Composition, form of production and packaging
Tablets are almost white, round, flat, with a bevelled edge, with a risk and code "XC" on one side, with the inscription "SANDOZ" on the other.
1 tab.
bromocriptine mesylate 2.87 mg,
which corresponds to the content of bromocriptine 2.5 mg
Excipients: silicon colloidal dioxide, disodium edetate, magnesium stearate, maleic acid, corn pregelatinized starch, corn starch, lactose monohydrate.
10 pieces. - blisters (3) - packs of cardboard.
30 pcs. - bottles of dark glass (1) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2012.
PHARMACHOLOGIC EFFECT
Stimulator of dopamine receptors. Inhibits the secretion of the hormone of the anterior lobe of the pituitary gland - prolactin, without affecting the normal content of other pituitary hormones. However, Parlodel В® is able to reduce the elevated levels of STH in patients with acromegaly. This action is due to the stimulation of dopamine receptors.
In the postpartum period, prolactin is needed to start and maintain lactation. In other periods of life, an increase in prolactin secretion leads to pathological lactation (galactorrhea) and / or disorders of ovulation and the menstrual cycle.
Parlodel В® , 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. With amenorrhea and / or anovulatory menstrual cycles (accompanied or not accompanied by galactorrhea) Parlodel В® can be used to restore the menstrual cycle and ovulation.
When applying Parlodela for suppressing lactation, there is no need to limit the use of liquid. In addition, Parlodel В® does not disrupt the postnatal involution of the uterus and does not increase the risk of thromboembolism.
Parlodel В® stops growth or decreases the size of prolactin secretive pituitary adenomas (prolactin).
In patients with acromegaly, in addition to reducing the concentration of STH and prolactin in the plasma, Parlodel В® has a beneficial effect on clinical manifestations and glucose tolerance.
In Parkinson's disease, characterized by a specific deficiency of dopamine in the region of the striatum and black nuclei of the brain, stimulation of dopamine receptors by Parlodel can restore the neurochemical balance in the basal ganglia.
Patients with Parkinson's disease, bromocriptine is usually prescribed in higher doses than those used for endocrinological indications.
Parlodel В® reduces tremor, stiffness, slowness of movements and other symptoms of Parkinsonism at all stages of the disease. The effectiveness of the drug usually persists for many years (by now, good results of therapy are described with a treatment duration of 8 years).
Parlodel В® reduces the severity of symptoms of depression in patients with Parkinsonism. This is due to its inherent antidepressant properties, confirmed in controlled trials in patients with endogenous or psychogenic depression who did not suffer from Parkinsonism.
Prolactin-lowering effect begins 1-2 hours after taking the drug inside, reaches a maximum (decrease in prolactin concentration by more than 80%) after 5-10 hours and remains at a level close to the maximum for 8-12 hours.
PHARMACOKINETICS
Suction
After taking the drug inside, bromocriptine is well absorbed from the digestive tract. In healthy volunteers after ingestion of Parlodela in the form of tablets, the half-absorption period of bromocriptine is 0.2-0.5 hours, C max is reached within 1-3 hours. When administered bromocriptine in a dose of 5 mg C max is 0.465 ng / ml.
Distribution
Binding to plasma proteins is 96%.
Metabolism
Bromocriptine undergoes intensive metabolism during "first passage" through the liver with the formation of a number of metabolites. In urine and feces, unchanged bromocriptine is practically absent. Bromocriptine has a high affinity for CYP3A. The main way of metabolism is hydroxylation of the proline ring in the composition of the cyclopeptide.
Bromocriptine is a potent inhibitor of CYP3A4 with a calculated IC50 value of 1.69 Ојmol. However, due to the low therapeutic concentrations of free bromocriptine in the blood, there is not expected to be a significant change in the metabolism of concomitantly used drugs, the clearance of which is carried out with the participation of CYP3A4.
Excretion
The removal of unchanged bromocriptine from the plasma occurs biphasic, the final T 1/2 is about 15 hours (8 to 20 hours). Bromocriptine and its metabolites are almost completely excreted through the liver, only 6% of the dose is excreted by the kidneys.
Pharmacokinetics in special clinical cases
In patients with impaired hepatic function, the rate of bromocriptine elimination may decrease, and plasma levels may increase, which requires correction of the dosing regimen.
Simultaneous use of inhibitors and / or potential substrates of CYP3A4 can lead to a decrease in the clearance of bromocriptine and an increase in its concentration in the blood plasma.
INDICATIONS
Violations of the menstrual cycle, female infertility
Prolactin-dependent diseases and conditions, accompanied or not accompanied by hyperprolactinaemia:
- amenorrhea (accompanied and not accompanied by galactorrhea), oligomenorrhea;
- Luteal phase insufficiency;
- secondary hyperprolactinemia caused by drugs (for example, some psychotropic or antihypertensive drugs).
Prolactin-independent female infertility:
- Polycystic ovary syndrome;
- Anovulatory cycles (in addition to anti-estrogens, for example clomiphene).
Hyperprolactinemia in men
- Prolactin-dependent hypogonadism (oligospermia, loss of libido, impotence).
Prolactinomas
- conservative treatment of prolactin secreting micro- and macroadenomas of the pituitary gland;
- preoperative preparation to reduce the volume of the tumor and facilitate its removal;
- Postoperative treatment if the level of prolactin remains elevated.
Acromegaly
- as an additional remedy or, in special cases, as an alternative to surgical or radiotherapy.
Suppression of lactation
- prevention or cessation of postpartum lactation due to medical indications, incl. at the initial stage of postpartum mastitis;
- prevention of lactation after abortion.
Parkinson's disease
- all stages of idiopathic Parkinson's disease and postencephalitic parkinsonism - either in monotherapy or in combination with other antiparkinsonian agents.
DOSING MODE
Parlodel В® is taken orally during meals.
Violations of the menstrual cycle, female infertility
Assign to 1.25 mg (1/2 table.) 2-3 times / day; if the therapeutic effect is insufficient, the dose of the drug is gradually increased to 5-7.5 mg / day (the frequency of reception 2-3 times / day).
Treatment continues until the menstrual cycle is normalized and / or ovulation is restored.
If necessary, for the prevention of relapse, treatment can be continued for several cycles.
Hyperprolactinemia in men
Assign 1.25 mg (1/2 table.) 2-3 times / day, gradually increasing the dose to 5-10 mg (2-4 tab.) Per day.
Prolactinomas
Assign 1.25 mg (1/2 tab.) 2-3 times / day with a gradual increase in dose and the selection of a dose that provides an adequate decrease in the concentration of prolactin in the plasma.
The maximum recommended dose for children and adolescents aged 7-12 years is 5 mg / day, at the age of 13-17 years - 20 mg.
Acromegaly
The initial dose is 1.25 mg (1/2 table) 2-3 times / day, further, depending on the clinical effect and tolerability, the daily dose of the drug is gradually increased to 10-20 mg (4-8 tab.).
The maximum recommended dose for children and adolescents aged 7-12 years is 10 mg / day, at the age of 13-17 years - 20 mg.
Suppression of lactation for medical reasons
On the first day, 1.25 mg (1/2 table) are prescribed 2 times (during meals at breakfast and dinner), then within 14 days - 2.5 mg (1 tab.) 2 times / day. To prevent lactation , the drug should be taken several hours after birth or abortion , but only after stabilizing vital functions. After 2 or 3 days after drug withdrawal, there is sometimes a slight secretion of milk. It can be eliminated by recommencing the drug at the same dose for another 1 week.
Beginning postpartum mastitis
On the first day, 1.25 mg (1/2 table) are prescribed 2 times (during meals at breakfast and dinner), then within 14 days - 2.5 mg (1 tab.) 2 times / day. Additionally, an antibiotic is prescribed.
Parkinson's disease
In order to ensure optimal tolerability during the first week, treatment should be started with a low dose of 1.25 mg (1/2 tab.) 1 time / day (preferably in the evening).To select an individual minimum effective dose, increase it slowly, by titration: every day the daily dose is increased by 1.25 mg; The daily dose is divided into 2-3 doses. An adequate therapeutic response is achieved on average for 6-8 weeks of treatment. In the absence of clinical effect after 6-8 weeks of use, it is possible to further increase the daily dose by 2.5 mg every week.
Typically, the therapeutic range of doses of bromocriptine for mono- or combination therapy is 10 mg to 40 mg per day, but some patients may require higher doses.
If unwanted reactions occur during the selection of a dose, the daily dose should be reduced and maintained at a lower level for at least 1 week. When reversing side effects, the dose of the drug can be raised again.
Patients with motor disabilities on the background of taking levodopa are recommended before the application of Parlodela reduce the dose of levodopa. After achieving a satisfactory clinical effect in the treatment of Parlodel, a further gradual decrease in the dose of levodopa can be made. In some patients taking Parlodel В® , complete cancellation of levodopa is possible.
SIDE EFFECT
Determination of the frequency of adverse reactions: very often (? 1/10); often (? 1/100, <1/10); sometimes (? 1/1000, <1/100); rarely (? 1/10 000, <1/1000); very rarely (<1/10 000), including individual messages.
From the side of the central nervous system and peripheral nervous system often - headache, drowsiness, dizziness; sometimes - motor disorders, confusion, psychomotor agitation, hallucinations; rarely - drowsiness, paresthesia, psychotic disorders, insomnia; very rarely - increased libido, hypersexuality, increased drowsiness during the day, sudden falling asleep.
From the senses: rarely - impaired vision, blurred vision, tinnitus.
From the cardiovascular system: sometimes - arterial hypotension, orthostatic hypotension (very rarely leading to fainting); rarely - pericardial effusion, constrictive pericarditis, tachycardia, bradycardia, arrhythmia; very rarely fibrosis of the heart valves, reversible paleness of the fingers and toes caused by hypothermia (especially in patients with Raynaud's syndrome in the anamnesis).
From the respiratory system: often - nasal congestion; rarely - pleural effusion, pleural fibrosis, pleurisy, pulmonary fibrosis, dyspnea.
From the side of the digestive system: often - nausea, constipation, vomiting; sometimes - dry mouth; rarely - diarrhea, abdominal pain, retroperitoneal fibrosis, ulcerative lesions of the digestive tract, gastrointestinal bleeding (black feces, blood in vomit masses).
Dermatological reactions: sometimes - hair loss.
Allergic reactions: sometimes skin manifestations.
From the musculoskeletal system: sometimes - cramps calf muscles.
Other: sometimes - increased fatigue; rarely - peripheral edema; very rarely - in the event of a sharp reversal of Parlodela, the development of a condition similar to the NSA.
When applying Parlodel in high doses (as well as other dopamine agonists), a reversible change in sexual behavior, increased libido and hypersexuality, which disappeared after a reduction in the dose of the drug or discontinuation of treatment, were rarely noted.
Application Parlodela for suppression of physiological lactation in the postpartum period in rare cases was accompanied by the development of arterial hypertension, myocardial infarction, seizures, stroke or mental disorders.
CONTRAINDICATIONS
uncontrolled arterial hypertension;
- gestosis (including eclampsia, preeclampsia);
- arterial hypertension in pregnancy and in the postpartum period;
- IHD and other severe cardiovascular diseases;
- severe mental disorders at present and / or in anamnesis;
- Children under 7 years of age (experience with the drug is limited);
- hypersensitivity to the components of the drug;
- Hypersensitivity to ergot alkaloids.
It is not recommended to use for the treatment of premenstrual syndrome and benign breast diseases due to the limited amount of clinical data.
PREGNANCY AND LACTATION
After confirming the planned pregnancy, Parlodel, like other medicines, should be withdrawn except for the need to continue therapy for medical reasons. The abolition of Parlodela during pregnancy did not lead to an increase in the incidence of its spontaneous interruption. Clinical experience shows that the use of Parlodel in pregnancy does not adversely affect its course or outcome. If Parlodel is withdrawn in pregnant women with pituitary adenoma, careful monitoring of the patients throughout the gestation period is necessary. In case of signs of pronounced increase in prolactinoma, for example, headaches or narrowing of the fields of vision, treatment with Parlodel may be resumed or performed surgical intervention.
When lactating Parlodel В® is used according to the indications. The drug inhibits lactation, so it is not prescribed to nursing mothers.
Treatment Parlodel can restore fertility. Therefore, women of childbearing age who do not want pregnancy, should use a reliable method of contraception.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
The drug is contraindicated in patients with portal hypertension (including with cirrhosis of the liver).
APPLICATION FOR CHILDREN
Contraindications: children under 7 years of age (experience with the drug is limited).
The efficacy and safety of Parlodel В® was established for children older than 7 years and adolescents with prolactinomas and acromegaly. In clinical studies and medical practice, tolerability of the drug in adults and children was the same. It is necessary to take into account the difficult predictable sensitivity to the drug in this category of patients.
APPLICATION IN ELDERLY PATIENTS
In clinical studies, the number of patients aged 65 years and older was not sufficient to perform a comparative evaluation of the efficacy of Parlodel treatment in younger patients. However, in clinical trials and medical practice, the tolerability of the drug in patients older than 65 years and younger was the same. It is necessary to take into account the difficult predictable tolerability of the drug in this category of patients.
SPECIAL INSTRUCTIONS
Women with a pathology that is not associated with hyperprolactinemia, Parlodel В® should be prescribed in the effective minimum dose necessary for relief of symptoms. This is important to prevent a decrease in the concentration of prolactin in the plasma below the normal level, which leads to a violation of the function of the yellow body.
In women who took Parlodel В® in the postpartum period to suppress lactation, there were rare cases of serious adverse reactions: arterial hypertension, myocardial infarction, convulsions, stroke or mental disorders. In some patients, development of seizures or cerebrovascular disorders was preceded by severe headaches and / or transient visual impairment. Although the causal relationship of these reactions to Parlodela is not established, in women taking the drug in the puerperium to suppress lactation, as well as in patients receiving Parlodel В® for any other indication, BP should be monitored. With the development of hypertension or severe, progressive or persistent headache (accompanied and not accompanied by visual impairment), or signs of a violation of the CNS Parlodel В® should be canceled and immediately conducted a patient examination. Particular care should be taken when administering Parlodel to patients who have recently received or continue to take drugs that affect blood pressure, for example, vasoconstrictors (sympathomimetics or ergot alkaloids, including ergometrine or methylergometrine). Women in the postpartum period do not recommend the simultaneous use of parlodela with vasoconstrictive drugs.
In clinical studies, the number of patients aged 65 years and older was not sufficient to perform a comparative evaluation of the efficacy of Parlodel treatment in younger patients. However, in clinical trials and medical practice, the tolerability of the drug in patients older than 65 years and younger was the same. It is necessary to take into account the difficult predictable tolerability of the drug in this category of patients.
During Parlodel treatment, careful monitoring of patients with a history of peptic ulcer is necessary.
A careful examination and monitoring of patients with pleuropulmonary diseases of unclear etiology and discontinuation of Parlodel therapy in the course of progression of the disorders is necessary.
For early diagnosis of retroperitoneal fibrosis reversible initial stage of the process the doctor recommended monitor symptoms such as back pain, lower extremity edema, renal dysfunction. Parlodel В® should be canceled when the confirmed fibrotic changes in the retroperitoneum or suspected their presence.
Application of prolactin adenomas
in patients with macroadenomas pituitary hypopituitarism may experience symptoms as a result of compression or destruction of pituitary tissue, so before Parlodel appointment should conduct a full functional assessment of pituitary and assign the appropriate replacement therapy. In patients with secondary adrenal insufficiency should be carried out substitution therapy GCS.
Patients with pituitary macroadenomas should continually assess the dynamics of the size of the tumor. By increasing the possible application of surgical tumor therapies. Careful surveillance of pregnant patients, previously treated with Parlodel В® over the prolactin pituitary adenoma, as during pregnancy may increase the size of the tumor. In these patients, treatment Parlodel often leads to reduction in size of the tumor and fast positive dynamics from defects of fields of view. In severe cases, the development of compression of the optic or other cranial nerves is possible to conduct emergency surgery on the pituitary gland.
Makroprolaktinom known complication is loss of visual fields. Effective treatment of hyperprolactinemia Parlodel reduces and eliminates the violation of the visual fields. However, some patients may be secondary changes of the fields, despite the normalization of prolactin levels and tumor shrinkage. This may be due to displacement of the optic chiasm down by the release amount in sella. In this case, reduction in the dose of bromocriptine, which leads to an increase in prolactin levels and an increase to some extent in tumor size may help to eliminate defects in the visual field. In this context, field monitoring of patients macroprolactinoma indicated for the early detection of secondary loss of visual fields,caused by protrusion of the space in the cavity of the optic chiasm seat and adaptation to a given dose of drug action. In some patients with prolactin secreting adenomas, taking ParlodelВ® , there were cases cerebrospinal rhinorrhea. According to the results of clinical studies cerebrospinal rhinorrhea may be caused by a decrease in volume of invasive tumors. Patients with rare hereditary forms of galactose intolerance, severe lactase deficiency, glucose-galactose malabsorption should not take Parlodel В® .
Use in Pediatrics
Efficacy and safety of the drug Parlodel В® have been established for children over 7 years and adolescents with prolactinomas and acromegaly. In clinical trials and medical practice tolerability in adults and children is the same. It should be taken into account are difficult to predict sensitivity to the drug in these patients.
Impact on the ability to drive vehicles and manage mechanisms
Patients receiving Parlodel В® , must be particularly careful when road management or operation of the mechanisms, since against application of the preparation, especially during the first days of treatment, may develop hypotension, resulting in poor reaction rates.
During treatment parlodel marked somnolence and episodes of sudden sleep, especially in patients with Parkinson's disease. Sudden episodes of falling asleep on the background of daily wakefulness arise without preceding sleepiness occurred rarely. Before the appointment of Parlodel the doctor should inform the patient about these risk factors and recommend to refrain from driving vehicles, control mechanisms, as well as training in other potentially hazardous activities that require attention and speed of reaction. If severe drowsiness or sudden sleep episodes appearance, should reduce the dose or cancel it completely.
OVERDOSE
Symptoms: in all cases, when the overdose occurred only parlodel deaths were observed. The maximum single dose taken Parlodel known to date is 325 mg. In case of overdose observed nausea, vomiting, dizziness, hypotension, postural hypotension, tachycardia, drowsiness, somnolence, lethargy, hallucinations.
When accidentally taking Parlodel inside kids (isolated reports) noted the development of vomiting, fever and drowsiness. Improvement of patients occurred spontaneously after a few hours or after appropriate therapy.
Treatment:In case of overdose it is recommended to take the activated carbon; possible to conduct gastric lavage immediately after ingestion. symptomatic treatment of acute poisoning. For the relief of emesis or hallucinations can be assigned to metoclopramide.
DRUG INTERACTION
Bromocriptine is both a substrate and inhibitor of isozyme CYP3A4. Caution must be exercised while appointing bromocriptine and other inhibitors and / or CYP3A4 substrates (azole antifungal agents, HIV protease inhibitors). Simultaneous administration of macrolide antibiotics and Parlodel (erythromycin or josamycin) causes an increase in the bromocriptine concentration in blood plasma. Concomitant use of octreotide and bromocriptine in patients with acromegaly is accompanied by an increase in the level of the latter in the blood plasma.
Therapeutic efficacy bromocriptine, related to the stimulation of central dopamine receptors, may be reduced when used dopamine receptor antagonists, such as neuroleptics (phenothiazines, butyrophenones and thioxanthenes), as well as metoclopramide and domperidone.
Simultaneous administration Parlodel with antihypertensive drugs can lead to increased severity of reducing blood pressure.
Parlodel В® can be administered either as monotherapy or in combination with other antiparkinsonian drugs (both early and late stages of the disease). Combination with levodopa leads to increased protivoparkinsonicheskogo action, which often makes it possible to reduce the dose of levodopa. The use of Parlodel in patients receiving treatment with levodopa, especially useful with the weakening of the therapeutic effect of levodopa or developing complications such as abnormal involuntary movements (choreo-athetoid dyskinesia and / or painful dystonia), wasting syndrome effect by the end of the action of levodopa dose, the phenomenon of "vklyucheniya- off "(on-off).
Possible deterioration tolerability in patients receiving Parlodel ethanol.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be kept out of the reach of children, protected from light at a temperature not higher than 25 В° C. Shelf life - 3 years.
