Diferelin dosage. Diferelin for IVF: a drug for a desired pregnancy

• Instructions for use Diferelin ® 3.75 mg
• Composition of the drug Diferelin ® 3.75 mg
• Indications for the drug Diferelin ® 3.75 mg
• Storage conditions for the drug Diferelin ® 3.75 mg
• Shelf life of the drug Diferelin ® 3.75 mg

ATX Code: Antitumor drugs and immunomodulators (L) > Antitumor hormonal drugs (L02) > Hormones and their derivatives (L02A) > Gonadotropin-releasing hormone analogues (L02AE) > Triptorelin (L02AE04)

Release form, composition and packaging

lyophilisate for preparation. susp. d/i/m administration prolonged. actions 3.75 mg: vial. 1 PC. included with solvent, syringe and 2 needles
Reg. No.: RK-LS-5-No. 003064 dated 08/10/2011 - Valid

Lyophilisate for the preparation of a suspension for intramuscular administration of prolonged action in the form of a sintered powder of almost white color; solvent - transparent colorless liquid; the prepared suspension is milky, homogeneous.

Excipients: copolymer of D, L-lactic and glycolic acids, mannitol, polysorbate 80, sodium carmellose.

Solvent: mannitol, d/i water.

Glass bottles with a capacity of 4 ml (1) complete with solvent (amp. 2 ml 1 pc.), disposable syringe, disposable needles (2 pcs.) - contour cell packaging (1) - cardboard boxes.

Description of the drug DIFERELIN ® 3.75 mg based on officially approved instructions for use of the drug and made in 2014. Update date: 03/21/2014

pharmachologic effect

Analog of natural GnRH (gonadotropin-releasing hormone), synthetic decapeptide.

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

In addition, animal studies show a different mechanism of action:

• direct effect on the gonads by reducing the sensitivity of peripheral receptors to GnRH.

Prostate cancer

When using triptorelin, there may be an initial increase in the levels of LH and FSH in the blood, and, as a consequence, an increase in the initial level of testosterone (the “flash” effect). Continued treatment with triptorelin reduces LH and FSH levels to concentrations that lead to castration levels of steroids within 2-3 weeks after the first injection and throughout the duration of drug use.

Suppression of pituitary gonadotropic hyperactivity in both sexes manifests itself as suppression of estradiol or testosterone secretion, a decrease in the LH peak, and an improvement in the height-to-bone age ratio.

Initial stimulation of the gonads may cause mild bleeding from the genital tract, which can be prevented by the administration of medroxyprogesterone or cyproterone acetate.

Endometriosis

Long-term treatment with triptorelin suppresses the secretion of estradiol and thus leads to the death of ectopic endometriotic tissue.

Uterine fibroids

Studies have shown a constant and pronounced decrease in the volume of confirmed uterine fibroids. This decrease is most pronounced during the third month of treatment.

Treatment with triptorelin causes amenorrhea after the first month of treatment in most patients. This makes it possible to correct possible anemia caused by menorrhagia and/or metrorrhagia.

Female infertility

Long-term treatment with triptorelin suppresses gonadotropic secretion (FSH and LH). Treatment thus provides suppression of the spontaneous peak of endogenous LH and leads to an improvement in the quality of folliculogenesis and increases the follicular response.

Pharmacokinetics

After intramuscular administration of the extended-release form of the drug, an initial phase of release of the active substance occurs, followed by a phase of continuous release of triptorelin for 28 days.

Dosage regimen

The drug is administered only intramuscularly.

Prostate cancer

Mammary cancer

Diferelin ® 3.75 mg is administered intramuscularly at 3.75 mg every 4 weeks. The treatment is long-term. The duration of treatment is determined by the attending physician individually for each patient.

Precocious puberty

Children weighing less than 20 kg:

• administer half (1/2) dose every 4 weeks (28 days), i.e. 1/2 the volume of the reconstituted suspension should be administered.

Children weighing from 20 to 30 kg:

• administer two-thirds (2/3) of the dose every 4 weeks (28 days), i.e. 2/3 of the volume of the reconstituted suspension should be administered.

Children weighing more than 30 kg:

• 1 dose is administered every 4 weeks (28 days), i.e. the entire volume of the reconstituted suspension should be administered.

Endometriosis

Diferelin ® 3.75 mg is administered at a dose of 3.75 mg every 4 weeks. Treatment should begin in the first 5 days of the menstrual cycle. The duration of treatment depends on the severity of endometriosis and the observed clinical changes (functional and anatomical). The course of treatment should continue for at least 4 months, but not more than 6 months. It is not recommended to prescribe a second course of treatment with triptorelin or other GnRH analogues.

Uterine fibroids before surgery

Diferelin ® 3.75 mg is administered at a dose of 3.75 mg every 4 weeks. Treatment should begin in the first 5 days of the menstrual cycle. The duration of treatment is no more than 3 months.

Female infertility

Diferelin ® 3.75 mg is administered at a dose of 3.75 mg on the 2nd day of the cycle. The combination with gonadotropins is carried out after desensitization of the pituitary gland (estrogens concentration in the blood plasma is less than 50 pg/ml), usually on the 15th day after injection of Diferelin 3.75 mg.

Rules for administering the drug

1 package of the drug contains 1 dose for intramuscular administration and is intended for a single injection to 1 patient.

A suspension of the powder in the supplied solvent should be prepared immediately before administration by gently stirring the contents of the vial until a homogeneous mixture is obtained.

Instances of incomplete injection resulting in loss of more suspension than would normally remain in the syringe after injection should be reported.

Administration should be carried out in strict accordance with the instructions.

1. Patient preparation

The patient should lie on his stomach, the skin of the buttocks must be disinfected.

2. Preparation of injection

The presence of bubbles on the surface of the lyophilisate is a normal appearance of the drug.

Break the isthmus of the ampulla (point in front).

Draw up all the solvent into a syringe with a needle.

Remove the green cap from the bottle lid.

Transfer the solvent into a bottle with lifilizate.

The needle should be kept above the liquid level. Do not remove the needle from the bottle.

Stir without inverting the bottle until a homogeneous mixture is obtained.

Before collecting the suspension, you should make sure that there are no lumps (if there are lumps, you must continue stirring until complete homogenization).

Draw up the entire suspension into the syringe without turning the bottle over.

Remove the needle used to prepare the drug. Attach another needle to the syringe (screw tightly). To attach the needle, touch only the colored cannula.

Force the air out of the syringe.

3. IM injection

Immediately inject the drug into the gluteal muscle.

4. After the injection

Place the needles in a specially designed container.

Side effects

In men

As with other GnRH agonists or after surgical castration, the most frequently observed side effects associated with triptorelin treatment were those that were related to its expected pharmacological action:

• an initial increase in testosterone levels followed by almost complete suppression. These effects are hot flashes (50%), erectile dysfunction (4%) and decreased libido (3%).

• very often (≥1/10);
• often (from ≥1/100 to<1/10);
• uncommon (from ≥1/1000 to<1/100);
• rare (from ≥1/10,000 to<1/1 000). Не было надлежащей возможности определять частоту побочных эффектов после начала поставок препарата на рынок. Следовательно, частота таких эффектов отмечалась как "неизвестно".

Often	Often	Infrequently	Rarely	Frequency unknown
Infections and infestations
			Nasopharyngitis
From the blood and lymphatic system
			Purpura
From the immune system
			Anaphylactic reaction Hypersensitivity
From the endocrine system
			Diabetes
Metabolism and nutrition
		Anorexia Gout Increased appetite
Mental disorders
		Depression Insomnia Irritability Mood swings	Confusion Decreased activity Euphoria	Anxiety
From the nervous system
Paresthesia of the lower extremities	Dizziness Headache	Paresthesia	Memory disorders
From the side of the organ of vision
			Feeling of discomfort in the eyes Visual disorders	Decreased visual acuity
From the organ of hearing and labyrinth
		Noise in ears	Vertigo/dizziness
Hot flashes		Arterial hypertension	Nose bleed Arterial hypotension
		Dyspnea	Orthopnea
	Nausea	Abdominal pain Constipation Diarrhea Vomit	Bloating Dry mouth Dysgeusia (taste disorder) Flatulence
Hyperhidrosis		Acne Alopecia Itching Rash	Blisters
Allergic reactions
				Angioedema Hives
Lower back pain	Musculoskeletal pain Pain in limbs	Arthralgia Muscle cramps Muscle weakness Myalgia	Joint stiffness Swollen joints Musculoskeletal stiffness Osteoarthritis	Bone pain
	erectile disfunction Decreased/loss of libido	Gynecomastia Pain in the mammary glands Testicular atrophy Testicular pain	Ejaculation disorder
General reactions
Asthenia	Fatigue	Lethargy Pain Shiver Drowsiness	Chest pain Dystasia Flu-like syndrome Pyrexia	Malaise
Local reactions
	Erythema, inflammation, pain, swelling at the injection site
		Increased activity of ALT, AST Increased creatinine levels in the blood Increased urea levels in the blood Weight gain	Increased alkaline phosphatase Increased body temperature Weight loss	Increased blood pressure

Triptorelin causes a temporary increase in testosterone levels in the bloodstream during the first week after the first injection of the sustained-release drug. As a result, a small number of patients (5%) may experience a temporary worsening of symptoms and signs of prostate cancer (the “flare-up” effect), usually manifesting as increased urinary symptoms (2%) and metastatic pain (5%). These conditions should be treated symptomatically. These symptoms are temporary and usually disappear after 1-2 weeks.

There have been isolated cases of exacerbation of symptoms of the disease - either the development of urethral obstruction or compression of the bone marrow by metastases. Therefore, patients with spinal metastases and/or upper or lower urinary tract obstruction should be closely monitored during the first few weeks of therapy.

The use of GnRH agonists to treat prostate cancer may result in decreased bone mass, which may cause osteoporosis and an increased risk of bone fractures.

An increase in lymphocyte counts was observed in patients treated with GnRH analogues. This secondary lymphocytosis is likely due to GnRH-induced castration and suggests that sex hormones are involved in thymic involution.

Among women

As a consequence of decreased estrogen levels, the most commonly reported side effects (with an expected incidence of 10% of women or higher) were headache, decreased libido, sleep disturbance, mood changes, dyspareunia, dysmenorrhea, genital bleeding, ovarian hyperstimulation syndrome, ovarian hypertrophy, pelvic pain, abdominal pain, vulvovaginal dryness, hyperhidrosis, hot flashes.

The following side effects have been reported and considered likely to be related to triptorelin treatment. Most of these effects are known to be associated with biochemical or surgical castration.

Determination of the frequency of side effects:

• very often (≥1/10);
• often (from ≥1/100 to<1/10). Не было надлежащей возможности определять частоту побочных эффектов после начала поставок препарата на рынок. Следовательно, частота таких эффектов отмечалась как "неизвестно".

Often	Often	Frequency unknown
From the immune system
Mental disorders
Sleep disturbance Mood swings		Depression Anxiety Confusion
From the nervous system
Headache		Dizziness
From the side of the organ of vision
		Decreased visual acuity Visual disorders
From the organs of hearing and labyrinth
		Vertigo/dizziness
From the cardiovascular system
Hot flashes
From the respiratory system
		Dyspnea
From the digestive system
	Nausea Abdominal pain Discomfort in the abdomen	Diarrhea Vomit
From the skin and subcutaneous tissue
Hyperhidrosis		Itching Rash
Allergic reactions
		Angioedema Hives
From the musculoskeletal system
	Arthralgia Muscle cramps	Myalgia Muscle weakness
From the reproductive system
Dyspareunia Dysmenorrhea Genital bleeding (menorrhagia, metrorrhagia) Decreased libido Ovarian hyperstimulation syndrome Ovarian hypertrophy Pelvic pain Vulvovaginal dryness	Pain in the mammary glands	Amenorrhea
General reactions
		Pyrexia Malaise
Local reactions
	Erythema at the injection site Inflammation at the injection site Pain at the injection site
Laboratory tests and research
	Weight gain	Increased blood pressure

At the beginning of treatment, symptoms of endometriosis, including pelvic pain and dysmenorrhea, may very often (≥10%) worsen, which is associated with a period of initial transient increase in plasma estradiol levels. These symptoms are temporary and usually disappear after 1-2 weeks.

Within one month after the first injection, genital bleeding may develop, including menorrhagia and metrorrhagia.

When using the drug in the treatment of infertility, its combination with gonadotropins can lead to ovarian hyperstimulation syndrome. Ovarian hypertrophy, pelvic pain, and/or abdominal pain may occur.

Long-term use of GnRH analogues can lead to decreased bone mass, which is a risk factor for osteoporosis.

In children

Determination of the frequency of side effects:

• often (from ≥1/100 to<1/10). There was no adequate ability to determine the incidence of side effects after the drug was placed on the market. Consequently, the frequency of such effects was reported as “unknown.”

Often	Frequency unknown
From the immune system
Hypersensitivity reactions
Mental disorders
	Affective lability Nervousness
Headache
From the side of the organ of vision
	Decreased visual acuity Visual disorders
From the cardiovascular system
Hot flashes
From the respiratory system
	Nose bleed
From the digestive system
	Vomit Abdominal pain Discomfort in the abdomen
From the skin and subcutaneous tissue
	Angioedema Rash Hives
From the musculoskeletal system
	Myalgia
From the reproductive system
Genital bleeding Vaginal bleeding
General reactions
	Malaise
Local reactions
Pain, erythema, inflammation at the injection site
Laboratory tests and research
	Increased blood pressure Weight gain

Use during pregnancy and breastfeeding

The drug is contraindicated for use during pregnancy and lactation.

Pregnancy should be excluded before prescribing Diferelin ® 3.75 mg, incl. before use for the treatment of infertility.

The use of GnRH agonists during pregnancy is associated with a theoretical risk of abortion or abnormal fetal development. Before starting treatment, potentially fertile women should be carefully examined to exclude pregnancy. Non-hormonal methods of contraception should be used during therapy and until menstruation resumes.

When triptorelin is used to treat infertility, there is no clinical evidence of a causal relationship between triptorelin and any subsequent abnormalities in egg maturation or pregnancy or pregnancy outcome.

special instructions

In men

The use of GnRH agonists may lead to a decrease in bone mineral density (BMD). Preliminary evidence suggests that in men, the use of bisphosphonates in combination with GnRH agonists may reduce loss of bone mineral density. Particular caution is required in patients with additional risk factors for osteoporosis (eg, chronic alcohol abuse, smoking, long-term therapy with drugs that reduce BMD, such as anticonvulsants or corticosteroids, family history of osteoporosis, malnutrition).

In rare cases, treatment with GnRH agonists may reveal the presence of a previously unknown gonadotropic pituitary adenoma. These patients may present with pituitary apoplexy, characterized by sudden headache, vomiting, blurred vision, and ophthalmoplegia.

Mood changes, including depression, have been reported. Patients with depression should be closely monitored during treatment.

Diferelin ® 3.75 mg contains less than 1 mmol sodium (23 mg) per dose, which is essentially a “sodium-free” drug.

Patients receiving anticoagulants require observation because hematomas may potentially appear at the injection site.

Prostate cancer

Initially, triptorelin, like other GnRH agonists, causes a transient increase in serum testosterone levels. As a result, isolated cases of transient worsening of prostate cancer signs and symptoms may sometimes develop during the first weeks of treatment. During the initial phase of treatment, consideration should be given to the need for additional administration of a suitable antiandrogen drug to counteract the initial increase in testosterone levels and worsening of clinical symptoms.

In a small number of patients, there may be a temporary worsening of prostate cancer symptoms and a temporary increase in metastatic pain, which can be treated symptomatically.

As with other GnRH agonists, isolated cases of spinal cord compression or urethral obstruction have been observed. If spinal cord compression or renal failure develops, standard treatment for these complications should be initiated and, in extreme cases, immediate orchiectomy (surgical castration) should be considered. Careful monitoring is indicated during the first week of treatment, especially in patients with spinal metastases, at risk of spinal cord compression, and in patients with urinary tract obstruction. For the same reason, patients with suspected symptoms of spinal cord compression should be under special supervision at the beginning of treatment.

After surgical castration, triptorelin does not cause a further decrease in serum testosterone levels.

Long-term androgen deprivation, either after bilateral orchiectomy or after use of GnRH analogues, is associated with an increased risk of loss of BMD and may lead to osteoporosis and an increased risk of bone fractures.

In addition, based on epidemiological data, it has been noted that with androgen blockade, patients may develop metabolic changes (eg, impaired glucose tolerance) or an increased risk of cardiovascular disease. However, prospective data have not confirmed an association between treatment with GnRH analogues and increased cardiovascular mortality. Patients at high risk for developing metabolic and cardiovascular disease should be carefully assessed before initiating treatment and adequately monitored during use of androgen blockade therapy.

The use of triptorelin in therapeutic doses leads to suppression of the pituitary-gonad system. Normal function is usually restored after treatment is stopped. Therefore, the results of diagnostic tests of pituitary-gonadal axis function performed during treatment and after discontinuation of treatment with GnRH analogues may be misleading.

At the beginning of treatment, a transient increase in acid phosphatase levels may be observed.

Periodic testing of plasma testosterone levels with an accurate method may be useful and should not exceed 1 ng/ml.

Among women

Before prescribing Diferelin ® 3.75 mg, pregnancy must be excluded.

The use of GnRH agonists may cause a decrease in BMD of an average of 1% per month over a six-month treatment period. Every 10% decrease in BMD results in a 2- or 3-fold increase in the risk of fractures.

Current evidence suggests that most women recover bone mass after cessation of therapy.

There are no specific data in patients with established osteoporosis or with risk factors for osteoporosis (eg, chronic alcohol abuse, smoking, long-term therapy with drugs that reduce BMD, such as anticonvulsants or corticosteroids, family history of osteoporosis, malnutrition, such as nervous anorexia). Because decreased BMD is likely to be more detrimental in these patients, treatment with triptorelin should be considered on an individual basis after careful benefit/risk assessment. Additional measures should be considered to counteract the loss of BMD.

Female infertility

Follicular maturation induced by injection of triptorelin in combination with gonadotropins may be significantly enhanced in some predisposed patients, especially in cases of polycystic ovarian disease. As with other GnRH analogues, there have been reports of ovarian hyperstimulation syndrome associated with the use of triptorelin in combination with gonadotropins.

The ovarian response to the triptorelin-gonadotropin association may vary at the same dose in different patients and, in certain cases, from one cycle to another in the same patient.

Inducible ovulation should be carefully monitored with precise and regular biological and clinical control:

• Frequent assessment of plasma estrogen and ultrasound.

If the response from the ovaries is excessive, it is recommended to interrupt the stimulation by stopping the gonadotropin injections.

In patients with renal or hepatic impairment, the average T1/2 for triptorelin is 7-8 hours compared to healthy individuals whose T1/2 is 3-5 hours. Despite this prolonged exposure, triptorelin will not be present in the blood at the time of embryo transfer.

Endometriosis and treatment of uterine fibroids before surgery

Regular use, every 4 weeks, of 1 bottle of Diferelin ® 3.75 mg leads to permanent hypogonadotropic amenorrhea.

If genital bleeding occurs after the first month of therapy, the content of estradiol in plasma should be determined. If this level is below 50 pg/ml, it is necessary to exclude a possible organic lesion.

Because menstruation should cease during treatment with triptorelin, the patient should be instructed to notify the physician if regular menstruation continues.

It is necessary to use non-hormonal methods of contraception during the entire treatment period, including one month after the last injection.

Ovarian function resumes after treatment ends, and ovulation occurs approximately 2 months after the last injection.

It is recommended to regularly determine the size of the fibroids during treatment of uterine fibroids. There have been several reports of bleeding in patients with submucosal uterine fibroids due to therapy with GnRH analogues. Typically, bleeding occurred 6-10 weeks after the start of therapy.

In children

Precocious puberty

Treatment of children with triptorelin should be carried out under the general supervision of a pediatric endocrinologist or pediatrician or endocrinologist experienced in the treatment of central precocious puberty.

Treatment of children with advanced brain tumors should be carried out after a careful individual assessment of the benefit/risk ratio.

In girls, initial gonadal stimulation may result in light to moderate vaginal bleeding during the first month of treatment.

After cessation of treatment, the development of signs of puberty resumes.

Information regarding fertility in patients treated with GnRH analogues during childhood is limited. For most girls, regular menstruation begins on average 1 year after stopping therapy.

It is necessary to exclude false precocious puberty (tumor or hyperplasia of the gonads or adrenal glands) and gonadotropin-independent precocious puberty (testotoxicosis, familial Leydig cell hyperplasia).

BMD may decrease during GnRH therapy for central precocious puberty. However, following cessation of treatment, there is a subsequent restoration of bone mass gain and treatment ultimately has no effect on maximum bone mass in late adolescence.

Epiphysiolysis of the femoral head may be detected after discontinuation of GnRH treatment. A speculative theory for this phenomenon is that low estrogen concentrations during GnRH agonist treatment may weaken the epiphyseal plate. The increase in growth rate after cessation of treatment subsequently leads to a decrease in the force required to displace the epiphysis.

Impact on the ability to drive vehicles and operate machinery

No studies have been conducted on the effect of Diferelin ® 3.75 mg on the ability to drive vehicles and operate machinery. However, the ability to drive and operate machines may be impaired as a result of dizziness, drowsiness and visual disturbances, which may be either undesirable effects of treatment or manifestations of an underlying disease.

Drug interactions

When using triptorelin in combination with other drugs that alter the secretion of gonadotropins by the pituitary gland, it is necessary to take special precautions; it is recommended to carefully monitor hormone levels.

Lyophilisate for preparing a solution for subcutaneous administration - 1 vial:

• active ingredients: triptorelin acetate (in terms of triptorelin) - 0.1 mg;
• excipients: mannitol - 10.0 mg;
• solvent composition (1 ampoule): sodium chloride; water for injections.

In bottles (complete with solvent); there are 7 sets in the contour cell packaging; in a cardboard pack 1 package.

• active ingredients: triptorelin acetate (in terms of triptorelin) - 3.75* mg;

Lyophilisate for the preparation of a suspension for intramuscular administration of prolonged action - 1 vial:

• active ingredients: triptorelin pamoate (in terms of triptorelin) - 11.25* mg;
• excipients: copolymer of DL-lactic and glycolic acids; mannitol; carmellose sodium; polysorbate-80;
• solvent composition (1 ampoule): mannitol; water for injections.

*Taking into account the characteristics of the dosage form, the drug contains an excess of the active component to ensure the administration of an effective dose.

In bottles (complete with solvent in ampoules, a syringe and two needles) in a cardboard pack 1 set.

Description of the dosage form

Diferelin® 0.1 mg: lyophilisate, almost white in color, dispersible in the supplied solvent to form a clear solution, practically free of particles.

Diferelin® 3.75 mg: white or off-white lyophilisate, dispersible in the supplied solvent to form a white or off-white suspension.

Diferelin® 11.25 mg: white or slightly yellowish lyophilisate, dispersible in the supplied solvent to form a white or slightly yellowish suspension.

The supplied solvent is a clear, colorless solution.

pharmachologic effect

Antigonadotropic.

Pharmacokinetics

Diferelin® 0.1 mg

Following subcutaneous injection into healthy adult volunteers at a dose of 0.1 mg, triptorelin is rapidly absorbed (time to reach Cmax - (0.63 ± 0.26) hours with a peak plasma concentration of (1.85 ± 0.23) ng /ml).

T1/2 is (7.6±1.6) hours, after 3–4 hours the distribution phase ends.

Total plasma clearance - (161±28) ml/min.

Volume of distribution - (1562±158) ml/kg.

Diferelin® 3.75 mg

After intramuscular administration of a prolonged form of the drug, an initial stage of rapid release of the drug occurs, followed by a phase of continuous release of triptorelin. Cmax is (0.32±0.12) ng/ml.

The average amount of triptorelin continuously released is (46.6 ± 7.1) mcg/day.

The bioavailability of the drug is about 53% over 1 month.

Diferelin® 11.25 mg

With intramuscular administration of Diferelin® at a dose of 11.25 mg, the Cmax of triptorelin in blood plasma (in men and women) is determined approximately 3 hours after injection. After a phase of reduction in concentration, which lasts during the first month, until the 90th day, the concentration of circulating triptorelin remains constant (about 0.04–0.05 ng/ml in the treatment of endometriosis and about 0.1 ng/ml in the treatment of prostate cancer ).

Pharmacodynamics

Triptorelin is a synthetic decapeptide, an analogue of the natural gonadotropin-releasing hormone that releases gonadotropin.

Diferelin® 0.1 mg

Animal and clinical studies have shown that after an initial period of stimulation, long-term use of Diferelin® 0.1 mg suppresses the secretion of gonadotropins with subsequent suppression of ovarian function.

Continuous use of Diferelin® 0.1 mg suppresses the secretion of gonadotropins (FSH and LH). Suppression of intermediate endogenous LH peaks makes it possible to improve the quality of folliculogenesis, increasing the number of maturing follicles, and, as a result, increase the likelihood of pregnancy per cycle.

Diferelin® 3.75 mg

After a short initial period of stimulation of the gonadotropic function of the pituitary gland, triptorelin suppresses the secretion of gonadotropins and, accordingly, the function of the testes and ovaries. Chronic use of the drug inhibits the secretion of estrogen by the ovaries until menopause, and also reduces the secretion of testosterone, the concentration of which can reach levels observed after surgical castration.

iferelin® 11.25 mg

In the initial period of use, Diferelin® 11.25 mg temporarily increases the concentration of LH and FSH in the blood, correspondingly increasing the concentration of testosterone in men and estradiol in women. Long-term treatment reduces the concentration of LH and FSH, which leads to a decrease in testosterone (to levels corresponding to the state after testiculectomy) and estradiol (to levels corresponding to the state of postovariectomy) by approximately the 20th day after the first injection and then remain unchanged throughout the entire period administration of the drug.

Long-term treatment with triptorelin suppresses the secretion of estradiol in women and thus prevents the development of endometrioid ectopia.

Instructions

Diferelin® 3.75 mg. V/m. Rules for preparing the suspension

1. Treat the injection site with an alcohol wipe. Remove the cap from the needle with the pink tip and attach it to the syringe. Draw up all the solvent from the ampoule into the syringe.
2. Gently shake the contents until a homogeneous suspension is obtained, without turning the bottle over.
3. Without turning the bottle over, draw the entire suspension into the syringe.
4. Remove the pink needle from the syringe. Attach the green needle to the syringe (screw it tightly), grasping only the colored tip.
5. Remove air from the syringe.
6. Give the injection immediately. The injection should only be administered intramuscularly.

• push the safety device towards the tip of the needle. Close the needle and snap the device;
• turn the syringe over. Using a flat surface, press down on the device and close the needle.

Use a colored tip to detach the needle. Dispose of needles in sharps containers.

Diferelin® 11.25 mg. V/m Rules for preparing the suspension

Dissolution of the lyophilisate in the supplied solvent should be carried out immediately before administration. Mix the contents of the vial with caution until a homogeneous suspension is obtained.

Cases of incomplete injection resulting in the loss of more suspension than usually remains in the injection syringe should be reported to your doctor.

Administration must be carried out in strict accordance with the instructions.

1. Treat the injection site with an alcohol wipe. Remove the cap from the pink-tipped needle and attach it to the syringe. Draw up all the solvent from the ampoule into the syringe.
2. Remove the plastic cap from the lyophilisate bottle. Insert the needle through the chlorobutyl rubber stopper and transfer the solvent into the vial.
3. Pull the needle so that it remains in the vial but does not touch the suspension.
4. Without turning the bottle over, gently shake the contents until a homogeneous suspension is obtained.
5. Without turning the bottle over, draw the entire suspension into the syringe.
6. Remove the pink-tipped needle from the syringe. Attach a needle with a green tip (or a needle with a green tip and a protective device) to the syringe, screw tightly, grasping only the colored tip.
7. Remove air from the syringe.
8. Give the injection immediately.
9. If using a green-tipped needle with a safety device, then:
10. Immediately after injection, cover the needle using a safety device in one of the following ways:

• Press the safety device towards the tip of the needle. Close the needle and snap the device into place.
• Turn the syringe over using a flat surface, press down on the device and close the needle.

The needle is covered if the needle tip is covered by the device. Check that the device is securely closed.

Use a colored tip to detach the needle.

Dispose of needles in sharps containers.

Indications for use Diferelin

Diferelin® 0.1 mg

Female infertility. Carrying out ovarian stimulation in conjunction with gonadotropins (human menopausal, human chorionic), FSH in in vitro fertilization and embryo transfer programs, as well as other assisted reproductive technologies.

Diferelin® 3.75 mg

• prostate cancer;
• premature puberty;
• genital and extragenital endometriosis;
• uterine fibroids (before surgery);
• female infertility (in the in vitro fertilization program).

Diferelin® 11.25 mg

• prostate cancer with metastases;
• genital and extragenital endometriosis (stages I–IV).

Contraindications to the use of Diferelin

Common to all dosages:

• hypersensitivity;
• pregnancy;
• lactation.

• hormone-independent prostate cancer;
• condition after previous surgical testiculectomy.

Diferelin® 3.75; 11.25 mg (optional):

• With caution - with osteoporosis.

Diferelin® 11.25 mg (additional):

• With caution - in women with polycystic ovary syndrome.

Diferelin Use during pregnancy and children

Currently, gonadotropin-releasing hormone analogues are used in combination with gonadotropins to stimulate ovulation and pregnancy.

Pregnancy is a contraindication for the use of the drug. However, practice has shown that after ovulation stimulated in the previous cycle, some women became pregnant without stimulation and continued the further course of ovulation stimulation.

Summary data: animal experiments have shown that the drug does not have a teratogenic effect.

Thus, the development of congenital anomalies in humans is not expected when using this drug, because 2 well-performed animal studies did not reveal its teratogenic effect.

The results of clinical studies involving a small number of pregnant women using a gonadotropin-releasing hormone analogue showed the absence of fetal malformations or fetotoxicity.

However, further study of the effects of the drug on pregnancy is necessary.

Since there is no data on the penetration of the drug into breast milk and its possible effects on a breast-fed baby, treatment should not be administered during breastfeeding.

Diferelin Side effects

Common to all dosages

At the beginning of treatment. When treating infertility, combination with gonadotropins can lead to ovarian hyperstimulation. In this case, there is an increase in the size of the ovaries and pain in the abdominal area.

During treatment. The most common side effects are: sudden hot flashes, vaginal dryness, decreased libido and dyspareunia associated with pituitary-ovarian blockade.

Long-term use of gonadotropin-releasing hormone analogues can lead to bone demineralization and the risk of developing osteoporosis (the above-described side effects were not observed with short-term use of Diferelin® 0.1 mg).

Allergic reactions: urticaria, rash, itching, rarely - Quincke's edema.

In rare cases - nausea, vomiting, weight gain, increased blood pressure, emotional lability, blurred vision, pain at the injection site.

Extremely rare - headache, joint and muscle pain.

Diferelin® 3.75 mg additionally

In men - decreased potency. At the beginning of treatment, patients with prostate cancer may experience a temporary increase in pain in the bones affected by metastases (treatment is symptomatic). In some cases, ureteral obstruction and symptoms associated with compression by spinal cord metastases are observed (they disappear in 1–2 weeks). Also during this period, a temporary increase in the activity of acid phosphatase in the blood plasma may be observed.

When treating precocious puberty, girls may experience bloody vaginal discharge.

Long-term use of the drug may cause hypogonadotropic amenorrhea.

After cessation of treatment, ovarian function is restored and ovulation occurs on average on the 58th day after the last injection of the drug. The first menstruation occurs on the 70th day after the last injection of Diferelin®. This must be taken into account when planning contraception.

Diferelin 11.25 mg additionally

At the beginning of treatment. Dysuric disorders (difficulty urinating, incomplete emptying of the bladder, pain), bone pain associated with metastases and compression of spinal cord metastases, which may be aggravated due to a temporary increase in testosterone in the blood plasma at the beginning of treatment. These symptoms disappear within 1–2 weeks. Also during this period, a temporary increase in the activity of liver enzymes in the blood plasma may be observed.

During treatment: flushing of the face, decreased libido, gynecomastia, impotence, which is associated with a decrease in testosterone levels in the blood plasma.

At the beginning of treatment. Symptoms associated with endometriosis (pelvic pain, dysmenorrhea), which may intensify due to an initial transient increase in the concentration of estradiol in the blood plasma and disappear after 1–2 weeks.

One month after the first injection, metrorrhagia may occur.

For men and women:

Mood disturbances, irritability, depression, fatigue, sleep disturbance, weight gain, profuse sweating, paresthesia, blurred vision, fever.

Drug interactions

Not described.

Diferelin dosage

Diferelin® 0.1 mg. PC.

Short protocol. Starting from the 2nd day of the cycle (at the same time starting ovarian stimulation), and ending treatment 1 day before the planned administration of human chorionic gonadotropin. The course of treatment is 10–12 days.

Long protocol. Daily subcutaneous injections of Diferelin® 0.1 mg begin on the 2nd day of the cycle. With desensitization of the pituitary gland (E2

Rules for preparing the solution. Immediately before injection, transfer the solvent into a vial with lyophilisate. Shake until completely dissolved. Used needles should be placed in a designated sharps container.

Diferelin® 3.75 mg. V/m.

Prostate cancer. Diferelin® is administered at a dose of 3.75 mg every 4 weeks, long-term.

Premature puberty. Children weighing more than 20 kg - 3.75 mg every 28 days; children weighing less than 20 kg - 1.875 mg every 28 days.

Endometriosis. The drug should be administered in the first 5 days of the menstrual cycle - at a dose of 3.75 mg every 4 weeks. Duration of therapy is no more than 6 months.

Female infertility. Diferelin® should be administered on the second day of the cycle at a dose of 3.75 mg. The relationship with gonadotropins should be monitored after desensitization of the pituitary gland (plasma estrogen concentrations less than 50 pg/ml are usually determined 15 days after Diferelin® injection).

Uterine fibroids. The drug should be administered in the first 5 days of the menstrual cycle. Diferelin® should be administered every 4 weeks at a dose of 3.75 mg. The duration of treatment is 3 months (for patients preparing for surgery).

Diferelin® 11.25 mg. V/m

Prostate cancer. Diferelin® is administered at a dose of 11.25 mg every 3 months.

Endometriosis. Diferelin® is administered at a dose of 11.25 mg every 3 months. Treatment should begin in the first five days of the menstrual cycle. The duration of treatment depends on the severity of endometriosis and the observed clinical picture (functional and anatomical changes) during therapy. As a rule, treatment is carried out for 3–6 months. It is not recommended to carry out a repeated course of treatment with triptorelin or gonadotropin-releasing hormone.

Overdose

Cases of drug overdose are unknown.

Precautionary measures

Diferelin® 0.1 mg

Warning. The ovarian response to the administration of Diferelin® 0.1 mg in combination with gonadotropins may be markedly increased in predisposed patients and, in particular, in cases of polycystic ovarian diseases.

The response of the ovaries to the administration of the drug in combination with gonadotropins may vary among patients, and it may also be different in the same patients during different cycles.

Preventive action. Stimulation of ovulation should be carried out under the supervision of a physician and with regular biological and clinical analysis methods: increasing the content of estrogen in plasma and ultrasound echocardiography. If the ovarian response is excessive, it is recommended to interrupt the stimulation cycle and stop gonadotropin injections.

Diferelin® 3.75 mg

At the beginning of treatment, an increase in clinical symptoms may be observed, and therefore Diferelin® should be prescribed with caution to patients with prostate cancer who are at risk of developing ureteral obstruction or spinal cord compression. Careful monitoring of these patients is necessary during the first month of therapy.

Before starting Diferelin® therapy, it is necessary to confirm the absence of pregnancy.

Use with caution in patients with polycystic ovary syndrome during ovulation stimulation regimens. This is because the number of induced follicles may increase in a small number of patients.

It is necessary to carefully monitor the level of cycle stimulation during in vitro fertilization to identify patients at risk of developing ovarian hyperstimulation syndrome, since the severity and frequency of manifestations of the syndrome may depend on the gonadotropin dosage regimen. If necessary, administration of human chorionic gonadotropin should be discontinued.

Diferelin® 11.25 mg

Treatment of endometriosis. Before starting treatment, pregnancy must be excluded.

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

Intramuscular injection of the drug leads to persistent hypogonadotropic amenorrhea.

The occurrence of metrorrhagia during treatment, not counting the first month, is not the norm, and therefore it is necessary to determine the concentration of plasma estradiol. When the concentration of estradiol decreases to a level of less than 50 pg/ml, the presence of other organic lesions may be present.

Ovarian function is restored after completion of therapy. The first menstruation occurs on average 134 days after the last injection. For this reason, you should start using contraception 15 days after stopping treatment, i.e. 3.5 months after the last injection.

In the treatment of prostate cancer. The most pronounced beneficial effect is observed in patients in the absence of other previously administered hormonal therapy.

At the beginning of treatment, the appearance and intensification of clinical symptoms (in particular bone pain, dysuric disorders), which are transient in nature, may occur.

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

Treatment with Diferelin® must be carried out in strict accordance with the instructions for use. Any change in the volume of intramuscular suspension administered should be recorded.

One bottle contains triptorelin acetate . It acts as an auxiliary substance. The solvent contains sodium chloride and water.

• Lyophilisate for production solution for subcutaneous administration– 1 fl. Triptorelin (triptorelin acetate) – 0.1 mg. Mannitol – 10 mg. 1 ampoule of solvent – ​​water for injection, sodium chloride.
• Lyophilisate for suspensions for intramuscular administration 3.75 mg. Excipients: carmellose sodium, copolymer of glycolic and DL-lactic acids, polysorbate-80, mannitol . 1 ampoule of solvent – ​​water for injection, mannitol. Considering the characteristics of this dosage form, the drug contains the active component in excess. The goal is to ensure that the optimal dose is administered.
• Lyophilisate for cooking suspensions for intramuscular administration long-acting – 1 fl. Triptorelin (triptorelin acetate) – 11.25 mg. Excipients: carmellose sodium, copolymer of glycolic and DL-lactic acids, polysorbate-80, mannitol. 1 ampoule of solvent – ​​water for injection, mannitol. Considering the characteristics of this dosage form, the drug contains the active component in excess. The goal is to ensure that the optimal dose is administered.

Release form

Diferelin – 0.1 mg

Available in bottles. The kit includes ampoules with solvent. There are 7 sets in the blister outline packaging. There is one package in a cardboard box. S.C. is introduced.

Diferelin – 3.75 mg

Diferelin – 11.25 mg

Available in bottles. The kit includes ampoules with solvent, a syringe, and two needles. There is one set in a cardboard box. Injected intramuscularly.

pharmachologic effect

Hormone a drug that is an analogue gonadotropin-releasing hormone.

Pharmacodynamics and pharmacokinetics

Is synthetic decapeptide , an analogue of natural gonadotropin-releasing hormone , which releases gonadotropin . The drug is quickly absorbed after administration. When administered intramuscularly, the active substance is quickly released.

Indications for use

Diferelin 0.1 mg

Rarely: increased blood pressure, nausea, vomiting, emotional lability, weight gain, blurred vision, pain in the area of ​​drug administration.

Very rare: joint and muscle pain, headache.

Additionally, Diferelin 3.75 mg

With prolonged use, it is possible that hypogonadotropic amenorrhea .

After treatment is completed, ovarian function is restored. Ovulation occurs approximately on the 58th day from the last injection. The first menstruation is on the 70th day. Important for contraceptive planning.

Additionally, Diferelin 11.25 mg

Men: possible at the beginning of treatment dysuric disorders , bone pain. Symptoms disappear within one to two weeks.

During treatment: decreased libido, impotence , gynecomastia , flushes of blood to the face.

Women: at the beginning of taking the drug, pelvic pain is possible. Disappears within one to two weeks.

Possible occurrence metrorrhagia one month from the start of injections.

Men and women: fatigue, , disturbed mood, irritability, sleep disturbance, blurred vision, paresthesia , profuse sweat, weight gain.

Instructions for Diferelin (Method and dosage)

Instructions for Diferelin 0.1 mg contains a short and a long protocol. The drug is administered subcutaneously.

Short protocol: The drug is taken from the second day of the cycle. At the same time, ovarian stimulation is carried out. Treatment ends one day before administration gonadotropin . The general course of treatment is 10-12 days.

Long protocol for Diferelin: The drug begins to be administered on the second day of the cycle. Entered daily. Approximately on the 15th day of taking the drug, stimulation with gonadotropins is carried out in parallel. The duration of treatment is individual and adjusted by the doctor.

Preparation of the solution: Before administering the drug, the solvent is introduced into the vial with the lyophilisate. Dissolve completely.

Diferelin 3.75. V/m. In case of illness prostate cancer - administered in an appropriate dose - 3.75 mg for a long time every 4 weeks. At premature puberty – 3.75 mg administered every 28 days. In case of illness endometriosis diferelin depot drug is administered in the first five days of the cycle every month. At female infertility the drug is administered on the second day of the cycle.

Diferelin 11.25 administered in a volume of 11.25 mg every three months.

Preparation of the solution: Immediately before administering the drug, the solvent is introduced into the vial with the lyophilisate. Dissolve completely, gently shaking the contents of the bottle.

Overdose

To date, there have been no reports of overdoses.

Interaction

Cases of interaction have not been described.

Terms of sale

On prescription.

Storage conditions

At temperatures up to 25°C, out of reach of children.

Best before date

Diphereline and alcohol

When taking any drug, it is not advisable to use alcohol . When combined, the effect of treatment may be reduced. If we are talking about female infertility , then in this case it is prohibited to combine the drug with alcohol.

Diferelin: instructions for use and reviews

Diferelin is a drug with antitumor activity.

Release form and composition

Diferelin is produced in the following dosage forms:

• Lyophilisate for the preparation of solution for subcutaneous administration: almost white, dispersible in the supplied solvent to form an almost particle-free, clear solution; solvent – ​​colorless transparent solution (in colorless glass bottles, 7 bottles in a cardboard box complete with solvent (in ampoules of 1 ml, 7 ampoules per package));
• Lyophilisate for the preparation of a suspension for intramuscular administration of prolonged action: white with a creamy (3.75 mg each) or yellowish (11.25 mg each) tint or white, dispersing in the included solvent to form a suspension of white with creamy (3.75 mg each) ) or yellowish (11.25 mg each) tint or white (in slightly darkened glass bottles, 1 bottle in a cardboard box complete with a disposable polypropylene syringe, solvent (in ampoules of 2 ml, 1 ampoule per package), needles for injection (2 pcs.)).

The composition of 1 bottle with lyophilisate for preparing a solution for subcutaneous administration of Diferelin includes:

• Active substance: triptorelin – 0.1 mg (in the form of triptorelin acetate);
• Auxiliary component: mannitol – 10 mg.

Solvent: sodium chloride – 9 mg, water for injection – up to 1000 mg.

The composition of 1 bottle with lyophilisate for the preparation of a suspension for intramuscular administration of prolonged action Diferelin includes:

• Active substance: triptorelin – 3.75 or 11.25 mg (in the form of triptorelin acetate; to ensure the administration of an effective dose, an excess of the substance is included in the drug);
• Auxiliary components (3.75/11.25 mg, respectively): copolymer of D, L-lactic and glycolic acids - about 160/250 mg, mannitol - 85/85 mg, carmellose sodium - 30/30 mg, polysorbate 80 - 2/ 2 mg.

Solvent: mannitol – 16 mg, water for injection – up to 2000 mg.

Pharmacological properties

Diferelin is a hormonal drug considered an analogue of natural gonadotropin-releasing hormone.

Pharmacodynamics

Triptorelin is a synthetic decapeptide. Immediately after entering the body, it stimulates the gonadotropic function of the pituitary gland for a short period of time, after which inhibition of the secretion of gonadotropins is observed, followed by inhibition of ovarian and testicular function. At the initial stage of using Diferelin, the level of follicle-stimulating (FSH) and luteinizing hormones (LH) in the blood temporarily increases, which causes an increase in the concentration of estradiol in women and testosterone in men (“flare”). With long-term treatment with triptorelin, the concentration of FSH and LH decreases, which helps to reduce the content of estradiol (to values ​​corresponding to the state of postovariectomy) and testosterone (to values ​​​​corresponding to the state after testiculectomy). A similar phenomenon is observed approximately on the 20th day after the first injection of Diferelin. Subsequently, the concentration of hormones remains unchanged throughout the entire period of therapy.

Long-term use of triptorelin reduces the production of estradiol in women and, accordingly, prevents the development of endometrioid ectopia.

Triptorelin inhibits gonadotropic hyperfunction of the pituitary gland during premature puberty in both boys and girls, which is expressed in suppressing the secretion of testosterone or estradiol, reducing the maximum concentration of LH and improving the ratio of bone and calendar ages.

Pharmacokinetics

With intramuscular administration of Diferelin at a dose of 11.25 mg, the maximum concentration of its active component in the blood plasma is determined approximately 3 hours after injection. The duration of the phase of gradual reduction in concentration is 1 month after the start of treatment, after which until the 90th day the content of circulating triptorelin remains stable: approximately 0.04‒0.05 ng/ml - when treating endometriosis, about 0.1 ng/ml - when treatment of prostate cancer.

Indications for use

According to the instructions, Diferelin is prescribed for the treatment of female infertility: for ovarian stimulation together with gonadotropins (human menopausal gonadotropin (hMG), human chorionic gonadotropin (hCG), follicle-stimulating hormone (FSH)) in in vitro fertilization and embryo transfer programs, as well as for other assisted reproductive technologies.

• Prostate cancer (locally advanced (as monotherapy or as an adjuvant agent during radiation therapy), metastatic);
• Premature puberty;
• Endometriosis (extragenital and genital);
• Uterine fibroids (before surgery);
• Female infertility (in in vitro fertilization programs).

Contraindications

• Hormone-independent prostate cancer, conditions after surgical testiculectomy;
• Pregnancy and breastfeeding period;
• Hypersensitivity to the components of the drug and other analogues of gonadotropin-releasing hormone (GnRH).

Diferelin suspension 3.75 mg and 11.25 mg should be prescribed with caution in osteoporosis and polycystic ovary syndrome.

Instructions for use of Diferelin: method and dosage

Solution for subcutaneous administration

Diferelin is used subcutaneously.

One of 2 courses of treatment is possible:

• Short: daily 0.1 mg per day, starting from the second day of the cycle (at the same time, ovarian stimulation begins). Therapy is completed 1 day before the planned administration of human chorionic gonadotropin. Course duration – 10-12 days;
• Long-term: daily 0.1 mg per day, starting from the second day of the cycle. When the pituitary gland is desensitized (E2 is less than 50 pg/ml, i.e., approximately on the fifteenth day after the start of therapy), stimulation of the ovaries with gonadotropins begins, continuing subcutaneous injections at the same dose. The course is completed 1 day before the planned administration of human chorionic gonadotropin. The doctor determines the duration of treatment individually.

To prepare the solution, the supplied solvent must be added to the bottle with the lyophilisate, then shaken until completely dissolved.

Long-acting suspension for intramuscular administration

Diferelin is administered only intramuscularly, into the gluteal muscle.

The dosage regimen depends on the indications:

• Prostate cancer: long-term 3.75 mg (1 injection) every 4 weeks or every 3 months 11.25 mg. When treated simultaneously with radiation therapy, long-term antiandrogen therapy (3 years) is preferable to short-term (6 months);
• Precocious puberty: every 28 days, 1.875 mg (with body weight up to 20 kg) or 3.75 mg (with body weight over 20 kg);
• Endometriosis: 3.75 mg once every 4 weeks or 11.25 mg once every 3 months; the injection must be carried out in the first 5 days of the menstrual cycle. Course duration is up to 6 months. The duration of therapy is determined by the severity of endometriosis and the clinical picture (anatomical and functional changes) during therapy. Repeated treatment with triptorelin or another GnRH analogue is not recommended;
• Female infertility: 1 injection of 3.75 mg on the second day of the cycle. The connection with gonadotropins must be monitored after desensitization of the pituitary gland (plasma estrogen concentrations less than 50 pg/ml are usually determined 15 days after administration of Diferelin);
• Uterine fibroids: every 4 weeks 3.75 mg. The suspension must be administered in the first 5 days of the menstrual cycle. For patients preparing for surgery, the duration of treatment is 3 months.

A suspension for intramuscular administration is prepared immediately before the procedure by dissolving the lyophilisate in the supplied solvent.

Side effects

Solution for subcutaneous administration

At the beginning of the use of Diferelin, when combined with gonadotropins, reproductive system disorders may occur in the form of ovarian hyperstimulation (abdominal pain, increase in ovarian size).

During therapy, the following side effects may develop:

• Reproductive system: very often - vaginal dryness, sudden hot flashes, dyspareunia and decreased libido associated with pituitary-ovarian blockade;
• Digestive system: vomiting, nausea, increased activity of liver transaminases;
• Central and peripheral nervous system: visual impairment, emotional lability, headache;
• Musculoskeletal system: joint and muscle pain; with long-term therapy with GnRH analogues - demineralization of bones, the risk of developing osteoporosis (this disorder is not observed with short-term use of Diferelin at a dose of 0.1 mg);
• Cardiovascular system: increased blood pressure;
• Allergic reactions: skin rash, urticaria, itching; rarely - Quincke's edema;
• Local reactions: pain at the site of injection of the solution;
• Other: weight gain.

Long-acting suspension for intramuscular administration

• Musculoskeletal system: with prolonged therapy, bone demineralization occurs, which is a risk factor for the development of osteoporosis. At the beginning of therapy for prostate cancer, patients may experience a temporary increase in pain in the bones affected by metastases (symptomatic treatment is indicated). In some cases, ureteral obstruction and the appearance of signs associated with compression by spinal cord metastases (dissipate in 7-14 days). Also at this time, a short-term increase in the activity of acid phosphatase in the blood plasma may be observed;
• Cardiovascular system: in isolated cases - a feeling of hot flashes, arterial hypertension;
• Central nervous system: in isolated cases – visual impairment, increased emotional lability;
• Reproductive system: men – decreased potency; women - depression, headache, changes in libido, sweating, changes in the size of the mammary glands, dryness of the vaginal mucosa, dyspareunia; when used simultaneously with gonadotropins - the development of ovarian hyperstimulation syndrome; during the treatment of premature puberty in girls - bloody vaginal discharge; with prolonged treatment - hypogonadotropic amenorrhea;
• Digestive system: in isolated cases - vomiting, nausea;
• Allergic reactions: rash, urticaria, itching; very rarely - Quincke's edema;
• Local reactions: in isolated cases - pain at the injection site of the suspension;
• Other: in isolated cases - increased body temperature, increased body weight.

Overdose

There are currently no reports of cases of Diferelin overdose. Experiments on animals have obtained results suggesting the effect of triptorelin in very high doses on the level of sex hormones and, accordingly, on the state of the reproductive system. In case of overdose of the drug, symptomatic therapy is prescribed if necessary.

special instructions

Before starting to use Diferelin, pregnancy must be excluded.

Solution for subcutaneous administration

The response of the ovaries to subcutaneous administration of the solution simultaneously with gonadotropins in predisposed patients can increase significantly, in particular with polycystic ovary syndrome.

The response of the ovaries to the administration of Diferelin together with gonadotropins may vary in different patients, even in the same women during different cycles the reaction may be different.

Stimulation of ovulation must be carried out under the supervision of a physician, conducting regular tests using clinical and biological methods: ultrasound echography and increasing the content of estrogen in plasma. If the ovarian response is excessive, it is recommended to interrupt the stimulation cycle by stopping gonadotropin injections.

Since in some cases visual impairment may occur during therapy, caution should be exercised when driving vehicles and performing potentially dangerous types of work that require high concentration and rapid psychomotor reactions.

Long-acting suspension for intramuscular administration

At the beginning of therapy, clinical signs may increase, which is why Diferelin should be prescribed with caution to patients with prostate cancer who are at risk of developing spinal cord compression or ureteral obstruction. During the first month of therapy, the condition of such patients requires careful medical supervision.

Against the background of polycystic ovary syndrome, when carrying out ovulation stimulation schemes, Diferelin should be used with caution, as this can lead to an increase in the number of induced follicles.

During in vitro fertilization, the level of cycle stimulation must be carefully monitored (to identify patients at risk of developing ovarian hyperstimulation syndrome). If necessary, the administration of human chorionic gonadotropin should be discontinued.

Use during pregnancy and lactation

During pregnancy, the administration of triptorelin is contraindicated, since such treatment can provoke abortion or the appearance of intrauterine malformations in the fetus. Before starting treatment in patients of reproductive age, pregnancy should be excluded by conducting a thorough examination. During the course of Diferelin therapy, it is necessary to use non-hormonal methods of contraception until the menstrual cycle is restored.

During lactation, the use of Diferelin is strictly prohibited.

Drug interactions

There is no data on the interaction of Diferelin with other drugs.

Analogs

An analogue of Diferelin is Decapeptyl Depot.

Terms and conditions of storage

Store out of the reach of children at temperatures up to 25 °C.

Best before date:

• Lyophilisate for preparing a solution for subcutaneous administration – 2 years;
• Lyophilisate for preparing a suspension for intramuscular administration: 3.75 mg - 2 years, 11.25 mg - 3 years; solvent – ​​5 years.

Diferelin is an antitumor hormonal drug, an analogue of gonadotropin-releasing hormone. This medicine helps to provide antigonadotropic effects.

Diferelin is available in the form of a lyophilisate for the preparation of a suspension intended for intramuscular administration.

The active ingredient is triptorelin acetate. The lyophilisate is accompanied by a solvent, which includes water for injection, as well as sodium chloride.

The medication is administered in strict accordance with the manufacturer's instructions. In this case, the patient should be in a lying position.

• It is necessary to break the neck of the ampoule and withdraw the solvent into the syringe.
• Remove the protective cap from the bottle and pour in the solvent.
• Pull the needle - it should remain in the bottle and not touch the suspension.
• Mix the contents of the bottle until a homogeneous liquid is obtained. The bottle must not be turned over.
• Draw the resulting contents of the bottle into the syringe.
• Remove the needle that was used during the preparation of the suspension and attach a clean needle.
• Remove any remaining air from the syringe and immediately inject the drug into the area of ​​the gluteal muscle (the skin must be previously disinfected).
• Dispose of needles and syringe.

Adverse reactions

General information for all dosages. Diferelin may contribute to the development of the following undesirable side effects:

• Quincke's edema, urticaria, itching, rash.
• When treating infertility, which is carried out in combination with gonadtropins, manifestations of ovarian hyperstimulation may be observed: the development of pain in the abdominal area, an increase in the size of the ovaries.
• During treatment, the development of hot flashes, vaginal dryness, and decreased libido may occur. Long-term use of the drug increases the risk of developing osteoporosis.
• Rarely: development of nausea, vomiting, visual disturbances, increased blood pressure, weight gain, disturbance of psycho-emotional state, pain at the injection site.
• Isolated cases: development of joint and muscle pain, headache.

During treatment, men may experience a lack or decrease in potency. At the beginning of therapy, patients with prostate cancer may experience bone pain. In this case, symptomatic treatment is required.

If the drug is used in the treatment of premature puberty in girls, short-term bleeding from the vagina may be observed.

Long-term use of the drug Diferelin can provoke the development of hypogonadotropic amenorrhea.

After discontinuation of therapy with Diferelin at a dosage of [information on the dose of the drug has been removed], the restoration of ovulation and normal ovarian function occurs approximately on the 58th day after the last injection. The first menstruation may occur approximately 70 days after the last injection. This should be taken into account when planning contraception.

The interaction of the drug Diferelin with other groups of drugs has not been described. If it is necessary to combine this drug with other drugs, you must first consult with your doctor.

At the beginning of therapy, all symptoms of the disease may intensify, so Diferelin is used with extreme caution during the treatment of malignant neoplasms of the prostate gland. Due to the risk of developing ureteral obstruction and spinal cord compression, patients should be under systematic medical supervision in the first 30 days of therapy.

Before starting treatment with the drug, it is necessary to exclude the patient's possible pregnancy.

Analogues, cost

The cost of the drug Diferelin for the period of autumn 2016 was formed as follows:

• Lyophilisate for preparing a solution 0.1 mg, 7 pcs. – 2500-3000 rub.
• Powder for intramuscular injection 3.75 mg, 1 bottle – 7400-8700 rub.
• Lyophilisate for preparing a solution 11.25 mg - 18,000 - 20,000 rubles.

The following drugs can be analogues of the drug Diferelin: Decapeptyl, Triptorelin.