Diferelin

General characteristics. Structure:

Active agent: a triptorelina памоат, in terms of трипторелин 11.25 mg *
* - taking into account features of a dosage form in drug excess of active agent for ensuring introduction of an effective dose is put.

Excipients: copolymer D, L-milk and glycolic acids - 250 mg, Mannitolum - 85 mg, a karmelloza of sodium (sodium carboxymethylcellulose) - 30 mg, polysorbate of 80 - 2 mg.

Solvent: Mannitolum - 16 mg, water for and - to 2000 mg.

Pharmacological properties:

Synthetic decapeptide, analog of natural GNRG.
After a short initial stage of stimulation of gonadotropic function of a hypophysis трипторелин has an inhibiting effect on secretion of gonadotrophins with the subsequent suppression of function of testicles and ovaries.
In an initial stage of use of Diferelin® temporarily increases concentration of LG and FSG in blood, concentration of testosterone at men and oestradiol at women respectively increases. Prolonged treatment reduces concentration of LG and FSG that leads to reduction of indicators of testosterone (to the levels corresponding to a state after a testikulektomiya) and to reduction of indicators of oestradiol (to the levels corresponding to a condition of a post-ovariectomy) - approximately by 20th day after the first injection and further remains invariable throughout the entire period of administration of drug.
Prolonged treatment triptoreliny suppresses secretion of oestradiol at women and, thus, interferes with development of endometrioid ektopiya.

Pharmacokinetics. Absorption and distribution. At introduction in oil Diferelina in a dose of 11.25 mg of Cmax of a triptorelin in a blood plasma (at men and women) is defined approximately by 3 h after an injection. After a phase of decrease in the concentration proceeding within the first month, till 90 in the afternoon concentration of the circulating triptorelin remains to a constant (from about 0.04 to 0.05 ng/ml at treatment of endometriosis and about 0.1 ng/ml at cancer therapy of a prostate).

Indications to use:

Prostate cancer:
— treatment of a locally-spread prostate cancer in monotherapy or as adjuvant means against the background of radiation therapy;
— treatment of a metastatic prostate cancer.

Genital and extragenital endometriosis (stage of I-IV).

Route of administration and doses:

At a prostate cancer of Diferelin® enter in oil each 3 months in a dose of 11.25 mg. At treatment in a combination with radiation therapy long anti-androgenic therapy (3 years) is more preferable than short-term anti-androgenic therapy (6 months).
At endometriosis the drug is administered by in oil each 3 months in a dose of 11.25 mg. Treatment needs to be begun in the first 5 days of a menstrual cycle. Duration of treatment depends on severity of endometriosis and an observed clinical picture (functional and anatomic changes) against the background of therapy. As a rule, treatment is carried out for 3-6 months. It is not recommended to carry out a repeated course of treatment triptoreliny or other analog of GNRG.

Rules of preparation of suspension
Dissolution of lyophilisate in the enclosed solvent has to be carried out just before introduction. It is necessary to mix bottle contents with care before receiving homogeneous suspension.
About the cases of implementation of an incomplete injection leading to loss of bigger amount of suspension than usually remains in the syringe for an injection, it is necessary to tell the attending physician.

Introduction has to be carried out in strict accordance with the instruction.
The patient has to be in a prone position. Disinfect buttock skin.
1. Break an ampoule neck (a point on the face from above).
2. Gather solvent in the syringe with a needle.
3. Remove a green protective plastic cover from an upper part of a bottle.
4. Transfer solvent to a bottle with lyophilisate.
5. Pull a needle so that it remained in a bottle, but did not concern suspension.
6. Without overturning a bottle, accurately shake up contents before receiving homogeneous suspension.
7. Check lack of agglomerates before you gather suspension in the syringe (in case of lack of agglomerates, shake up to total homogeneity).
8. Without overturning a bottle, gather all suspension in the syringe.
9. Remove the needle used for suspension preparation and densely attach other needle on a syringe tip. You hold only a color tip.
10. Remove air from the syringe.
11. Immediately make an injection in a gluteus.
12. Utilize needles in the containers intended for sharp objects.

Features of use:

At treatment of endometriosis
Before an initiation of treatment it is necessary to exclude pregnancy.

Within the first month of therapy it is necessary to use non-hormonal contraceptive means.

The injection of drug in oil leads to a resistant hypogonadotropic amenorrhea.

Treatment should not be recommended for the period more than 6 months. It is not recommended to conduct a repeated course of therapy triptoreliny or other analog of GNRG.

Emergence of a metrorrhagia during treatment, apart from the first month, is not norm in this connection it is necessary to define concentration of oestradiol in a blood plasma. At decrease in concentration of oestradiol less than 50 pg/ml are possible existence of other organic lesions.

Function of ovaries is recovered after completion of therapy. The first periods come on average in 134 days after the last injection. Therefore measures of contraception should begin to be applied in 15 days after the treatment termination, that is in 3.5 months after the last injection.

At cancer therapy of a prostate

The most expressed favorable effect is noted at patients in the absence of other earlier carried out hormonal therapy.

In an initiation of treatment emergence and strengthening of the clinical symptoms (in particular, ostealgias, the dysuric phenomena) having passing character can be observed.

It assumes careful observation of these patients within the first several weeks of therapy (testosterone level in a blood plasma should not exceed 1 ng/ml).

For the same reason careful observation in an initiation of treatment needs to be made for patients with the diagnosed compression of a spinal cord.

Besides, in an initiation of treatment temporary increase in acid phosphatases can be observed.

At the patients receiving GNRG agonists the risk of development of a hyperglycemia and diabetes mellitus is registered. Besides, the risk of development of cardiovascular diseases is possible and, at prolonged use, osteoporosis.

Influence on ability to driving of motor transport and to control of mechanisms
Data are absent.

Side effects:

At men
In an initiation of treatment: a dysuria (difficulty of an urination, incomplete bladder emptying, morbidity), ostealgias connected with metastasises and a compression metastasises of a spinal cord which can be aggravated because of temporary increase in content of testosterone in a blood plasma in an initiation of treatment. These symptoms pass through 1-2 weeks. Also during this period temporary increase in activity of liver enzymes in a blood plasma can be observed.
During treatment: inflows, decrease a libido, a gynecomastia, impotence that is connected with reduction of content of testosterone in a blood plasma.

At women
In an initiation of treatment: the symptoms connected with endometriosis (pelvic pains, a dysmenorrhea) which can amplify in connection with initial passing increase in concentration of oestradiol in a blood plasma and disappear in 1-2 weeks. In 1 month after the first injection there can be genital bleedings including both a menorrhagia, and a metrorrhagia.
During treatment: dryness of a vagina, inflows, decrease in a libido, increase in mammary glands, a dispareuniya that is connected with pituitary and ovarian blockade; seldom - a headache, an arthralgia, a mialgiya.

At men and at women
Allergic reactions, such as small tortoiseshell, rash, itch and it is very rare - a Quincke's edema; disturbance of mood, irritability, a depression, feeling of fatigue, a sleep disorder, nausea, vomiting, increase in body weight, profuse sweat, arterial hypertension, paresthesias, deterioration in sight, pain in the place of an injection and a feverish state.

Prolonged use of analogs of GNRG can lead to demineralization of bones and is possible risk factor of developing of osteoporosis.

According to the data collected during use of analogs of GNRG patients can have following side reactions: erectile dysfunction, a ring in ears, dizziness, a diabetes mellitus (hyperglycemia), an abdominal pain, a lock, diarrhea, abdominal distention, dryness of a mucous membrane of an oral cavity, a dysgeusia, a meteorism, an adynamy; drowsiness, grippopodobny syndrome, anaphylactic reactions; increase in activity of ALT, nuclear heating plant, ShchF; a giperkreatininemiya, increase in urea in blood, anorexia, gout, the increased appetite, musculoskeletal pains, extremity pains, muscular spasms, muscular weakness, dizziness, a memory impairment, sleeplessness, confusion of consciousness, alarm, an atrophy of testicles, an asthma, an orthopnea, nasal bleeding, an acne, an alopecia, decrease in the ABP; in the place of an injection - an erythema, an inflammation, pain.

Interaction with other medicines:

Medicinal interaction of the drug Diferelin® is not described.

Contraindications:

— hypersensitivity to a triptorelin, other components of drug or other analogs of GNR.

At men:
— a gormononezavisimy prostate cancer, a state after the previous surgical testikulektomiya.

At women:
— pregnancy;
— period of a lactation (breastfeeding).

With care it is necessary to appoint drug at osteoporosis, to women with a syndrome of a polycystosis of ovaries.

Use of the drug ДИФЕРЕЛИН® 11.25 of mg at pregnancy and feeding by a breast
Диферелин® it is contraindicated to use at pregnancy and in the period of a lactation (breastfeeding).
As there are no data on removal of a triptorelin in with breast milk and its possible effects on the nursed child, it is not necessary to carry out treatment by the drug Diferelin® during breastfeeding.
According to the available data, any teratogenic effects at pilot studies on animals are not revealed. In isolated cases of use of analogs of GNRG (on imprudence) any defects of fetation and fetotoksichnost are not revealed.

Overdose:

So far cases of overdose of the drug Diferelin® are unknown.

Storage conditions:

Drug should be stored in the place, unavailable to children, at a temperature not above 25 °C.

Issue conditions:

According to the recipe

Packaging:

Lyophilisate for пригот. сусп. for introduction in oil пролонгир. actions of 11.25 mg: фл. 1 pieces in set. with solvent, one-time. syringe and 2 needles.