Cabergoline (Tablets) Instructions for Use

ATC Code

G02CB03 (Cabergoline)

Active Substance

Cabergoline (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Dopamine receptor agonist. Inhibitor of prolactin secretion

Pharmacotherapeutic Group

Other agents used in gynecology; prolactin inhibitors

Pharmacological Action

An ergoline alkaloid derivative, a dopamine D₂ receptor agonist. By stimulating these pituitary receptors, it causes a pronounced and prolonged inhibition of the secretion of the anterior lobe hormone – prolactin. It has a therapeutic effect in hyperprolactinemia, reducing the severity of its manifestations such as menstrual cycle disorders (oligomenorrhea, amenorrhea), infertility, galactorrhea; impotence, decreased libido. Prevents and suppresses physiological lactation.

In doses higher than those required to suppress prolactin secretion, Cabergoline causes a central dopaminergic effect due to stimulation of dopamine D₂ receptors. The effect is dose-dependent. Cabergoline reduces daily motor fluctuations in patients with Parkinson’s disease who are receiving treatment with a levodopa/carbidopa combination. Cabergoline has selective activity without affecting the basal secretion of other pituitary hormones and cortisol.

The only pharmacodynamic effect of cabergoline not related to therapeutic activity is a decrease in blood pressure. After a single dose, the maximum hypotensive effect is observed within the first 6 hours and is dose-dependent.

Pharmacokinetics

After oral administration, Cabergoline is rapidly absorbed from the gastrointestinal tract. C_max in blood plasma is reached in 0.5-4 hours. Food does not affect the absorption or distribution of cabergoline. Pharmacokinetics are linear up to a dose of 7 mg/day.

The binding of cabergoline (at a concentration of 0.1-10 ng/ml) to plasma proteins is 41-42%.

The following metabolites of cabergoline were found in urine: 6-allyl-8β-carboxy-ergoline in an amount of 4-6% of the administered dose, as well as three other metabolites with a total content of less than 3%. All metabolites inhibit prolactin secretion to a much lesser extent (compared to cabergoline). Cabergoline has a long T_1/2. T_1/2 in healthy volunteers is 63-68 hours, T_1/2 in patients with hyperprolactinemia is 79-115 hours. With such a T_1/2, steady state is reached after 4 weeks. 18% and 72% of the administered dose were found in urine and feces, respectively. The content of unchanged cabergoline in urine is 2-3%.

Indications

Prevention of physiological lactation after childbirth; suppression of already established postpartum lactation; treatment of disorders associated with hyperprolactinemia, including amenorrhea, oligomenorrhea, anovulation, galactorrhea; prolactin-secreting pituitary adenomas (micro- and macroprolactinomas); idiopathic hyperprolactinemia; empty sella syndrome in combination with hyperprolactinemia.

ICD codes

Dosage Regimen

Take orally. Swallow the tablet whole with water. The dose and regimen are set individually, based on the indication and therapeutic response.

For hyperprolactinemic disorders, the initial dose is typically 0.5 mg per week, administered as one 0.5 mg tablet or as two 0.25 mg tablets. Divide the weekly dose into two or more administrations.

Increase the dose gradually, at monthly intervals, by 0.5 mg. Titrate until a therapeutic response is achieved. The therapeutic dosage usually ranges from 0.25 mg to 2 mg per week.

Do not exceed a weekly dose of 4.5 mg. For maintenance, use the lowest effective dose.

For the prevention of lactation, take 1 mg (two 0.5 mg tablets) as a single dose on the first day after delivery.

For suppression of established lactation, take 0.25 mg every 12 hours for two days (total dose 1 mg).

Take with food to improve gastrointestinal tolerance and reduce the incidence of nausea.

Regularly monitor serum prolactin levels to guide dosage titration and assess efficacy.

In patients with severe hepatic impairment, use lower doses and titrate with caution.

Adverse Reactions

From the cardiovascular system palpitations, angina pectoris; with long-term use, Cabergoline usually has a hypotensive effect, in some cases orthostatic arterial hypotension may occur; asymptomatic decrease in blood pressure is possible during the first 3-4 days after childbirth.

From the nervous system dizziness/vertigo, tremor, headache, increased fatigue, drowsiness, depression, asthenia, paresthesia, fainting, nervousness, anxiety, insomnia, impaired concentration, impulse control disorder (excessive passion for shopping, overeating, spending money).

From the digestive system nausea, vomiting, epigastric pain, abdominal pain, constipation, gastritis, dyspepsia, dry oral mucosa, diarrhea, flatulence, toothache, sensation of pharyngeal mucosa irritation.

From the respiratory system pleurisy.

Other mastodynia, dysmenorrhea, nosebleed, rhinitis, facial flushing, transient hemianopia, vascular spasms of the fingers and muscle cramps of the lower extremities, visual disturbances, flu-like symptoms, malaise, periorbital and peripheral edema, anorexia, acne, skin itching, joint pain.

During long-term therapy with cabergoline, deviations from the norm of standard laboratory parameters were rarely noted; in women with amenorrhea, a decrease in hemoglobin content was observed during the first few months after the restoration of menstruation.

Contraindications

Hypersensitivity to cabergoline and ergot alkaloids; impaired cardiac and respiratory function due to fibrotic changes in the lungs, pericardium, heart valves or retroperitoneal space, or a history of such conditions; for long-term therapy – anatomical signs of pathology of the heart valve apparatus (such as valve leaflet thickening, valve narrowing, mixed pathology of narrowing and valve stenosis), confirmed by echocardiography performed at the beginning of therapy; risk of postpartum psychosis; breastfeeding period; children under 16 years of age.

With caution: arterial hypertension that developed during pregnancy, for example, preeclampsia or postpartum arterial hypertension; severe cardiovascular diseases, Raynaud’s syndrome; hypotension, Parkinson’s disease; severe psychotic or cognitive disorders (including history); peptic ulcer, gastrointestinal bleeding; severe hepatic insufficiency (lower doses are recommended); renal failure; simultaneous use with drugs that have a hypotensive effect (due to the risk of developing orthostatic hypotension).

Use in Pregnancy and Lactation

Use during pregnancy is indicated only in cases where the intended benefit to the mother outweighs the potential risk to the fetus.

If pregnancy occurs during treatment with cabergoline, its use should be discontinued immediately, also with a thorough assessment of the benefit-risk ratio for the woman and the fetus.

Cabergoline restores ovulation and fertility in women with hyperprolactinemic hypogonadism. Since pregnancy can occur before the restoration of menstruation, it is recommended to perform pregnancy tests at least once every 4 weeks during the period of amenorrhea, and after the restoration of menstruation – every time a delay in menstruation of more than 3 days is noted. Women who wish to avoid pregnancy should use barrier methods of contraception during treatment with cabergoline, and also after its discontinuation until anovulation recurs. Women who become pregnant should be under medical supervision for timely detection of symptoms of pituitary enlargement, since during pregnancy an increase in the size of pre-existing pituitary tumors is possible.

There is no information on the excretion of cabergoline in breast milk. If it is necessary to use it during lactation, the issue of stopping breastfeeding should be decided.

Use in Hepatic Impairment

Contraindicated in severe hepatic insufficiency (lower doses are recommended).

Use in Renal Impairment

Use with caution in patients with renal failure.

Pediatric Use

Contraindicated in children under 16 years of age (safety and efficacy of cabergoline have not been established).

Special Precautions

Before prescribing cabergoline for the treatment of disorders associated with hyperprolactinemia, a complete examination of the pituitary gland is necessary.

Before prescribing cabergoline, the state of the cardiovascular system should be assessed, including echocardiography to identify asymptomatic dysfunction of the valve apparatus.

Cabergoline can cause symptomatic arterial hypotension, especially when taken concomitantly with drugs that lower blood pressure. It is recommended to regularly measure blood pressure during the first 3-4 days after starting treatment.

With long-term use of cabergoline and other ergot derivatives that are active against serotonin 5-HT_2B receptors, the risk of developing fibrotic and serous-inflammatory diseases, such as exudative pleurisy, pleural fibrosis, pulmonary fibrosis, pericarditis, damage to one or more heart valves (aortic, mitral, tricuspid), retroperitoneal fibrosis, increases. Discontinuation of cabergoline in case of development of the specified pathology led to an improvement in signs and symptoms.

Before starting long-term therapy with cabergoline, all patients should undergo a complete examination to identify heart valve damage, determine the functional state of the lungs and kidneys to prevent worsening of concomitant diseases.

If new clinical symptoms from the respiratory system appear, lung radiography is recommended. In patients with pleural effusion/fibrosis, an increase in ESR was noted, therefore, with an increased ESR without obvious clinical signs, an X-ray examination should also be performed.

During long-term therapy with cabergoline, fibrotic disorders may gradually develop, so during treatment it is necessary to monitor the appearance of symptoms such as shortness of breath, dyspnea, cough, chest pain, lower back pain, swelling of the lower extremities, signs of retroperitoneal fibrosis, heart failure.

After starting therapy with cabergoline, to prevent fibrotic disorders, the condition of the heart valves should be monitored and an ECG examination should be performed within 3-6 months. Further, the frequency of ECG monitoring is set by the doctor individually for each patient, but not less than once every 6-12 months. If valve regurgitation appears or worsens, narrowing of the lumen or thickening of the valve wall, therapy with cabergoline should be discontinued.

The patient’s need for other types of clinical examination is established by the doctor on an individual basis.

It is recommended to check the serum prolactin content every month, because after achieving an effective therapeutic regimen, the normal prolactin level is maintained for 2-4 weeks. After discontinuation of cabergoline, hyperprolactinemia usually recurs. However, some patients experience a persistent decrease in prolactin concentration for several months.

Effect on the ability to drive vehicles and mechanisms

Cabergoline lowers blood pressure, which may impair reaction speed in some patients. Patients receiving Cabergoline should refrain from driving vehicles and other activities requiring high concentration and speed of psychomotor reactions.

Drug Interactions

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

The mechanism of action of cabergoline is associated with direct stimulation of dopamine receptors, so it should not be used in combination with dopamine receptor antagonists (phenothiazines, butyrophenones, thioxanthenes, metoclopramide).

The combination with ergot alkaloids and their derivatives is not recommended.

Considering the pharmacodynamics of cabergoline (hypotensive effect), interaction with drugs that lower blood pressure should be taken into account.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.