Dostinex® - (IR): composition and pharmaceutical form
One tablet contains 0.5 mg of cabergoline. The tablets are divisible, which makes it possible to use a dose of 0.25 mg — precisely the one that lies at the heart of most schemes of use.
The medicine is taken by mouth. Dopaminergic agents are better tolerated when taken together with food, so cabergoline is taken during a meal.
How Dostinex® - (IR) works
Cabergoline is an ergoline derivative with dopaminergic activity. It directly stimulates the D2 dopamine receptors of the cells of the anterior lobe of the pituitary, because of which the secretion of prolactin is inhibited strongly and for a long time. At doses exceeding those needed to lower prolactin, a central dopaminergic action through the same receptors is added.
The effect develops quickly — a fall in the serum prolactin level is noticeable within 3 hours of a single dose of 0.3–1.5 mg. It lasts a long time: up to 7–28 days in healthy volunteers and patients with hyperprolactinaemia and up to 14–21 days in women in the postpartum period. The reason for this duration is the prolonged presence of the substance in the target organ. Both the depth and the length of the fall in prolactin depend on the dose, while on other endocrine functions cabergoline acts very selectively.
Indications
Cabergoline is used to suppress lactation straight after childbirth and to stop a flow of milk that has already begun.
The second direction is the treatment of disorders caused by an excess of prolactin. These include hyperprolactinaemia with disturbances of the menstrual cycle (absence of periods, scanty or irregular periods), absence of ovulation and galactorrhoea, and also pituitary adenoma, idiopathic hyperprolactinaemia and empty sella syndrome associated with hyperprolactinaemia.
Method of use and dosage
The scheme depends on what the medicine has been prescribed for: a single dose to suppress lactation, a short two-day course to stop a flow of milk that has already begun, and prolonged weekly use in hyperprolactinaemia. The maximum daily dose is 3 mg.
| Situation | Dose |
|---|---|
| Suppression of lactation after childbirth | 1 mg as a single dose (2 tablets of 0.5 mg) on the first day after the birth |
| Stopping the flow of milk | 0.25 mg every 12 hours for 2 days |
| Hyperprolactinaemia, start | 0.5 mg a week — all at once or in two doses |
| Hyperprolactinaemia, increase | By 0.5 mg a week at monthly intervals |
| Hyperprolactinaemia, maintenance dose | 0.25–2 mg a week, on average 1 mg; above 1 mg — in several doses |
Poor tolerance and monitoring of treatment
If the patient tolerates dopaminergic medicines poorly, treatment starts with 0.25 mg a week and the dose is built up slowly. With persistent or severe undesirable reactions the dose is temporarily reduced and then one returns to the therapeutic one, adding 0.25 mg every two weeks. Once the dose has been chosen, the prolactin level is monitored monthly — it usually returns to normal within 2–4 weeks. After treatment is stopped hyperprolactinaemia most often returns, although in some patients the lowered prolactin level holds for months, and in most women ovulatory cycles are retained for at least six months. In severe hepatic failure the dose is reduced; in patients under 16 the medicine has not been studied.
Contraindications
The medicine is not used in the following cases:
- hypersensitivity to cabergoline or to any excipient;
- hypersensitivity to other ergot derivatives;
- previous fibrosis of the lungs, the pericardium or the retroperitoneal space;
- a heart valve defect found by echocardiography before the start of prolonged treatment.
Special warnings and precautions
Cabergoline is an ergot derivative with activity as an agonist of the 5-HT2B serotonin receptors, and with prolonged use fibrotic and serosal complications have been described for this group of medicines: pleurisy, pleural effusion, fibrosis of the pleura and the lungs, pericarditis, pericardial effusion, fibrosis of the pericardium and defects of the aortic, mitral or tricuspid valves. The risk is linked to the total cumulative dose, so treatment is conducted with the lowest effective dose and at every visit it is reassessed whether continuing it is justified. In some patients the manifestations of the valve defect diminished after the medicine was withdrawn.
- before therapy begins all patients have an echocardiogram to rule out an asymptomatic valve defect, and the ESR or other markers of inflammation are also determined, lung and kidney function are assessed and a chest radiograph is taken;
- the first control echocardiogram is done after 3–6 months, thereafter at least once every 6–12 months; the appearance or increase of regurgitation, stenosis or thickening of the leaflets means the medicine is withdrawn;
- if fibrosis of the valves has already been found, cabergoline is not prescribed at all; the onset of fibrosis can be covert, so the monitoring must be regular;
- breathlessness, shortness of breath, a stubborn cough and chest pain may indicate involvement of the pleura and the lungs;
- pain in the lower back or the side, swelling of a leg and abdominal tenderness make one think of retroperitoneal fibrosis with compression of the ureters or the vessels;
- with signs of heart failure, fibrosis of the valves and constrictive pericarditis are ruled out;
- an unexplained rise in the ESR calls for a chest radiograph: with pleural effusion and fibrosis this parameter grows noticeably;
- caution is needed in severe diseases of the heart and vessels, Raynaud's syndrome, peptic ulcer and bleeding from the gastrointestinal tract, and also with severe mental disorders, especially psychoses, in the past.
The medicine can cause orthostatic hypotension, so its combination with other agents that lower blood pressure requires caution. Like other dopamine agonists, cabergoline is capable of provoking disturbances of impulse control — a passion for gambling, increased libido and hypersexuality, compulsive shopping and overeating; both the patient and those close to them are warned of this possibility.
Drug interactions
There are no data on the interaction of cabergoline with other ergot alkaloids, so in prolonged treatment their concomitant use is not recommended.
The therapeutic effect of cabergoline rests on the direct stimulation of the dopamine receptors, so medicines with the opposite action — phenothiazines, butyrophenones, thioxanthenes, metoclopramide — weaken it, and they should not be combined. Macrolide antibiotics, for example erythromycin, raise the bioavailability of cabergoline, and that combination is likewise not recommended.
Pregnancy and breastfeeding
No adequate controlled studies have been carried out in pregnant women. In animals no teratogenic effect was found; however, a reduction in fertility and a toxic influence on the foetus were seen, linked to the pharmacodynamic activity of the substance. An observational study lasting 12 years collected data on 256 pregnancies after treatment with cabergoline: significant malformations or a miscarriage were recorded in 17 cases, that is, in 6.6%. In the general population the frequency of significant malformations is estimated, according to recent publications, at 6.9% and above, but an exact conclusion about an additional risk cannot be drawn — the study had no control group.
In pregnancy the medicine is used only where there are clear indications and after a careful assessment of the balance of benefit and risk. Because of the long half-life, women planning a pregnancy are advised to stop taking it a month before the intended conception and, if a pregnancy occurs during treatment, to withdraw the medicine as soon as it is confirmed.
Adverse effects
The severity and frequency of the reactions depend above all on the dose. In the suppression of lactation about 14% of the women reported at least one undesirable reaction; in the treatment of hyperprolactinaemia with doses of 1–2 mg a week, 68% of the patients did. The reactions are mostly mild or moderate, arise in the first two weeks and pass in the course of treatment; because of them about 3% of the patients stopped therapy.
- very common — headache and dizziness;
- very common — heart valve defects, including regurgitation, pericarditis, pericardial effusion;
- common — drowsiness, depression, a fall in blood pressure in prolonged treatment, orthostatic hypotension, flushes;
- uncommon — palpitations, breathlessness, pleural effusion, pulmonary fibrosis, nosebleed;
- uncommon — fainting, paraesthesia, transient hemianopia, hypersensitivity reactions, increased libido, spasm of the vessels of the fingers;
- very rare — pleural fibrosis;
- frequency not known — angina pectoris, respiratory failure, pleurisy, chest pain, visual disturbances, tremor, episodes of sudden sleep onset;
- frequency not known — aggressiveness, delusions, hypersexuality, a tendency to gambling, psychotic disorders, hallucinations.
In the first 3–4 days after childbirth an asymptomatic fall in blood pressure is possible. Cabergoline, as an ergot derivative, can constrict the vessels: spasm of the vessels of the fingers and cramps in the leg muscles have been described. Deviations in the standard laboratory tests with prolonged use are unlikely, although in women, once their periods had returned, a fall in haemoglobin was noted in the first months.
Overdose
An overdose shows itself through signs of excessive stimulation of the dopamine receptors: nausea, vomiting, gastric discomfort, orthostatic hypotension, confusion, psychosis or hallucinations.
Care consists in removing the unabsorbed medicine and maintaining stable blood pressure and, if necessary, in giving dopamine antagonists.
How to get a prescription for Dostinex® - (IR) online
Cabergoline is dispensed on prescription: prescribing it requires a confirmed indication, an assessment of the state of the heart and the choice of the minimum effective dose.
During the online consultation the doctor will go through your situation and the results of your investigations, will explain the scheme of use and the need to monitor prolactin and to have echocardiograms and, if there are no contraindications, will issue an electronic prescription — the medicine can be collected from a pharmacy using its code.
