Differelin

The antitumor hormonal agent Diphereline belongs to the pharmacological group of analogues (agonists) of the hormone gonadotropin-releasing hormone (gonadotropin-releasing hormone or GnRH).

Other trade names: Triptorelin, Decapeptyl depot. Analogues: Goserelin (Zoladex), Buserelin (Buserelin-long), Leuprorelin (Lupron depot, Leuprolide, Lecrin depot).

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Indications Differelina.

The main indications for the use of Diphereline as an antitumor agent include hormone-dependent disseminated prostate carcinoma in men, and can also be prescribed for endometriosis, uterine fibromatosis and benign myometrial neoplasia (myomas) in women.

The drug is used in the treatment of hypogonadotropic amenorrhea (i.e. caused by decreased ovarian function).

Diphereline has found application in reproductive medicine – for the treatment of endocrine infertility in women and preparation (ovarian stimulation) for in vitro fertilization (IVF).

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Release form

Lyophilisate for the preparation of a solution for subcutaneous administration and for intramuscular administration of prolonged action

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Pharmacodynamics

The pharmacodynamics of the drug Diphereline is due to the action of a synthetic analogue of the endogenous hypothalamic hormone gonadotropin-releasing hormone (gonadotropin-releasing hormone or GnRH) – triptorelin (D-tryptophan-6-gonadorelin acetate).

The effect of Diphereline is two-stage. First, there is stimulation of the anterior pituitary gland with an increase in the release of gonadotropic hormones - luteinizing (LH) and follicle-stimulating (FSH), which leads to a temporary increase in the level of estradiol in the body of women, and in men, through indirect activation of interstitial cells of the testicles, to an increase in testosterone synthesis.

But at the second stage, the effect of this drug on the pituitary gland completely blocks the sensitivity of its receptors to gonadotropin-releasing hormone, and the secretion of LH and FSH decreases with a gradual cessation of their production. Accordingly, the content of female and male sex hormones is sharply reduced: women experience artificial menopause, and men stop spermatogenesis. Both processes are reversible after stopping the use of Diphereline.

The factor of reducing sex hormones and their influence on the growth of cancer cells is used in oncology for the treatment of prostate cancer in men, as well as in drug therapy for benign uterine tumors associated with increased cell proliferation in women.

Diphereline is used in IVF due to its effect on ovulation, since suppression of LH synthesis prevents the egg from leaving the ovary too early (premature ovulation). Suppression of spontaneous surges of luteinizing hormone promotes better folliculogenesis and increases the likelihood of pregnancy.

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Pharmacokinetics

The bioavailability of triptorelin after subcutaneous injection of Diphereline is 70%; the drug quickly enters the blood, but does not bind to plasma proteins. The maximum concentration in the blood is noted 30-40 minutes after administration.

The half-life ranges from 3.5 to 6.5 hours.

Triptorelin is broken down in the liver, but the biochemical mechanism of this

Dosing and administration

The drug Diphereline is used by subcutaneous injections. When treating prostate cancer, the first seven days are daily injected into the skin of the abdominal wall at a dose of 0.5 mg (once). Then the dose is reduced to 0.1 mg - once a day.

The method of administration and dosage for the treatment of endometriosis, uterine fibroids and myoma in women is similar.

For long-term use, doctors recommend a slow-release drug of triptorelin - Diphereline extended-release (containing 3.75 mg of the active substance), which is administered once every four weeks (the injection should be done in the first five days of the menstrual cycle).

Diphereline for IVF in a short protocol is administered on the first day of the menstrual cycle - 0.1 mg (once a day) for 10 days.

To stimulate ovulation, Diphereline in IVF in a long protocol is administered starting in the middle of the luteal phase (i.e. on the 21st-23rd day of the menstrual cycle) - once a day (at the same time), subcutaneously into the anterior abdominal wall; the dose is determined by the doctor for each patient individually - based on the results of blood tests for hormone levels. The following injections can be done independently, the nurse should instruct the patient how to inject Diphereline into the abdomen. The drug is administered for 12-22 days: the duration is also determined by the doctor during ultrasound monitoring of the ovaries every three days - in order to accurately determine the time of administration of chorionic gonadotropin drugs and subsequent ovarian puncture (to obtain a mature egg). Normally, menstruation should be absent after Diphereline, since the drug blocks the production of luteotropin by the pituitary gland, which leads to aminorrhea.

Diphereline is used in a lower dosage in the cryoprotocol, and before implantation the embryo is kept frozen (cryopreservation in liquid nitrogen).

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Use Differelina. during pregnancy

Diphereline is not used during pregnancy and lactation.

Contraindications

Diphereline is contraindicated in case of hypersensitivity to the drug and other synthetic analogues of gonadotropin-releasing hormone, during pregnancy and lactation, with pituitary adenoma, severe forms of allergy, osteoporosis, polycystic ovary disease and in patients under 18 years of age.

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Side effects Differelina.

The most likely side effects of Diphereline are:

• nausea and loss of appetite;
• itching and hyperemia of the skin:
• hyperhidrosis, night sweats, hot flashes to the face and chest;
• increased blood pressure;
• dizziness, fainting and headaches;
• shortness of breath and irregular heartbeat;
• numbness of the limbs (paresthesia);
• abdominal, muscle and joint pain;
• decreased visual acuity;
• increased levels of glucose and cholesterol in the blood;
• frequent mood swings, depression, sleep disorders, decreased sexual desire (decreased potency in men);
• dryness of the vaginal mucosa, dyspareunia, uterine bleeding, painful menstruation, the appearance of ovarian cysts in women;
• reduction of testicles and hair growth, enlargement of mammary glands in men;
• decreased bone density.

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Overdose

Overdose of Diphereline may lead to increased side effects; in such cases, treatment should be discontinued.

Interactions with other drugs

Interactions of Diphereline with other drugs have not been studied, so they should not be excluded. In any case, combining this antitumor hormonal agent and antibiotics, antihistamines, neuroleptics, etc. is not recommended.

In addition, Diphereline and alcohol can aggravate such side effects of the drug as dizziness and increased blood pressure.

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Storage conditions

The drug should be stored in a dark place at t +2-10°C (do not freeze).

Shelf life

36 months.