Differelin lyophilizate 11.25mg

Pharmacodynamics

A synthetic decapeptide analog of natural GnRH.

After a short initial period of stimulation of the gonadotropic function of the pituitary gland, tryptorelin has an inhibitory effect on gonadotropin secretion with subsequent suppression of testicular and ovarian function.

In the initial period of use, Dyferelin® temporarily increases the concentration of LH and FSH in the blood; accordingly, the concentration of testosterone in men and estradiol in women increases.

Long-term treatment reduces concentrations of LH and FSH, which leads to a decrease in testosterone levels (to levels corresponding to the post-testiculectomy condition) and a decrease in estradiol levels (to levels corresponding to the post-ovariectomy condition) – by about 20 days after the first injection and remains unchanged throughout the duration of the drug administration. Long-term treatment with triptorelin suppresses estradiol secretion in women and thus prevents the development of endometrioid ectopias.

Pharmacokinetics

Absorption and distribution

When Dyferelin is administered by m/m at a dose of 11.25 mg, the Cmax of triptorelin in plasma (in men and women) is determined approximately 3 hours after injection. After a declining phase of concentration lasting for the first month until day 90, the concentration of circulating tryptorelin remains constant (approximately 0.04 to 0.05 ng/mL in the treatment of endometriosis and approximately 0.1 ng/mL in the treatment of prostate cancer).

Indications

Prostate cancer:

Genital and extragenital endometriosis (stages I-IV).

Active ingredient

Composition

1 vial contains:

Active ingredient:

Tryptorelin acetate, converted to tryptorelin 11.25 mg*.

* – Due to the nature of the dosage form, the drug has an excess of the active ingredient to provide an effective dose.

Auxiliary substances:

D,L-lactic and glycolic acid copolymer – 250 mg,

mannitol – 85 mg,

How to take, the dosage

In prostate cancer, Differelin® is given by injection/m at a dose of 11.25 mg every 3 months. When treated in combination with radiation therapy, long-term antiandrogen therapy (3 years) is preferable to short-term antiandrogen therapy (6 months).

In endometriosis, the drug is administered by injection/m at a dose of 11.25 mg every 3 months. Treatment should be started in the first 5 days of the menstrual cycle. The duration of treatment depends on the severity of endometriosis and the observed clinical picture (functional and anatomical changes) against the background of therapy. As a rule, the treatment is carried out for 3-6 months. Repeated treatment with triptorelin or another GnRH analogue is not recommended.

Regulations for preparation of suspension

Dissolution of the lyophilizate in the included solvent should be performed immediately prior to administration. The contents of the bottle should be stirred with care until a homogeneous suspension is obtained.

In cases of incomplete injection resulting in loss of more of the suspension than normally remains in the syringe for injection, the attending physician should be informed.

Injection must be carried out strictly according to the instructions.

The patient must be in a supine position.

Disinfect the skin on the buttock.

Interaction

Drug interactions of the drug Differelin® have not been described.

Special Instructions

In the treatment of endometriosis

Pregnancy must be ruled out before starting treatment.

In the first month of therapy, non-hormonal contraceptives should be used.

Injection of the drug in m/m leads to persistent hypogonadotropic amenorrhea.

The treatment should not be recommended for more than 6 months. Repetitive therapy with triptorelin or another GnRH analogue is not recommended.

The occurrence of metrorrhagia during treatment, apart from the first month, is not normal, and therefore plasma estradiol concentrations should be determined. If estradiol concentrations fall below 50 pg/mL, other organic lesions may be present.

The ovarian function is restored after completion of therapy. The first menstruation occurs on average 134 days after the last injection. Therefore, contraceptive measures should be started 15 days after discontinuation of treatment, i.e. 3.5 months after the last injection.

In the treatment of prostate cancer

The most pronounced beneficial effect is seen in patients in the absence of other previous hormonal therapy.

In the beginning of treatment, there may be a transient onset and an increase in clinical symptoms (such as bone pain and dysuria).

This suggests careful monitoring of these patients during the first few weeks of therapy (plasma testosterone levels should not exceed 1 ng/ml).

For the same reason, close monitoring at the beginning of treatment should be done for patients with diagnosed spinal cord compression.

In addition, there may be a temporary increase in acid phosphatases at the beginning of treatment.

In patients receiving GnRH agonists, the risk of hyperglycemia and diabetes mellitus has been reported. There is also a possible risk of cardiovascular disease and, with long-term use, osteoporosis.

Impact on the ability to drive vehicles and other mechanisms requiring increased concentration

There is no information available.

Contraindications

In men:

In women:

With caution: the drug should be prescribed in osteoporosis, women with polycystic ovarian syndrome.

Side effects

In men

In the beginning of treatment: dysuria (difficulty urinating, incomplete emptying of the bladder, soreness), bone pain associated with metastases and spinal cord compression by metastases, which may be exacerbated by a temporary increase in plasma testosterone at the beginning of treatment. These symptoms go away after 1 to 2 weeks. There may also be a temporary increase in plasma hepatic enzyme activity during this period.

During treatment: hot flashes, decreased libido, gynecomastia, impotence, which is associated with a decrease in plasma testosterone.

In women

In the beginning of treatment: symptoms associated with endometriosis (pelvic pain, dysmenorrhea), which may increase due to an initial transient increase in plasma concentration of estradiol and disappear after 1-2 weeks. In 1 month after the first injection, genital bleeding may occur, including both menorrhagia and metrorrhagia.

During treatment: vaginal dryness, hot flashes, decreased libido, increased mammary glands, dyspareunia, which is associated with pituitary-ovarian blockade; rarely – headache, arthralgia, myalgia.

In men and women

Allergic reactions such as urticaria, rash, itching and very rarely – Quincke’s edema; Mood disorders, irritability, depression, fatigue, sleep disturbances, nausea, vomiting, weight gain, profuse sweats, arterial hypertension, paresthesias, visual impairment, pain at the injection site, and fever.

Long-term use of GnRH analogues may lead to bone demineralization and is a possible risk factor for osteoporosis.

According to data collected during the use of GnRH analogues, the following adverse reactions may occur in patients: erectile dysfunction, tinnitus, dizziness, diabetes mellitus (hyperglycemia), abdominal pain, constipation, diarrhea, bloating, dry oral mucosa, dysgeusia, flatulence, asthenia; drowsiness, flu-like syndrome, anaphylactic reactions; increased ALT, AST, ALP activity hypercreatininemia, increased blood urea, anorexia, gout, increased appetite, musculoskeletal pain, pain in extremities, muscle cramps, muscle weakness, dizziness, memory impairment, insomnia, confusion, anxiety, testicular atrophy, shortness of breath, orthopnea, nosebleed, acne, alopecia, BP decrease; erythema, inflammation, pain on injection site.

Overdose

To date, there have been no known cases of overdose of Differelin®.

Pregnancy use

Differelin® is contraindicated in pregnancy and during lactation (breastfeeding).

Since there are no data on excretion of triptorelin in the breast milk and its possible effects on the breast-fed child, treatment with Dyferelin® during breast-feeding should not be performed.

According to available data, no teratogenic effects were found in experimental studies on animals. In single cases of use of GnRH analogues (by negligence) no fetal development defects or fetotoxicity were found.