Cabergoline (Cabergolinum)

Pharmacodynamics Pharmacokinetics Indications Carefully Contraindications Dosing and Administration Side effects
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Clinical and pharmacological group: & nbsp

Dopaminomimetics

Included in the formulation
  • Agalates
    pills inwards 
    Teva Pharmaceutical Enterprises Co., Ltd.     Israel
  • Bergolak
    pills inwards 
    VEROPHARM SA     Russia
  • Dostinex®
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    Pfizer Italy Sr.L.     Italy
  • Cabergoline
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    OBNINSKAYA CHEMICAL - PHARMACEUTICAL COMPANY, CJSC     Russia
    • АТХ:

    G.02.C.B.03   Cabergoline

    Pharmacodynamics:

    It is an agonist of long-acting dopamine receptors. Has a high affinity for D2dopamine receptors, low - to D1dopamine, alpha1- and alpha2-adrenergic, 5-HT1- and 5-HT2-serotonin receptors. Pharmacological action - hypoprolactinemic.

    Pharmacokinetics:

    After oral administration cabergoline quickly absorbed from the digestive tract. Cmax in blood plasma is achieved in 0.5-4 hours. Food has no effect on the absorption or distribution of cabergoline. Pharmacokinetics has a linear character up to a dose of 7 mg per day.

    The binding of cabergoline (at a concentration of 0.1-10 ng / ml) with plasma proteins is 41-42%. In the urine, cabergoline metabolites are found: 6-allyl-8β-carboxy-ergoline in an amount of 4-6% of the dose taken, as well as three other metabolites with a total content of less than 3%. All metabolites to a much lesser extent (in comparison with cabergoline) inhibit the secretion of prolactin. Cabergoline has a long half-life. Half-life in healthy volunteers is 63-68 hours, in patients with hyperprolactinemia - 79-115 hours. With this half-life the equilibrium state is reached after 4 weeks.

    In urine and feces 18% and 72% of the dose respectively. The content of unchanged cabergoline in urine is 2-3%.

    Indications:

    Hyperprolactinemia (macro- and microadenomas of the pituitary gland, idiopathic hyperprolactinemia). Prevention or suppression of physiological lactation in the postpartum period.

    ICD-10

    IV.E20-E35.E22.1   Hyperprolactinemia

    Contraindications:

    Pronounced violations of the liver, pregnancy, postpartum psychosis in history, lactation, hypersensitivity to cabergoline and ergot alkaloids.

    Carefully:

    Arterial hypertension associated with pregnancy (eclampsia, pre-eclampsia), simultaneous administration of dopamine D antagonists2-receptors, drugs with antihypertensive effect, impaired liver function, children's age (safety and efficacy not established).

    Pregnancy and lactation:

    FDA Action Category - B.

    Contraindicated in pregnancy and during breastfeeding.

    Pregnancy should be excluded before taking the drug.It is recommended to avoid pregnancy during at least 1 month after discontinuation of treatment.

    Dosing and Administration:

    Intended for oral administration. To prevent lactation - once on the first day after childbirth at a dose of 1 mg. To suppress the already available lactation - for two days to 250 mcg every 12 h. In the treatment of hyperprolactinemia, doses are selected individually. The initial dose is usually 500 μg per week, usually in a single dose (sometimes in the form of two divided doses). In the future, if necessary, the dose is gradually increased - by 500 mcg per week at an interval of 1 month. Usually, the therapeutic dose is 1-2 mg per week, in some cases it can be increased to 4.5 mg per week. If the weekly dose exceeds 1 mg, then it is recommended to divide it into 2 divided doses. In some cases, an effective dose of 250-500 μg per week is effective.

    Side effects:

    When used to prevent or suppress lactation, mild dizziness, headache, nausea, abdominal pain, drowsiness, and some reduction in blood pressure are possible.

    With a systematic use (hyperprolactinemia), nausea, headache,dizziness, asthenia, dyspepsia, abdominal pain, gastritis, constipation, vomiting, "hot flashes", soreness of the mammary glands, paresthesia, lowering blood pressure, depression.

    Overdose:

    Symptoms: congestion of the nose, fainting, hallucinations.

    Treatment: symptomatic, maintenance blood pressure.

    Interaction:

    Neuroleptics and dopamine antagonists (metoclopramide) - a decrease in their effectiveness and deterioration of the condition. It is necessary to adjust the dose of each drug.

    In the combined use of amisulpride with cabergoline, when used not for the treatment of Parkinson's disease, there is a mutual antagonism between the dopaminergic receptor agonist and the neuroleptic. Cabergoline can cause or exacerbate psychotic symptoms. Amisulpride can enhance the symptoms of Parkinson's disease (the combination is contraindicated).

    In clinical studies in patients with Parkinson's disease, no pharmacokinetic interaction between cabergoline and levodopa has been detected.

    Because the cabergoline has a therapeutic effect by direct stimulation of dopamine receptors, it can not be administered concomitantly with metoclopramide (a dopamine D antagonist2-receptors), since it can weaken the hypoprolactinemic effect of cabergoline.

    With the combined use of periciazine with cabergoline - a dopaminergic agonist - a mutual antagonism between cabergoline and pericyazin. Cabergoline can exacerbate psychotic disorders. The combined use of pericyazine and cabergoline is contraindicated (except for their use in patients with Parkinson's disease). If patients with Parkinson's disease who receive cabergoline, treatment with pericyazine is required, then cancellation of cabergoline should be effected by gradual reduction of doses (sudden cancellation may increase the risk of malignant neuroleptic syndrome).

    In clinical studies in patients with Parkinson's disease, no pharmacokinetic interaction between cabergoline and selegiline was detected.

    Cabergoline, like other ergot derivatives, can not be used concomitantly with erythromycin, as this can lead to an increase in the systemic bioavailability of cabergoline.

    Special instructions:

    They are used with caution in patients with cardiovascular diseases, Raynaud's syndrome, impaired renal function,peptic ulcer of the stomach and duodenum, gastrointestinal bleeding, serious mental illness in the anamnesis, and also with treatment with antihypertensive drugs.

    For the prevention (suppression) of lactation is not recommended in patients with preeclampsia, as well as with postpartum hypertension.

    It is not recommended to apply simultaneously with antibiotics macrolides (including erythromycin), as the bioavailability of cabergoline and the severity of its side effects increase.

    It is not recommended simultaneous use with antipsychotic agents, metoclopramide, since, by blocking dopamine receptors, they reduce the effect of cabergoline.

    Combination with ergot alkaloids and their derivatives is not recommended.

    Valvulopathy. Cases of cardiac valvulopathy were reported in patients who received long-term high doses of cabergoline (> 2 mg in dayki) in the treatment of Parkinson's disease. Rare cases have been reported due to short-term treatment (<6 months) or in patients receiving low doses in the treatment of hyperprolactinaemia.

    Doctors should prescribe the lowest effective dose of cabergoline for the treatment of hyperprolactinaemia and periodically assess the need for continuing this therapy. In addition, patients receiving long-term treatment need periodic monitoring of the condition of the heart, including echocardiography. Any patient who develops signs or symptoms of heart disease during treatment with cabergoline, including shortness of breath, swelling, congestive heart failure, or a new heart murmur, should be examined for possible valvulopathy.

    Cabergoline should be used with caution in patients with existing hemodynamically significant valve diseases or taking other drugs associated with valvulopathy.

    Fibrosis. As with other ergot derivatives, prolonged admission of cabergoline, there were cases of pleural effusion or pulmonary fibrosis (some reports were from patients who had previously been treated with ergotamine agonists of dopamine). Cabergoline Do not use in patients with signs and / or clinical symptoms of respiratory or cardiac disorders associated with tissue fibrosis, in the history or at the moment.It is reported that after the diagnosis of pleural effusion or pulmonary fibrosis and as a result of this cessation of cabergoline treatment, symptom improvement was noted.

    It was found that the indicator erythrocyte sedimentation rate was abnormally increased due to pleural effusion / fibrosis. In cases of unexplained increase erythrocyte sedimentation rate X-ray examination of the chest is recommended. In addition, measurement of serum creatinine can also help in the diagnosis of fibrotic disorders.

    The use of cabergoline in an initial dose of more than 1.0 mg may cause orthostatic hypotension. Cabergoline is not intended to inhibit or suppress physiological lactation (use of bromocriptine for this purpose was associated with a risk of hypertension, stroke, seizures). It should be used with caution cabergoline elderly people, given the likelihood of a violation of the liver, kidneys, heart, as well as concomitant pathology and the medicines used in connection with this.

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