Bromergon - instructions for use, dose, side effects, contraindications

Excipients: butyl hydroxy anisole 0.500 mg; tragacanth 1,250 mg; corn starch 16,800 mg; magnesium stearate 0.450 mg; color yellow E 104 (A1 lake) 0.075 mg, lactose 123.925 mg; sodium starch glycolate 4,500 mg.

Description:

yellow or yellow-brown color round flat tablets with bevel and risk.

Pharmacotherapeutic group:Dopamine receptor agonist.

ATX: & nbsp

N.04.B.C Stimulants of dopamine receptors

N.04.B.C.01 Bromocriptine

Pharmacodynamics:

Bromocriptine is an ergot derivative, an agonist (D2) of dopamine receptors. Reduces the secretion of prolactin in the anterior pituitary gland and does not affect the production and release of other pituitary hormones, except for patients with acromegaly, in whom bromocriptine reduces the concentration of growth hormone.

In the postpartum period, prolactin is needed to start and maintain lactation. In other periods of life, an increase in prolactin secretion leads to pathological lactation (galactorrhea) and / or disorders of ovulation and the menstrual cycle. Bromocriptine, being a specific inhibitor of prolactin secretion, can be used to prevent or suppress physiological lactation, as well as to treat pathological conditions caused by prolactin hypersecretion. With amenorrhea and / or anovulatory menstrual cycles (accompanied or not accompanied by galactorrhea), bromocriptine normalizes the function of the ovaries, restoring endocrine regulation at the level of the ovaries - the pituitary gland. Bromocriptine does not disrupt the postnatal involution of the uterus and does not increase the risk of thromboembolism. In the syndrome of polycystic ovaries, the drug reduces the severity of clinical manifestations. Bromocripin stops growth or decreases the size of prolactin secreting adenomas (prolactin).

The drug has no effect on the secretion of other pituitary hormones, however, in patients with acromegaly, it reduces the increased concentration of growth hormone.In patients with acromegaly, in addition to reducing the concentration of growth hormone and prolactin in the blood plasma, bromocriptine has a beneficial effect on clinical manifestations and glucose tolerance.

With Parkinson's disease, characterized by a lack of dopamine in some structures of the brain, bromocriptine is used in higher doses than for the treatment of endocrine diseases. Bromocriptine stimulates the receptors of dopamine, contributing to the restoration of the neurochemical balance in these structures. The drug reduces tremor, stiffness, akinesia and gait disorders at all stages of the disease. Bromocriptine reduces the severity of the symptoms of depression, often observed in patients with Parkinsonism.

Bromocriptine can lower blood pressure (BP), but the mechanism of this action remains unclear. Perhaps this effect is a consequence of the agonistic effect on the central dopamine receptors, the result of which is a decrease in vascular tone, as well as a decrease in plasma concentrations of catecholamines, and, indirectly, the drug acts as a vasodilator.

Pharmacokinetics:

Absorption after oral administration is 25-30%. The maximum concentration in the blood plasma is reached within 1-3 hours. After ingestion of bromocriptine in a dose of 5 mg, the maximum concentration in the blood plasma is 0.465 ng / ml. Bromocriptine is associated with plasma proteins - 96%. Prolactin-lowering effect begins 1-2 hours after taking the drug inside, reaching a maximum after 5-10 hours (decrease in prolactin level is about 80%), and remains approximately at this level for 8-12 hours.

Bromocriptine has the effect of "primary passage" through the liver, its bioavailability is 6%. In in vitro studies, it was shown that bromocriptine has a high affinity for the enzyme CYP3A. Inhibitors and / or competing substrate for CYP of ZA4 can slow the metabolism of bromocriptine and increase its concentration in the blood plasma. The effect on bismocriptine metabolism of liver microsomal oxidation enzymes such as CYP 2D6, CYP 2C8, CYP 2C19 has not been studied. Bromocriptine is an inhibitor of CYP α4.

Removal of unchanged drug from the blood plasma biphasic, the final half-life is about 15 hours (8 to 20 hours).

Bromocriptine and its metabolites are almost completely secreted through the liver, only 6% is excreted through the kidneys.

In patients with impaired hepatic function, the rate of bromocriptine elimination can be slowed down, and the concentration in the blood plasma may increase, which requires correction of the dose.

The effect on the pharmacokinetics of bromocriptine and its metabolites of age, race and sex has not been studied.

Indications:

Violation of the menstrual cycle, female infertility

Prolactin-dependent diseases and conditions, accompanied or not accompanied by hyperprolactinaemia:

amenorrhea (accompanied or not accompanied by galactorrhea), oligomenorrhea;
Luteal phase insufficiency;
hyperprolactinemic disorders caused by drugs (eg, some psychotropic or antihypertensive drugs).

Prolactin-independent female infertility:

polycystic ovarian syndrome;
anovulatory cycles (in addition to anti-estrogens, for example clomiphene).

Hyperprolactinemia in men

Prolactin-dependent hypogonadism (oligospermia, loss of libido, impotence).

Prolactinomas

Conservative treatment of prolactin-secreting micro- and macroadenomas of the pituitary gland.
Preoperative preparation to reduce the volume of the tumor and facilitate its resection.
Postoperative treatment if the concentration of prolactin remains elevated.

Acromegaly

As an additional remedy or, in special cases, as an alternative to surgical or radiotherapy.

Suppression of lactation

Prevention or suppression of postpartum lactation for medical reasons, including at the initial stage of postpartum mastitis.
Suppression of lactation during postnatal engorgement of mammary glands (with ineffectiveness of adequately conducted therapy with analgesics, antispasmodics, wearing of supporting underwear, regular decantation, etc.).

Prevention of lactation after abortion.

Bromergon is not recommended for use as a prophylactic or for reducing postpartum engorgement of mammary glands in cases where simple analgesics and breast support are effective.

Parkinson's disease

All stages of idiopathic Parkinson's disease and postencephalic parkinsonism - either in monotherapy or in combination with other antiparkinsonian agents.

Due to the limited amount of clinical data, Bromergon is not recommended for the treatment of premenstrual syndrome and benign breast diseases.

Contraindications:

Hypersensitivity to bromocriptine, ergot alkaloids or other components of the drug.
Uncontrolled hypertension.
Preeclampsia of the second half of pregnancy (including preeclampsia, eclampsia). Arterial hypertension during pregnancy and in the postpartum period.
Ischemic heart disease and other diseases of the cardiovascular system of a serious degree (including unstable angina, heart valve disease (for long-term treatment)).
Severe mental disorders (including history).
Rare hereditary forms of lactose intolerance, lactase deficiency or impaired absorption of glucose / galactose (because the composition contains lactose).

Since the experience of the drug in children younger than 7 years is limited, the drug is not recommended for use in this category of patients.

Carefully:

Applied in patients with cardiovascular diseases, impaired liver and kidney function; Parkinsonism with symptoms of dementia; porphyria.

Use in children and adolescents <18 years

The efficacy and safety of bromocriptine have been established for children and adolescents with prolactomies and acromegaly older than 7 years. The experience of using the drug in children younger than 7 years is limited. In clinical studies and medical practice, tolerability of the drug in adults and children was the same. Given the hard-to-predictable sensitivity of children and adolescents, caution should be exercised when using the drug in this category of patients.

Patient use> 65 years

The number of patients 65 years of age or older in clinical trials was not sufficient to assess the possible differences in response to bromocriptine compared to younger patients. In clinical trials and medical practice, the tolerability of the drug in patients> 65 years and younger was the same.

Given the difficult predictable tolerability of the drug in patients> 65 years of age, caution should be exercised when using the drug in this category of patients.

Application in the puerperium

Women taking bromocriptine in the puerperium for the suppression of lactation,especially at the beginning of treatment, rare cases of serious adverse events: hypertension, myocardial infarction, seizures, stroke or mental disorders. In some patients, development of seizures or cerebrovascular disorders was preceded by severe headaches and / or transient visual impairment. Although the causal relationship between the development of these phenomena and the use of bromocriptine has not been established, all patients taking Bromergon should be monitored for blood pressure (BP). With the development of hypertension or severe, progressive or persistent headache (accompanied or not accompanied by a visual impairment) or signs of a CNS disorder, the use of Bromergon should be discontinued and the patient should be immediately examined.

Particular care should be taken when using Bromergon in patients who have recently or continue to take drugs that affect blood pressure, such as vasoconstrictors (sympathomimetics, ergot alkaloids, including ergometrine or methylergomethrin).Women in the postpartum period do not recommend the simultaneous use of Bromergon with vasoconstrictor drugs.

Pregnancy and lactation:

Treatment with bromocriptine during pregnancy should be discontinued, except when the potential effect of treatment exceeds the possible risk to the fetus. The intake of bromocriptine in the first 8 weeks of pregnancy does not adversely affect the course and outcome pregnancy. After discontinuing the drug, the risk of abortion does not increase.

Bromocriptine reduces the secretion of milk, so its use is not recommended during breastfeeding.

Dosing and Administration:

Inside. The drug Bromergon should always be taken after meals.

Typically, treatment begins with a small dose, which is then gradually increased to achieve the optimal effect.

The maximum daily dose is 30 mg.

Menstrual irregularities, female infertility

For ½ tablets (1.25 mg) 2-3 times a day; if the effect is insufficient, the dose of the drug Bromergon is gradually increased to 5-7.5 mg (2-3 tablets) per day; before the normalization of the menstrual cycle and / or the restoration of ovulation.To prevent relapse, treatment can continue for several menstrual cycles.

Hyperprolactinemia in men

By ½ tablets (1.25 mg) 2-3 times a day, gradually increasing the dose by 1.25 mg to 5-10 mg (2 to 4 tablets) with an interval of 2-3 weeks.

Prolactinoma

By ½ tablets (1.25 mg) 2-3 times a day, gradually increasing the dose to several tablets per day, necessary to maintain an adequate decrease in the concentration of prolactin in the blood plasma. The maximum recommended dose for children and adolescents aged 7-12 years is 5 mg / day, for age 13-17 years - 20 mg / day.

Acromegaly

By ½ tablets (1.25 mg) 2-3 times a day, then, if necessary, gradually increase the dose to several tablets per day, further, depending on the clinical effect and side effects, the daily dose of the drug is gradually increased to 10-20 mg (4-8 tablets).

Cessation of lactation

On the first day, ½ tablets (1.25 mg) 2 times (during meals at breakfast and dinner), then for 14 days - 1 tablet (2.5 mg) 2 times a day. Treatment should begin several hours after childbirth or abortion, however, but not earlier than 4 hours after them - only after stabilization of vital functions.After 2-3 days after the drug is withdrawn, there is sometimes a slight secretion of milk. It is removed by resuming the drug at the same dose for another week.

Beginning postpartum mastitis

Apply the same scheme as when suppressing lactation. After three days, the symptoms of inflammation disappear and if the mother decides to resume breastfeeding the baby, the treatment is stopped. Otherwise, the treatment is continued 1 tablet 2 times a day for 11 days. If necessary, prescribe antibiotics.

Postpartum engorgement of mammary glands

2.5 mg once, after 6-12 hours the dose can be repeated if necessary, there is no undesirable stopping of lactation.

Parkinson's disease

The drug Bromergon is prescribed to patients with Parkinson's disease in the following cases: a) in case of ineffective treatment with levodopa and a decarboxylase inhibitor; b) in the initial stage of treatment, in combination with levodopa / carbidopa.

Treatment begins with low doses, which are slowly increased until the maximum therapeutic effect is achieved. Usually the patient takes the initial dose of the drug (1.25 mg, i.е. ½ tablet) at bedtime, for 1 week. Then the dose is increased by 1.25 mg with an interval of 2-3 days to a maximum daily dose of 30 mg. The daily dose is divided into 2 - 3 doses. An adequate therapeutic result can be achieved within 6-8 weeks of treatment. If this does not happen, the daily dose can be increased further - every week by 2.5 mg / day.

With a gradual increase in the dose of the drug Bromocriptine The dose of levodopa should also be gradually reduced.

At the beginning of treatment of patients with Parkinson's disease with bromocriptine and levodopa, the side effects of levodopa appear later than when taking only levodopa. At the beginning of treatment, the doses of both drugs are low - they are increased gradually and in turn. At the beginning of the combination therapy for Parkinson's disease, the average dose of Bromergone is 15-30 mg, whereas levodopa is 250 mg.

Side effects:

According to the World Health Organization (WHO), unwanted effects are classified according to their frequency of development as follows: often (> 1/100, <1/10), infrequently (> 1/1000, <1/100), rarely (> 1 / 10000, <1/1000) and very rarely (<1/10000), including individual messages. The risk of undesired reactions can be minimized by a gradual increase or decrease in the dose, followed by a more gradual titration.

From the cardiovascular system:

infrequently: marked reduction in blood pressure (very rarely leading to syncope);

rarely: when using large doses - pericardial effusion,

constrictive pericarditis, rhythm disturbance (bradycardia, tachycardia); rarely: collapse, increased blood pressure, myocardial infarction, stroke, peripheral angiospasm, valvular heart disease (including regurgitation of blood), peripheral edema, reversible paleness of fingers and toes caused by hypothermia, with prolonged use - Raynaud's syndrome.

From the gastrointestinal tract:

often: nausea, vomiting, constipation;

infrequently: dryness of the oral mucosa;

rarely: caries, periodontal disease, oral candidiasis, diarrhea, long-term treatment with high doses - abdominal pain, retroperitoneal fibrosis, ulcerative lesions of the gastrointestinal tract, gastrointestinal bleeding (black feces, blood in vomit masses).

From the nervous system:

often: dizziness, headache, drowsiness,

infrequently: dyskinesia, psychomotor agitation, hallucinations, psychoses, confusion;

rarely: general weakness, paresthesia, mental disorders, insomnia; rarely: sudden falling asleep, increased libido, hypersexuality, convulsions, spasms of the muscles of the lower limbs.

From the sense organs:

rarely: reduction of visual acuity, "blurring of vision", "ringing, noise" in the ears.

From the respiratory system: often: nasal congestion;

rarely: when using large doses - pleural effusion, pleural fibrosis, pleurisy, pulmonary fibrosis, dyspnea.

Allergic reactions: infrequently: skin rash.

From the side of the musculoskeletal system and connective tissue

infrequently: cramps calf muscles.

Other:

infrequently: alopecia, increased fatigue.

It is very rare in the case of a sharp discontinuation of the drug Bromergon possible development of a condition similar to a malignant neuroleptic syndrome.

In patients with Parkinson's disease, high doses of bromocriptine may result in the development of a pathological attraction to gambling, increased libido and hypersexuality, usually reversible after dose reduction or Bromergon withdrawal.

When using the drug Bromergon to suppress physiological lactation in the postpartum period in rare cases was accompanied by the development of a marked increase in blood pressure,myocardial infarction, seizures, stroke or mental disorders.

Overdose:

Symptoms: nausea, vomiting, headache, changes in blood pressure (BP), with a decrease in blood pressure, a weak pulse, rapid heartbeat, cold extremities, chest pain, drowsiness, confused consciousness, hallucinations.

Treatment: symptomatic. During the first three hours after taking the drug, gastric lavage, the use of activated charcoal to reduce the absorption of the drug from the gastrointestinal tract. To stop vomiting or hallucinations metoclopramide.

Interaction:

When used simultaneously with oral contraceptives, the concentration of prolactin in the blood plasma increases.

It is not recommended to appoint ergot along with alkaloids.

Enhances the effects of levodopa, hypotensive drugs. The effectiveness of bromocriptine may decrease with simultaneous admission dopamine agonists (phenothiazines, butyrophenones) or tricyclic antidepressants (imipramine, amitriptyline).

Inhibitors monoamine oxidase, furazolidone, loxapine, methyldopa, metoclopramide, reserpine, thioxanthins and phenothiazines increase the concentration of bromocriptine in the blood plasma and the risk of side effects.

When used simultaneously with ritonavir a 50% reduction in dose is recommended.

Side effects of bromocriptine may be enhanced by combined therapy sympathomimetics.

Bioavailability and maximum concentration in blood plasma of bromocriptine increases with simultaneous application erythromycin, josamycin, clarithromycin, macrolide antibiotics and octreotide.

Ethanol can lead to the development of disulfiram-like reactions: chest pain, hyperemia, tachycardia, nausea, vomiting, reflex cough, pulsating headache, decreased visual acuity, weakness, convulsions.

Special instructions:

Treatment of women with prolactin-dependent dysmenorrhea leads to the normalization of ovulation, in connection with which, the patient should be warned about the need for contraception (except for oral contraceptive means).

In the treatment of acromegaly before the appointment of the drug should exclude the presence of gastric ulcer and duodenal ulcer and warn the patient about the need to put the doctor in the knowledge of the occurrence of gastrointestinal disorders.

There are reports of bleeding from the gastrointestinal tract with a lethal outcome when using bromocriptine. There is no evidence that this is due to the use of bromocriptine. Therefore, it is not recommended to apply bromocriptine in patients with erosive-ulcerative lesions of the gastrointestinal tract in the stage of exacerbation.

Patients are recommended to visit the gynecologist on an annual basis; for women before the onset of menopause - every six months. You should also regularly monitor blood pressure.

With prolonged therapy with Bromergon, histological examination of the epithelium of the cervix and endometrium is necessary, with the obligatory informing of the pathomorphologist about taking the drug. For long-term treatment (2-10 years) with high doses of the drug (30 mg per day), it is necessary to closely observe the possible appearance of signs of retroperitoneal fibrosis in patients (for example, back pain, swelling lower limbs, impaired renal function), in which it is necessary to stop treatment.

In patients receiving bromocriptine, symptomatic hypotension may occur; in some cases, the appearance of hypotension at the beginning of treatment, especially in the second week of therapy.Daily monitoring of blood pressure, especially in a few days of therapy. In the case of hypertension, the emergence of severe ceaseless headaches (with or without visual impairment) or the presence of signs of toxic effects on the CNS, discontinue treatment and conduct a medical examination of the patient. Caution should be exercised in treating patients with Parkinson's disease who may have a mild degree of dementia. Bromocriptine with monotherapy or in combination with levodopa can cause auditory or visual hallucinations. In most cases, hallucinations can be eliminated by lowering the dose of bromocriptine; sometimes it is required to stop treatment.

Bromocriptine It is not effective in essential and family tremor, as well as in Huntington's chorea.

If bromocriptine treatment is prescribed to women for non-hyperprolactinemia-related pathology, the drug should be used in the minimally effective dose necessary to relieve the symptoms; this is necessary so that the concentration of prolactin in the blood plasma does not decrease below the normal level, as this can cause developmental disorders of the yellow body.

In patients who are supposed to be treated with bromocriptine for mastalgia, nodular and / or cystic changes in the mammary glands, it is necessary to exclude malignant neoplasms.

In patients with pituitary macroadenomas, the dynamics of tumor size should be systematically evaluated.

Before starting treatment of patients with macroprolactinoma, a complete examination of the pituitary gland function is necessary. In patients with secondary adrenal insufficiency, glucocorticosteroid replacement therapy is of great clinical importance. It is necessary to regularly monitor the size of the pituitary tumor (macrohypophysis adenoma), and in case of an increase in its size, in spite of the therapy, it is necessary to solve the problem of surgical treatment.

If pregnancy occurs during treatment with Bromergon in patients with a pituitary tumor, careful monitoring of the patients is necessary. Prolactin-secreting adenomas may increase during pregnancy. In severe cases, it is possible to squeeze the optic or other cranial nerves, which may require emergency surgery.

Visual impairment (loss of visual fields) is a known complication of prolactinoma. Effective treatment with the drug Bromergon leads to a decrease in plasma concentrations of prolactin and often there is an improvement in vision. However, in some patients it is possible to develop a secondary loss of the visual fields, despite the normal plasma concentrations of prolactin and the reduction in tumor size, which can result from the displacement of the optic nerve cross in the direction of the Turkish saddle (the formation of a herniated cross of the optic nerves). Therefore, for early diagnosis of secondary loss of the visual field due to a herniated cross of the optic nerves, monitoring of the visual fields in patients with macroprolactinoma for timely correction of the dose of bromocriptine is necessary.

To prevent nausea and / or vomiting at the beginning of treatment, an antagonist of peripheral dopamine receptors, for example, domperidone, for several days, no later than 1 hour before taking bromocriptine.

If gastrointestinal bleeding or stomach ulcers and 12 duodenal ulcers occur, the drug should be discontinued.

Careful hygiene of the oral cavity is necessary.If the dryness of the mucous membrane of the oral cavity persists for more than 2 weeks, consult a physician.

The use of bromocriptine can cause drowsiness or episodes of sudden onset of sleep (in particular, in patients with Parkinson's disease) during the day, without any previous signs. In such cases, consideration should be given to reducing the dose of the drug.

There is no need for special precautions when destroying an unused preparation.

Effect on the ability to drive transp. cf. and fur:

When taking the drug, Bromergon should refrain from driving the car and doing activities that require increased attention and speed of physical and psychomotor reactions (possibly sudden falling asleep, reduced visual acuity).

Form release / dosage:

Tablets 2.5 mg.

Packaging:

For 30 tablets in a bottle of dark glass.

1 bottle in a cardboard pack together with instructions for use.

Storage conditions:

Store in a dark place at a temperature of no higher than 25 ° C. Keep out of the reach of children.

Shelf life:

3 years.

Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:P N008603

Date of registration:04.04.2012 / 31.05.2013

Date of cancellation:2017-02-10

The owner of the registration certificate:Sandoz d.Sandoz d. Slovenia

Manufacturer: & nbsp

SANDOZ, d.d. Slovenia

Representation: & nbspSANDOZ SANDOZ Switzerland

Information update date: & nbsp10.02.2017

Illustrated instructions

Instructions

Bromergon (Bromergon)