Diferelin

Diferelin – drug with antineoplastic activity.

Form of release and structure

Diferelin release in the following dosage forms:

• Lyophilisate for preparation of solution for hypodermic introduction: almost white, dispersed in the enclosed solvent with the subsequent education almost free from particles, transparent solution; solvent – colourless transparent solution (in colourless glass bottles, on 7 bottles in a cardboard pack complete with solvent (in ampoules on 1 ml, on 7 ampoules in packaging));
• Lyophilisate for preparation of suspension for intramuscular introduction of the prolonged action: white with creamy (on 3,75 mg) or yellowish (on 11,25 mg) a shade or white color, dispersed in the enclosed solvent with formation of suspension white with creamy (on 3,75 mg) or yellowish (on 11,25 mg) a shade or white color (in slightly darkened glass bottles, on 1 bottle in a cardboard pack complete with the one-time polypropylene syringe, solvent (in ampoules on 2 ml, on 1 ampoule in packaging), injection cannulas (2 pieces)).

With lyophilisate for preparation of solution for hypodermic introduction is a part of 1 bottle:

• Active agent: трипторелин – 0,1 mg (in the form of acetate of a triptorelin);
• Auxiliary component: Mannitolum – 10 mg.

Solvent: sodium chloride – 9 mg, water for injections – to 1000 mg.

With lyophilisate for preparation of suspension for intramuscular introduction of the prolonged action is a part of 1 bottle:

• Active agent: трипторелин – 3,75 or 11,25 mg (in the form of acetate of a triptorelin; for ensuring introduction of an effective dose in drug excess of substance is put);
• Auxiliary components (respectively 3,75/11,25 mg): copolymer D, L-milk and glycolic acids – about 160/250 mg, Mannitolum – 85/85 mg, a karmelloza of sodium – 30/30 mg, mg polysorbate 80 - 2/2.

Solvent: Mannitolum – 16 mg, water for injections – to 2000 mg.

Indications to use

Solution for hypodermic introduction

Diferelin appoint at treatment of female infertility: for carrying out stimulation of ovaries together with gonadotrophins (a human menopauzny gonadotrophin (chMG), a human chorionic gonadotrophin (chHG), follicle-stimulating hormone (FSG)) in programs of extracorporal fertilization and transfer of an embryo, and also at other auxiliary reproductive technologies.

Suspension of the prolonged action for intramuscular introduction

• Prostate cancer (locally-spread (as monotherapy or as adjuvant means against the background of performing radiation therapy), metastatic);
• Premature puberty;
• Endometriosis (extragenital and genital);
• Uterus fibromyoma (before performing surgery);
• Female infertility (in programs of extracorporal fertilization).

Contraindications

• Gormononezavisimy prostate cancer, states after carrying out a surgical testikulektomiya;
• Pregnancy and period of breastfeeding;
• Hypersensitivity to components of drug and other analogs of gonadotrophin-rileasing-hormone (GNRG).

Diferelin in the form of suspension it is necessary to appoint with care at osteoporosis and a syndrome of a polycystosis of ovaries.

Route of administration and dosage

Solution for hypodermic introduction

Diferelin apply subcutaneously.

Carrying out one of 2 courses of treatment is possible:

• Short: daily on 0,1 mg a day, since second day of a cycle (at the same time begin carrying out stimulation of ovaries). Therapy is completed in 1 day prior to the planned introduction of a human chorionic gonadotrophin. Course duration – 10-12 days;
• Long: daily on 0,1 mg a day, since second day of a cycle. At desensitization of a hypophysis (E2 is less than 50 pg/ml, i.e. approximately for the fifteenth day after the beginning of therapy) begin stimulation of ovaries with gonadotrophins, continuing subcutaneous injections in the same dose. The course is completed in 1 day prior to the planned introduction of a human chorionic gonadotrophin. The doctor determines treatment duration individually.

To prepare solution, the enclosed solvent needs to be entered into a bottle with lyophilisate then to shake up before full dissolution.

Suspension of the prolonged action for intramuscular introduction

Diferelin enter only intramusculary, into a gluteus.

The mode of dosing depends on indications:

• Prostate cancer: about 3,75 mg (1 injection) each 4 weeks or each 3 months on 11,25 mg are long. At treatment along with performing radiation therapy long anti-androgenic therapy (3 years) is more preferable short-term (6 months);
• Premature puberty: each 28 days on 1,875 mg (at body weight to 20 kg) or 3,75 mg (at body weight from 20 kg);
• Endometriosis: 1 time in 4 weeks on 3,75 mg or 1 time in 3 months on 11,25 mg; the injection needs to be carried out in the first 5 days of a menstrual cycle. Course duration – up to 6 months. Duration of therapy is defined by severity of endometriosis and a clinical picture (anatomic and functional changes) against the background of therapy. It is not recommended to carry out a repeated course of treatment triptoreliny or other analog of GNRG;
• Female infertility: 1 injection on 3,75 mg for the second day of a cycle. Communication with gonadotrophins needs to be controlled after desensitization of a hypophysis (concentration of estrogen in a blood plasma less than 50 »¬ú/ml usually is defined in 15 days after administration of drug);
• Uterus fibromyoma: each 4 weeks on 3,75 mg. Suspension needs to be entered in the first 5 days of a menstrual cycle. For the patients preparing for operation duration of a course of treatment makes 3 months.

Suspension for intramuscular introduction is prepared just before the procedure by dissolution of lyophilisate in the enclosed solvent.

Side effects

Solution for hypodermic introduction

At the beginning of Diferelin's use at a combination to gonadotrophins there can be disturbances of reproductive system in the form of hyper stimulation of ovaries (an abdominal pain, increase in the sizes of ovaries).

In the course of therapy development of the following side effects is possible:

• Reproductive system: very often – the dryness of a vagina, sudden inflows, a dispareuniya and decrease in a libido connected with gipofizo-ovarian blockade;
• Alimentary system: vomiting, nausea, increase in activity of hepatic transaminases;
• Central and peripheral nervous system: vision disorder, emotional lability, headache;
• Musculoskeletal system: joint and muscular pains; at long therapy by GNRG analogs – demineralization of bones, risk of development of osteoporosis (this disturbance is not observed at short-term use of Diferelin in a dose of 0,1 mg);
• Cardiovascular system: increase in arterial pressure;
• Allergic reactions: skin rash, small tortoiseshell, itch; seldom – a Quincke's edema;
• Local reactions: pain in a solution injection site;
• Others: increase in body weight.

Suspension of the prolonged action for intramuscular introduction

• Musculoskeletal system: at long therapy – demineralization of bones that is risk factor of development of osteoporosis. At the beginning of therapy at a prostate cancer patients can experience temporary strengthening of pains in the bones affected with metastasises (carrying out a symptomatic treatment is shown). In some cases – impassability of ureters and emergence of the signs connected with a compression metastasises of a spinal cord (pass in 7-14 days). Also at this time short increase in activity of acid phosphatase in a blood plasma can be observed;
• Cardiovascular system: in isolated cases – feeling of inflows, arterial hypertension;
• Central nervous system: in isolated cases – a vision disorder, the increased emotional lability;
• Reproductive system: men – decrease in a potentiality; women – a depression, a headache, change a libido, perspiration, change of the size of mammary glands, dryness of a mucous membrane of a vagina, a dispareuniya; at simultaneous use with gonadotrophins – development of a syndrome of hyper stimulation of ovaries; at therapy of premature puberty at girls – bloody allocations from a vagina; at long treatment – a hypogonadotropic amenorrhea;
• Alimentary system: in isolated cases – vomiting, nausea;
• Allergic reactions: rash, urticaria, itch; very seldom – a Quincke's edema;
• Local reactions: in isolated cases – pain in a suspension injection site;
• Others: in isolated cases – fervescence, increase in body weight.

Special instructions

Before Diferelin's use it is necessary to exclude pregnancy.

Solution for hypodermic introduction

Response of ovaries to hypodermic administration of solution along with gonadotrophins at predisposed patients can increase considerably, in particular, at a polycystosis of ovaries.

Response of ovaries to Diferelin's introduction together with gonadotrophins at different patients can differ, even the same women at different cycles can have various reaction.

Stimulation of an ovulation needs to be carried out under observation of the doctor, carrying out regular analyses by means of clinical and biological methods: carrying out an ultrasonic ekhografiya and increase in content of estrogen in plasma. At excess response of ovaries, the cycle of stimulation is recommended to be interrupted, having stopped gonadotrophin injections.

As in certain cases during therapy there can be a vision disorder, it is necessary to be careful at control of motor transport and performance of potentially dangerous types of the works demanding high concentration of attention and bystry psychomotor reactions.

Suspension of the prolonged action for intramuscular introduction

At the beginning of therapy strengthening of clinical signs because of what Diferelin it is necessary to appoint with care the patient with cancer of a prostate who are subject to risk of development of a prelum of a spinal cord or impassability of ureters is possible. Within the first month of therapy behind a condition of such patients careful medical observation is necessary.

Against the background of a polycystosis of ovaries when carrying out schemes of stimulation of an ovulation Diferelin it is necessary to apply with care as it can lead to growth of quantity of the induced follicles.

At extracorporal fertilization it is necessary to monitorirovat carefully the level of stimulation of a cycle (for identification of patients with risk of development of a syndrome of hyper stimulation of ovaries). In need cases introduction of a chorionic gonadotrophin of the person needs to be stopped.

Medicinal interaction

There are no data on Diferelin's interaction with other medicines.

Terms and storage conditions

To store in the place, unavailable to children, at a temperature up to 25 °C.

Period of validity:

• Lyophilisate for preparation of solution for hypodermic introduction – 2 years;
• Lyophilisate for preparation of suspension for intramuscular introduction: on 3,75 mg – 2 years, on 11,25 mg – 3 years; solvent – 5 years.