Buserelin (Lyophilisate, Spray) Instructions for Use

ATC Code

L02AE01 (Buserelin)

Active Substance

Buserelin (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Gonadotropin-releasing hormone analogue – depot form

Pharmacotherapeutic Group

Antineoplastic agent, gonadotropin-releasing hormone analog

Pharmacological Action

An antineoplastic drug, a synthetic analogue of GnRH. Buserelin competitively binds to receptors of the anterior pituitary gland cells, causing a short-term increase in the level of sex hormones in the blood plasma.

On average, after 12-14 days of using the drug in therapeutic doses, it leads to a complete blockade of the gonadotropic function of the pituitary gland, thus inhibiting the release of LH and FSH.

As a result, suppression of sex hormone synthesis in the gonads is observed, manifested by a decrease in estradiol concentration in the blood plasma to postmenopausal values in women and a decrease in testosterone content to post-castration levels in men.

The concentration of testosterone during continuous treatment for 2-3 weeks decreases to a level characteristic of the state of orchiectomy, i.e., the drug causes pharmacological castration.

Pharmacokinetics

Bioavailability is high. C_max in plasma is reached approximately 2-3 hours after intramuscular administration and is maintained at a level sufficient to inhibit pituitary gonadotropin synthesis for at least 4 weeks.

Indications

• Hormone-dependent prostate cancer;
• Breast cancer;
• Endometriosis (pre- and postoperative periods);
• Uterine fibroids;
• Hyperplastic processes of the endometrium;
• Infertility treatment (when performing an in vitro fertilization program).

ICD codes

Dosage Regimen

Spray

For the treatment of endometriosis, uterine fibroids, hyperplastic processes of the endometrium, the drug is administered into the nasal passages after their cleansing at a dose of 900 mcg/day. A single dose of the drug with a full pump press is 150 mcg. The daily dose of the drug is administered in equal portions, one spray into each nostril 3 times/day at equal intervals (6-8 hours) in the morning, afternoon, and evening. Treatment with Buserelin should be started on the first or second day of the menstrual cycle and administered continuously throughout the entire course of treatment. The course of treatment is 4-6 months.

For the treatment of infertility by in vitro fertilization, the drug is administered intranasally, one spray (150 mcg) into each nostril 3-4 times/day at equal intervals. The daily dose is 900-1200 mcg. Buserelin is prescribed at the beginning of the follicular phase (on the 2nd day of the menstrual cycle) or in the middle of the luteal phase (days 21-24) of the menstrual cycle preceding stimulation. After 14-17 days, when serum estradiol in patients decreases by at least 50% from the baseline level, in the absence of ovarian cysts, and with an endometrial thickness of no more than 5 mm, stimulation of superovulation with gonadotropic hormones begins under ultrasound monitoring and control of serum estradiol levels. If necessary, the dose of Buserelin may be adjusted.

Lyophilisate

For hormone-dependent prostate cancer – 3.75 mg IM every 4 weeks.

For the treatment of endometriosis, hyperplastic processes of the endometrium – 3.75 mg IM once every 4 weeks. Treatment should be started within the first five days of the menstrual cycle. The duration of treatment is 4-6 months.

For the treatment of uterine fibroids – 3.75 mg IM once every 4 weeks. Treatment should be started within the first five days of the menstrual cycle. The duration of treatment is 3 months before surgery, in other cases – 6 months.

For the treatment of infertility by in vitro fertilization – 3.75 mg IM once at the beginning of the follicular phase (on the 2nd day of the menstrual cycle) or in the middle of the luteal phase (days 21-24) of the menstrual cycle preceding stimulation. After blockade of pituitary function, confirmed by a decrease in serum estrogen concentration by at least 50% from the baseline level (usually determined 12-15 days after the Buserelin-depot injection), in the absence of ovarian cysts (according to ultrasound), and with an endometrial thickness of no more than 5 mm, stimulation of superovulation with gonadotropic hormones begins under ultrasound monitoring and control of serum estradiol levels.

Rules for the preparation of the suspension and administration of the drug

The drug is administered intramuscularly only. The suspension for intramuscular injection is prepared using the supplied solvent immediately before administration. The drug must be prepared and administered only by specially trained medical personnel.

The vial with Buserelin-depot should be held strictly vertically. By tapping the vial lightly, ensure that all the lyophilisate is at the bottom of the vial.

Open the syringe, attach the needle with the pink hub (1.2 × 50 mm) for drawing up the solvent.

Open the ampoule and draw all the contents of the ampoule with the solvent into the syringe, set the syringe to a dose of 2 ml.

The plastic cap should be removed from the vial containing the lyophilisate. Disinfect the rubber stopper of the vial with an alcohol swab. Insert the needle into the vial with the lyophilisate through the center of the rubber stopper and carefully introduce the solvent along the inner wall of the vial without the needle touching the contents of the vial. Remove the syringe from the vial.

The vial should remain motionless until the lyophilisate is completely saturated with the solvent and a suspension is formed (approximately 3-5 minutes). After that, without inverting the vial, check for the presence of dry lyophilisate on the walls and bottom of the vial. If dry residues of the lyophilisate are found, leave the vial until complete saturation.

After no dry lyophilisate residues remain, the contents of the vial should be gently mixed with circular motions for 30-60 seconds until a homogeneous suspension is formed. Do not invert or shake the vial, as this may cause flaking and render the suspension unusable.

Quickly insert the needle through the rubber stopper into the vial. Then lower the needle bevel down and, tilting the vial at a 45° angle, slowly draw the entire suspension into the syringe. Do not invert the vial during aspiration. A small amount of the drug may remain on the walls and bottom of the vial. The residue on the walls and bottom of the vial is accounted for.

Immediately replace the needle with the pink hub with the needle with the green hub (0.8×40 mm), carefully invert the syringe and remove air from the syringe.

The Buserelin-depot suspension should be administered immediately after preparation.

Using an alcohol swab, disinfect the injection site. Insert the needle deep into the gluteal muscle, then slightly pull the syringe plunger back to ensure that no blood vessel has been damaged. Administer the suspension intramuscularly slowly with constant pressure on the syringe plunger. If the needle becomes clogged, it is replaced with another needle of the same diameter.

Adverse Reactions

Allergic reactions urticaria, skin hyperemia; rarely – angioedema.

From the CNS frequent mood swings, sleep disorders, depression, headache.

From the musculoskeletal system bone demineralization, which is a risk for the development of osteoporosis.

In women – headache, depression, sweating and change in libido, dryness of the vaginal mucosa, lower abdominal pain; rarely – menstrual-like bleeding (usually during the first weeks of treatment).

In men during prostate cancer treatment – within the first 2-3 weeks after the first injection, exacerbation and progression of the underlying disease may occur (associated with stimulation of gonadotropin synthesis and, accordingly, testosterone), gynecomastia, “hot flashes” are possible, increased sweating and decreased potency (rarely requires a change in therapy), transient increase in the concentration of androgens in the blood, urinary retention, “renal” edema (edema of the face, eyelids, legs), muscle weakness in the lower extremities. At the beginning of treatment for patients with prostate cancer, temporary increased bone pain may occur; in this case, symptomatic therapy should be carried out. Isolated cases of ureteral obstruction and spinal cord compression have been reported.

Others in isolated cases (causal relationship not clearly established) – pulmonary embolism, dyspeptic phenomena.

Contraindications

• pregnancy;
• lactation period;
• hypersensitivity to the components of the drug.

Use in Pregnancy and Lactation

Use during pregnancy and lactation is contraindicated.

Special Precautions

Women. Patients with any form of depression during treatment with Buserelin-depot should be under close medical supervision. Induction of ovulation should be carried out under strict medical supervision. In the initial stage of treatment with the drug, the development of an ovarian cyst is possible.

Before starting treatment with the drug, it is recommended to exclude pregnancy and stop taking hormonal contraceptives; however, during the first two months of using the drug, other (non-hormonal) methods of contraception must be used.

Men. For effective prevention of possible side effects in the first phase of the drug’s action, it is necessary to use antiandrogens 2 weeks before the first injection of Buserelin-depot and for 2 weeks after the first injection.

Effect on the ability to drive vehicles and operate machinery

Caution should be exercised when prescribing the drug to patients engaged in potentially hazardous activities that require increased attention and speed of psychomotor reactions.

Overdose

To date, no cases of overdose with Buserelin-depot have been reported.

Drug Interactions

Concomitant use of Buserelin-depot with drugs containing sex hormones (for example, in an ovulation induction regimen) may contribute to the occurrence of ovarian hyperstimulation syndrome.

With simultaneous use, Buserelin may reduce the effectiveness of hypoglycemic agents.

Storage Conditions

The drug should be stored out of the reach of children, protected from light, at a temperature from 8°C (46.4°F) to 25°C (77°F).

Shelf Life

Shelf life of the lyophilisate – 3 years, solvent – 5 years.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.