Dostinex

Dostinex (cabergoline) is a drug that contains the active ingredient cabergoline, which is an antiprolactin. It is used to treat various disorders associated with hyperprolactinemia, that is, increased levels of prolactin in the blood. Prolactin is a hormone that plays a role in the regulation of the mammary gland and affects various functions of the reproductive system.

Dostinex is commonly used to treat hyperprolactinemia caused by patients with pituitary pathologies such as prolactinomas (prolactin-secreting tumors) and to reduce the release of prolactin associated with the use of certain medications, such as antidepressants.

It works by reducing the release of prolactin from the pituitary gland, which can lead to normalization of prolactin levels in the blood and improvement of symptoms associated with hyperprolactinemia, such as infertility, menstrual irregularities and decreased libido.

Indications Dostinexa

1. Prolactinomas: Dostinex is used to treat prolactinomas, which are prolactin-secreting tumors of the pituitary gland. This may include macroadenomas (large tumors) or microadenomas (small tumors), which can lead to hyperprolactinemia.
2. Hyperprolactinemia without a tumor: In addition to prolactinomas, Dostinex can also be used to treat hyperprolactinemia without a tumor, when prolactin levels are elevated but no tumor is detected.
3. Nephrotic syndrome: Dostinex may sometimes be prescribed to treat nephrotic syndrome, a condition characterized by loss of protein in the urine, including those associated with high levels of prolactin.

Release form

Dostinex is available in tablet form.

• Tablets are white, oblong, scored and engraved with “P” and “U” on one side and “700” on the other.
• Tablets are supplied in glass bottles that contain 2 or 8 tablets.

Pharmacodynamics

1. Mechanism of action:

   • Cabergoline is a dopamine D2 receptor agonist and has a direct stimulating effect on these receptors.
   • In the pituitary gland, cabergoline suppresses the release of prolactin by blocking dopamine D2 receptors, which leads to a decrease in prolactin levels in the blood.
   • In addition, cabergoline has an inhibitory effect on the secretion of prolactin in the mammary glands, which also helps reduce its level in the blood.

2. Use in hyperprolactinemia:

   • In patients with hyperprolactinemia, cabergoline reduces prolactin levels and improves symptoms of hyperprolactinemia, such as amenorrhea, galactorrhea and infertility.

3. Use in suppression of lactation:

   • After childbirth, cabergoline is used to suppress lactation due to its ability to reduce prolactin levels.

4. Use in the treatment of empty sella syndrome:

   • In empty sella syndrome, cabergoline is used to reduce prolactin production and reduce the size of prolactinomas.

5. Effects on other hormonal axes:

   • Cabergoline may also affect other hormonal axes, such as the gonadotropin axis and growth hormone (GH) release.

Pharmacokinetics

1. Absorption: Cabergoline is generally well absorbed from the gastrointestinal tract after oral administration. The maximum concentration in the blood is reached approximately 2-3 hours after administration.
2. Bioavailability: The bioavailability of cabergoline is about 30-40% due to the high first pass rate through the liver.
3. Metabolism: Cabergoline is metabolized in the liver, mainly via the CYP3A4 isoenzyme.
4. Half-life: The half-life of cabergoline is approximately 63-68 hours.
5. Excretion: Cabergoline is mainly excreted in the urine (some unchanged and some in the form of metabolites) and to a lesser extent in the feces.
6. System concentration: The concentration of cabergoline in the blood reaches a stable level after 4 weeks of regular use.
7. Effects of food: Taking cabergoline with food may slow the rate of absorption but does not usually have a significant effect on overall bioavailability.

Dosing and administration

Method of application:

• Tablets are intended for oral administration.
• The tablet should be taken with food to reduce the risk of gastrointestinal side effects.

Dosage:

To suppress postpartum lactation:

• The recommended dose is 1 mg (2 tablets of 0.5 mg) once.

To stop already established lactation:

• It is recommended to take 0.25 mg (half a tablet) every 12 hours for 2 days (total dose - 1 mg).

For the treatment of hyperprolactinemia:

• Initial dose is 0.5 mg per week (0.25 mg twice weekly).
• The dose can be increased by 0.5 mg per week at intervals of at least 4 weeks until the optimal therapeutic effect is achieved.
• The maximum dose should not exceed 4.5 mg per week.

Special instructions:

• Patients who take Dostinex for a long time should undergo regular examinations to monitor heart function, including echocardiography.
• Treatment with Dostinex should be carried out under the supervision of a physician.
• If a dose is missed, do not double the next dose. The next dose should be taken at the usual time.

Use Dostinexa during pregnancy

The use of Dostinex during pregnancy requires a careful approach and strict supervision by a doctor. The main reason for prescribing Dostinex is hyperprolactinemia, which often causes infertility. Here are the research-based highlights:

1. Cabergoline Safety Study in Pregnancy: The study assessed the effects of cabergoline on pregnancy and the fetus in women who became pregnant while receiving cabergoline therapy. Based on data from 103 pregnancies, no significant complications were identified during pregnancy. A few cases of spontaneous abortions have been reported, and newborns are generally healthy with no significant malformations (Stalldecker et al., 2010).
2. No direct negative effect on pregnancy: Another study confirmed that cabergoline does not have a direct negative effect on the course and outcome of pregnancy in women receiving the drug in therapeutic doses before pregnancy and in the first 8 weeks of gestation (Dzeranova et al., 2016 ).

Cabergoline can be used during pregnancy to treat hyperprolactinemia under strict medical supervision. However, its use should occur under the careful supervision of a specialist, taking into account the potential risks and benefits for the patient and the fetus.

Contraindications

1. Allergy: People with known hypersensitivity or allergy to cabergoline or any other component of the drug should avoid its use.
2. Pregnancy: The use of cabergoline is not recommended during pregnancy, as its safety for the fetus has not been established. If you are planning to become pregnant or are pregnant, you should discuss the risks and benefits of using the drug with your doctor.
3. Hypotension: Cabergoline may cause a drop in blood pressure, so its use may be contraindicated in patients with low blood pressure or a recent heart attack.
4. Cardiovascular disease: Cabergoline may be contraindicated in patients with serious cardiovascular disease, such as heart failure or hypertension.
5. Heart valvular disease: In people with heart valvular disease, the use of cabergoline may also be contraindicated due to its possible effect on heart valve function.
6. Hyperprolactinemic tumors: The use of cabergoline may be undesirable in patients with hyperprolactinemic tumors, such as prolactinoma, without first consulting a doctor.
7. Renal failure: Patients with severe renal impairment should use cabergoline with caution and under medical supervision.

Side effects Dostinexa

1. Dizziness or drowsiness.
2. Headache.
3. Nausea, vomiting, or abdominal pain.
4. Constipation or diarrhea.
5. Fatigue or weakness.
6. Insomnia or other sleep disorders.
7. Feeling nervous or anxious.
8. Mental changes such as depression or mood changes.
9. Visual disturbances or changes in visual perception.
10. Chest pain.
11. Swelling, especially in the legs or lower legs.
12. Unusual or unexplained weight changes.
13. Sexual dysfunction, including decreased libido or erection problems.
14. Allergic reactions such as itching, hives, or swelling of the face, lips, or tongue.

Overdose

1. Hypotension: a decrease in blood pressure to dangerous levels, which can lead to fainting or collapse.
2. Mental disorders: drowsiness, dizziness, slow reactions, possibly daytime sleepiness and depression.
3. Digestive disorders: nausea, vomiting, diarrhea, possibly severe abdominal pain.
4. Other symptoms: headache, sleep disturbances, changes in appetite.

Interactions with other drugs

1. Drugs that affect the dopamine receptor: Because cabergoline is a dopamine receptor agonist, combination with other drugs that affect the dopamine system (eg, dopamine antagonists) may cause an interaction and alter their effectiveness.
2. Drugs metabolized via CYP3A4: Cabergoline is metabolized primarily via the CYP3A4 isoenzyme in the liver. Therefore, drugs that are CYP3A4 inhibitors or inducers may alter cabergoline blood concentrations. Examples include CYP3A4 inhibitors such as ketoconazole, clarithromycin, ritonavir, and inducers such as carbamazepine, phenytoin, rifampicin.
3. Drugs that increase somatostatin: Cabergoline may interact with drugs that increase somatostatin levels in the body, such as octreotide. This may cause a change in the effect of both cabergoline and other drugs.
4. Antihypertensive drugs: Cabergoline may enhance the hypotensive effect of antihypertensive drugs such as alpha-blockers or blood pressure-lowering drugs. This may lead to increased side effects such as dizziness or orthostatic hypotension.
5. Serotonin-increasing drugs: Cabergoline may interact with drugs that increase serotonin levels, such as serotonin reuptake inhibitors (SSRIs) or monoamine oxidase inhibitors (MAOIs), which may increase the risk of serotonin hyperstimulation syndrome.