Differelin, lyophilizate 0.1 mg 7 pcs

Pharmacodynamics

A synthetic decapeptide analog of natural GnRH. Animal and clinical studies have shown that after an initial period of stimulation, long-term use of Dyferelin® suppresses gonadotropin secretion with subsequent suppression of ovarian function.

Continued use of Dyferelin® suppresses gonadotropin (FSH and LH) secretion. Suppression of intermediate endogenous LH peaks improves folliculogenesis and increases the number of maturing follicles, resulting in an increased likelihood of pregnancy per cycle.

Pharmacokinetics

In healthy volunteers

Absorption

After a 100 mcg dose of tryptorelin is rapidly absorbed by injection. Cmax in plasma is reached after 0.63±0.26 h and is 1.85±0.23 ng/mL.

Distribution

The distribution phase ends in 3-4 h, Vd is 1562±158 ml/kg.

Excretion

T1/2 is 7.6±1.6 h. Total plasma clearance is 161±28 ml/min.

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Indications

Female infertility. Ovarian stimulation together with gonadotropins (hCG, hCG, FSH) in programs of in vitro fertilization and embryo transfer, as well as other assisted reproductive technologies.

Active ingredient

Composition

1 vial contains:

The active ingredient:

Tryptorelin acetate, in terms of tryptorelin 100 mcg.

Excipients:

Mannitol – 10 mg.

Solvent:

Sodium chloride – 9 mg,

water d/i – up to 1000 mg.

How to take, the dosage

The short course of treatment

Diferelin® is administered by injection at a dose of 100 mcg/day daily, starting on day 2 of the cycle (while starting ovarian stimulation) and ending 1 day before the scheduled administration of human chorionic gonadotropin. The course of treatment is 10-12 days.

The long-term course of treatment

Differelin® is administered by p/c in a dose of 100 mcg/day daily, starting on day 2 of the cycle. In case of pituitary desensitization (E2 less than 50 pg/ml, i.e. on about the 15th day after the start of treatment) gonadotropin stimulation of the ovaries is started and Diferelin® injections are continued by p/c at a dose of 100 mcg/day, ending 1 day before the planned injection of human chorionic gonadotropin. The duration of treatment is determined by the doctor individually.

Regulations for preparation of the solution

The enclosed solvent is introduced into the vial with lyophilisate and shaken until complete dissolution. Used needles should be placed in a container designed for sharp objects.

Interaction

Drug interactions have not been described.

Special Instructions

Pregnancy should be excluded before starting treatment.

The ovarian response to p/c administration of Dyferelin in combination with gonadotropins may be markedly increased in predisposed patients, particularly in cases of polycystic ovaries.

The ovarian response to administration of the drug in combination with gonadotropins may vary among patients, and in addition, the response may be different in the same patients with different cycles.

Ovulation stimulation should be performed under medical supervision with regular analysis by biological and clinical methods: increasing plasma estrogen levels and performing ultrasound echography. If the ovarian response is excessive, it is recommended to interrupt the stimulation cycle and stop the gonadotropin injections.

Impact on ability to drive vehicles and other mechanisms requiring high concentration

As the drug may cause visual impairment in rare cases, in this case during the treatment by Diferelin® it is not recommended to drive vehicles and engage in other potentially dangerous activities requiring high concentration and quick psychomotor reactions.

Contraindications

Side effects

In the beginning of treatment

Reproductive system disorders: when combined with gonadotropins, ovarian hyperstimulation is possible (increased ovarian size, abdominal pain).

In the course of treatment

Reproductive system disorders: most often – sudden hot flashes, vaginal dryness, decreased libido and dyspareunia associated with pituitary-ovarian blockade. Digestive system: nausea, vomiting, increased liver transaminase activity.

CNS and peripheral nervous system disorders: emotional lability, visual impairment, headache.

Muscular system disorders: muscle and joint pain. Long-term use of GnRH analogues may cause bone demineralization and risk of osteoporosis (this side effect was not observed with short-term use of Diferelin® 0.1 mg).

Cardiovascular system: increase in BP.

Allergic reactions: urticaria, skin rash, itching; Quincke’s edema rarely.

Local reactions: pain at the site of administration of the drug.

Others: weight gain.

Overdose

In cases of overdose with Differelin® are not known.

Pregnancy use

Currently, GnRH analogues are used in combination with gonadotropins to stimulate ovulation and pregnancy.

Pregnancy is a contraindication for the use of the drug. However, practice has shown that after ovulation stimulated in the previous cycle, in some cases pregnancy occurred without stimulation, and the further course of ovulation stimulation was continued.

Two qualitative experimental studies in animals showed no teratogenic effects of Dyferelin.

Hence, the use of the drug is not expected to cause congenital anomalies in humans.

The results of clinical studies involving a small number of pregnant women who received the GnRH analogue showed no fetal malformations or fetotoxicity. Nevertheless, further study of the effects of the drug on pregnancy is needed.