Kaʙergolin (When ATH G02CB03)
When ATH:
G02CB03
Characteristic.
White powder. Soluble in ethanol, xloroforme, N,N-dimethylformamide, sparingly soluble in 0,1 n. hydrochloric acid, slightly soluble in n-hexane, insoluble in water.
Pharmacological action.
Gipoprolaktinemicheskoe.
Application.
According to Physicians Desk Reference (2005), cabergoline is indicated for hyperprolactinemia, idiopathic or caused by a pituitary adenoma.
Contraindications.
Hypersensitivity (incl. to derivatives of ergot alkaloids), uncontrolled hypertension, symptoms of dysfunction of the heart and breathing due to fibrosis or the presence of such symptoms in history.
Restrictions apply.
Arterial hypertension, associated with pregnancy (eclampsia, preэklampsiya), concomitant use of dopamine antagonists D2-receptors, means, having hypotensive effect, abnormal liver function, childhood (Safety and efficacy have not been established).
Pregnancy and breast-feeding.
If pregnancy should be used with caution, if the expected benefit to the mother outweighs the potential risk to the fetus (adequate controlled trials of cabergoline in pregnant women has not been). Patients should be warned of the need to inform the physician about the planned, alleged pregnancy or held to decide on the continuation or termination of therapy.
Category actions result in FDA - B. (The study of reproduction in animals revealed no risk of adverse effects on the fetus, and adequate and well-controlled studies in pregnant women have not done.)
Investigation of the effect of cabergoline on reproductive function was conducted in mice, rats and rabbits, receiving his gavage, inserted through the nose. Mice, treated with cabergoline in the dose to 8 mg / kg / day (55-fold excess MRDC) during the period of organogenesis, marked toxic effect on the mother's body; teratogenic effects were observed. Rats, receiving 0,012 mg/kg/day kabergolina (about 1/7 MRDC) during the period of organogenesis, was an increase in post-implantation loss embriofetalnyh. In rabbits with the introduction of kabergolina during the period of organogenesis at dose 0,5 mg / kg / day (19 MRDC) marked toxic effect on the mother's body (weight loss and exhaustion). At a dose of 4 mg / kg / day (150 MRDC) increased incidence of various fetal malformations. However, in other studies at doses up to kabergolina 8 mg / kg / day (300 MRDC) malformations in rabbits, embrio- and foetotoxic effects were noted. Radiological studies in pregnant female rats showed a high concentration of cabergoline and its metabolites in the uterine wall and the lack of their accumulation in the tissues of the fetus. With the rats at doses of kabergolina more 0,003 mg / kg / day (1/28 MRDC) for 6 days before the birth and during lactation slows the growth of newborns, there have been cases of deaths due to reduced secretion of milk.
Unknown, whether cabergoline allocated to breast milk in humans. Cabergoline, and its metabolites were found in the breast milk of lactating rats. Because many drugs are excreted in the milk of women and possibly serious adverse effect on the infant cabergoline, should decide whether to terminate breast-feeding, or refuse to accept the cabergoline (given the degree of need of the drug to the mother).
Side effects.
Safety of Cabergoline was studied in more than 900 patients with hyperprolactinemia; the severity of most adverse events were mild or moderate. The 4-week double-blind, placebo-controlled study, patients received fixed-dose cabergoline 0,125, 0,5, 0,75 and 1,0 mg twice a week; dose were halved in the first week. We note the following side effects (next to the percentage of occurrence of this side effect in the group of cabergoline, in parentheses in the placebo group):
From the nervous system and sensory organs: headache 26% (25%), dizziness 15% (5%), vertigo 1% (0%), paraesthesia 1% (0%), drowsiness 5% (5%), depression 3% (5%), nervousness 2% (0%), asthenia 9% (10%), fatiguability 7% (0%), blurred vision 1% (0%).
Cardio-vascular system and blood (hematopoiesis, hemostasis): orthostatic hypotension 4% (0%).
On the part of the digestive tract: dyspepsia 2% (0%), nausea 27% (20%), vomiting 2% (0%), constipation 10% (0%), abdominal pain 5% (5%).
Other: hot flashes 1% (5%), breast pain 1% (0%), dysmenorrhoea 1% (0%).
Safety of Cabergoline was investigated in controlled and uncontrolled trials in approximately 1200 patients with Parkinson's disease, receiving cabergoline doses, far exceeding MRDC for patients with hyperprolactinemia (to 11,5 mg / day). These patients were additionally identified side effects, how dyskinesia, hallucinations, confusion, peripheral edema. Rarely observed heart failure, pleural effusion, lyegochnyi fibrosis, a stomach ulcer or duodenal ulcer, there is a report of one case of constrictive pericarditis.
In post-marketing studies registered the following adverse reactions, associated with the use of cabergoline (cm. Precautions): valvulopatyya, fibrous, hypersexuality, increased libido, alopecia, aggressiveness.
Cooperation.
It should not be used in conjunction with antagonists of dopamine D2-receptors (phenothiazines, butyrofenona, thioxanthen, metoclopramide). Simultaneous treatment with drugs, having a high degree of binding to plasma proteins, unlikely to be affected by the connection of cabergoline plasma proteins. Caution should be used simultaneously with the means, having hypotensive effect.
Overdose.
Symptoms: nasal congestion, fainting, hallucinations.
Treatment: symptomatic, maintaining blood pressure.
Dosing and Administration.
Inside, at an initial dose 0,25 mg 2 times a week. Possibly increasing doses up to 1 mg 2 times a week (under the control of plasma prolactin). The dose is increased no more, once a 4 Sun. If the normal level of plasma prolactin maintained during 6 Months, Treatment can be stopped, However, it should regularly monitor the content of prolactin, if necessary, to resume therapy. The effectiveness of therapy lasting more than 24 Months not installed.
Precautions.
Valvulopatyya. Cases of cardiac valvulopatii have been reported in patients, long treated with high doses of cabergoline (>2 mg / day) in the treatment of Parkinson's disease. Rare cases have been reported in connection with the short-term treatment (<6 Months) or in patients, receiving low doses in the treatment of hyperprolactinemia.
Doctors should prescribe the lowest effective dose of cabergoline for the treatment of hyperprolactinemia, and periodically evaluate the need to continue this therapy. Besides, patients, receiving long-term treatment, A periodic monitoring of the heart, incl. echocardiography. Any patient, which during treatment with cabergoline develop signs or symptoms of heart disease, incl. breathlessness, swelling, congestive heart failure or re-appearing heart murmur, It should be examined for possible valvulopatii.
Cabergoline should be used with caution in patients with existing hemodynamically significant valve disease or are taking other drugs, associated with valvulopatiey.
Fibrous. As with other ergot derivatives, chronic administration of cabergoline have been reported cases of pleural effusion or pulmonary fibrosis (Some messages were from patients, who had previously been treated ergotaminovymi dopamine agonists). Cabergoline should not be used in patients with signs and / or clinical symptoms of respiratory or cardiac disorders, fibrosis associated with tissue, history of or currently. Reported, after diagnosis of pleural effusion or pulmonary fibrosis and thereby stopping treatment with cabergoline, showed improvement of symptoms.
It was found, that the rate of erythrocyte sedimentation rate was abnormally increased in association with pleural effusion / fibrosis. In cases of unexplained ESR it is recommended to increase the chest x-ray. Besides, measurement of serum creatinine can also help in the diagnosis of fibrotic disorders.
Use of cabergoline in the initial dose, exceeding 1,0 mg, may cause orthostatic hypotension. Cabergoline is not intended to inhibit or suppress physiological lactation (Use of bromocriptine for that purpose associated with the risk of hypertension, stroke, seizures). It should be used with caution in elderly cabergoline, given the likelihood of liver function abnormalities, kidney, hearts, and comorbidities and used in connection with drugs.
