Agalates, tablets 0.5 mg 2 pcs

Pharmacotherapeutic group: dopamine receptor agonist
ATC code: G02CB03.
PHARMACOLOGICAL PROPERTIES

Pharmacodynamics
Cabergoline is a synthetic ergot alkaloid, ergoline derivative, a long-acting dopamine agonist that inhibits prolactin secretion. The mechanism of action of cabergoline includes stimulation of central hypothalamic dopaminergic receptors. In doses higher than those required for inhibition of prolactin secretion, the drug induces central dopaminergic effect, which is caused by stimulation of dopamine D2-receptors. The action of the drug is dose-dependent. Decrease of prolactin in blood is usually observed after 3 hours and remains during 2-3 weeks, in this connection a single dose of the preparation is usually enough to suppress milk secretion. When hyperprolactinemia is treated, blood prolactin levels normalize after 2-4 weeks of using the drug in an effective dose. Normal prolactin levels may persist for several months after withdrawal of the drug.
Cabergoline is highly selective and does not affect basal secretion of other pituitary hormones and cortisol. The only pharmacodynamic effect that is not related to the therapeutic action is the reduction of arterial blood pressure (BP). The maximum hypotensive effect usually develops 6 hours after a single drug administration; the degree of BP reduction and the frequency of development of the hypotensive effect are dose-dependent.

Pharmacokinetics

Intake
After oral administration, cabergoline is rapidly absorbed from the gastrointestinal tract (GIT). Maximal concentration in plasma is reached within 0.5-4 hours.
Food has no effect on absorption or distribution of cabergoline.
Distribution
Binding of cabergoline (at concentration of 0.1-10 ng/ml) with plasma proteins is 41-42%.
Metabolism
Metabolites of cabergoline were found in urine: 6-allyl-8β-carboxy-ergoline in the amount of 4-6% of the dose taken, as well as three other metabolites with a total content of less than 3%. All metabolites inhibit prolactin secretion to a much lesser degree (compared to cabergoline).

Elimination
Cabergoline has long half-life: T1/2 was 63-68 h in healthy volunteers and 79-115 h in patients with hyperprolactinemia.
With this half-life equilibrium is reached after 4 weeks. In the urine and feces 18% and 72% of the administered dose were found, respectively. The urinary content of unchanged cabergoline is 2-3%.
Pharmacokinetics are linear up to a dose of 7 mg/day.
Preclinical safety data
As shown in preclinical studies, cabergoline is safe over a significant dose range and has no teratogenic, mutagenic or carcinogenic effects.

Indications

Active ingredient

Composition

How to take, the dosage

Orally, preferably with meals.

Adults

Treatment of disorders associated with hyperprolactinemia: The recommended starting dose is 0.5 mg weekly in 1 or 2 doses (e.g., Monday and Thursday). The dosage is increased gradually, usually by 0.5 mg/week at 1 month intervals until optimal therapeutic effect is achieved. The maximum daily dose should not exceed 3 mg.

The maintenance dose is 1 mg/week (0.25-2 mg/week); in selected cases in patients with hyperprolactinemia, up to 4.5 mg/week.

When using Agalates at doses above 1 mg/week, it is recommended that the weekly dose be divided into 2 or more doses, depending on tolerance.

For suppression of physiological postpartum or established lactation: the recommended dose is 1 mg once within the first 24 hours after birth.

Perhaps for use in patients with hepatic or renal impairment: see Contraindications and Special Precautions for information.

Patient use over 65 years of age: Based on the indication for use, there is limited experience with the use of cabergoline in patients over 65 years of age. The available data indicate that there is no specific risk.

Interaction

The effect of macrolide antibiotics on plasma levels of cabergoline when used together has not been studied. Taking into account the possibility of increasing the level of cabergoline, the drug is not recommended to use in combination with macrolides.

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

There is no information about interactions of cabergoline with other ergot alkaloids; however, long-term use of these combinations is not recommended.

With regard to the pharmacodynamics (hypotensive effect) of cabergoline, interactions with BP lowering drugs must be taken into consideration.

In clinical studies in patients with Parkinson’s disease no pharmacokinetic interaction was found with levodopa or selegiline. Pharmacokinetic interactions with other drugs cannot be predicted based on the available information about the metabolism of cabergoline.

Special Instructions

To open the vial, first press the cap, then rotate it as shown on the cap. Do not remove the silica gel capsule from the bottle and do not ingest.

There are limited data on the efficacy and safety of Agalates in patients with hepatic or renal impairment. The pharmacokinetics of cabergoline are not significantly altered in moderate to severe renal impairment. It has not been studied in patients with terminal renal failure or in hemodialysis. Therefore, Agalates should be used with caution in these patients. The effect of alcohol on the overall tolerability of Agalates has not been established.

The use of the drug Agalates may cause symptomatic arterial hypotension, especially when combined with BP lowering drugs. It is recommended to measure BP regularly in the first 3-4 days after the start of treatment.

. Prolonged use of Agalates and other ergot derivatives that are active against serotonin 5HT2B receptors may increase the risk of fibrotic and serous inflammatory disease, such as exudative pleurisy, pleural fibrosis, pulmonary fibrosis, pericarditis, damage of one or more heart valves (aortic, mitral, tricuspid), retroperitoneal fibrosis. Withdrawal of Agalates for the above pathology resulted in improvement of signs and symptoms.

Before starting therapy with Agalates, all patients should undergo a complete evaluation to detect cardiac valve damage and to determine lung and kidney function to prevent a worsening of the course of concomitant diseases.

If new clinical symptoms of the respiratory system occur, lung fluoroscopy is recommended. In patients with pleural effusions/fibrosis, elevated sedimentation rate has been noted; therefore, if elevated sedimentation rate without overt clinical signs is present, radiological examination should also be performed.

Agalates therapy over a prolonged period may gradually progress to fibrosis, therefore symptoms such as dyspnea, shortness of breath, cough, chest pain, low back pain, swelling of lower extremities, signs of retroperitoneal fibrosis, and heart failure should be monitored during treatment.

After initiation of Agalates therapy for the prevention of fibrotic disorders, the condition of the heart valves should be monitored and an ECG examination should be performed for 3-6 months. The frequency of ECG monitoring is then determined by the physician individually for each patient, but at least once every 6-12 months. If valve regurgitation, narrowing of the lumen or thickening of the valve wall occurs or worsens, therapy with Agalates should be discontinued.

The patient’s need for other clinical examinations is determined by the physician on an individual basis.

Drowsiness and episodes of sudden falling asleep may occur with Agalates, especially in patients with Parkinson’s disease (see “Effect on driving and operating ability”).

When using Agalates, increased libido, hypersexuality, and pathological cravings for gambling were noted. These symptoms were reversible and disappeared with dose reduction or discontinuation of Agalates.

Hyperprolactinemia combined with amenorrhea and infertility may be associated with pituitary tumors, so the cause of the hyperprolactinemia should be investigated before starting Agalates therapy.

It is recommended that serum prolactin levels be checked every month, because normal prolactin concentrations are maintained for 2-4 weeks after an effective therapy regimen has been achieved.

After discontinuation of Agalates, hyperprolactinemia usually occurs again. However, some patients have a persistent decrease in prolactin concentrations for several months.

The use of Agalates restores ovulation and fertility in women with hyperprolactinemic hypogonadism. Because pregnancy can occur before menstruation resumes, pregnancy tests are recommended during amenorrhea, and after menstrual cycle recovery, in all cases of a delay of more than 3 days. For women who are not planning a pregnancy, effective non-hormonal contraception should be used during and after treatment with Agalates. It is recommended that women who plan to become pregnant conceive at least 1 month after discontinuation of Agalates.

Impact on driving and operating machinery

Patients should be advised to exercise caution when driving or operating machinery. Patients who have already experienced drowsiness and/or episodes of sudden falling asleep while treated with Agalates should refrain from driving or other activities requiring increased concentration and rapid psychomotor reactions.

Synopsis

Contraindications

Postpartum or uncontrolled arterial hypertension; hypersensitivity to cabergoline, other ergot alkaloids, or any drug component; severe hepatic impairment; pulmonary adverse events such as pleurisy or fibrosis (including a history) associated with dopamine agonists; psychosis (including a history) or risk of developing it; Pregnancy and pre-eclampsia and eclampsia developed against it; breastfeeding period; children under 16; cardiac valve defects after long-term therapy with cabergoline confirmed by echocardiography; concomitant use with macrolide antibiotics; lactose intolerance; lactase deficiency; glucose-galactose malabsorption syndrome.

WARNING

. Patients with cardiovascular disease, arterial hypotension, Raynaud’s syndrome, peptic ulcers or gastrointestinal bleeding, somnolence, sudden onset of sleep, patients with end-stage renal failure or on hemodialysis, patients over 65; long-term treatment with cabergoline.

Side effects

The frequency of side effects is classified in accordance with the recommendations of the World Health Organization: very frequently – at least 10%; frequently – at least 1%, but less than 10%; infrequently – at least 0.1%, but less than 1%; rarely – at least 0.01%, but less than 0.1%; very rarely (including single cases) – less than 0.01%.

Immune system disorders: infrequent – hypersensitivity reactions, skin rash.

Blood and lymphatic system disorders: infrequent – erythromelalgia.

Nervous system disorders: frequently – hallucinations, sleep disorders, confusion, dizziness, dyskinesia, increased libido, headache, somnolence, depression, infrequently – hyperkinesis, psychotic disorder, delirium, paresthesia, transient hemianopsia, fainting, very rarely – sudden sleep attack, pathological craving for gambling.

Cardiovascular system disorders: often – postural hypotension, angina pectoris, heart valve involvement (including regurgitation), pericarditis, pericardial effusion, flushes, palpitations, peripheral edema.

Gastrointestinal disorders: very frequently – nausea, abdominal pain, frequently – dyspepsia, vomiting, gastritis, constipation, rarely – pain in epigastric region, very rarely – retroperitoneal fibrosis.

Respiratory system: often – dyspnea, infrequently – pleural effusion, pulmonary fibrosis, nasal bleeding.

Others: frequent – asthenia, weakness, liver function abnormality, breast pain, visual impairment, very rare – cramps in the muscles of the lower extremities, increased creatine phosphokinase activity.

Overdose

Symptoms: There are no reports of drug overdose. Based on animal experiments, symptoms due to dopamine receptor hyperstimulation can be expected: nausea, vomiting, decreased BP, impaired consciousness/psychosis or hallucinations.

Treatment: if indicated, measures should be taken to restore BP. In addition, the use of dopamine antagonists may be required if there is significant CNS symptomatology (hallucinations).

Pregnancy use

The drug is contraindicated in pregnancy and lactation.

Pregnancy should be excluded before starting to take the drug. It is recommended to avoid pregnancy for at least 1 month after discontinuation of treatment. There are limited data on the use of the drug during pregnancy obtained during the first 8 weeks after conception. Cabergoline use has not been associated with an increased risk of abortion, premature birth, multiple pregnancies, or congenital abnormalities. No other data are available to date.

There have been no direct or indirect adverse effects of cabergoline on pregnancy, embryo/fetal development, labor or postnatal development in animal studies.

In view of the limited experience with the use of cabergoline in pregnancy, the drug should be discontinued if pregnancy is planned. If pregnancy occurs during treatment, cabergoline should be withdrawn immediately. Due to the possibility of expansion of a pre-existing tumor, signs of pituitary enlargement in pregnant women should be monitored.

Because cabergoline suppresses lactation, the drug should not be administered to mothers who prefer to breastfeed their infants. Breastfeeding should be stopped during treatment with cabergoline.

Similarities