Differelin, lyophilizate 3.75mg

Pharmacodynamics

A synthetic decapeptide analog of natural GnRH. Differelin®, after a short initial period of stimulation of the gonadotropic function of the pituitary gland, has an inhibitory effect on gonadotropin secretion with subsequent suppression of testicular and ovarian function.

Continued use of Dyferelin® inhibits ovarian estrogen secretion to the menopausal state and also reduces testosterone secretion, which concentrations can reach levels that can be seen after surgical castration.

Pharmacokinetics

Absorption and distribution

After the administration of the suspension, there is an initial phase of rapid release of the active substance followed by a phase of sustained release. The Cmax of tryptorelin in plasma is 0.32±0.12 ng/mL, and the average amount of permanently released tryptorelin is 46.6±7.1 µg/day.

The bioavailability of the drug when administered once a month is 53%.

Indications

Cancer, Infertility

Prostate cancer; genital and extragenital endometriosis; premature puberty; female infertility (in the program of in vitro fertilization); uterine fibroids (before surgical intervention).

Active ingredient

Triptorelin

Composition

1 vial contains:

Active ingredient:

Tryptorelin acetate, in terms of tryptorelin 3.75 mg*

* – given the specifics of the dosage form, the drug contains an excess of the active ingredient to ensure the administration of an effective dose.

Associates:

D,L-lactic acid and glycolic acid copolymer – about 160 mg (amount depends on level of encapsulation)

Mannitol – 85 mg,

sodium carmellose – 30 mg,

Polysorbate 80 – 2 mg.

Solvent:

mannitol – 16 mg,

d/i water – up to 2000 mg.

How to take, the dosage

The drug is given only by injection.

In cases of prostate cancer, Dyferelin® is given at a dose of 3.75 mg (1 injection) every 4 weeks, long-term.

In patients with premature puberty the drug is prescribed in patients with body weight over 20 kg 3.75 mg every 28 days, in patients with body weight less than 20 kg 1.875 mg every 28 days.

In patients with endometriosis, the drug is administered in a dose of 3.75 mg once every 4 weeks. The injection is carried out in the first 5 days of the menstrual cycle. The duration of treatment is not more than 6 months.

In female infertility the drug is administered in a dose of 3.75 mg (1 injection) on the 2nd day of the cycle. The relation with gonadotropins should be controlled after pituitary desensitization (concentration of estrogens in blood plasma less than 50 pkg/ml is usually determined 15 days after Diferelin® injection).

In case of uterine fibroids, the drug should be injected in the first 5 days of the menstrual cycle. The drug is prescribed 3.75 mg every 4 weeks. The duration of treatment is 3 months for patients preparing for surgery.

Regulations for preparation and administration of suspension

The suspension for intravenous administration is prepared by dissolving the lyophilizate in the provided solvent immediately before 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 the supine position. Disinfect the skin on the buttocks.

1. Crack the neck of the ampoule (point upwards on the front).
2. Push the solvent into the syringe with the needle.
3. Remove the protective plastic cap from the top of the bottle.
4. Push the solvent into the lyophilizate vial.
5. Pull the needle so that it stays in the vial but does not touch the suspension.
6. Without inverting the vial, shake the contents gently until a homogeneous suspension is formed.
7. Check for agglomerates before placing the suspension in the syringe (if no agglomerates are present, shake until completely homogeneous).
8. Without inverting the vial, draw the entire suspension into the syringe.
9. Remove the needle used to prepare the suspension and attach another needle tightly to the tip of the syringe. Hold only the colored tip.
10. Remove air from the syringe.
11. Inject immediately into the gluteal muscle.
12. Dispose of needles in containers designated for sharp objects.

Interaction

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

Special Instructions

At the beginning of treatment, clinical symptoms may worsen, and therefore Diferelin® should be used with caution in patients with prostate cancer at risk of ureteral obstruction or spinal cord compression. These patients should be closely monitored by a physician during the first month of therapy.

Before therapy with Dyferelin is started, the absence of pregnancy should be confirmed.

The drug is used with caution in patients with polycystic ovarian syndrome during ovulation stimulation schemes. This is because in a small number of patients the number of induced follicles may increase.

The level of cycle stimulation during in vitro fertilization should be closely monitored to identify patients at risk of developing ovarian hyperstimulation syndrome, as the severity and frequency of manifestations of the syndrome may depend on the gonadotropin dosing regimen. Human chorionic gonadotropin administration should be discontinued if necessary.

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

There is no information available.

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Contraindications

• Pregnancy
• lactation period (breastfeeding)
• high sensitivity to triptorelin, other drug components and other GnRH analogues.

With caution: the drug should be prescribed in osteoporosis.

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Side effects

Allergic reactions: urticaria, rash, itching; very rare – Quincke’s edema. Sexual system: in men – decreased potency; in women – headache, depression, sweating and changes in libido, vaginal mucosa dryness, dyspareunia and changes in breast size.

When used in combination with gonadotropins, cases of ovarian hyperstimulation syndrome have been reported. During treatment of precocious puberty in girls bloody vaginal discharge may be observed. Prolonged use of the drug may cause hypogonadotropic amenorrhea.

Skeletal and muscular system disorders: with long-term use – demineralization of bones, which is a risk of osteoporosis development. At the beginning of treatment in prostate cancer patients may experience a temporary increase of pain in the bones affected by metastases (treatment is symptomatic). Individual cases of ureteral obstruction and the appearance of symptoms associated with compression of the spinal cord by the metastases have been noted (goes away after 1-2 weeks). Also during this period there may be a temporary increase in the activity of acid phosphatase in the blood plasma.

Digestive system disorders: in single cases – nausea, vomiting.

CNS disorders: in single cases – increased emotional lability, visual impairment.

Cardiovascular system: in single cases – arterial hypertension and hot flashes.

Local reactions: in single cases – pain at the injection site.

Others: in single cases – weight gain, increased body temperature.

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Overdose

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

Pregnancy use

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