Bromocriptine-Richter tablets 2.5 mg No. 30 No. 1 - Planet Health

Pharmacological properties of the drug Bromocriptine

Specific agonist of dopamine receptors (mainly type D2); is a semi-synthetic derivative of ergot alkaloid - ergocryptine. Bromocriptine suppresses the secretion of the anterior pituitary hormone, prolactin, by stimulating dopamine receptors. Bromocriptine does not affect the normal levels of other pituitary hormones, but may reduce the elevated concentrations of growth hormone (GH) in acromegaly. Prolactin is necessary for the initiation and maintenance of lactation in the postpartum period. In other cases, an increase in prolactin secretion leads to pathological lactation (galactorrhea) and/or ovulation and menstrual cycle disorders. Bromocriptine prevents or suppresses physiological lactation, and can also be used in the treatment of pathological conditions caused by increased secretion of prolactin. In amenorrhea or anovulation, with or without galactorrhea, bromocriptine helps restore the menstrual cycle and ovulation. In Stein-Leventhal syndrome, it has a beneficial clinical effect, normalizing LH secretion. For benign breast diseases, bromocriptine helps reduce the size and number of cysts or nodes, eliminating the imbalance between progesterone and estrogens; with prolactin-secreting pituitary adenomas (prolactinomas) - slowing their growth or reducing their size. In acromegaly, it reduces the concentration of growth hormone and prolactin in the blood plasma, increases tolerance to carbohydrates and has a beneficial clinical effect. Bromocriptine in higher doses is used in neurology for Parkinson's disease, characterized by specific dopamine deficiency in the region of the striatum (corpus striatum) and the black nucleus (substantia nigra) of the brain. Bromocriptine stimulates dopamine receptors, restoring neurochemical balance in these parts of the brain. The therapeutic effect of bromocriptine is manifested by a weakening of tremor, rigidity, slowing of movements and a decrease in the severity of other symptoms of parkinsonism at all stages of the disease. Bromocriptine remains clinically effective over several years of use (to date, there have been reports of positive results from its use for 8 years). Bromocriptine can be prescribed as monotherapy or in combination with other antiparkinsonian drugs (for example, levodopa), which allows you to reduce their dose and avoid some side effects. Bromocriptine has some antidepressant effect, reduces the severity of depressive symptoms in Parkinson's disease, as well as in patients with endogenous or psychogenic depression. The maximum concentration of bromocriptine in blood plasma is achieved 1–3 hours after oral administration. The binding of bromocriptine to plasma proteins is 96%. Bromocriptine and its metabolites are excreted primarily in bile and only 6% in urine.

Bromocriptine 2.5 mg No. 30 tablet.

Instructions for medical use of the drug

Tradename

Bromocriptine-Richter

International nonproprietary name

Bromocriptine

Dosage form

Tablets, 2.5 mg

Compound

One tablet contains

active substance – bromocriptine 2.5 mg (in the form of bromocriptine mesylate 2.87 mg),

excipients: anhydrous colloidal silicon dioxide, magnesium stearate, talc, povidone, microcrystalline cellulose, corn starch, lactose monohydrate.

Description

Tablets are round in shape, with a flat surface, almost white in color, scored on one side and engraved “2.5” on the other, with a diameter of about 7 mm.

Pharmacotherapeutic group

Drugs for the treatment of diseases of the urogenital organs and sex hormones. Other drugs for the treatment of gynecological diseases. Prolactin secretion inhibitors. Bromocriptine.

ATX code G02CB01

Pharmacological properties

Pharmacokinetics

Absorption, distribution, excretion

Bromocriptine is quickly and well absorbed from the gastrointestinal tract after oral administration. The parent substance and its metabolites are metabolized in the liver and excreted in the feces; only 6% of the dose is excreted in the urine. The degree of binding to blood plasma proteins reaches 96%. Maximum plasma levels are achieved 1-3 hours after administration. The prolactin-lowering effect develops within 1-2 hours after taking the drug, reaching a maximum after approximately 5 hours, and lasts for 8-12 hours. The elimination of the parent substance from blood plasma is biphasic, with a terminal half-life of about 15 hours.

There are no direct changes in the pharmacokinetic properties of bromocriptine in elderly people. However, in patients with impaired liver function, delayed elimination of the drug may lead to increased plasma levels, requiring dose adjustment.

Biotransformation

Bromocriptine undergoes active biotransformation during the “first” passage through the liver, which is reflected in the complex profile of metabolites and the almost complete absence of the parent substance in urine and feces. It shows high affinity for CYP3A, and the main route of metabolism is hydroxylation of the proline ring of the cyclopeptide molecule. Therefore, it can be expected that inhibitors and/or potent substrates of CYP3A4 are able to inhibit the elimination of bromocriptine and lead to an increase in its concentration in blood plasma. Bromocriptine is also a potent CYP3A4 inhibitor. However, given the low therapeutic concentrations of free bromocriptine in patients, significant alteration in the metabolism of a second drug whose clearance is mediated by CYP3A4 should not be expected.

Pharmacodynamics

The active substance of the drug Bromocriptine-Richter is bromocriptine, which suppresses the secretion of prolactin and stimulates dopamine receptors. The drug is used in endocrinological and neurological practice.

Endocrinology

The drug blocks the secretion of prolactin without affecting the normal levels of other hormones of the anterior pituitary gland. Bromocriptine-Richter prevents or suppresses lactation that has already begun, restores the prolactin-dependent menstrual cycle and ovulation. Thus, it is effective in the treatment of amenorrhea and anovulation (with or without galactorrhea). Bromocriptine-Richter reduces the size of pituitary adenoma secreting prolactin. The drug improves the clinical picture of polycystic ovary syndrome. The drug does not increase the risk of thromboembolic diseases. In patients with acromegaly, the drug reduces the level of growth hormone in the blood plasma, thus having a positive effect on the clinical picture of the disease and glucose tolerance.

Neurology

Due to its dopaminergic activity, bromocriptine-Richter is used to treat Parkinson's disease, but in doses exceeding those prescribed in endocrinology. Parkinson's disease is characterized by a specific nigrostriatal dopamine deficiency. The drug stimulates dopamine receptors and restores neurochemical balance. Clinically, bromocriptine reduces the severity of parkinsonism (including tremor, rigidity, bradykinesia) and depression at all stages of the disease. Bromocriptine-Richter can be prescribed in monotherapy or in combination with other antiparkinsonian drugs. The use of the drug allows you to reduce the dose of other antiparkinsonian drugs (for example, levodopa) and avoid the possibility of side effects such as deterioration at the end of the dose, the “on-off” phenomenon, and dyskinesia.

Indications for use

prevention or suppression of lactation solely for medical reasons (such as abortion, neonatal death, HIV infection of the mother).

Bromocriptine is not recommended for routine suppression of lactation or for the relief of symptoms of postpartum pain and breast engorgement in cases where non-pharmacological interventions (gentle breast support, cold compresses) and/or analgesics are effective.

hyperprolactinemia in women and men (with or without galactorrhea)
female infertility associated with hyperprolactinemia
infertility of women not accompanied by hyperprolactinemia
pituitary macroadenomas or as an alternative to surgical treatment of transsphenoidal hypophysectomy in patients with microadenomas
acromegaly (to reduce the level of growth hormone in the blood), in combination with surgical treatment and/or radiation therapy
Parkinson's disease, as monotherapy or in combination with other antiparkinsonian drugs (levodopa).

Directions for use and doses

The tablets must be taken with meals (breakfast or dinner). In most cases, the drug is started with a gradual increase in dose until the optimal therapeutic effect and minimal side effects are achieved. The maximum dose should not exceed 30 mg per day.

Reception scheme

The initial dose of the drug is 1.25 mg (1/2 tablet) with meals, at dinner. After 2-3 days, the dose of Bromocriptine-Richter is increased to 2.5 mg.

In the future, the dose of the drug can be increased every 2-3 days by 1.25 mg, until a daily dose of 5 mg is reached (2.5 mg 2 times a day). If necessary, further increases in the dose of the drug can be carried out according to the same scheme.

Prevention of lactation

On the day of birth, 2.5 mg (1 tablet) 1 time per day, and subsequently 2 times per day, 2.5 mg Bromocriptine-Richter for 14 days. In this case, there is no need to gradually increase the dose of the drug.

Suppression of lactation

On the first day you need to take 2.5 mg of the drug, and in the next 2-3 days the dose of the drug is increased to 5 mg (2.5 mg 2 times a day). The drug is continued for 14 days. In this case, there is no need to gradually increase the dose of the drug.

Hypogonadism / Galactorrhea syndrome, infertility

It is proposed to gradually increase the dose of the drug according to the above scheme. Most patients with galactorrhea respond well to a dose of 7.5 mg Bromocriptine-Richter per day, divided into several doses. If necessary, this dose can be increased to 30 mg per day. For infertility without an increase in the level of prolactin in the blood, the generally accepted dose of the drug is 5 mg per day, taken 2.5 mg 2 times a day.

Prolactinomas

Gradually increase the dose of bromocriptine according to the proposed scheme. When the daily dose of 2.5 mg is reached, the dosage can be increased by 2.5 mg per day at 2-3 day intervals as follows: 2.5 mg every 8 hours, 2.5 mg every 6 hours, 5 mg every 6 hours , under the control of prolactin levels. The therapeutic effect is expected when a dose of 30 mg of the drug per day is reached.

Acromegaly

Parkinson's disease

It is necessary to carry out a gradual dose increase scheme.

1 week: 1.25 mg per day before bedtime.
Week 2: 2.5 mg per day before bedtime.
Week 3: 2 times 2.5 mg per day.
Week 4: 3 times 2.5 mg per day.

Subsequently, the daily dose may be increased by 2.5 mg over 3-14 days, depending on the effect noted in the patient. Dose increases can be continued until the optimal dose is achieved; which usually ranges from 10 to 30 mg per day. At the same time, the dose of levodopa can be gradually reduced until the optimal balance is determined.

Use in elderly patients

Elderly age is not a particular risk group for Bromocriptine-Richter therapy.

Use of the drug in patients with liver dysfunction

If liver function is impaired, there may be a delay in elimination and an increase in the concentration of Bromocriptine-Richter in the blood plasma. In this regard, a dose adjustment of the drug may be required.

Childhood and adolescence

Bromocriptine is not recommended for use in children under 18 years of age due to limited data on the safety and effectiveness of the drug, unless used on the recommendation of an endocrinologist.

Side effects

Nausea, vomiting, loss of appetite, headache, dizziness and fatigue may occur during the first days of treatment; however, these reactions do not usually require discontinuation of bromocriptine treatment.

The risk of adverse reactions can be reduced by gradually increasing the dose and taking bromocriptine tablets with food. If necessary, the daily dose can be reduced and treatment continued at this reduced dose for several days. After the disappearance of adverse reactions, you can try again to increase the dose.

Bromocriptine may cause orthostatic hypotension, so blood pressure in outpatients should be measured in an upright position.

In patients with Parkinsonism, drowsiness, hallucinations, confusion, visual disturbances, dry mouth, leg muscle cramps and retroperitoneal fibrosis may develop during treatment with high doses of the drug. All these side effects are dose-dependent.

With prolonged treatment, cases of reversible blanching or whitening of the fingers and toes in the cold have occurred, especially in patients with a history of Raynaud's phenomenon.

In extremely rare cases (postpartum women receiving bromocriptine to prevent lactation), serious side effects may develop, including hypertension, myocardial infarction or stroke, although their causal relationship to the drug has not been established. In some cases, the development of a stroke was preceded by severe headache and/or transient visual disturbances.

In very rare cases, heart valve pathology (including regurgitation) and associated disorders (pericarditis and pericardial effusion) have been reported.

Hyponatremia and portosystemic encephalopathy may occur in patients with cirrhosis.

In extremely rare cases, bromocriptine may cause people to suddenly fall asleep during the day.

Patients treated with dopamine agonists, including Bromocriptine-Richter, may experience pathological gambling, increased libido, hypersexuality, compulsive spending or shopping, compulsive eating and binge eating.

Dopamine agonists, which belong to the group of ergot alkaloids, may increase the risk of developing regurgitation of the heart valves.

Adverse effects are summarized by frequency of occurrence:

Common (≥1/100 to <1/10)

headache
loss of appetite
nausea, constipation
drowsiness
nasal congestion

Uncommon(≥1/1000 to <1/100)

confusion, hallucinations
dyskinesia, psychomotor agitation
dizziness, orthostatic hypotension
dry mouth, vomiting
allergic skin reaction, allergic dermatitis, alopecia
muscle spasms, weakness

Rare (≥1/10000 to <1/1000)

insomnia, psychotic disorders, paresthesia
noise in ears
pericardial effusion, constrictive pericarditis, tachycardia, bradycardia, arrhythmia
pleural effusion, pleural fibrosis, pulmonary fibrosis, pleurisy, dyspnea
retroperitoneal fibrosis, gastrointestinal bleeding, ulcers on the mucous membrane of the gastrointestinal tract
peripheral edema

Very rare (<1/10000)

blurred vision, blurred vision
acute cerebrovascular accident, neuroleptic malignant syndrome (bromocriptine withdrawal syndrome)
sudden sleep in the middle of the day
cerebrospinal fluid rhinorrhea
pathological gambling, increased libido and hypersexuality
myocardial infarction, heart valve diseases
arterial hypertension
pale skin
hyponatremia

Contraindications

hypersensitivity to bromocriptine or other ergot alkaloids (ergocryptine derivatives), as well as to the excipients of the drug
hypertensive conditions associated with pregnancy: gestosis of pregnancy, preeclampsia or gestational hypertension
arterial hypertension during childbirth or the postpartum period
uncontrolled arterial hypertension
peptic ulcer of the stomach and duodenum
idiopathic or familial tremor
Huntington's chorea
for non-life-threatening indications in patients (including suppression of lactation) with cardiovascular diseases (including coronary heart disease) or other cardiovascular pathology currently and in history
for long-term treatment in the presence of heart valve diseases
connective tissue diseases, including a history of
current or history of severe mental illness
hereditary intolerance to galactose, lactose, lactase deficiency, malabsorption of glucose, galactose
combined use with oral contraceptives
simultaneously with other ergot alkaloids
breastfeeding period

Drug interactions

When using the drug Bromocriptine-Richter together with

ethanol leads to the development of disulfiram-like reactions (chest pain, skin flushing, tachycardia, nausea, vomiting, reflex cough, throbbing headache, blurred vision, weakness, convulsions), decreased tolerance of the drug Bromocriptine-Richter
antihypertensive drugs: enhances the effect of antihypertensive drugs
erythromycin, clarithromycin, troleandomycin, the concentration and bioavailability of the drug Bromocriptine-Richter in blood plasma may increase
dopamine antagonists (for example: butyrophenones, phenothiazines) - may reduce the prolactin-lowering and antiparkinsonian effects of bromocriptine
metoclopramide and domperidone - may reduce the severity of the prolactin-lowering effect of bromocriptine
sympathomimetic drugs, including phenylpropanolamine and isometheptene, increase the risk of toxicity.

The simultaneous use of the drug with other ergot alkaloids should be avoided.

Caution should be exercised when co-administering bromocriptine with CYP3A4 inhibitors (eg, azole antifungals, HIV protease inhibitors).

special instructions

The use of Bromocriptine-Richter in patients with premenstrual syndrome and benign breast tumors is not recommended due to insufficient evidence of effectiveness in treatment.

In rare cases, serious adverse events, including hypertension, myocardial infarction, stroke, or psychiatric disorders, have been reported in postpartum women receiving bromocriptine to suppress lactation. The development of epileptic seizures or stroke in some patients was preceded by severe headache and/or transient visual disturbances.

When using the drug after childbirth, especially in the first days of use, it is necessary to regularly and carefully monitor blood pressure. It is especially necessary to monitor patients who are taking or have recently taken drugs that affect blood pressure.

In case of development of arterial hypertension, chest pain, severe and unrelenting headache with or without visual disturbances, as well as any signs of toxic effects on the central nervous system, treatment with the drug should be stopped immediately and the patient should be examined immediately.

Concomitant use of bromocriptine with vasoconstrictors such as sympathomimetics or ergot alkaloids, including ergometrine or methylergometrine, is not recommended during the postpartum period.

Idiopathic hyperprolactinemia, caused by drugs or associated with a disease of the hypothalamic-pituitary system, may occur. Bromocriptine-Rich effectively reduces prolactin levels in patients who suffer from a pituitary tumor, but in acromegaly this does not eliminate the need for radiation therapy or surgery.

When treating women of fertile age without symptoms of hyperprolactinemia, the drug should be prescribed in the lowest effective dose to prevent a decrease in the level of prolactin in the blood below the normal value and to prevent disruption of the functioning of the corpus luteum. During a course of therapy with Bromocriptine-Richter, it is necessary to use reliable, non-hormonal methods of contraception, since oral hormonal contraceptives increase the level of prolactin in the blood serum.

With long-term use of the drug, it is necessary to conduct a gynecological examination of the woman with the collection of cytological material. This examination should be performed every 6 months when treating postmenopausal women and annually when treating women of fertile age.

Patients with acromegaly who have a history of gastric ulcers should be treated with other methods if possible. If treatment with bromocriptine is necessary, the patient should be instructed to immediately notify the physician of the occurrence of adverse gastrointestinal effects.

Patients with severe cardiovascular disease or psychiatric disorders taking bromocriptine for macroadenomas should receive it only if the expected benefits of treatment outweigh the potential risks.

Because patients with pituitary macroadenomas may have concomitant hypopituitarism due to compression or destruction of pituitary tissue, a full assessment of the functional status of the pituitary gland should be performed and adequate replacement therapy should be prescribed before bromocriptine is prescribed. In patients with secondary adrenal insufficiency, corticosteroid replacement therapy is mandatory.

Changes in tumor size in patients with pituitary macroadenomas should be closely monitored, and surgery should be considered if there is evidence of tumor growth.

Prolactin-secreting adenomas may increase in size during pregnancy. In such cases, monitoring of patients with macroadenoma is necessary. In such patients, treatment with bromocriptine often leads to a reduction in tumor size and rapid recovery of narrowed visual fields. In severe cases, compression of the optic or other cranial nerves may require emergency pituitary surgery.

Visual field impairment is a known complication of prolactinoma. Effective treatment with bromocriptine leads to a reduction in tumor size and severity of hyperprolactinemia, and often to the disappearance of visual impairment. However, some patients may subsequently develop secondary visual field loss despite normalization of prolactin levels and tumor shrinkage. In these cases, the visual field defect may improve with bromocriptine at a reduced dosage, despite a slight increase in prolactin levels and some re-enlargement of the tumor. Therefore, visual field monitoring is recommended for early detection of secondary visual field loss and individualized dosage adjustment of bromocriptine.

Some patients with prolactin-secreting adenomas treated with bromocriptine have had cerebrospinal fluid rhinorrhea, which may occur due to tumor shrinkage with invasive growth.

During the first few days of treatment, in isolated cases, arterial hypotension may develop.

Caution should be exercised when prescribing bromocriptine in high doses to patients with a history of psychotic disorders or severe cardiovascular disease.

Treatment with the drug in high doses for parkinsonism requires caution in patients with a history of psychosis or severe cardiovascular disease.

Isolated cases of pleural and pericardial effusions, as well as pleural and pulmonary fibrosis and constrictive pericarditis have been reported in patients receiving bromocriptine, especially in high doses or for long periods of time. Patients with unexplained pleuropulmonary disorders should be carefully evaluated and, if necessary, bromocriptine therapy should be discontinued.

Retroperitoneal fibrosis has been reported in several patients receiving bromocriptine, especially at high doses or for long periods of time. For timely recognition of retroperitoneal fibrosis at an early reversible stage, it is recommended to monitor its manifestations (such as back pain, swelling of the lower extremities, impaired renal function).

Bromocriptine should be discontinued if fibrosing changes in the retroperitoneum are diagnosed or suspected.

You should pay attention to the following signs and symptoms:

lung diseases manifested by shortness of breath, suffocation, persistent cough or chest pain;
impaired renal function or obstruction of the urethra/abdominal vessels, which may be accompanied by pain in the lumbar region/lateral abdomen and swelling of the lower extremities, as well as the presence of any space-occupying lesions in the abdominal cavity or its tenderness on palpation, which may indicate retroperitoneal fibrosis;
heart failure caused by pericardial fibrosis (if such symptoms occur, constrictive pericarditis should be excluded).

Measurements of erythrocyte sedimentation rate (ESR) and blood creatinine concentrations, as well as chest x-rays, are helpful in diagnosing fibrosing disorder. In addition, it is advisable to determine baseline levels of other inflammatory markers and renal function indicators before starting treatment.

During treatment, patients should be closely monitored for signs of progressive fibrosing disorders. If retroperitoneal fibrosis is diagnosed or suspected, treatment with bromocriptine should be discontinued.

The use of bromocriptine may be accompanied by drowsiness and episodes of sudden sleep onset, especially in patients with Parkinson's disease. Sudden sleep onset during daytime activities, in some cases without any warning or warning signs, has been reported extremely rarely. Patients should be informed of the possibility of this phenomenon and should use caution when driving or operating machinery while being treated with bromocriptine. Patients who experience drowsiness and/or episodes of sudden sleep onset should refrain from driving vehicles or operating machinery. In addition, the advisability of dose reduction or discontinuation of treatment should be considered.

Impulse control disorder

Patients should be regularly monitored for the development of impulse control disorder. Patients and their caregivers should be aware of the possibility that patients treated with dopamine agonists (including Bromocriptine-Richter) may develop behavioral symptoms of impulse control disorder, including pathological gambling, increased sexual desire, hypersexuality , compulsive spending or shopping addiction, constant need for food and compulsive overeating. If such symptoms develop, the advisability of dose reduction/gradual withdrawal of the drug should be considered.

In clinical studies of cabergoline and pergolide, an increased risk of developing heart valve pathology was noted. It can be assumed that this effect may be characteristic of other ergot alkaloid derivatives, such as bromocriptine.

The drug contains 41.0 mg of lactose monohydrate. Patients with rare hereditary diseases such as galactose intolerance, lactose intolerance or glucose-galactose malabsorption should not take this drug.

Pregnancy and lactation

If you become pregnant, you should stop taking the drug.

In pregnant patients with pituitary adenoma, after discontinuation of the drug, careful monitoring (including repeated determination of visual fields) is necessary throughout pregnancy.

If prolactinoma grows, therapy must be restarted. According to data obtained from more than 2,000 pregnant women, the use of Bromocriptine-Richter did not increase the number of spontaneous abortions, premature births and neonatal abnormalities. According to these data, Bromocriptine-Richter does not have embryotoxic or teratogenic effects.

Because bromocriptine suppresses lactation and is excreted in breast milk, it should not be given to women who are breastfeeding.

Features of the effect of the drug on the ability to drive a vehicle or potentially dangerous machinery

The use of the drug can cause hypotension, blurred vision, and dizziness, especially in the first days of therapy, so care must be taken when driving or when working in conditions of increased trauma.

The use of Bromocriptine-Richter may cause drowsiness or a symptom of sudden falling asleep, which can occur in the daytime without warning signs. This should be paid attention to by persons driving vehicles or working in conditions of increased injury. Those patients who exhibit such symptoms are prohibited from driving.

Overdose

Symptoms: nausea, vomiting, decreased blood pressure, headache, hallucinations, confusion.

Treatment: removal of all unabsorbed drug, maintaining blood pressure if necessary.

Release form and packaging

30 tablets in brown glass bottles.

1 bottle, along with instructions for medical use in the state and Russian languages, is placed in a cardboard pack.

Storage conditions

Store in original packaging, protected from light at a temperature not exceeding 25 ºС.

Keep out of the reach of children!

Shelf life

3 years.

Do not use after expiration date.

Conditions for dispensing from pharmacies

On prescription.

Indications for use of the drug Bromocriptine

Prolactin-dependent menstrual disorders and female infertility, caused by increased and possibly normal levels of prolactin secretion - amenorrhea with or without galactorrhea, oligomenorrhea, luteal phase insufficiency; disorders due to increased secretion of prolactin caused by taking certain psychotropic, antihypertensive and other drugs; prolactin-independent female infertility - Stein-Leventhal syndrome, anovulatory cycles (an adjuvant in therapy with antiestrogens, for example clomiphene); premenstrual syndrome - breast tenderness, swelling associated with the phase of the cycle, flatulence, mood changes; suppression of lactation - prevention or cessation of postpartum lactation for medical reasons, prevention of lactation after abortion, postpartum mammary hypertrophy; benign diseases of the mammary glands - mastalgia, benign nodular or cystic mastopathy, especially fibrocystic; prolactin-dependent hypogonadism in men - oligospermia, decreased libido, impotence; pituitary prolactinomas - conservative treatment of prolactin-secreting micro- and macroadenomas of the pituitary gland, reducing the size of the tumor before its removal, postoperative treatment while maintaining an elevated level of prolactin in the blood; acromegaly - as an additional remedy (sometimes alternative) during surgical or radiation treatment; all stages of idiopathic Parkinson's disease and postencephalitic parkinsonism (as monotherapy or in combination with other antiparkinsonian drugs).

Use of the drug Bromocriptine

In gynecological and endocrinological practice, the dose of bromocriptine depends on the specific indications for its use. For menstrual irregularities and female infertility, 1.25 mg 2-3 times a day is prescribed, the dose can be gradually increased to 2.5 mg 2-3 times a day. Treatment is continued until the menstrual cycle and/or ovulation normalizes. To prevent relapses, several courses of treatment can be carried out. For premenstrual syndrome, treatment begins on the 14th day of the cycle with a dose of 1.25 mg/day, increasing the dose by 1.25 mg daily to 5 mg/day in 2 divided doses. Treatment is continued until the menstrual cycle is restored. To suppress lactation, on the 1st day, 1.25 mg is prescribed 2 times a day (morning and evening), then 2.5 mg for 14 days. To prevent lactation, therapy should begin a few hours after childbirth or abortion, but only after the vital functions of the body have stabilized. 2-3 days after stopping bromocriptine, a slight secretion of milk is sometimes observed, which can be eliminated by taking the drug in higher doses for another 1 week. For postpartum mammary hypertrophy, bromocriptine is taken once at a dose of 2.5 mg; after 6 or 12 hours, this dose can be taken again, which will not cause undesirable suppression of lactation. For initial manifestations of postpartum mastitis, on the 1st day, 1.25 mg 2 times a day is prescribed, then 2.5 mg 2 times a day for 14 days. If necessary, treatment is carried out in combination with antibiotics. For benign diseases of the mammary glands, 1.25 mg is prescribed 2-3 times a day, gradually increasing the dose to 5-7.5 mg/day. For male hypogonadism, 1.25 mg is prescribed 2-3 times a day, gradually increasing the dose to 5-10 mg/day. For prolactinomas, 1.25 mg is prescribed 2-3 times a day, gradually increasing the dose until a stable suppression of prolactin secretion is achieved (depending on the level of prolactin concentration in the blood plasma), which is usually achieved by taking several tablets per day. For acromegaly, treatment begins with a dose of 1.25 mg/day, gradually increasing the daily dose to 10–20 mg, depending on the clinical effect and the presence of side effects. In Parkinson's disease and postencephalitic parkinsonism, treatment with bromocriptine begins with a daily dose of 1.25 mg for the 1st week, then the daily dose is gradually increased (by 1.25 mg/week) to the minimum effective dose. The daily dose is taken in 2-3 doses. The clinical effect is usually achieved within 6–8 weeks; if necessary, the daily dose continues to be increased by 1.25 mg/week. Therapeutic doses of bromocriptine when used alone or in combination with other antiparkinsonian drugs are 10–40 mg/day, but higher doses may be required. If side effects occur during dose selection, bromocriptine should be taken at a reduced dose for at least 1 week, and if side effects disappear, the dose can be increased. Before starting bromocriptine, patients with movement disorders while taking levodopa are recommended to reduce the dose of the latter, and after achieving a therapeutic effect as a result of using bromocriptine, a gradual reduction in its dose can be continued. In some cases, levodopa can be discontinued. Bromocriptine should be taken with meals, morning and evening, and in the evening for a single dose.

Bromocriptine-richter 2.5 mg 30 pcs. pills

pharmachologic effect

Bromocriptine is a synthetic derivative of ergot alkaloid.
An inhibitor of prolactin secretion and an agonist of central and peripheral dopamine D2 receptors. Specifically inhibits the secretion of the hormone of the anterior pituitary gland - prolactin, without affecting the normal secretion of other pituitary hormones. However, bromocriptine may reduce elevated growth hormone (GH) concentrations in patients with acromegaly. This action is due to stimulation of dopamine receptors. The effect of reducing the concentration of prolactin begins 1-2 hours after taking bromocriptine orally, reaches a maximum (decrease in prolactin concentration by more than 80%) after 5-10 hours and lasts 8-12 hours. In the postpartum period, prolactin is necessary for the initiation and maintenance of lactation . In other periods of life, an increase in prolactin secretion leads to pathological lactation (galactorrhea) and/or ovulation and menstrual cycle disorders. As a specific inhibitor of prolactin secretion, bromocriptine can be used to prevent or suppress physiological lactation, as well as to treat pathological conditions caused by hypersecretion of prolactin. For amenorrhea and/or anovulatory menstrual cycles (with or without galactorrhea), bromocriptine can be used to restore the menstrual cycle and ovulation. When using bromocriptine to suppress lactation, fluid intake restrictions are not required. In addition, bromocriptine does not affect postpartum uterine involution and does not increase the risk of thromboembolism.

Bromocriptine, by normalizing the secretion of luteinizing hormone, improves the clinical manifestations of polycystic ovary syndrome (PCOS).

Bromocriptine inhibits the growth or reduces the volume of prolactin-secreting pituitary adenomas (prolactinomas). In patients with acromegaly, in addition to reducing the concentration of GH and prolactin in the blood plasma, bromocriptine has a beneficial effect on the clinical manifestations of acromegaly and glucose tolerance.

In Parkinson's disease, which is characterized by a specific dopamine deficiency in the striatum and nucleus nigra, stimulation of dopamine receptors with bromocriptine can restore neurochemical balance in the basal ganglia.

In patients with Parkinson's disease, bromocriptine is usually prescribed at higher doses compared to doses used for endocrinological indications. Clinically, taking bromocriptine reduces slowness of movement, rigidity, tremor and other symptoms of parkinsonism at all stages of the disease. The therapeutic effect usually lasts for many years (good results were observed with a duration of therapy of up to 8 years). Bromocriptine can be prescribed as monotherapy or in combination with other antiparkinsonian drugs at the onset and later stages of the disease. Combination with levodopa leads to an increase in the antiparkinsonian effect, which makes it possible to reduce the dose of levodopa. Bromocriptine reduces symptoms of depression in patients with Parkinson's disease. This is due to its inherent antidepressant properties, confirmed in controlled clinical studies in patients with endogenous or psychogenic depression without Parkinson's disease.

Composition and release form Bromocriptine-richter 2.5 mg 30 pcs. pills

Tablets - 1 tablet:

Active ingredient: bromocriptine mesylate 2.87 mg, which corresponds to the content of bromocriptine 2.5 mg.
Excipients: colloidal silicon dioxide - 0.65 mg, magnesium stearate - 1.3 mg, talc - 3.9 mg, povidone K30 - 5.2 mg, corn starch - 35.08 mg, microcrystalline cellulose - 40 mg, lactose monohydrate - 41 mg.

30 pcs. - dark glass bottles (1) - cardboard packs.

Description of the dosage form

The tablets are almost white, round, flat, beveled, scored on one side and engraved “2.5” on the other.

Directions for use and doses

The drug should always be taken orally with meals.

Menstrual irregularities, female infertility

Prescribe 1.25 mg (1/2 tablet) 2-3 times/day; if the effect is insufficient, the dose is gradually increased to 5-7.5 mg/day (dose frequency 2-3 times/day). Treatment is continued until the menstrual cycle normalizes and/or ovulation is restored. If necessary, to prevent relapses, treatment can be continued for several cycles.

Hyperprolactinemia in men

Prescribe 1.25 mg (1/2 tablet) 2-3 times/day, gradually increasing the dose to 5-10 mg (2-4 tablets)/day.

Prolactinomas

Prescribe 1.25 mg (1/2 tablet) 2-3 times a day with a gradual increase in dose and selection of dosage that ensures an adequate reduction in the concentration of prolactin in the blood plasma. The maximum daily dose for children and adolescents aged 7 to 12 years is 5 mg/day, for those aged 13 to 18 years - 10 mg.

Acromegaly

The initial dose is 1.25 mg (1/2 tablet) 2-3 times a day, then, depending on the clinical effect and tolerability, the daily dose is gradually increased to 10-20 mg (4-8 tablets). The maximum daily dose for children and adolescents aged 7 to 18 years is 10 mg/day.

Suppression of lactation for medical reasons

On the first day, 1.25 mg (1/2 tablet) is prescribed 2 times (with meals at breakfast and dinner), then for 14 days - 2.5 mg (1 tablet) 2 times a day. To prevent the onset of lactation, administration should begin a few hours after childbirth or abortion, but only after stabilization of vital functions. Slight milk secretion sometimes occurs 2 or 3 days after stopping bromocriptine. This can be resolved by resuming the same dose for another 1 week.

Incipient postpartum mastitis

On the first day, 1.25 mg (1/2 tablet) is prescribed 2 times (with meals at breakfast and dinner), then for 14 days - 2.5 mg (1 tablet) 2 times a day. If necessary, an additional antibiotic is prescribed.

Parkinson's disease

In order to ensure optimal tolerability during the first week, treatment should begin with a low dose of 1.25 mg (1/2 tablet) 1 time / day (preferably in the evening). To select an individual minimum effective dose, the amount of bromocriptine taken should be increased slowly, using the titration method. The dose is increased gradually - the daily dose is increased by 1.25 mg once a week; The daily dose is divided into 2-3 doses. An adequate therapeutic response is achieved on average within 6-8 weeks of treatment. If there is no clinical effect after 6-8 weeks of use, a further increase in the daily dose by 2.5 mg once a week is possible. The maximum daily dose of bromocriptine in monotherapy or as part of combination therapy should not exceed 30 mg/day. Long-term therapy with high doses of bromocriptine more than 20 mg/day for 6 months can lead to pleuropulmonary fibrotic changes.

If adverse reactions occur during dose selection, the daily dose should be reduced and maintained at a lower level for at least 1 week. When undesirable reactions are relieved, the dose can be increased again. In patients with movement disorders while taking levodopa, it is recommended that the dose of levodopa be reduced before starting bromocriptine. After achieving a satisfactory clinical effect during treatment with bromocriptine, a further gradual reduction in the dose of levodopa can be carried out. In some patients taking bromocriptine, complete withdrawal of levodopa is possible.

Special patient groups

The effectiveness and safety of bromocriptine in children under 7 years of age have not been studied. The use of the drug in this age group is contraindicated.

Due to the higher incidence of decreased liver, renal, or cardiac function and the use of concomitant medications, bromocriptine should be used with caution in elderly patients (over 65 years of age) and initiated at the lowest dose in the appropriate dosage range.

The use of bromocriptine in patients with renal failure has not been studied. Since bromocriptine and its metabolites are excreted almost exclusively in the bile, no dosage adjustment is required in patients with mild to moderate renal impairment.

The use of bromocriptine in patients with hepatic impairment has not been studied. Since the elimination of bromocriptine is slower in hepatic impairment, dosage adjustment may be necessary. In severe liver failure (class C according to the Child-Pugh classification), the use of bromocriptine is contraindicated.

Pharmacokinetics

Suction

After oral administration, bromocriptine is rapidly and well absorbed. In healthy volunteers, after oral administration in tablet form, the half-absorption period of bromocriptine is 0.2-0.5 hours, and the maximum plasma concentration (Cmax) is achieved within 1-3 hours. When taken orally 5 mg of bromocriptine, Cmax is 0.465 ng/ml. Concomitant food intake does not have a significant effect on the pharmacokinetics of bromocriptine, however, for better gastrointestinal tolerability, it is recommended to take the drug with meals.

Distribution

Plasma protein binding is 96%.

Metabolism

Bromocriptine is almost completely metabolized in the liver to form a number of inactive metabolites. Has a high affinity for the CYP3A isoenzyme. The main route of metabolism of bromocriptine is hydroxylation of the proline ring in the cyclopeptide. Concomitant use of inhibitors and/or potential substrates of CYP3A4 may inhibit the clearance of bromocriptine and increase its plasma concentrations. Bromocriptine is a strong CYP3A4 inhibitor with a calculated IC50 value of 1.69 pM. However, due to the low therapeutic concentrations of free bromocriptine, a significant change in the metabolism of concomitantly used drugs that are cleared by CYP3A4 is not expected.

Removal

The elimination of unchanged bromocriptine from plasma occurs in two phases: T1/2 is about 3-4 hours for bromocriptine and 50 hours for metabolites. Bromocriptine and its metabolites are almost completely excreted in the bile, only 6% of the dose is excreted by the kidneys.

Pharmacokinetics in selected patient groups

Children and teenagers under 18 years of age. No data. The pharmacokinetics of bromocriptine have only been studied in adults.

Elderly patients (over 65 years old). The effect of age on the pharmacokinetics of bromocriptine has not been studied.

Patients with renal failure. The effect of renal impairment on the pharmacokinetics of bromocriptine has not been studied.

Patients with liver failure. The pharmacokinetics of bromocriptine in patients with hepatic impairment have not been studied. If liver function is impaired, the rate of elimination of bromocriptine may decrease, and the concentration in the blood plasma may increase, which requires adjustment of the drug dosage regimen.

Indications for use Bromocriptine-Richter 2.5 mg 30 pcs. pills

Acromegaly

as an additional remedy or in special cases as an alternative to surgery or radiation therapy.

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 removal;
postoperative treatment if the concentration of prolactin in the blood plasma remains elevated.

Suppression of lactation for medical reasons

prevention or suppression of lactation in the postpartum period (for example, with intrapartum fetal death, stillbirth, HIV infection in the mother), incl. at the initial stage of postpartum mastitis;
prevention of lactation after termination of pregnancy.

Menstrual irregularities and infertility in women

prolactin-dependent diseases and conditions, accompanied or not accompanied by hyperprolactinemia:
amenorrhea (with or without hyperprolactinemia);
luteal phase deficiency;
hyperprolactinemic conditions caused by drugs (for example, some psychotropic or antihypertensive drugs);
female infertility not caused by hyperprolactinemia:
polycystic ovary syndrome;
anovulatory cycles (in addition to the use of antiestrogenic agents, such as clomiphene).

Parkinson's disease

all stages of idiopathic Parkinson's disease and postencephalic parkinsonism - in the form of monotherapy or in combination with other antiparkinsonian drugs.

Hyperprolactinemia in men

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

Contraindications

Hypersensitivity to bromocriptine, any excipient of the drug or other ergot alkaloids;
uncontrolled arterial hypertension;
arterial hypertension during pregnancy and the postpartum period;
gestosis in the second half of pregnancy (including preeclampsia and eclampsia).
the postpartum period in women with a history of severe cardiovascular diseases;
coronary heart disease and other severe diseases of the cardiovascular system;
history of cerebrovascular diseases;
obliterating endarteritis;
Raynaud's syndrome;
temporal arteritis;
peptic ulcers of the gastrointestinal tract and gastrointestinal bleeding;
sepsis;
severe mental disorders (including a history);
smoking abuse;
simultaneous use with methylergometrine or other ergot alkaloids, moderate or potent cytochrome P450 inhibitors (for example, itraconazole, voriconazole, clarithromycin);
children under 7 years of age (the safety and effectiveness of bromocriptine in children under 7 years of age has not been confirmed);
lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome.

Carefully:

children over 7 years old and teenagers under 18 years old;
patients over 65 years of age;
patients with cardiovascular diseases (for example, arterial hypertension, arrhythmias, a history of myocardial infarction);
Parkinson's disease (with long-term treatment with high doses of the drug);
liver dysfunction;
severe renal failure;
pregnancy (in patients with pituitary adenoma);
postpartum period;
Particular caution should be exercised when using bromocriptine in the postpartum period in patients with arterial hypertension who have recently taken vasoconstrictors (sympathomimetics or ergot alkaloids, for example, ergometrine or methylergometrine);
simultaneous administration of antihypertensive therapy.

Application Bromocriptine-Richter 2.5 mg 30 pcs. pills during pregnancy and breastfeeding

Pregnancy

If pregnancy is diagnosed during bromocriptine therapy, the drug should be discontinued unless continued therapy is necessary for medical reasons. Discontinuation of bromocriptine during pregnancy did not lead to an increase in the incidence of spontaneous abortion. Clinical experience shows that the use of bromocriptine during pregnancy does not have a negative effect on its course or outcome. When discontinuing bromocriptine in pregnant women with pituitary adenoma, patients should be closely monitored throughout pregnancy. If signs of a pronounced increase in prolactinoma appear, for example, headaches or narrowing of visual fields, treatment with bromocriptine may be resumed or surgery may be performed.

Breastfeeding period

Because bromocriptine suppresses milk secretion; its use during breastfeeding is contraindicated, unless it is necessary to suppress lactation for medical reasons.

Use in children

The use of the drug in children under 7 years of age is contraindicated (the safety and effectiveness of bromocriptine in children under 7 years of age has not been confirmed).

The drug should be prescribed with caution to children over 7 years of age and adolescents under 18 years of age.

special instructions

During bromocriptine therapy, the patient needs to monitor blood pressure, especially at the beginning of treatment and at certain intervals. If blood pressure increases, vasospastic or thrombotic symptoms appear, severe progressive or persistent headache (with or without visual disturbances) or other nervous system disorders, stop taking the drug immediately and consult a doctor.

During the first few days of treatment, arterial hypotension may develop in isolated cases.

It is recommended to periodically monitor blood pressure, kidney and liver function, and in case of parkinsonism, additionally the functions of the cardiovascular system and blood picture.

Treatment with bromocriptine can restore a woman's reproductive potential. Therefore, women of reproductive age for whom pregnancy is undesirable should use a reliable method of contraception and regularly (at least once every 4 weeks) carry out a pregnancy test during the period of amenorrhea. For women with pathology not associated with hyperprolactinemia, bromocriptine should be prescribed at the lowest effective therapeutic dose necessary to relieve symptoms. This is important to prevent a decrease in the concentration of prolactin in the blood plasma below normal, leading to dysfunction of the corpus luteum.

Women receiving bromocriptine for an extended period of time should undergo a gynecological examination (including cytological examination). Postmenopausal women should undergo such examination every 6 months, while women of childbearing age should undergo examination once a year.

In patients with pituitary adenoma, after stopping treatment with bromocriptine, regular monitoring of the adenoma's condition, including visual field testing, is necessary. Prolactin-secreting adenomas may increase in size during pregnancy. In such cases, monitoring of patients with macroadenoma is necessary. In such patients, treatment with bromocriptine often leads to a reduction in tumor size and rapid recovery of narrowed visual fields. The use of bromocriptine to prevent or suppress lactation in the postpartum period should not be routine (prescribing the drug is advisable if the use of antispasmodics, analgesics, or wearing comfortable supportive underwear is ineffective).

When postpartum lactation is suppressed, regular monitoring of blood pressure is necessary, especially in the first week of treatment with bromocriptine.

In case of arterial hypertension, chest pain, sharp, persistent headache with or without visual impairment, treatment with bromocriptine should be stopped and the patient should be examined immediately. In rare cases, serious adverse events, including hypertension, myocardial infarction, seizure, stroke, or psychiatric disorders, have been reported in postpartum women receiving bromocriptine to suppress lactation. The development of epileptic seizures or stroke in some patients was preceded by severe headache and/or transient visual disturbances.

Particular caution is required in patients receiving concomitant therapy (or who have recently received it) with drugs that can affect blood pressure.

If there is a history of gastric ulcer, it is advisable to refuse treatment of acromegaly with bromocriptine and, if possible, use other therapy. If treatment with bromocriptine is nevertheless carried out, the patient should be warned about the possible development of gastrointestinal disorders and the importance of contacting their doctor in such cases.

Because In patients with pituitary macroadenomas, signs of hypopituitarism may occur as a result of compression or destruction of pituitary tissue; a full examination of pituitary function and appropriate replacement therapy should be performed before prescribing bromocriptine. Careful monitoring of tumor size is necessary. If the tumor enlarges, surgical treatment options should be considered. Careful monitoring of the condition of pregnant patients who have previously received bromocriptine for prolactin-secreting pituitary adenomas is necessary, because During pregnancy, the size of the tumor may increase. In patients with clinical manifestations of prolactinoma growth (local headache, pain in the facial area), bromocriptine therapy should be resumed. In this case, treatment often leads to a reduction in tumor size and rapid improvement in visual field defects. In severe cases, when compression of the optic or other cranial nerves develops, emergency surgery on the pituitary gland may be required. A known complication of macroprolactinoma is loss of visual fields. Effective bromocriptine therapy reduces hyperprolactinemia and eliminates visual field impairment. However, in some patients, secondary changes in visual fields are possible, despite normalization of plasma prolactin concentrations and a decrease in tumor size. This may be due to a downward shift of the optic chiasm due to the release of volume in the area of the sella turcica. In this case, reducing the dose of bromocriptine, leading to an increase in the concentration of prolactin in the blood plasma and an increase, to some extent, in the size of the tumor, can help eliminate visual field defects. For early detection of secondary loss of visual fields caused by spatial protrusion of the optic chiasm into the cavity of the sella turcica and the pharmacological effect of a given dose of bromocriptine, monitoring of visual fields in patients with macroprolactinoma is indicated.

Careful oral hygiene is necessary. If dry mouth persists for more than 2 weeks, you should consult your doctor.

In the presence of mental disorders or severe cardiovascular diseases, the administration of large doses of bromocriptine requires special caution.

Some patients with prolactin-secreting adenomas treated with bromocriptine have had cerebrospinal fluid rhinorrhea, which may occur due to tumor shrinkage with invasive growth.

It is possible to develop “cold” vasospasm in patients with acromegaly.

In case of a pronounced increase in the size of prolactinoma, it is necessary to start treatment again.

In patients receiving bromocriptine, especially in high doses or for a long time, the development of pleuropulmonary symptoms (lung infiltration, pleural effusion, as well as fibrosis of the pleura and lungs) and constrictive pericarditis is possible. In these cases, treatment should be stopped immediately and a thorough medical examination of the patient should be performed.

Heart failure due to pericardial fibrosis may develop.

Due to the possible development of retroperitoneal fibrosis, patients with Parkinson's disease receiving long-term high doses of bromocriptine should be carefully monitored. For timely recognition of retroperitoneal fibrosis at an early reversible stage, it is recommended to monitor its manifestations (such as back pain, swelling of the lower extremities, impaired renal function). Bromocriptine should be discontinued if fibrosing changes in the retroperitoneum are diagnosed or suspected. Particular caution is required in patients with secondary adrenal insufficiency.

Patients and their relatives should be informed about the possible development of behavioral control disorders in patients (gaming addiction; hypersexuality; compulsive shopping; spending money; overeating). If such symptoms occur, dose reduction or discontinuation of treatment should be considered.

The drug contains lactose monohydrate. Patients with rare hereditary diseases such as galactose intolerance, lactose intolerance or glucose-galactose malabsorption should not take this drug.

Impact on the ability to drive vehicles and operate machinery

Patients taking bromocriptine should be especially careful when driving or operating machinery, as During therapy, especially during the first days, arterial hypotension may develop, leading to a decrease in concentration. Due to the possible development of drowsiness and the appearance of episodes of sudden falling asleep, especially in patients with Parkinson's disease, during drug therapy, before prescribing bromocriptine, the doctor should inform the patient about these risk factors and recommend refraining from driving vehicles and machinery, as well as from engaging in other activities. Potentially hazardous activities that require increased attention and quick reactions.

Overdose

Symptoms: lethargy, nausea, vomiting, dizziness, drowsiness, apathy, confusion, hallucinations, tachycardia, decreased blood pressure, orthostatic hypotension.

Treatment: gastric lavage, taking activated charcoal, carrying out symptomatic therapy.

Side effects Bromocriptine-richter 2.5 mg 30 pcs. pills

Nausea, vomiting, headache, dizziness and fatigue may occur during the first days of treatment; however, these reactions do not usually require discontinuation of bromocriptine treatment.

The risk of adverse reactions can be reduced by gradually increasing the dose and taking bromocriptine tablets with food. If necessary, the daily dose can be reduced, and treatment continued at this reduced dose for several days. After the disappearance of adverse reactions, you can try again to increase the dose.

When using bromocriptine, side effects may develop, which, depending on the frequency of occurrence, are regarded as frequent (≥1/100 and

Mental disorders: infrequently - depressed mood, confusion, psychomotor agitation, hallucinations; rarely - psychosis.

From the nervous system: often - headache, dizziness, drowsiness; infrequently - dyskinesia; rarely - insomnia, paresthesia; very rarely - episodes of sudden falling asleep, rhinorrhea of cerebrospinal fluid.

On the part of the organ of vision: rarely - decreased visual acuity, blurred vision.

From the organ of hearing and labyrinthine disorders: rarely - ringing or tinnitus.

From the cardiovascular system: infrequently - decreased blood pressure, orthostatic hypotension (very rarely leading to fainting); rarely - tachycardia, bradycardia, arrhythmia, pericarditis, constrictive pericarditis; very rarely - fibrosis of the heart valves, reversible pallor of the fingers of the upper and lower extremities (especially in patients with a history of Raynaud's syndrome); frequency unknown - increased frequency of angina attacks.

From the respiratory system: often - nasal congestion; rarely - shortness of breath, pleurisy, pleural effusion, pleural fibrosis, pulmonary fibrosis.

From the gastrointestinal tract: often - nausea, vomiting, constipation; uncommon - dry mouth; rarely - abdominal pain, diarrhea, ulcerative lesions of the walls of the stomach and intestines, gastrointestinal bleeding, retroperitoneal fibrosis.

From the skin and subcutaneous tissues: infrequently - allergic dermatitis, alopecia.

From the musculoskeletal system: infrequently - muscle spasm.

From the urinary system: infrequently - urinary incontinence.

General disorders and disorders at the injection site: uncommon - increased fatigue; rarely - peripheral edema; very rarely - the occurrence of a syndrome resembling neuroleptic malignant syndrome in case of abrupt withdrawal of the drug.

From laboratory and instrumental studies: very rarely - hyponatremia.

Rare cases (when using bromocriptine to suppress lactation in the postpartum period) of increased blood pressure, myocardial infarction, stroke, seizures or mental disorders have also been reported.

When using high doses of bromocriptine for the treatment of Parkinson's disease, cases of possible development of pathological gambling, compulsive wastefulness or shopping addiction, constant need for food and compulsive gluttony, increased libido, hypersexuality (usually reversible after dose reduction or discontinuation of the drug) have been reported ).

If any of the side effects indicated in the instructions are aggravated or any other side effects not specified in the instructions are noted, the patient should inform the attending physician.

Drug interactions

Pharmacokinetic interaction

Bromocriptine is both a substrate and an inhibitor of the cytochrome P450 system (CYP3A4 isoenzyme).

Concomitant use of bromocriptine with strong and moderate CYP3A4 inhibitors (itraconazole, voriconazole, fluconazole, clarithromycin, erythromycin, indinavir, nelfinavir, grapefruit juice) may lead to increased plasma concentrations of bromocriptine. There are no data on interactions between bromocriptine and weak CYP3A4 inhibitors.

The simultaneous use of octreotide and bromocriptine in patients with acromegaly is accompanied by an increase in the concentration of the latter in the blood plasma and the number of adverse reactions.

Caution should be exercised when simultaneous use of drugs with a narrow therapeutic index (for example, amiodarone, imipramine, terbinafine) due to the possible prolongation of the QT interval.

Pharmacodynamic interaction

Concomitant use of bromocriptine with methylergometrine or other ergot alkaloids may increase the stimulatory effect on dopamine receptors and the development of unwanted dopaminergic effects such as headache, nausea and vomiting.

When used simultaneously with sympathomimetics, arterial hypertension and severe headache may occur.

Concomitant use with sumatriptan may increase the risk of vasospastic reactions due to additive pharmacological effects.

The therapeutic efficacy of bromocriptine, associated with stimulation of central dopamine receptors, may be reduced by the use of dopamine receptor antagonists such as antipsychotics (phenothiazines, butyrophenones and thioxanthenes), as well as metoclopramide and domperidone.

Tolerance to bromocriptine may be reduced by alcohol intake.

The simultaneous administration of bromocriptine with antihypertensive drugs may lead to a more pronounced decrease in blood pressure.

Bromocriptine can be prescribed either as monotherapy or in combination with other antiparkinsonian drugs (in both early and late stages of the disease). Combination with levodopa leads to an increase in antiparkinsonian effect, which often makes it possible to reduce the dose of levodopa. The use of bromocriptine in patients receiving treatment with levodopa is especially advisable when the therapeutic effect of levodopa is weakened or when complications such as pathological involuntary movements (choreoathetoid dyskinesia and/or painful dystonia), effect depletion syndrome towards the end of the levodopa dose, or the “on-off” phenomenon develop "("on-off").

Side effects of the drug Bromocriptine

In the first days of treatment, mild nausea may occur, and less commonly, dizziness, weakness, irritability, headache, orthostatic hypotension, vomiting, which do not require discontinuation of bromocriptine. The occurrence of these effects can be prevented by taking a peripheral dopamine antagonist (eg domperidone) 1 hour before taking bromocriptine for several days. Sometimes, with long-term treatment with bromocriptine, sudden, reversible blanching of the skin of the fingers and toes when exposed to cold is observed, especially in patients with a history of Raynaud's disease. When treating Parkinson's disease with bromocriptine in high doses, drowsiness may occur, and less commonly, confusion, psychomotor agitation, hallucinations, dyskinesia, a feeling of dry mouth and leg muscle cramps. These side effects are dose-dependent and usually resolve when the dose is reduced, after which it can be carefully increased.

Special instructions for the use of the drug Bromocriptine

Caution is required when using bromocriptine in the postpartum period, since hypertension (hypertension), myocardial infarction, seizures, stroke or mental disorders have been reported occasionally (approximately 1 in 100,000) when bromocriptine was used to prevent lactation; sometimes convulsions or cerebrovascular accidents were preceded by a severe headache or temporary visual disturbances. When prescribing bromocriptine in the early postpartum period, blood pressure should be carefully monitored, especially in the first days of treatment. Particular caution is required when treating patients with bromocriptine who have recently taken or are taking medications that regulate blood pressure. If hypertension (arterial hypertension), persistent headache or any signs of neurotoxicity occur, treatment should be discontinued immediately. Bromocriptine should be prescribed in the minimum therapeutically effective doses (except for pathology caused by increased secretion of prolactin) to prevent a decrease in the concentration of prolactin in the blood plasma below normal values, which may adversely affect the function of the corpus luteum in patients. In case of mastalgia and nodular and/or cystic changes in the mammary glands, the presence of malignant neoplasms should be excluded before using bromocriptine. In case of acromegaly, before using bromocriptine, the presence of erosive and ulcerative lesions of the digestive tract should be excluded, and if they are present, it is better to refuse to use bromocriptine or recommend that the patient immediately consult a doctor if any disturbances in the digestive system occur. Caution is warranted due to isolated reports of gastrointestinal bleeding in patients with acromegaly during treatment with bromocriptine, although a causal relationship has not been established. Caution is required when prescribing bromocriptine to patients with a history of psychiatric or severe cardiovascular disease. During treatment with bromocriptine, especially in the first days, arterial hypotension may occur, so caution is required when working with various mechanisms. Tolerance to bromocriptine may be impaired by alcohol consumption. There are isolated reports of the appearance of pleural effusion in patients with parkinsonism who have been receiving bromocriptine in high doses for a long time, therefore patients with pathology of the pleura and lungs of unknown origin should be carefully examined and, if a causal relationship is confirmed, treatment should be discontinued. Several cases of the development of retroperitoneal fibrosis have been described in patients receiving bromocriptine for a number of years at a daily dose of more than 30 mg. For timely diagnosis of retroperitoneal fibrosis in the early, reversible stages of the disease, it is recommended to pay attention to its manifestations (lower back pain, swelling of the lower extremities, impaired renal function, etc.) in this category of patients. If fibrotic changes in the retroperitoneal space are suspected or confirmed, bromocriptine should be discontinued. Treatment with bromocriptine can restore fertility, so if pregnancy is not desired, it is recommended to use reliable methods of contraception. If pregnancy occurs, it is recommended to discontinue bromocriptine and continue taking it only under strict indications. When bromocriptine was discontinued in the early stages of pregnancy, its negative effect on the course and outcome of pregnancy was not noted. When pregnancy occurs in patients with pituitary adenoma, treatment with bromocriptine is discontinued, and the patient is closely monitored during pregnancy. If signs of a pronounced increase in prolactinoma appear (for example, headache or narrowing of visual fields), treatment with bromocriptine can be resumed or surgery may be performed. The use of bromocriptine in the treatment of female infertility followed by pregnancy (over 2000 cases) was not associated with an increased risk of abortion, premature birth or birth defects.

Instructions for use BROMOCRIPTIN-RICHTER

There is insufficient evidence of the effectiveness of bromocriptine in the treatment of premenstrual syndrome and benign breast neoplasms. Therefore, the use of Bromocriptine-Richter in patients with this pathology is not recommended.

Bromocriptine is not recommended for use in the postpartum period in women with hypertension, coronary artery disease and/or a history of severe cardiovascular disease or serious mental disorders. In postpartum women receiving bromocriptine, blood pressure levels should be carefully monitored at regular intervals, especially during the first days of treatment.

Particular caution is required in patients receiving concomitant therapy (or who have recently received it) with drugs that can affect blood pressure.

Concomitant use of bromocriptine with vasoconstrictors such as sympathomimetics or ergot alkaloids, including ergometrine or methylergometrine, is not recommended during the postpartum period.

In rare cases, serious adverse reactions, including myocardial infarction, hypertension, stroke or psychiatric disorders, have been reported in postpartum women receiving bromocriptine to suppress lactation. The development of stroke in some patients was preceded by severe headache and/or transient visual disturbances.

If hypertension, severe and persistent headache with visual disturbances, or any signs of central nervous system toxicity develop, treatment with bromocriptine should be discontinued immediately.

Hyperprolactinemia can be idiopathic, drug-induced, or caused by diseases of the hypothalamus or pituitary gland. Bromocriptine effectively reduces prolactin levels in patients with pituitary tumors; however, its use does not eliminate the need for radiation therapy or surgery for acromegaly.

The drug should be prescribed in the minimum effective dose to women of childbearing age suffering from pathology not associated with hyperprolactinemia. Such precautions are necessary to avoid suppression of prolactin secretion to a level below normal with subsequent dysfunction of the corpus luteum. During treatment, such patients should use a reliable, non-hormonal method of contraception, because It is known that oral contraceptives can increase serum prolactin levels.

Women receiving bromocriptine for an extended period of time should undergo a gynecological examination (including cytological examination). Postmenopausal women should undergo such an examination every 6 months, while women of childbearing age need to be examined once a year.

In patients with acromegaly with a history of gastric ulcers, other types of treatment should be preferred, if possible. If treatment with bromocriptine is necessary, the patient should be instructed to immediately notify the physician of the occurrence of gastrointestinal adverse reactions.

Patients with severe cardiovascular disease or psychiatric disorders taking bromocriptine for macroadenomas should receive it only if the expected benefits of treatment outweigh the potential risks associated with it.

Changes in tumor size in patients with pituitary macroadenomas should be carefully monitored, and surgery should be considered if there is evidence of tumor growth.

Prolactin-secreting adenomas may increase in size during pregnancy. In such patients, treatment with bromocriptine often leads to a reduction in tumor size and rapid recovery of narrowed visual fields. In severe cases, compression of the optic or other cranial nerves may require emergency pituitary surgery.

Visual field impairment is a known complication of macroprolactinoma. Effective treatment with bromocriptine leads to a reduction in tumor size and severity of hyperprolactinemia, and often to the disappearance of visual impairment. However, some patients may subsequently develop secondary visual field loss despite normalization of prolactin levels and tumor shrinkage. In these cases, the visual field defect may decrease while taking bromocriptine at a reduced dose, despite a slight increase in prolactin levels and some re-enlargement of the tumor. Thus, monitoring of visual fields in patients with macroprolactinoma is recommended for early detection of secondary visual field loss and individual dose selection.

Cerebrospinal fluid rhinorrhea has been reported in some patients with prolactin-secreting adenomas treated with bromocriptine. Available evidence suggests that this phenomenon may occur due to tumor shrinkage with invasive growth.

During the first few days of treatment, arterial hypotension may develop in isolated cases.

Caution should be exercised when prescribing bromocriptine in high doses to patients with a history of psychotic disorders or severe cardiovascular disease.

Bromocriptine should be discontinued if fibrosing changes in the retroperitoneum are diagnosed or suspected.

You should pay attention to the following signs and symptoms:

lung diseases manifested by shortness of breath, suffocation, persistent cough or chest pain;
impaired renal function or obstruction of the urethra/abdominal vessels, which may be accompanied by pain in the lumbar region/lateral abdomen and swelling of the lower extremities, as well as the presence of any space-occupying lesions in the abdominal cavity or its tenderness on palpation, which may indicate retroperitoneal fibrosis;
heart failure caused by pericardial fibrosis (if such symptoms occur, constrictive pericarditis should be excluded).

In the diagnosis of fibrosing disorder, it is useful to determine the ESR and creatinine concentration in the blood, as well as performing a chest x-ray. In addition, it is advisable to determine baseline levels of other inflammatory markers and renal function indicators before starting treatment.

During treatment, patients should be closely monitored for signs of progressive fibrosing disorders. If retroperitoneal fibrosis is diagnosed or suspected, bromocriptine should be discontinued.

The use of bromocriptine may be accompanied by drowsiness and episodes of sudden sleep onset, especially in patients with Parkinson's disease. Sudden sleep onset during daytime activities, in some cases without any warning or warning signs, has been reported extremely rarely. Patients should be informed of the possibility of this phenomenon and should use caution when driving or operating machinery during treatment with bromocriptine. Patients experiencing drowsiness and/or episodes of sudden sleep onset should refrain from driving or operating machinery. In addition, the advisability of dose reduction or discontinuation of treatment should be considered.

Patients should be regularly monitored for the development of impulse control disorder. Patients and their caregivers should be aware of the possibility that patients receiving treatment with dopamine agonists (including Bromocriptine-Richter) may develop behavioral symptoms of impulse control disorder, including pathological gambling, increased sexual attraction, hypersexuality, compulsive spending or shopping addiction, constant need for food and compulsive gluttony. If such symptoms develop, the advisability of dose reduction/gradual withdrawal of the drug should be considered.

The drug contains 41 mg of lactose monohydrate. Patients with rare hereditary diseases such as galactose intolerance, lactose intolerance or glucose-galactose malabsorption should not take Bromocriptine-Richter.

Alcohol consumption may reduce bromocriptine tolerance and increase the risk of adverse reactions. Therefore, you should avoid drinking alcohol while taking this drug.

Any unused product or waste must be disposed of in accordance with local regulations.

Impact on the ability to drive vehicles and operate machinery

During the first few days of treatment, arterial hypotension, visual disturbances and dizziness may occur; therefore, special care should be taken when driving vehicles and operating machinery.

Patients who experience somnolence and/or episodes of sudden sleep onset should be advised to refrain from driving and other activities in which inattention may endanger others.

Drug interactions Bromocriptine

The combined use of bromocriptine and levodopa enhances the antiparkinsonian effect, which often makes it possible to reduce the dose of levodopa. Bromocriptine is especially indicated for patients in whom the effectiveness of levodopa is reduced or complications such as pathological involuntary movements (choreoathetoid dyskinesia and/or painful dystonia) arise, the effectiveness sharply decreases towards the end of action, or the effectiveness of bromocriptine is sharply fluctuating on and off. Erythromycin or josamycin may cause an increase in bromocriptine plasma concentrations.