Ovidrel

Ovidrel

choriogonadotropin alfa

Manufacturer:

Merck

Distributor:

Zuellig Pharma
Full Prescribing Info
Contents
Choriogonadotropin alfa.
Description
Choriogonadotropin alfa is produced by recombinant DNA technology in Chinese hamster ovary cells.
A dose of 250 mcg in 0.5 ml. (equivalent to approximately 6500 IU.)
The pH of the solution is 7.0 ±0.3, its osmolality 250-400 mOsm/kg.
Action
Pharmacotherapeutic group: 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 luteinizing hormone, the LH/CG receptor.
Pharmacodynamics effects: The principal pharmacodynamics 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 LH 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 a dose of 250 micrograms of Ovidrel was as effective as 5000 and 10000 IU of urinary hCG in inducing final follicular maturation and early luteinisation in assisted reproductive techniques, and as effective as 5000 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 metabolized 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 comparable 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 reveal no intrinsic toxicity of choriogonadotropin alfa. Studies on carcinogenic potential were not performed. This is justified, given the proteinous nature of the drug substance and the negative outcome of the genotoxicity testing.
Studies on reproduction were not performed in animals.
Indications/Uses
Ovidrel is indicated in the treatment of: Women undergoing superovulation prior to assisted reproductive techniques such as in vitro fertilization (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.
Dosage/Direction for Use
Ovidrel is intended for subcutaneous administration.
Treatment with Ovidrel should be performed under the supervision of a physician experienced in the treatment of fertility problems.
The following dosing regimen should be used: Women undergoing superovulation prior to assisted reproductive techniques such as in vitro fertilization (IVF): One pre-filled syringe of Ovidrel (250 micrograms) is administered 24 to 48 hours after the last administration of an FSH- or hMG preparation, i.e. when optimal stimulation of follicular growth is achieved.
Anovulatory or oligo-ovulatory women: One pre-filled syringe 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.
Special populations: Renal or hepatic impairment: Safety, efficacy and pharmacokinetics of Ovidrel in patients with renal or hepatic impairment have not been established.
Paediatric population: There is no relevant use of Ovidrel in the paediatric population.
Method of 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.
Overdosage
No case of overdosage has been reported.
Nevertheless, there is a possibility that ovarian hyperstimulation syndrome (OHSS) may result from an overdosage of Ovidrel (see Precautions).
Contraindications
Ovidrel is contraindicated for safety reasons in case of: Tumors of the hypothalamus and pituitary gland; Hypersensitivity to the active substance or to any of the excipients; 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 thrombo-embolic disorders; Primary ovarian failure; Malformations of sexual organs incompatible with pregnancy; Fibroid tumors of the uterus incompatible with pregnancy; Postmenopausal women.
Special Precautions
Before starting treatment, the couple's 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 tumors, and appropriate specific treatment given. There is no clinical experience with Ovidrel in the treatment of other conditions (such as corpus luteum insufficiency or male conditions) therefore Ovidrel is not indicated in these conditions.
Ovarian Hyperstimulation Syndrome (OHSS): Patients undergoing ovarian stimulation are at an increased risk of developing ovarian hyperstimulation syndrome (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 minimize the risk of OHSS, ultrasound scans as well as estradiol measurements are recommended. 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 > 3000 pg/mL (11000 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 pregnancy: In 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 Ovidrel dosage, regimen of administration and careful monitoring of therapy will minimize the incidence of ovarian hyperstimulation 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: No studies on the effects on the ability to drive and use machines have been performed.
Use In Pregnancy & Lactation
Considering the indication, Ovidrel should not be used during pregnancy and lactation. For Ovidrel no clinical data on exposed pregnancies are available. No reproduction studies with choriogonadotropin alfa in animals were performed. The potential risk for humans is unknown.
Breast-feeding: 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.
Adverse Reactions
In comparative trials with different doses of Ovidrel, the following undesirable effects were found to be associated with Ovidrel in a dose-related fashion: ovarian hyperstimulation syndrome, and vomiting and nausea.
Ovarian hyperstimulation syndrome was observed in approximately 4% of patients treated with Ovidrel. Severe ovarian hyperstimulation syndrome was reported in less than 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.
Psychiatric disorders: Uncommon: Depression, irritability, restlessness.
Nervous system disorders: Common: Headache.
Vascular disorders: Very rare: Thromboembolism (both in association with and separate from OHSS).
Gastrointestinal disorders: 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.
Drug Interactions
No specific interaction studies with Ovidrel and other medicines have been performed however no clinically significant drug interactions have been reported during hCG therapy.
Caution For Usage
Incompatibilities: In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
Instructions for use, handling and disposal: Ovidrel is given by injection under the skin. Each pre-filled syringe or prefilled pen is for single use only. Only clear solution without particles should be used. Any unused product or waste material should be disposed of in accordance with local requirements.
If administering Ovidrel to oneself, please carefully read the following instructions: Prefilled syringe: 1. Wash hands. It is important that hands and the items used are as clean as possible.
2. Assemble everything needed. Please note that alcohol swabs are not contained in the package. Find a clean area and lay out everything: two alcohol swabs, one pre-filled syringe containing the medicinal product.
3. Injection: Immediately inject the solution: The doctor or nurse will have already advised where to inject (e.g. tummy, front of thigh). Wipe the chosen area with an alcohol swab. Firmly pinch the skin together and insert the needle for injection at a 45° to 90° angle using a dart-like motion. Inject under the skin, as was taught. Do not inject directly into a vein. Inject the solution by pushing gently on the plunger.
Take as much time as needed to inject all the solution. Immediately withdraw the needle and clean the skin with an alcohol swab using a circular motion.
4. Dispose of all used items: Once finished with the injection, immediately discard the empty syringe in a sharps container. Any unused solution must be discarded.
Storage
Store at 2°C - 8°C (in a refrigerator). Store in the original package. Within its shelf-life, the solution may be stored at or below 25°C for up to 30 days without being refrigerated again during this period. It must be discarded if not used after 30 days.
Shelf-life: 2 years.
After opening, the product should be used immediately. However, the in-use stability has been demonstrated for 24 hours at +2° to 8°C.
MIMS Class
Trophic Hormones & Related Synthetic Drugs
ATC Classification
G03GA08 - choriogonadotropin alfa ; Belongs to the class of gonadotropins. Used as ovulation stimulants.
Presentation/Packing
Soln for inj (pre-filled syringe) 250 mcg/0.5 mL (clear, colorless to slightly yellowish) x 1's.
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