Parlodel

Active material: Bromocriptine
When ATH: G02CB01
CCF: The inhibitor of prolactin secretion. Of anti-drug
ICD-10 codes (testimony): D35.2, E22.0, E22.1, E28.2, E28.3, G20, G21, N46, N60, N61, N64.4, N91, N94.3, N97
When CSF: 02.06.01.02
Manufacturer: MEDA AB (Sweden)

Pharmaceutical form, composition and packaging

Pills nearly white, round, flat, with a beveled edge, risks and code “XC” on one side, with an inscription “SANDOZ” – another.

Excipients: colloidal silicon dioxide, disodium эdetat, magnesium stearate, maleic acid, pregelatinized corn starch, corn starch, lactose monohydrate.

10 PC. – blisters (3) – packs cardboard.
30 PC. – vials of dark glass (1) – packs cardboard.

Pharmacological action

The stimulator of dopamine receptors. It inhibits the secretion of the hormone of the anterior pituitary – prolactin, without affecting the normal content of other pituitary hormones. However Parlodel^® able to reduce elevated levels of growth hormone in patients with acromegaly. This effect is due to stimulation of dopamine receptors.

In the postpartum period, prolactin is necessary to initiate and sustain lactation. At other times of life increase prolactin secretion leads to pathological lactation (galaktoree) and / or disorders of ovulation and the menstrual cycle.

Parlodel^®, as a specific inhibitor of prolactin secretion, It can be used for the prevention or suppression of physiological lactation, and for the treatment of pathological conditions, caused by hypersecretion of prolactin. When amenorrhea and / or anovulatory menstrual cycles (accompanied or not by galactorrhea) Parlodel^® It can be used to restore the menstrual cycle and ovulation.

When using Parlodel^® suppression of lactation there is no need to limit the consumption of fluid. Besides, Parlodel^® It does not violate the postpartum involution of the uterus and does not increase the risk of thromboembolism.

Parlodel^® growth stops or reduces the size of prolactin pituitary adenomas (prolactin).

In patients with acromegaly, in addition to reducing the concentration of growth hormone and prolactin in plasma, Parlodel^® positive effect on the clinical manifestations and glucose tolerance.

In Parkinson's disease, characterized by a specific deficiency of dopamine in the striatum and black nuclei of the brain, Stimulation parlodel^® dopamine receptors can restore the neurochemical balance in the basal ganglia.

Patients with Parkinson's disease bromocriptine is usually prescribed at higher doses, than those applied by endocrinological indications.

Parlodel^® reduces tremors, rigidity, slowness of movement and other symptoms of Parkinson's disease at all stages of the disease. Efficacy is usually kept for many years (so far good results of therapy are described in the duration of treatment, reach 8 years).

Parlodel^® It reduces the severity of symptoms of depression in patients with Parkinson's. This is due to its inherent antidepressant properties, confirmed in controlled studies in patients with endogenous or psychogenic depression, not suffering from Parkinson's.

Prolaktinsnizhayuschy effect begins 1-2 hours after oral administration, peaks (a reduction in the concentration of prolactin, than 80%) through 5-10 h, and remained at close to the maximum level for 8-12 no.

Pharmacokinetics

Absorption

After oral administration of bromocriptine is well absorbed from the gastrointestinal tract. In healthy volunteers after oral administration of Parlodel^® in the form of tablets period of bromocriptine poluabsorbtsii 0.2-0.5 no, C_max It reached within 1-3 no. When administered at a dose of bromocriptine 5 mg C_max is 0.465 ng / ml.

Distribution

Plasma protein binding is 96%.

Metabolism

Bromocriptine subjected to intensive metabolism in the “first pass” through the liver with the formation of a number of metabolites. The urine and feces unchanged bromocriptine is virtually absent. Bromocriptine has a high affinity for CYP3A . The main route of metabolism is the hydroxylation of proline ring as part of the cyclopeptide.

Bromocriptine is a strong inhibitor of CYP3A4 with the calculated value of IC 50 1.69 mmol. However, due to the low therapeutic concentrations in the blood of free bromocriptine, It does not expect significant changes in the metabolism of the drugs at the same time, clearance are carried out by the participation of CYP3A4.

Deduction

Excretion of unchanged bromocriptine plasma is bi-phase, final T_1/2 is about 15 no (from 8 to 20 no). Bromocriptine and its metabolites are almost completely removed through the liver, only 6% of the dose is excreted by the kidneys.

Pharmacokinetics in special clinical situations

In patients with impaired liver function the elimination rate may be reduced bromocriptine, and plasma levels – increase, which requires correction dosing regimen.

The simultaneous use of inhibitors and / or potential substrates CYP3A4 may decrease clearance and increase bromocriptine its concentration in blood plasma.

Testimony

Menstrual irregularities, anogyny

Prolaktinzavisimye diseases and conditions, accompanied or not by hyperprolactinemia:

- Amenorrhea (accompanied and not accompanied by galactorrhea), spanomenorrhea;

- Failure of the luteal phase;

- Secondary hyperprolactinemia, drug-induced (eg, some psychotropic or antihypertensive agents).

Prolaktinnezavisimoe female infertility:

- Polycystic Ovarian Syndrome;

- Anovulatory cycles (in addition to antiestrogens, such as clomiphene).

Hyperprolactinemia in men

- Prolaktinzavisimy hypogonadism (oligospermatism, loss of libido, impotence).

Prolaktinomy

- Conservative treatment of micro prolactin- and pituitary macroadenomas;

- Preoperative preparation to reduce the tumor volume and facilitate its removal;

- Aftercare, if prolactin levels remain elevated.

Akromegalija

- As a further means or, in special cases, as an alternative to surgical or radiation treatment.

Suppression of lactation

- Prevention or termination of postpartum lactation for medical reasons, incl. at the initial stage of postpartum mastitis.

- Prevention of lactation after abortion.

Parkinson's Disease

- All stages of idiopathic Parkinson's disease and parkinsonism postentsefaliticheskogo – or as monotherapy, or in combination with other antiparkinsonian agents.

Dosage regimen

Parlodel^® is taken orally with meals.

Menstrual irregularities, anogyny

Assign 1.25 mg (1/2 tab.) 2-3 times / day; If the therapeutic effect is insufficient, the dose is gradually increased until 5-7.5 mg / day (the multiplicity of reception 2-3 times / day).

Treatment is continued until the normalization of the menstrual cycle and / or restoration of ovulation.

If necessary to prevent a recurrence treatment can continue for several cycles.

Hyperprolactinemia in men

Assign 1.25 mg (1/2 tab.) 2-3 times / day, gradually increasing the dose to 5-10 mg (2-4 tab.) per day.

Prolaktinomy

Assign 1.25 mg (1/2 tab.) 2-3 times / day with a gradual increase in dose and dose selection, ensuring an adequate reduction in the concentration of prolactin in plasma. The maximum recommended dose Children and adolescents 7-12 years is 5 mg / day, aged 13-17 years – 20 mg.

Akromegalija

The initial dose is on 1.25 mg (1/2 tab.) 2-3 times / day, further, depending on the clinical effect and tolerability, daily dose is gradually increased until 10-20 mg (4-8 tab.). The maximum recommended dose Children and adolescents 7-12 years is 10 mg / day, aged 13-17 years – 20 mg.

Inhibition of lactation for medical reasons

On the first day appoint 1.25 mg (1/2 tab.) 2 times (during meals for breakfast and dinner), then for 14 days – by 2.5 mg (1 tab.) 2 times / day. To preventing the onset of lactation the drug should be started within a few hours after childbirth or abortion, however, only after the stabilization of vital functions. Through 2 or 3 the day after the drug is sometimes a slight secretion of milk. It can be eliminated, resuming the drug at the same dose for a further 1 of the week.

Nachinayushtiysya poslerodovыy mastitis

On the first day appoint 1.25 mg (1/2 tab.) 2 times (during meals for breakfast and dinner), then for 14 days – by 2.5 mg (1 tab.) 2 times / day. Additionally prescribe antibiotics.

Parkinson's Disease

In order to ensure optimal tolerability during the first weeks of treatment should start with a low dose 1.25 mg (1/2 tab.) 1 time / day (preferably in the evening). For the selection of individual minimum effective dose should be increased slowly, titration: every week daily dose increased by 1.25 mg; the daily dose is divided into 2-3 admission. Adequate therapeutic response is achieved on average over 6-8 weeks of treatment. In the absence of clinical effect after 6-8 weeks of use, perhaps, further increase in the daily dose 2.5 mg weekly.

Typically, the therapeutic dose range of bromocriptine for mono- or combination therapy is from 10 mg 40 mg per day, however, some patients may need higher doses.

If the selection of doses adverse reactions occur, the daily dose should be reduced and maintained at a lower level of at least 1 of the week. When coping with side effects, the dose can be increased again.

Patients with movement disorders in patients receiving levodopa is recommended before the application of Parlodel^® reduce the dose of levodopa. After reaching a satisfactory clinical effect in the treatment Parlodel^® can be carried out further gradual reduction in the dose of levodopa. Some patients, taking Parlodel^®, possible the complete abolition of levodopa.

Side effect

Determination of the frequency of adverse reactions: Often (≥ 1/10); often (≥ 1/100, < 1/10); sometimes (≥ 1/1000, < 1/100); rarely (≥ 1/10 000, < 1/1000); rarely (< 1/10 000), including isolated reports.

From the central and peripheral nervous system often – headache, dremota, dizziness; sometimes – movement disorders, confusion, psychomotor agitation, hallucinations; rarely – drowsiness, paresthesia, psychotic disorders, insomnia; rarely – increased libido, hypersexuality, Increased daytime sleepiness, suddenly falling asleep.

From the senses: rarely – blurred vision, “blurred vision”, noise in ears.

Cardio-vascular system: sometimes – hypotension, orthostatic hypotension (very rarely leading to fainting); rarely – pericardial effusion, constrictive pericarditis, tachycardia, bradycardia, arrhythmia; rarely – fibrosis of the heart valves, reversible pallor of the fingers and toes, induced hypothermia (especially in patients with Raynaud's syndrome history).

The respiratory system: often – nasal congestion; rarely – pleural effusion, plyevralinyi fibrosis, pleurisy, lyegochnyi fibrosis, breathlessness.

From the digestive system: often – nausea, constipation, vomiting; sometimes – dry mouth; rarely – diarrhea, abdominal pain, ryetropyeritonyealinyi fibrosis, ulcerative lesions of the gastrointestinal tract , gastrointestinal bleeding (black stools, blood in vomit).

Dermatological reactions: sometimes - Hair Loss.

Allergic reactions: sometimes – cutaneous manifestations.

On the part of the musculoskeletal system: sometimes – leg cramps.

Other: sometimes – fatigue; rarely – peripheral edema; rarely – in the case of abrupt withdrawal of Parlodel^® Development status, shodnogo with NMS .

When using Parlodel^® high dose (as well as other dopamine agonists) In rare cases, there is a reversible change in sexual behavior, increased libido and hypersexuality, disappears after reducing the dose or treatment discontinuation.

Application of Parlodel^® to suppress physiological lactation in the postpartum period, in rare cases accompanied by the development of hypertension, myocardial infarction, seizures, stroke or mental disturbances.

Contraindications

- Uncontrolled hypertension;

- Gestosis (incl. eclampsia, preэklampsiya);

- Hypertension during pregnancy and the postpartum period;

- Ischemic heart disease and other serious cardiovascular disease;

- Severe mental disorder at the moment and / or a history of;

- Children up to age 7 years (limited experience with the drug);

- Hypersensitivity to the drug;

- Hypersensitivity to ergot alkaloids.

Not recommended for the treatment of premenstrual syndrome and benign breast diseases in connection with a limited amount of clinical data.

Pregnancy and lactation

After receiving confirmation of planned pregnancy Parlodel^®, as well as other drugs, should be abolished except where the need to continue therapy for medical reasons. Cancel Parlodel^® during pregnancy does not increase the frequency of its spontaneous abortion. Clinical experience shows, that the use of Parlodel^® Pregnancy does not adversely impact on the outcome of current or. If you cancel Parlodel^® in pregnant women with pituitary adenoma is necessary to carry out careful monitoring of the patients throughout the duration of pregnancy. If signs of a marked increase prolactinoma, eg, headaches or visual field loss, Parlodel treatment^® It can be resumed, or surgery performed.

When lactation Parlodel^® used according to indications. The drug suppresses lactation, so it is not prescribed for lactating mothers.

Treatment Parlodel^® can restore fertility. Therefore women of childbearing age, I do not wish to become pregnant, you must use reliable methods of contraception.

Cautions

Women with abnormal, not associated with hyperprolactinemia, Parlodel^® should be administered in an effective minimum dose, necessary for the relief of symptoms. This is important to prevent the fall of the concentration of prolactin in plasma below norm, leading to dysfunction of the corpus luteum.

Women, taking Parlodel^® in the postnatal period for suppression of lactation, noted rare cases of serious adverse reactions: arterial hypertension, myocardial infarction, convulsions, stroke or mental disturbances. Some patients develop seizures or cerebrovascular events were preceded by severe headache and / or transient visual disturbances. Although a causal relationship between these reactions taking Parlodel^® not installed, female, taking the drug in the postnatal period for suppression of lactation, as well as in patients, receiving Parlodel^® any other indications, blood pressure should be monitored. With the development of hypertension or severe, progressive or persistent headache (accompanied and not accompanied by visual impairment), or signs of CNS side effects Parlodel^® should be discontinued immediately and the patient to conduct a survey. Particular caution is required to comply with the appointment of Parlodel^® patients, It turns out recently or continue to take drugs, affecting blood pressure, eg, vasoconstrictors (sympathomimetics or ergot alkaloids, including ergometrine or metilergometrin). The women in the postpartum period is not recommended simultaneous use Parlodel^® with vasoconstrictor agents.

In clinical studies, the number of patients aged 65 and older was not sufficient for a comparative evaluation of the effectiveness of treatment parlodel^® younger patients. However, clinical trials and medical practice tolerability in patients over 65 years and younger age groups were similar. Keep in mind it is difficult to predictable tolerability in these patients.

During treatment parlodel^® Careful monitoring of patients, with a history of peptic ulcer disease.

Careful examination and monitoring of patients with pleuropulmonary disease of unknown etiology, and cessation of therapy parlodel^® the progression of disorders.

For early diagnosis of retroperitoneal fibrosis at an early stage of the process reversible doctor recommended to monitor symptoms such, pain in the back, lower extremity edema, renal dysfunction. Parlodel^® should be canceled upon confirmation of fibrotic changes in the retroperitoneum or suspected their presence.

Application of prolactin adenomas

In patients with pituitary macroadenomas signs of hypopituitarism may experience 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 replacement therapy should be carried GCS.

In patients with pituitary macroadenomas should continually assess the dynamics of the size of the tumor. With increasing tumor may use surgical treatments. Careful monitoring of pregnant patients, naïve Parlodel^® about prolactin pituitary adenoma, as during pregnancy may increase the size of the tumor. In these patients, treatment parlodel^® often leads to tumor shrinkage and rapid positive trend on the part of the visual field defects. In severe cases, the development of compression of the optic or other cranial nerves may conduct emergency surgery on the pituitary gland.

It is a known complication makroprolaktinom loss of visual fields. Effective treatment parlodel^® hyperprolactinemia reduces and eliminates the breach of the visual field. Nonetheless, some patients may be secondary changes in visual fields, despite the normalization of prolactin levels and tumor shrinkage. This may be due to the displacement of the optic chiasm down, due to the release of the volume in the sella. In this case, reduction in the dose of bromocriptine, leads to increased prolactin levels and an increase to some extent in tumor size, can help to eliminate defects of fields of vision. In this regard,, Monitoring of visual fields in patients macroprolactinoma indicated for the early detection of secondary loss of visual fields, caused by spatial protrusion of the optic chiasm into the cavity of the saddle and adaptation to the action of the drug dose. In some patients with prolactin adenomas, taking Parlodel^®, there have been cases of cerebrospinal rhinorrhea. According to the results of clinical trials cerebrospinal rhinorrhea may be caused by the decline in invasive tumors. Patients with rare hereditary form of galactose intolerance, severe lactase deficiency, glucose-galactose malabsorption, should not take Parlodel^®.

Use in Pediatrics

The efficacy and safety of the drug Parlodel^® They have been established for older children 7 years and adolescents with prolactinomas and acromegaly. In clinical trials and medical practice tolerability in adults and children it was the same. Keep in mind difficult to predict sensitivity to the drug in these patients.

Effects on ability to drive vehicles and management mechanisms

Patients, receiving Parlodel^®, Be particularly careful when driving or operating machinery, tk. during treatment with the drug, especially during the first days of treatment, may develop hypotension, leading to reduced reaction rates.

During treatment parlodel^® marked sleepiness and episodes of sudden sleep, particularly in patients with Parkinson's disease. The episodes of sudden sleep on the background of daily wakefulness, occur without prior sleepiness, occurred rarely. Before the appointment of Parlodel^® the physician should inform the patient about these risk factors and recommend to refrain from driving vehicles, Control mechanisms, as well as the other classes of potentially hazardous activities, require attention and speed of reaction. If severe drowsiness or sudden occurrence of episodes of falling asleep, dose should be reduced or completely cancel it.

Overdose

Symptoms: in all cases, When overdose occurred only parlodel^® deaths were observed. The maximum single dose taken Parlodel^®, known today, is 325 mg. In case of overdose have been observed nausea, vomiting, dizziness, hypotension, postural hypotension, tachycardia, dremota, drowsiness, lethargy, hallucinations.

If you accidentally taking Parlodel^® inside children (individual messages) It noted the development of vomiting, fever and drowsiness. Improving the condition of patients occurred spontaneously or after a few hours of appropriate therapy.

Treatment: In case of overdose it is recommended to take activated charcoal; possible to carry out gastric lavage immediately after ingestion. Symptomatic treatment of acute poisoning. For relief of vomiting or hallucinations can be assigned metoclopramide.

Drug Interactions

Bromocriptine is both a substrate and inhibitor of CYP3A4. Caution should be exercised with concomitant administration of bromocriptine and other inhibitors and / or substrates of CYP3A4 (azole antifungals, HIV protease inhibitors). Simultaneous treatment with macrolide antibiotics and Parlodel^® (erythromycin or josamycin) bromocriptine causes an increase in the concentration in blood plasma. Simultaneous application of octreotide and bromocriptine in patients with acromegaly is accompanied by increasing levels of the latter in the blood plasma.

Therapeutic efficacy bromokrintina, associated with the stimulation of central dopamine receptors, It can be reduced by the use of dopamine receptor antagonists, such as neuroleptics (fenotiazinы, butyrophenones and thioxanthine), and metoclopramide and domperidone.

Co-administration of Parlodel^® with antihypertensive drugs can lead to increased severity of BP reduction.

Parlodel^® It can be administered either as monotherapy, or in combination with other antiparkinsonian (as early, and late stages of the disease). Combination with levodopa leads to increased action protivoparkinsonicheskogo, which often makes it possible to reduce the dose of levodopa. Application of Parlodel^® patients, receiving treatment with levodopa, particularly useful with the weakening of the therapeutic effect of levodopa or developing complications such as pathological involuntary movements (Chorea-Athetoid dyskinesia and / or painful dystonia), wasting syndrome effect by the end of the action dose of levodopa, phenomenon “on-off” (on-off).

Possible deterioration of portability Parlodel^® while taking ethanol.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

The drug should be stored out of reach of children, dark place at a temperature no higher than 25 ° C. Shelf life – 3 year.