mm or more in diameter.OHSS due to excessive ovarian response can be avoided by withholding hCG administration. Therefore, if signs of ovarian hyperstimulation occur such as serum estradiol level > 5,500 pg/mL (20,000 pmol/L) and/or when there are 30 or more follicles in total, it is recommended to withhold hCG administration and the patient be advised to refrain from coitus or to use barrier contraceptive methods for at least 4 days.
Multiple pregnancyIn patients undergoing induction of ovulation, the incidence of multiple pregnancy and births (mostly twins) is increased compared with natural conception. The risk of multiple pregnancy following assisted reproductive techniques is related to the number of embryos replaced. Adherence to recommended Ovitrelle dose, regimen of administration and careful monitoring of therapy will minimise the risk of OHSS and multiple pregnancy.
MiscarriageThe rate of miscarriage, in both anovulatory patients and women undergoing assisted reproductive techniques, is higher than that found in the normal population but comparable with the rates observed in women with other fertility problems.
Ectopic pregnancySince infertile women undergoing ART, and particularly IVF, often have tubal abnormalities, the incidence of ectopic pregnancies might be increased. It is important to have early ultrasound confirmation that a pregnancy is intrauterine, and to exclude the possibility of extrauterine pregnancy.
Congenital malformationsThe incidence of congenital malformations after ART may be slightly higher than after spontaneous conceptions. This is thought to be due to differences in parental characteristics (e.g. maternal age, sperm characteristics) and the higher incidence of multiple pregnancies.
Thromboembolic eventsIn women with recent or ongoing thromboembolic disease or women with generally recognised risk factors for thromboembolic events, such as personal or family history, treatment with gonadotropins may further increase the risk for aggravation or occurrence of such events. In these women, the benefits of gonadotropin administration need to be weighed against the risks. It should be noted, however, that pregnancy itself as well as OHSS also carry an increased risk of thromboembolic events, such as pulmonary embolism, ischaemic stroke or myocardial infarction.
Interference with serum or urinary testingFollowing administration, Ovitrelle may interfere for up to ten days with the immunological determination of serum or urinary hCG, potentially leading to a false positive pregnancy test.Patients should be made aware of this.
Other informationDuring Ovitrelle therapy, a minor thyroid stimulation is possible, of which the clinical relevance is unknown.This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. it is essentially sodiumfree
PregnancyThere is no indication for the use of Ovitrelle during pregnancy. No clinical data on exposed pregnancies are available. No reproduction studies with choriogonadotropin alfa in animals were performed (see section 5.3). The potential risk for humans is unknown.
Breast-feedingOvitrelle is not indicated during breastfeeding.There are no data on the excretion of choriogonadotropin alfa in milk.
FertilityOvitrelle is indicated for use in infertility (see section 4.1).
Summary of the safety profileIn comparative trials with different doses of Ovitrelle, the following adverse reactions were found to be associated with Ovitrelle in a dose-related fashion: OHSS, vomiting and nausea. OHSS was observed in approximately 4% of patients treated with Ovitrelle. Severe OHSS was reported in less than 0.5% of patients (see section 4.4).
List of adverse reactionsThe following definitions apply to the frequency terminology used hereafter: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000), not known (cannot be estimated from the available data).
|Immune system disorders|
|Very rare:||Mild to severe hypersensitivity reactions including anaphylactic reactions and shock|
|Uncommon:||Depression, irritability, restlessness|
|Nervous system disorders|
|Very rare:||Thromboembolism, usually associated with severe OHSS|
|Common:||Vomiting, nausea, abdominal pain|
|Skin and subcutaneous tissue disorders|
|Very rare:||Mild reversible skin reactions manifesting as rash|
|Reproductive system and breast disorders|
|Common:||Mild or moderate OHSS|
|Uncommon:||Severe OHSS, breast pain|
|General disorders and administration site conditions|
|Common:||Tiredness, injection site reactions.|
Reporting of suspected adverse reactionsReporting 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 (see details below).
United KingdomYellow Card Scheme Website: www.mhra.gov.uk/yellowcard
IrelandHPRA Pharmacovigilance Earlsfort Terrace IRL - Dublin 2 Tel: +353 1 6764971 Fax: +353 1 6762517 Website: www.hpra.ie e-mail: email@example.com
Mechanism of actionOvitrelle is a medicinal product of choriogonadotropin alfa produced by recombinant DNA techniques. It shares the amino acid sequence with urinary hCG. Chorionic gonadotropin binds on the ovarian theca (and granulosa) cells to a transmembrane receptor shared with the luteinising hormone, the LH/CG receptor.
Pharmacodynamic effectsThe principal pharmacodynamic activity in women is oocyte meiosis resumption, follicular rupture (ovulation), corpus luteum formation and production of progesterone and estradiol by the corpus luteum.In women, chorionic gonadotropin acts as a surrogate luteinising hormone surge that triggers ovulation.Ovitrelle is used to trigger final follicular maturation and early luteinisation after use of medicinal products for stimulation of follicular growth.
Clinical efficacy and safetyIn comparative clinical trials, administration of a dose of 250 micrograms of Ovitrelle was as effective as 5,000 IU and 10,000 IU of urinary hCG in inducing final follicular maturation and early luteinisation in assisted reproductive techniques, and as effective as 5,000 IU of urinary hCG in ovulation induction.So far, there are no signs of antibody development in humans to Ovitrelle. Repeated exposure to Ovitrelle was investigated in male patients only. Clinical investigation in women for the indication of ART and anovulation was limited to one treatment cycle.
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