Choriogonadotropin alfa is produced by recombinant DNA technology in Chinese Hamster Ovary cells.
A dose of 250 micrograms in 0.5 ml. (equivalent to approximately 6500 IU).
Pharmacotherapeutic Group: Sex hormones and modulators of the genital system, gonadotropins. ATC Code: G03G A08.
Pharmacology: Pharmacodynamics: Mechanism of Action: Ovidrel is a medicinal product of chorionic gonadotropin 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 (LH), the LH/CG receptor.
Pharmacodynamic Effects: The 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.
Ovidrel is used to trigger final follicular maturation and early luteinisation after use of medicinal products for stimulation of follicular growth.
Clinical Efficacy and Safety: In comparative clinical trials, administration of Ovidrel 250 micrograms was as effective as 5,000 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 Ovidrel. Repeated exposure to Ovidrel was investigated in male patients only. Clinical investigation in women for the indication of ART and anovulation was limited to one treatment cycle.
Pharmacokinetics: Following intravenous administration, choriogonadotropin alfa is distributed to the extracellular fluid space with a distribution half-life of around 4.5 hours. The steady-state volume of distribution and the total clearance are 6 L and 0.2 L/h, respectively. There are no indications that choriogonadotropin alfa is metabolised and excreted differently than endogenous hCG.
Following subcutaneous administration, choriogonadotropin alfa is eliminated from the body with a terminal half-life of about 30 hours, and the absolute bioavailability is about 40%.
A comparative study between the currently registered freeze-dried formulation and the liquid formulation showed bioequivalence between the two formulations.
Toxicology: Preclinical Safety Data: Preclinical safety data reveals no intrinsic toxicity of choriogonadotropin α. Studies on carcinogenic potential were not performed. This is justified, given the proteinous nature of choriogonadotripin alfa and the negative outcome of the genotoxicity testing.
Studies on reproduction were not performed in animals.
Ovidrel is indicated in the treatment of: Women undergoing superovulation prior to assisted reproductive techniques such as in vitro fertilisation (IVF). Ovidrel is administered to trigger final follicular maturation and luteinisation after stimulation of follicular growth.
Anovulatory or oligo-ovulatory women: Ovidrel is administered to trigger ovulation and luteinisation in anovulatory or oligo-ovulatory patients after stimulation of follicular growth.
Treatment with Ovidrel should be performed under the supervision of a physician experienced in the treatment of fertility problems.
The maximum dose is 250 micrograms. The following dosing regimen should be used:
Women Undergoing Superovulation Prior to Assisted Reproductive Techniques such as In Vitro Fertilisation (IVF): One pre- filled pen of Ovidrel (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 Oligo-Ovulatory Women: One pre-filled pen of Ovidrel (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, Ovidrel injection.
Administration: For subcutaneous use. Self-administration of Ovidrel should only be performed by patients who are adequately trained and have access to expert advice.
Ovidrel is for single use only.
The effects of an overdose of Ovidrel is unknown.
Nevertheless, there is a possibility that OHSS may result from an overdose of Ovidrel (see Precautions).
Hypersensitivity to the active substance or to any of the excipients.
Tumours of the hypothalamus and pituitary gland; Ovarian enlargement or cyst due to reasons other than polycystic ovarian disease; Gynaecological haemorrhages of unknown aetiology; Ovarian, uterine or mammary carcinoma; Extrauterine pregnancy in the previous 3 months; Active thromboembolic disorders; Primary ovarian failure; Malformations of sexual organs incompatible with pregnancy; Fibroid tumours of the uterus incompatible with pregnancy; Postmenopausal women.
Before starting treatment, the couples infertility should be assessed as appropriate and putative contraindications for pregnancy evaluated. In particular, patients should be evaluated for hypothyroidism, adrenocortical deficiency, hyperprolactinemia and pituitary or hypothalamic tumours, and appropriate specific treatment given.
To date, there is no clinical experience with Ovidrel in other indications commonly treated with urine derived human chorionic gonadotropin.
Special precautions should be taken before administering Ovidrel to patients with clinically significant systemic disease where pregnancy could lead to a worsening of the condition.
Ovarian Hyperstimulation Syndrome (OHSS): Patients undergoing ovarian stimulation are at an increased risk of developing ovarian hyperstimulation syndrome (OHSS) due to multiple follicular development.
OHSS 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 >1,500 pg/ml (5,400 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 >5500 pg/mL (20000 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 Pregnancy: In patients undergoing induction of ovulation, the incidence of multiple pregnancy and births (mostly twins) is increased compared to natural conception.
The risk of multiple pregnancy following assisted reproductive techniques is related to the number of embryos replaced.
Adherence to recommended Ovidrel dosage, regimen of administration and careful monitoring of therapy will minimise the incidence of OHSS and multiple pregnancy.
Miscarriage: The 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 Pregnancy: Since 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 Malformations: The 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 Events: In 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 Testing: Following administration, Ovidrel 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 Information: During Ovidrel 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 "sodium free".
Effects on Ability to Drive and Use Machines: Ovidrel is expected to have no or negligible influence on the ability to drive and use machines.
Use in Pregnancy: There is no indication for the use of Ovidrel during pregnancy. No clinical data on exposed pregnancies are available. No reproduction studies with choriogonadotropin alfa in animals were performed (see Toxicology: Preclinical Safety Data under Actions). The potential risk for humans is unknown.
Use in Lactation: Ovidrel is not indicated during breastfeeding. There are no data on the excretion of choriogonadotropin alfa in milk.
Fertility: Ovidrel is indicated for use in infertility (see Indications).
Summary of Safety Profile:
In comparative trials with different doses of Ovidrel, the following adverse reactions were found to be associated with Ovidrel in a dose-related fashion: Ovarian hyperstimulation syndrome (OHSS), vomiting and nausea. OHSS was observed in approximately 4% of patients treated with Ovidrel. Severe OHSS was reported in <0.5% patients (see Precautions).
List of Adverse Reactions:
The 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. Uncommon: Diarrhoea.
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.
Ectopic pregnancy, ovarian torsion and other complications have been reported in patients after hCG administration. These are considered concomitant effects related to assisted reproductive techniques.
Interaction with Other Medicinal Products and Other Forms of Interaction: No specific interaction studies with Ovidrel and other medicinal products have been performed however no clinically significant medicinal product interactions have been reported during hCG therapy.
Incompatibilities: In the absence of incompatibility studies, Ovidrel must not be mixed with other medicinal products.
Store at 2°C-8°C (in a refrigerator). Do not freeze.
G03GA08 - choriogonadotropin alfa ; Belongs to the class of gonadotropins. Used as ovulation stimulants.
Soln for inj (pre-filled pen, clear, colourless soln) 250 mcg/0.5 mL x 1's.