A synthetic decapeptide analogue of natural GnRH.
After a short initial period of stimulation gonadotropic pituitary function triptorelin exerts an inhibitory effect on the secretion of gonadotropins, followed by suppression of testicular and ovarian function.
In the initial period of application Diferelin® temporarily increases the concentration of LH and FSH in the blood, respectively, increases the concentration of testosterone in men and estradiol in women.
Prolonged treatment reduces the concentration of LH and FSH, resulting in a reduction of testosterone indicators (to levels consistent state after testikulektomii) and reduced estradiol indicators (to levels consistent state postovarioektomii) – about a 20 day after the first injection and then remains unchanged throughout the the treatment period. Prolonged treatment with triptorelin suppresses oestradiol secretion in women and thus prevents the development of endometrial ectopia.
Absorption and distribution
When the / m Diferelin administered at a dose of 11.25 mg triptorelin Cmax in plasma (men and women) is determined after about 3 hours after injection. After phase reducing the concentration extending in the first month, 90 days triptorelin circulating concentration remained constant (approximately 0.04 to 0.05 ng / ml in the treatment of endometriosis and about 0.1 ng / ml in the treatment of prostate cancer).
Ipsen Pharma, France
1 vial contains:
The active ingredient is:
triptorelin acetate, triptorelin, based on the 11.25 mg *.
* – taking into account features of the dosage form in the formulation an excess of active agent incorporated for administration of an effective dose.
copolymer of D, L-lactic and glycolic acids – 250 mg
mannitol – 85 mg,
carmellose sodium (sodium carboxymethylcellulose) – 30 mg,
Polysorbate 80 – 2 mg.
mannitol – 16 mg,
water d / and – up to 2000 mg.
- the treatment of locally advanced prostate cancer as monotherapy or as an adjuvant agent to background radiation therapy;
- the treatment of metastatic prostate cancer.
Genital and extragenital endometriosis (stage I-IV).
- Increased sensitivity to triptorelin, other ingredients or other PLR counterparts.
- hormone-independent prostate cancer, a state after prior surgical testikulektomii.
- lactation (breastfeeding).
Be wary: should be prescribed for osteoporosis, women with polycystic ovary syndrome.
At the beginning of treatment: dysuria (difficulty of urination, incomplete voiding, pain), bone pain associated with metastatic and metastatic spinal cord compression, which may be aggravated due to the temporary increase of the testosterone concentration in plasma at the start of treatment. These symptoms disappear within 1-2 weeks. As temporary elevation of liver enzymes in the blood plasma can be observed during this period.
During treatment: hot flashes, decreased libido, gynecomastia, impotence, which is associated with a decrease in testosterone in the blood plasma.
At the beginning of the treatment: the symptoms associated with endometriosis (pelvic pain, dysmenorrhoea), which may be increased in connection with the initial transient increase in serum estradiol concentrations and disappear within 1-2 weeks. After 1 month after the first injection can be genital bleeding, including both menorrhagia and metrorrhagia.
During treatment: vaginal dryness, hot flashes, decreased libido, breast enlargement, dyspareunia, due to pituitary-ovarian blockade; rarely – headache, arthralgia, myalgia.
Men and women
Allergic reactions such as hives, rash, itching, and very rarely – angioedema; mood disorder, irritability, depression, fatigue, sleep disturbances, nausea, vomiting, weight gain, profuse sweating, hypertension, paresthesias, blurred vision, pain at the injection site and fever.
Prolonged use of GnRH analogues may lead to bone demineralization and is a possible risk factor for osteoporosis.
According to data collected during application of GnRH analogues, the following adverse reactions may occur in patients: erectile dysfunction, tinnitus, vertigo, diabetes (hyperglycemia), abdominal pain, constipation, diarrhea, bloating, dryness of the oral mucosa, dysgeusia, flatulence, asthenia; drowsiness, flu syndrome, anaphylactic reactions; increased ALT, AST, alkaline phosphatase; hypercreatininemia, increased urea in the blood, anorexia, gout, increased appetite, musculoskeletal pain, pain in extremities, muscle cramps, muscle weakness, dizziness, memory loss, insomnia, confusion, anxiety, testicular atrophy, dyspnea, orthopnea, epistaxis , acne, alopecia, blood pressure reduction; injection site – erythema, inflammation, and pain.
How to accept, acceptance rate and dosage
When prostate cancer is administered Diferelin® / m at a dose of 11.25 mg every 3 months. In the treatment in combination with radiotherapy prolonged antiandrogen therapy (3) has been a short-term preferred antiandrogen therapy (6 months).
In endometriosis introducing drug / m at a dose of 11.25 mg every 3 months. Treatment should begin during the first 5 days of the menstrual cycle. The duration of treatment depends on the severity of endometriosis and clinical picture observed (functional and anatomical changes) during therapy. Usually, treatment is carried out for 3-6 months. Not recommended for re-treatment triptorelin or another GnRH analogue.
Dissolving the lyophilisate in the enclosed solvent must be conducted immediately prior to administration. Mix the contents of the vial with caution until a homogeneous suspension.
Cases of incomplete injections resulting in the loss of more slurry than is normally left in the syringe for injection, it is necessary to inform the attending physician.
The introduction should be carried out in strict accordance with the instructions.
The patient should be in a prone position.
Disinfect the skin of the buttocks.
- Break the ampoule neck (the point on the right side on top).
- Enter the solvent into the syringe with a needle.
- Remove the green protective plastic cover from the top of the bottle.
- Drag the solvent into the vial of lyophilisate.
- Pull the needle so that it remains in the bottle, but not touch the suspension.
- Not turning the vial, gently shake the contents until a homogeneous suspension.
- Check the agglomerates before they will type suspension in the syringe (in the absence of agglomerates, stir until homogeneous).
- Not turning the vial into the syringe, type the entire suspension.
- Remove the needle that was used to prepare a suspension, and attach tightly onto the other needle tip of the syringe. Hold only the tip of the color.
- Remove air from the syringe.
- Immediately inject in the gluteal muscle.
- Dispose of the needle in the container for sharp objects.
At temperatures above 25 ° C
Drug interaction Diferelin® preparation is not described.
In the treatment of endometriosis
Before treatment to exclude pregnancy.
During the first month of therapy should be used hormonal contraceptives.
V / m injection drug leads to persistent hypogonadotropic amenorrhea.
Treatment should not be recommended for a period of more than 6 months. We do not recommend a second course of therapy triptorelin or another GnRH analogue.
The occurrence of metrorrhagia in the course of treatment, except for the first month, not the norm, and therefore it is necessary to determine the concentration of estradiol in the blood plasma. By reducing the concentration of estradiol below 50 pg / ml, there may be other organic lesions.
ovarian function is restored after completion of therapy. The first menstruation occurs after an average 134 days after the last injection. Therefore, contraceptive measures should begin to apply 15 days after cessation of treatment, ie after 3.5 months after the last injection.
In the treatment of prostate cancer
The most pronounced beneficial effect is observed in patients with no other previously conducted hormonal therapy.
At the beginning of treatment may be observed and the appearance of clinical symptoms of amplification (in particular, pain in the bones, dizuricheskih phenomena) bearing the transient.
This involves careful observation of these patients during the first few weeks of therapy (testosterone plasma level should not exceed 1 ng / ml).
For the same reason, careful observation at the beginning of treatment should be carried out for patients diagnosed with spinal cord compression.
In addition, at the beginning of treatment may experience a temporary increase in acid phosphatases.
In patients receiving GnRH agonists, registered with the risk of hyperglycemia and diabetes. In addition, the possible risk of developing cardiovascular disease and long-term use of osteoporosis.
Effects on ability to drive vehicles and other machines that require high concentration of attention
No data available.
Pregnancy and lactation
Diferelin® contraindicated during pregnancy and lactation (breastfeeding).
Since there is no data on the excretion of triptorelin in breast milk and its possible effects on the breastfed child, you should not treat drug Diferelin® during breastfeeding.
According to available data do not reveal any teratogenic effects in experimental animal studies. In rare cases, the use of GnRH analogues (inadvertently) any defects in fetal development and fetotoxicity were found.
So far, cases of drug overdose Diferelin® unknown.