Instructions Bromocriptine-KV tablets 2.5 mg blister No. 30
Composition
active ingredient:
1 tablet contains bromocriptine 2.5 mg;
Excipients: lactose monohydrate; colloidal anhydrous silica; disodium edetate; magnesium stearate; maleic acid; corn starch.
Dosage form
Pills.
Main physicochemical properties: round tablets with a flat surface with beveled edges and a score, white or almost white in color.
Pharmacotherapeutic group
Drugs used in gynecology. Prolactin inhibitors. ATX code G02C B01.
Pharmacological properties
Pharmacodynamics.
Dopamine receptor stimulator. Inhibits the secretion of the anterior pituitary hormone prolactin and does not affect normal levels of other pituitary hormones. However, Bromocriptine-KV is able to reduce elevated levels of GH in patients with acromegaly. This effect is due to the stimulation of dopamine receptors.
In the postpartum period, prolactin is necessary for the initiation and maintenance of lactation. At other times of life, increased prolactin secretion leads to pathological lactation (galactorrhea) and/or disruption of ovulation and the menstrual cycle.
Bromocriptine-KV as 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. In amenorrhea and/or anovulatory menstrual cycles (which are accompanied or not accompanied by galactorrhea), Bromocriptine-KV can be used to restore the menstrual cycle and ovulation.
When using Bromocriptine-KV to suppress lactation, there is no need to restrict fluid intake. In addition, Bromocriptine-KV does not disrupt postpartum uterine involution and does not increase the risk of thromboembolism.
Bromocriptine-KV stops the growth or reduces the size of prolactin-secreting pituitary adenomas (prolactinomas).
In patients with acromegaly, in addition to reducing the concentration of GH and prolactin in blood plasma, Bromocriptine-KV has a positive effect on clinical manifestations and glucose tolerance.
In Parkinson's disease, which is characterized by a specific dopamine deficiency in the striatum and substantia nigra of the brain, stimulation of dopamine receptors with Bromocriptine-CB can restore neurochemical balance in the basal ganglia.
Patients with Parkinson's disease should usually be prescribed Bromocriptine-KV in higher doses than those used for endocrinological diseases.
Bromocriptine-KV reduces tremor, rigidity, slowness of movement and other symptoms of parkinsonism at all stages of the disease. The effectiveness of the drug is usually maintained for several years (to date, positive results of therapy have been described with a duration of treatment of up to 8 years).
Bromocriptine-KV reduces the severity of depressive symptoms in patients with Parkinson's disease. This is due to its inherent antidepressant properties, which have been confirmed in controlled studies in patients with endogenous or psychogenic depression who did not have Parkinsonism.
Pharmacokinetics.
The prolactin-lowering effect begins 1-2 hours after taking the drug orally, reaches a maximum (a decrease in prolactin concentration of more than 80%) after 5-10 hours and remains at a level close to the maximum for 8-12 hours.
Absorption: After oral administration, bromocriptine is rapidly absorbed. Peak plasma concentrations are reached within 1-3 hours.
Distribution: Plasma protein binding is 96%.
Metabolism. Bromocriptine undergoes extensive first-pass metabolism through the liver to form a number of metabolites. Unchanged bromocriptine is virtually absent in urine and feces. Bromocriptine has a high affinity for CYP3A. The main metabolic pathway is hydroxylation of the proline ring in the cyclopeptide. Bromocriptine is a potent inhibitor of CYP3A4 with an estimated IC50 of 1.69 μmol. However, due to the low therapeutic blood concentrations of free bromocriptine, no significant change in the metabolism of concomitantly administered drugs cleared by CYP3A4 is expected.
Elimination: Elimination of unchanged bromocriptine from plasma is biphasic, with a terminal half-life of about 15 hours (range 8 to 20 hours). Bromocriptine and its metabolites are almost entirely eliminated by the liver, with only 6% excreted by the kidneys.
Special cases: In patients with impaired liver function, the rate of bromocriptine excretion may be reduced and plasma levels may increase, requiring adjustment of the dosage regimen.
Concomitant use of inhibitors and/or potential substrates of CYP3A4 may lead to a decrease in bromocriptine clearance and an increase in its plasma concentration.
Indication
Menstrual cycle disorders, female infertility
Prolactin-dependent diseases and conditions, accompanied or not accompanied by hyperprolactinemia:
-amenorrhea (with or without galactorrhea); oligomenorrhea;
-luteal phase insufficiency;
Prolactin-independent female infertility:
-polycystic ovary syndrome;
- anovulatory cycles (as an adjunct to antiestrogens, such as clomiphene).
Premenstrual syndrome:
- breast tenderness; swelling associated with the phase of the cycle; flatulence; mood swings.
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 removal;
-postoperative treatment if prolactin levels remain elevated.
Acromegaly:
-as an additional means or in special cases - as an alternative to surgical or radiation treatment).
Suppression of lactation:
-prevention or cessation of postpartum lactation for medical reasons, including in the initial stage of postpartum mastitis;
-prevention of lactation after abortion.
Benign diseases of the mammary glands:
-mastalgia (including in combination with premenstrual syndrome or benign nodular or cystic changes);
-benign nodular and cystic changes, especially fibrocystic mastopathy.
Parkinson's disease:
-all stages of idiopathic Parkinson's disease and postencephalitic parkinsonism either as monotherapy or in combination with other antiparkinsonian agents.
Contraindication
-Hypersensitivity (allergy) to bromocriptine or other ergot alkaloids;
-uncontrolled arterial hypertension;
-gestosis (including eclampsia, preeclampsia);
-arterial hypertension during pregnancy and in the postpartum period;
-ischemic heart disease and other severe cardiovascular diseases;
-severe mental disorders at present and/or in history;
-children under 7 years of age (experience of using the drug is limited);
- regarding long-term treatment: pathology of the valvular apparatus of the heart, confirmed by echocardiographic studies.
Interaction with other medicinal products and other types of interactions
Bromocriptine is both a substrate and an inhibitor of the CYP3A4 isoenzyme. Caution should be exercised when prescribing bromocriptine and other inhibitors and/or substrates of CYP3A4 (azole antifungals, HIV protease inhibitors). Simultaneous administration of erythromycin, josamycin, other macrolide antibiotics and Bromocriptine-KB causes an increase in the concentration of bromocriptine in the blood plasma. Simultaneous use of octreotide and bromocriptine in patients with acromegaly is accompanied by an increase in the level of the latter in the blood plasma.
The therapeutic efficacy of bromocriptine, which is associated with stimulation of central dopamine receptors, may be reduced by the use of dopamine receptor antagonists, such as neuroleptics (phenothiazines, butyrophenones and thioxanthenes), as well as metoclopramide and domperidone.
Concomitant administration of Bromocriptine-KV with antihypertensive drugs may lead to an increased severity of the decrease in blood pressure.
Bromocriptine-KV can be prescribed either as monotherapy or in combination with other antiparkinsonian agents (both in the early and late stages of the disease). The combination with levodopa leads to an increase in the antiparkinsonian effect, which often makes it possible to reduce the dose of levodopa. The use of Bromocriptine-KV in patients receiving levodopa treatment is especially appropriate when the therapeutic effect of levodopa is weakened or when complications such as pathological involuntary movements (choreoathetoid dyskinesia and/or painful dystonia) develop, the syndrome of exhaustion of the effect before the end of the dose of levodopa, the phenomenon of "on-off".
The tolerability of Bromocriptine-KV may deteriorate when used with ethanol.
Application features
Hyperprolactinemia may be idiopathic, drug-induced, or caused by a disease of the hypothalamus or pituitary gland. A complex of studies should be performed to detect pituitary tumors and a decision should be made regarding the appropriateness of treating such patients to reduce hyperprolactinemia. Bromocriptine-KV effectively lowers prolactin levels in such patients, but such therapy does not eliminate the need for radiation therapy or surgery if necessary.
If treatment with the drug is prescribed to women with a pathology not associated with hyperprolactinemia, the drug should be used in the minimum effective dose necessary to relieve symptoms; this is necessary in order to avoid a decrease in the concentration of prolactin in the plasma below the normal level and the development of associated disorders of the function of the corpus luteum. In patients who will be prescribed treatment with the drug for mastalgia, nodular and/or cystic changes in the mammary glands, malignant neoplasms should be excluded using appropriate diagnostic methods.
Postpartum Use. Serious adverse reactions, including hypertension, myocardial infarction, seizures, cerebral stroke, or psychiatric disorders, have been reported rarely in women taking bromocriptine in the postpartum period. In some patients, seizures or cerebrovascular disorders have been preceded by severe headache and/or transient visual disturbances. Although a causal relationship to bromocriptine has not been established, blood pressure should be monitored periodically in women taking the drug in the postpartum period for lactation suppression, as in patients receiving Bromocriptine-KV for any other indication. If hypertension develops or severe, progressive headache that does not resolve (with or without visual disturbances), or signs of central nervous system involvement, the drug should be discontinued and the patient should be evaluated immediately.
Particular caution should be exercised in patients who have recently taken or are taking drugs that affect blood pressure, such as vasoconstrictors (sympathomimetics or ergot alkaloids, including ergometrine or methylergometrine). Although there is no definitive evidence of an interaction between Bromocriptine-KV and these drugs, their concomitant use in the postpartum period is not recommended.
Use in prolactin-secreting adenomas. Since patients with pituitary macroadenomas may present with signs of hypopituitarism due to compression or destruction of pituitary tissue, a complete evaluation of pituitary function and appropriate replacement therapy should be performed before Bromocriptine-KV is prescribed to these patients. In patients with secondary adrenal insufficiency, corticosteroid replacement therapy is important.
Patients with pituitary macroadenomas should be systematically evaluated for tumor size dynamics. If tumor growth is noted, surgical treatment should be considered.
Pregnant patients with pituitary adenomas should be closely monitored because prolactin-secreting adenomas may enlarge during pregnancy. In such patients, treatment with bromocriptine often results in tumor reduction and rapid improvement in visual field defects. In severe cases, compression of the optic or other cranial nerves may warrant urgent pituitary surgery.
In clinical studies, the number of patients aged 65 and over was insufficient to conduct a comparative assessment of the effectiveness of treatment with Bromocriptine-KV with younger patients. However, in clinical studies and medical practice, the tolerability of the drug in patients aged 65 and over was the same as in younger patients. It should be taken into account that the tolerability of the drug in this category of patients is difficult to predict.
During treatment with Bromocriptine-KV, careful supervision of patients with a history of peptic ulcer disease is necessary.
Careful examination and monitoring of patients with pleuropulmonary diseases of unknown etiology is necessary and drug therapy should be discontinued if the disorders progress.
For early diagnosis of retroperitoneal fibrosis at the initial stage of the process, the doctor is advised to monitor the manifestations of such symptoms as back pain, swelling of the lower extremities, impaired renal function. Bromocriptine-KV should be discontinued if fibrotic changes in the retroperitoneal space are confirmed or suspected.
A well-known complication of macroprolactin is visual field loss. Effective treatment with the drug reduces hyperprolactinemia and eliminates visual field defects. However, in some patients, secondary changes in visual fields are possible, despite the normalization of prolactin levels and a decrease in tumor size. This may be due to the displacement of the optic chiasm downward due to the release of volume in the sella turcica area. In this case, reducing the dosage of bromocriptine, which leads to an increase in prolactin levels and an increase in tumor size to some extent, may contribute to the elimination of visual field defects. In this regard, visual field monitoring in patients with macroprolactinoma is indicated for the early detection of secondary visual field losses caused by spatial protrusion of the optic chiasm into the sella cavity and adaptation to the action of a given dose of the drug. Cerebrospinal rhinorrhea has been reported in some patients with prolactin-secreting adenomas taking Bromocriptine-CB. Clinical studies suggest that cerebrospinal rhinorrhea may be due to a reduction in the volume of invasive tumors.
Patients with rare hereditary forms of galactose intolerance, severe lactase deficiency, or glucose-galactose malabsorption should not take Bromocriptine-KV.
Impulse control disorders. Regular monitoring of patients suspected of being at risk of developing impulse control disorders is necessary. Patients and their caregivers should be made aware that impulse control disorders may occur with dopamine agonists, including bromocriptine, and may include symptoms such as gambling, increased libido, hypersexuality, compulsive spending or shopping, bulimia, and binge eating. In the event of such symptoms, the dosage of the drug should be reduced or therapy should be gradually discontinued.
Use during pregnancy or breastfeeding
In patients who wish to become pregnant, the drug may be discontinued after pregnancy is confirmed, except in cases where the possible positive effect of treatment outweighs the potential risk to the fetus.
Withdrawal of Bromocriptine-KV during pregnancy did not lead to an increase in the frequency of spontaneous abortions.
Clinical experience shows that the use of the drug during pregnancy does not have a negative effect on its course or childbirth.
If pregnancy occurs in the presence of a pituitary adenoma and treatment with Bromocriptine-KV is discontinued, close monitoring of the patient is necessary throughout the pregnancy. In the event of signs of a pronounced increase in prolactinoma, such as headache or narrowing of the visual fields, treatment with Bromocriptine-KV may be resumed or surgery may be prescribed.
Because Bromocriptine-KV suppresses lactation, it should not be prescribed to women who do not plan to discontinue breastfeeding.
Treatment with the drug may restore fertility. No embryotoxic or teratogenic effects of bromocriptine have been identified. Women of reproductive age who do not wish to become pregnant should use a reliable method of contraception.
Ability to influence reaction speed when driving vehicles or other mechanisms
Patients whose activities involve driving or operating machinery should be especially careful, as sometimes, especially in the first days of treatment, arterial hypotension may develop, leading to a decrease in the speed of psychomotor reactions.
During treatment with the drug, drowsiness and episodes of sudden sleep onset have been reported, especially in patients with Parkinson's disease. Episodes of sudden sleep onset during daytime wakefulness, which occurred without prior drowsiness, have been reported extremely rarely. Before prescribing the drug, the doctor should inform the patient about the above risk factors and recommend that he refrain from driving vehicles, operating mechanisms, and engaging in other potentially dangerous activities that require increased attention and speed of reactions. If severe drowsiness or episodes of sudden sleep onset occur, the dose of the drug should be reduced or completely discontinued.
Method of administration and doses
The tablets should always be taken with food. In most indications, it is necessary to gradually increase the dose of the drug to achieve the optimal response to therapy and minimize side effects.
General reception scheme
The initial dose of the drug is 1.25 mg before bedtime. After 2-3 days, the dose of Bromcryptine-KV should be increased to 2.5 mg. Then the dose of the drug can be increased every 2-3 days by 1.25 mg until a dose of 2.5 mg is reached. If necessary, further increase in the dose of the drug can be carried out according to the same scheme.
Menstrual cycle disorders, female infertility
1.25 mg (1/2 tablet) 2-3 times a day; if the effect is insufficient, the dose of the drug should be gradually increased to a dose of 2.5 mg 2-3 times a day. Treatment should be continued until the menstrual cycle is normalized and/or ovulation is restored. If necessary, treatment can be continued for several cycles to prevent relapses.
Galactorrhea syndrome, infertility
It is suggested to gradually increase the dose of the drug according to the above scheme. Most patients with hypergalactorrhea tolerate a dose of 7.5 mg of the drug per day, which should be taken in 2-3 doses. If necessary, the dose can be increased to 30 mg per day. In infertility without an increase in the level of prolactin in the blood, the generally accepted dose of the drug is 2.5 mg 2 times a day.
Premenstrual syndrome
Treatment should be started on the 14th day of the cycle with 1.25 mg (1/2 tablet) per day. Gradually increase the dose by 1.25 mg per day to a dose of 2.5 mg 2 times a day and use until menstruation begins.
Hyperprolactinemia in men
1.25 mg (1/2 tablet) 2-3 times a day, gradually increasing the dose to 5-10 mg per day.
Prolactinomas
The daily dose of 2.5 mg is achieved according to the general dosing regimen. Further dose increases (2.5 mg every 2-3 days) should be carried out according to the following scheme: 2.5 mg of the drug every 8 hours; 2.5 mg every 6 hours; 5 mg every 6 hours. The therapeutic effect is expected until a dose of 30 mg of the drug per day is reached.
Bromocriptine is prescribed to children and adolescents (aged 7-17 years) by a pediatric endocrinologist. Children aged 7 years and older should be prescribed 1 mg 2 or 3 times a day, gradually increasing the dose as needed to maintain an adequately reduced level of prolactin in the blood plasma.
The maximum recommended dose for children and adolescents aged 7-12 years is 5 mg per day; from 13 to 17 years - 20 mg.
The daily dose of 2.5 mg is achieved by the general dosing regimen. Further dose increases (2.5 mg every 2-3 days) should be carried out according to the following scheme: 2.5 mg of bromocriptine every 8 hours; 2.5 mg every 6 hours; 5 mg every 6 hours.
The maximum recommended dose for children and adolescents aged 7-12 years is 10 mg per day; from 13 to 17 years - 20 mg.
Suppression of lactation
On the first day, take 2.5 mg of the drug in 2 doses, and in the next 2-3 days, the dose of the drug should be increased to 2 times 2.5 mg of bromocriptine. Treatment should be continued for 14 days. There is no need to gradually increase the dose of the drug.
To prevent the onset of lactation, the drug should be started a few hours after childbirth or abortion, but only after stabilization of vital functions 2 or 3 days after discontinuation of the drug, sometimes a slight secretion of milk occurs. It can be stopped by resuming the drug at the same dose for another week. 2.5 mg of the drug is taken, and in the next 2-3 days the dose of the drug should be increased to 2 times 2.5 mg of bromocriptine
Lactation prevention
On the day of delivery, take 2.5 mg, and then 2 times 2.5 mg of Bromocriptine-KV for 14 days. There is no need to gradually increase the dose of the drug.
Benign diseases of the mammary glands
According to the above scheme, it is necessary to achieve a dose of the drug 2 times 2.5 mg.
Parkinson's disease
A gradual dose increase scheme should be followed.
1st week: 1.25 mg per day at bedtime.
Week 2: 2.5 mg per day at bedtime.
3rd week: 2.5 mg twice a day.
4th week: 2.5 mg 3 times a day.
After that, depending on the patient's condition, the dose of the drug can be increased by 2.5 mg over the next 3-14 days. The dose increase can be continued until the optimal dose is reached, which is within the range of 10-40 mg of Bromocriptine-KV per day.
If adverse reactions occur during dosage adjustment, the daily dose should be reduced and maintained at a lower level for at least one week. When side effects resolve, the dosage of the drug can be increased again.
Patients with movement disorders who are taking levodopa are recommended to reduce the dose of levodopa before starting Bromocriptine-KV. After achieving a satisfactory clinical effect during treatment with Bromocriptine-KV, a further gradual reduction in the dosage of levodopa can be carried out. In some patients taking Bromocriptine-KV, complete withdrawal of levodopa is possible.
With increasing the dose of bromocriptine, it becomes possible to reduce the dose of levodopa and establish equilibrium with the intake of optimal doses of drugs.
Elderly patients do not require dose adjustment. In case of impaired liver function, a delay in the excretion of the drug from the body and an increase in the concentration of bromocriptine in the blood plasma may be observed. In this regard, it may be necessary to change the dosage of the drug.
Children
Due to lack of experience, the drug should not be used in children under 7 years of age.
Overdose
Symptoms. In all cases of overdose with bromocriptine taken in isolation, no fatal consequences were noted. The maximum single dose of the drug, known at the moment, is 325 mg. In case of overdose, symptoms such as nausea, vomiting, dizziness, arterial hypotension, postural hypotension, tachycardia, drowsiness, lethargy, hallucinations were observed.
With accidental oral administration of Bromocriptine-KV to children (separate reports), vomiting, fever, and drowsiness were observed. Improvement in the patients' condition occurred suddenly or several hours after appropriate therapy.
Treatment. In case of overdose, it is recommended to take activated charcoal; gastric lavage is possible immediately after taking the drug. Treatment of acute poisoning is symptomatic. Metoclopramide can be used to stop vomiting or hallucinations.
Adverse reactions
From the side of the central nervous system and peripheral nervous system: headache, dizziness; movement disorders, confusion, psychomotor agitation, hallucinations; paresthesias, psychotic disorders, insomnia; increased libido, hypersexuality, increased daytime sleepiness, sudden onset of sleep.
From the sensory organs: visual impairment, "blurred vision", tinnitus.
Cardiovascular system: hypotension, orthostatic hypotension (very rarely leading to fainting); pericardial effusion, constrictive pericarditis, tachycardia, bradycardia, arrhythmia; fibrosis of heart valves, reversible pallor of fingers and toes caused by hypothermia (especially in patients with a history of Raynaud's syndrome).
Respiratory system: nasal congestion; pleural effusion, pleural fibrosis, pleurisy, pulmonary fibrosis, shortness of breath.
On the part of the digestive system: nausea, constipation, vomiting; dry mouth; diarrhea, abdominal pain, retroperitoneal fibrosis, ulcerative lesions of the gastrointestinal tract (GI), gastrointestinal bleeding (black stool, blood in vomit), dyskinesia.
Dermatological reactions: hair loss.
Allergic reactions: skin manifestations.
Musculoskeletal system: calf muscle cramps.
When using the drug in high doses (as with other dopamine agonists), reversible sexual behavior disorders, increased libido and hypersexuality have rarely been observed, which disappeared after reducing the dosage of the drug or stopping treatment. Hypersensitivity reactions are possible in individuals with individual intolerance to any component of the drug.
The use of Bromocriptine-KV to suppress physiological lactation in the postpartum period was rarely accompanied by the development of arterial hypertension, myocardial infarction, seizures, stroke, or mental disorders.
Expiration date
2 years.
Storage conditions
Store in the original packaging at a temperature not exceeding 25 °C.
Keep out of reach of children.
Packaging
10 tablets in a blister, 3 blisters in a pack.
Vacation category
According to the recipe.
Producer
PJSC "Kyiv Vitamin Plant".
Location of the manufacturer and its business address
Ukraine, 04073, Kyiv, Kopylivska St., 38.
