n
Distribution, metabolism and elimination of corifollitropin alfa are very similar to other gonadotropins, such as FSH, hCG and LH. After absorption into the blood, corifollitropin alfa is distributed mainly to the ovaries and the kidneys. The steady state volume of distribution is 9.2 L (6.5-13.1 L1). Exposure to corifollitropin alfa increases proportionally with dose within the range of 60 micrograms to 240 micrograms.
Elimination
Corifollitropin alfa has an elimination half-life of 70 hours (59-82 hours1) and a clearance of 0.13 L/h (0.10-0.18 L/h1). Elimination of corifollitropin alfa predominantly occurs via the kidneys, and the rate of elimination may be reduced in patients with renal insufficiency (see sections 4.2 and 4.4). Hepatic metabolism contributes to a minor extent to the elimination of corifollitropin alfa.
Other special populations
Hepatic impairment
Although data in hepatically impaired patients are not available, hepatic impairment is unlikely to affect the pharmacokinetic profile of corifollitropin alfa.
1 Predicted range for 90% of subjects.
5.3 Preclinical safety data
Preclinical data revealed no special hazard for humans based on conventional studies of single and repeated dose toxicity and safety pharmacology.
Reproduction toxicology studies in rats and rabbits indicated that corifollitropin alfa does not adversely affect fertility. Administration of corifollitropin alfa to rats and rabbits, prior to and directly after mating, and during early pregnancy, resulted in embryotoxicity. In rabbits, when administered prior to mating, teratogenicity has been observed. Both embryotoxicity and teratogenicity are considered a consequence of the superovulatory state of the animal not able to support a number of embryos above a physiological ceiling. The relevance of these findings for the clinical use of Elonva is limited.
6. Pharmaceutical particulars
6.1 List of excipients
Sodium citrate
Sucrose
Polysorbate 20
Methionine
Sodium hydroxide (for pH adjustment)
Hydrochloric acid (for pH adjustment)
Water for injections
6.2 Incompatibilities
In the absence of compatibility studies, the medicinal product must not be mixed with other medicinal products.
6.3 Shelf life
3 years
6.4 Special precautions for storage
Store in a refrigerator (2°C-8°C).
Do not freeze.
For convenience, the patient is allowed to store the product at or below 25°C for a period of not more than 1 month.
Keep the syringe in the outer carton in order to protect from light.
6.5 Nature and contents of container
Elonva is supplied in pre-filled luerlock syringes of 1 mL (type I hydrolytic glass), closed with a bromobutyl elastomer plunger and a tip cap. The syringe is equipped with an automatic safety system to prevent needle stick injuries after use and is packed together with a sterile injection needle. Each pre-filled syringe contains 0.5 mL solution for injection.
Elonva is available in pack sizes of 1 pre-filled syringe.
6.6 Special precautions for disposal and other handling
Do not use Elonva if the solution is not clear.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
7. Marketing authorisation holder
Merck Sharp & Dohme B.V.
Waarderweg 39
2031 BN Haarlem
The Netherlands
8. Marketing authorisation number(s)
Elonva 100 micrograms solution for injection: EU/1/09/6 |
