Dostinex, 0.5 mg tablets 2 pcs

Dostinex is a dopamine receptor agonist. Cabergoline is a dopaminergic derivative of ergoline, characterized by a pronounced and long-lasting prolactin-lowering effect. The mechanism of action is associated with direct stimulation of dopamine D2-receptors of lactotropic pituitary cells. In doses higher than those for reduction of plasma levels of prolactin it has central dopaminergic action, caused by stimulation of dopamine D2-receptors.

Decrease of prolactin level in plasma is noticed in 3 hours after Dostinex usage and is maintained during 7-28 days in healthy volunteers and patients with hyperprolactinemia and till 14-21 days in women in postpartum period. The prolactin-lowering effect is dose-dependent with respect to both the severity and duration of action.

Cabergoline is highly selective and therefore has no effect on basal secretion of other pituitary hormones as well as cortisol.

The non-therapeutic pharmacological effects of cabergoline include a decrease in BP. With single use of the drug, the maximum hypotensive effect is seen during the first 6 h and is dose-dependent.

Pharmacokinetics

Intake

After oral administration, cabergoline is rapidly absorbed from the GI tract. Cmax in plasma is reached after 0.5-4 hours. Food intake has no effect on absorption and distribution of cabergoline.

Distribution

The Css is reached after 4 weeks of therapy due to the long T1/2. Binding to plasma proteins is 41-42%.

Metabolism

The major metabolic product of cabergoline identified in the urine is 6-allyl-8β-carboxy-ergoline at concentrations up to 4-6% of the dose taken. The urinary content of 3 additional metabolites does not exceed 3% of the administered dose. The metabolic products have significantly less effect on suppressing prolactin secretion compared to cabergoline.

Elimation

The T1/2, estimated by urinary excretion rate, is 63-68 h in healthy volunteers and 79-115 h in patients with hyperprolactinemia.

In 10 days after the use of the drug, 18% and 72% of the administered dose are detected in the urine and feces, respectively, and the proportion of unchanged drug in the urine is 2-3%.

Indications

Active ingredient

Composition

1 tablet contains:

The active ingredient:

cabergoline 500 mcg;

Associates:

leucine;

anhydrous lactose.

How to take, the dosage

Dostinex should be taken orally, preferably with meals.

To prevent lactation, a dose of 1 mg (2 pills) is given once on the first day after delivery.

To inhibit steady lactation, we use 0.25 mg (1/2 tablet) 2 times a day for 2 days (the total dose is 1 mg).

To treat disorders associated with hyperprolactinemia, the drug is prescribed in a dose of 0.5 mg per week in 1 or 2 doses (1/2 tablet, for example, on Monday and Thursday). The weekly dose should be increased gradually – by 0.5 mg at one month intervals until the optimal therapeutic effect is achieved. The average therapeutic dose is 1 mg per week, but can range from 0.25 mg to 2 mg per week. In patients with hyperprolactinemia, doses up to 4.5 mg per week are used.

If a dose of 1 mg per week or higher is prescribed, the drug should be divided into 2 or more doses per week depending on tolerance.

Interaction

There is no information about interactions between cabergoline and ergot alkaloids; however, concomitant use of these drugs during long-term therapy with Dostinex is not recommended.

Phenothiazine, butyrophenone, thioxanthene, and metoclopramide derivatives have been shown to decrease the effects of Dostinex when used concomitantly.

Simultaneous use of Dostinex with macrolide antibiotics increases the risk of side effects because it can increase the systemic bioavailability of Cabergoline.

Special Instructions

After selection of an effective dosing regimen, it is recommended that serum prolactin levels be determined regularly (once a month). Normalization of prolactin levels is usually observed within 2-4 weeks of treatment.

Persons with cardiovascular diseases, Raynaud’s syndrome, peptic ulcer or gastrointestinal bleeding, and patients with a history of severe psychiatric diseases, especially psychosis, should use Dostinex with caution.

In long-term therapy, Dostinex should be prescribed in lower doses in patients with severe hepatic impairment.

After discontinuation of Dostinex a recurrence of hyperprolactinemia is usually observed. However, a number of patients show persistent suppression of prolactin levels for several months. Most women register ovulatory cycles for at least 6 months after Dostinex withdrawal.

The single dose of 0.25 mg of Dostinex should not be exceeded in breastfeeding mothers who are being treated to suppress already established lactation to prevent orthostatic hypotension.

Before starting Dostinex therapy, a complete pituitary function study is indicated.

Dostinex restores ovulation and fertility in women with hyperprolactinemic hypogonadism. Because pregnancy can occur even before menstruation is restored, it is recommended that pregnancy tests be performed at least once every 4 weeks during the amenorrheic period and every time menstruation is delayed for more than 3 days after menstruation is restored. Women who want to avoid pregnancy should use non-hormonal methods of contraception for the period of Dostinex treatment as well as after Dostinex withdrawal and until anovulation returns.

Women who become pregnant should be monitored by a physician for timely detection of symptoms of pituitary enlargement, since pre-existing pituitary tumors may increase in size during pregnancy.

The side effects associated with taking the drug are dose-dependent. The likelihood of side effects can be reduced by starting therapy with Dostinex at lower doses (e.g., 0.25 mg once a week), with subsequent gradual increase of the dose until the therapeutic dose level is reached. If persistent or severe adverse events occur, a temporary dose reduction and then a more gradual dose increase (e.g., 0.25 mg weekly every 2 weeks) will improve tolerance.

On long-term therapy with Dostinex no abnormalities in standard laboratory tests were observed; women with amenorrhea had lower hemoglobin levels during the first few months after menstrual recovery.

Contraindications

Side effects

System effects: palpitations; rarely – orthostatic hypotension (with long-term use Dostinex® usually has hypotensive effect); asymptomatic BP decrease during the first 3-4 days after delivery (BP – more than 20 mmHg, BP – more than 10 mmHg) is possible.

Nervous system disorders: dizziness/vertigo, headache, increased fatigue, somnolence, depression, asthenia, paresthesias, fainting.

In the digestive system: nausea, vomiting, epigastric pain, abdominal pain, constipation, gastritis, dyspepsia.

Others: mastodynia, nasal bleeding, skin flushing, transient hemianopsia, finger spasms and lower limb muscle cramps (like other ergot derivatives, Dostinex® may have a vasoconstrictor effect).

Overdose

Symptoms: nausea, vomiting, dyspeptic disorders, orthostatic hypotension, confusion/psychosis or hallucinations.

Treatment: measures aimed at elimination of nonabsorbed drug (gastric lavage) and maintenance of BP should be performed. Administration of dopamine antagonists is recommended.

Pregnancy use

Pregnancy should be avoided for at least 1 month after discontinuation of Dostinex treatment because of its long half-life, and there are limited data about its effect on the fetus, although Dostinex 0.5-2 mg per week in hyperprolactinemia-related diseases is not associated with an increased risk of miscarriage, premature birth, various pregnancy abnormalities, and congenital fetal malformations.

Similarities