Dostinex®: composition and pharmaceutical form
Dostinex® comes as tablets, each of which contains 0.5 mg of cabergoline. The tablet can be divided in half — this matters, since most schemes are built on doses of 0.25 mg.
The medicine is intended to be taken by mouth. Dopaminergic agents are better tolerated if taken with food, so cabergoline is recommended to be taken during a meal.
How Dostinex® works
Cabergoline is an ergoline derivative with dopaminergic activity that lowers the prolactin level strongly and for a long time. It directly stimulates the D2 dopamine receptors in the cells of the anterior lobe of the pituitary and thereby inhibits the release of prolactin. At doses above those needed to lower prolactin, cabergoline also has a central dopaminergic action through the same D2 receptors.
The duration of the effect is explained by the fact that the substance remains in the target organ for a long time. After a single dose of 0.3–1.5 mg the serum prolactin level falls noticeably within 3 hours, and this effect is maintained for up to 7–28 days in healthy volunteers and patients with hyperprolactinaemia and for up to 14–21 days in women after childbirth. Both the extent and the duration of the fall in prolactin depend on the dose, while on the other parts of the endocrine system cabergoline acts very selectively.
Indications
The first group of indications is the suppression of lactation: cabergoline is used to prevent it straight after childbirth or to stop the flow of milk once it has begun.
The second group is disorders linked to an excessive production of prolactin. The medicine is prescribed in hyperprolactinaemia with disturbances of the menstrual cycle (absence of periods, scanty or irregular periods), absence of ovulation and galactorrhoea, and also in pituitary adenoma, idiopathic hyperprolactinaemia and empty sella syndrome accompanied by hyperprolactinaemia.
Method of use and dosage
The dose is chosen according to the aim. If the patient tolerates dopaminergic medicines poorly, one starts with a reduced dose — for example 0.25 mg once a week — and raises it gradually to the therapeutic one. With persistent or severe undesirable reactions the dose is temporarily reduced and then one returns slowly to the previous one, adding 0.25 mg every two weeks. The maximum daily dose is 3 mg.
| Aim | Scheme of use |
|---|---|
| Prevention of lactation after childbirth | A single dose of 1 mg (2 tablets of 0.5 mg) on the first day after the birth |
| Stopping lactation that has already begun | 0.25 mg (half a tablet) every 12 hours for 2 days |
| Hyperprolactinaemia, starting dose | 0.5 mg a week — as a single dose or divided into two (for example, Monday and Thursday) |
| Hyperprolactinaemia, dose titration | An increase of 0.5 mg a week at monthly intervals until the optimum effect |
| Hyperprolactinaemia, therapeutic dose | 0.25–2 mg a week, on average 1 mg; a dose above 1 mg is divided into several doses |
Monitoring and special groups of patients
During the titration of the dose the patient is monitored in order to find the lowest effective one. Once the dose has been established, the prolactin level is checked monthly: it usually normalises within 2–4 weeks. After cabergoline is withdrawn hyperprolactinaemia as a rule returns, although in some patients the lowered prolactin level persists for months, and in most women ovulatory cycles continue for at least six months after the end of treatment. In severe hepatic failure the dose is reduced. Safety and efficacy in patients under 16 have not been studied.
Contraindications
Dostinex® is not prescribed in the following cases:
- hypersensitivity to cabergoline or to any excipient;
- hypersensitivity to other ergot derivatives;
- fibrosis of the lungs, the pericardium or the retroperitoneal space identified in the past;
- in prolonged treatment — a heart valve defect found by echocardiography before therapy begins.
Special warnings and precautions
The main feature of cabergoline as an ergot derivative with activity as an agonist of the 5-HT2B serotonin receptors is the risk of fibrotic and serosal lesions with prolonged use: pleurisy, pleural effusion, fibrosis of the pleura and the lungs, pericarditis, pericardial effusion, fibrosis of the pericardium and defects of one or several heart valves — the aortic, mitral, tricuspid. Such changes are linked to the cumulative dose, so treatment is conducted with the lowest effective dose, and at every visit the benefit and the risk of continuing therapy are weighed anew. After the medicine is withdrawn, the signs of a valve defect diminished in some cases.
- all patients undergo an assessment of the cardiovascular system with echocardiography before treatment begins, so that asymptomatic valve disease is not missed; a baseline ESR or other markers of inflammation, an assessment of lung function, a chest radiograph and an assessment of kidney function are also recommended;
- the first control echocardiogram is done 3–6 months after the start of treatment, thereafter no less often than once every 6–12 months; if regurgitation, stenosis or thickening of the valve leaflets appears or increases, the medicine is withdrawn;
- where fibrosis of the valves has been found, cabergoline is not used; fibrosis can begin covertly, so the patient is monitored regularly;
- warning signs are breathlessness, difficulty breathing, a persistent cough or chest pain — signs of involvement of the pleura and the lungs;
- pain in the lower back or the side, swelling of a leg and abdominal tenderness may point to retroperitoneal fibrosis with obstruction of the ureters or the vessels;
- symptoms of heart failure make it necessary to rule out fibrosis of the valves and constrictive pericarditis;
- an unexplained rise in the ESR is a reason to take a chest radiograph: with effusion and fibrosis of the pleura this parameter can be abnormally high;
- caution is needed in severe cardiovascular disease, Raynaud's syndrome, peptic ulcer and gastrointestinal bleeding, and also with a history of serious mental disorders, above all psychoses.
After the medicine is taken orthostatic hypotension is possible, so combination with other agents that lower blood pressure requires particular caution. With dopamine agonists disturbances of impulse control are possible: a passion for gambling, increased libido and hypersexuality, compulsive spending and shopping, compulsive or binge eating — it is worth warning the patient and those close to them about this.
Drug interactions
There is no information about the interaction of cabergoline with other ergot alkaloids, so in prolonged therapy their concomitant use is not recommended.
Since the action of cabergoline rests on the direct stimulation of the dopamine receptors, it should not be combined with medicines that block those receptors — phenothiazines, butyrophenones, thioxanthenes, metoclopramide: they weaken the therapeutic effect. Combination with macrolide antibiotics, for example erythromycin, is also not recommended, since the bioavailability of cabergoline increases with them.
Pregnancy and breastfeeding
There are no adequate controlled studies in pregnant women. In animal studies no teratogenic effect was found, but a reduction in fertility and toxicity to the foetus were noted, linked to the pharmacodynamic activity of the substance. A 12-year observational study collected data on 256 pregnancies following treatment with cabergoline: in 17 of them (6.6%) significant malformations or a miscarriage were recorded. For comparison, according to recent publications the frequency of significant malformations in the general population is estimated at 6.9% and above, and it is not possible to assess accurately whether there is an additional risk, since the study did not include a control group.
Cabergoline is used in pregnancy only where there are clear indications and after a careful assessment of the balance of benefit and risk. Because of the long half-life and the limited data on the effect on the foetus, women planning a pregnancy are advised to stop the medicine a month before the intended conception. If a pregnancy occurs during therapy, treatment is stopped as soon as it is confirmed, in order to limit the exposure of the foetus.
Adverse effects
The frequency of the reactions depends above all on the dose. In the suppression of lactation about 14% of the women reported at least one undesirable reaction, and in the treatment of hyperprolactinaemia with doses of 1–2 mg a week, 68% of the patients did, though most of the reactions were mild or moderate, appeared in the first two weeks and passed in the course of treatment. About 3% of the patients had to stop therapy because of the adverse effects.
- very common — headache, dizziness of central or peripheral origin;
- very common — heart valve defects, including regurgitation, and the accompanying conditions: pericarditis, pericardial effusion;
- common — drowsiness, depression, a fall in blood pressure in prolonged treatment, orthostatic hypotension, flushes;
- uncommon — palpitations, breathlessness, pleural effusion, fibrosis including 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, breathing disorders and respiratory failure, pleurisy, chest pain, visual disturbances, tremor, episodes of sudden sleep onset;
- frequency not known — aggressiveness, delusions, hypersexuality, a pathological tendency to gambling, psychotic disorders, hallucinations.
In the first 3–4 days after childbirth an asymptomatic fall in blood pressure is possible — of 20 mm Hg or more in the systolic and of 10 mm Hg or more in the diastolic. As an ergot derivative, cabergoline can constrict the vessels: spasm of the vessels of the fingers and cramps in the leg muscles have been described. With prolonged use deviations in the standard laboratory tests are unlikely, although in women whose periods had returned a fall in haemoglobin was seen in the first months.
Overdose
The symptoms of an overdose are linked to excessive stimulation of the dopamine receptors: nausea, vomiting, gastric discomfort, orthostatic hypotension, confusion, psychosis or hallucinations.
If necessary, measures are taken to remove the unabsorbed medicine and blood pressure is kept stable. In addition, the administration of dopamine antagonists may be justified.
How to get a prescription for Dostinex® online
Cabergoline is dispensed on prescription: the doctor must confirm the indication, assess the state of the heart and choose the lowest effective dose and, with prolonged use, arrange a control echocardiogram.
During the online consultation the doctor will go through the results of the tests and investigations, will discuss the scheme of use and the monitoring of prolactin and, if there are no contraindications, will issue an electronic prescription — the medicine can be collected from a pharmacy using its code.
