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, elevated levels of prolactin in the blood. Prolactin is a hormone that plays a role in regulating the mammary gland and affects various functions of the reproductive system.

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

It works by decreasing 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 Dostinex

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) that can lead to hyperprolactinemia.
2. Non-tumor hyperprolactinemia: In addition to prolactinomas, Dostinex can also be used to treat non-tumor hyperprolactinemia, where 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 that associated with high levels of prolactin.

Release form

Dostinex is available in tablet form.

• White, oblong tablets with a score line and engraving "P" and "U" on one side and "700" on the other.
• The tablets are supplied in glass bottles containing 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 the level of prolactin in the blood.
   • In addition, cabergoline has an inhibitory effect on the secretion of prolactin in the mammary glands, which also helps to reduce its level in the blood.

2. Use in hyperprolactinemia:

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

3. Use in suppressing 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. Effect on other hormonal axes:

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

Pharmacokinetics

1. Absorption: Cabergoline is generally well absorbed from the gastrointestinal tract after oral administration. Peak blood concentrations are reached approximately 2-3 hours after administration.
2. Bioavailability: The bioavailability of cabergoline is approximately 30-40% due to a high degree of first pass through the liver.
3. Metabolism: Cabergoline is metabolized in the liver, primarily by the CYP3A4 isoenzyme.
4. Elimination half-life: The elimination half-life of cabergoline is approximately 63-68 hours.
5. Excretion: Cabergoline is excreted primarily in the urine (partly unchanged and partly as metabolites) and to a lesser extent in the feces.
6. Systemic concentration: Blood concentrations of cabergoline reach a steady state after 4 weeks of regular administration.
7. Food effects: Taking cabergoline with food may slow the rate of its absorption, but usually does not significantly affect overall bioavailability.

Dosing and administration

Directions for use:

• The 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:

• The starting dose is 0.5 mg per week (0.25 mg twice per week).
• 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 taking Dostinex long-term should have regular check-ups to monitor their heart function, including echocardiography.
• Treatment with Dostinex should be carried out under the supervision of a physician.
• If you miss a dose, do not double the next dose. Take the next dose at the usual time.

Use Dostinex during pregnancy

Using Dostinex during pregnancy requires a cautious approach and strict monitoring by a physician. The main reason for prescribing Dostinex is hyperprolactinemia, which often causes infertility. Here are the main points based on research:

1. Cabergoline Pregnancy Safety Study: The study evaluated 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 during pregnancy were observed. A few cases of spontaneous abortions were reported, and the newborns were mostly healthy, without significant malformations (Stalldecker et al., 2010).
2. No direct negative impact on the course of pregnancy: Another study confirmed that cabergoline does not have a direct negative impact on the course and outcome of pregnancy in women who received the drug in therapeutic doses before pregnancy and in the first 8 weeks of gestation (Dzeranova et al., 2016).

Cabergoline may be used during pregnancy to treat hyperprolactinemia under strict medical supervision. However, its use should be under close specialist supervision, 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: 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 decrease in blood pressure, so its use may be contraindicated in patients with low blood pressure or a recent heart attack.
4. Cardiovascular disease: The use of cabergoline may be contraindicated in patients with serious cardiovascular disease such as heart failure or hypertension.
5. Heart valve disease: In people with heart valve disease, the use of cabergoline may also be contraindicated due to its possible effects on heart valve function.
6. Hyperprolactinemic tumors: The use of cabergoline may be inadvisable in patients with hyperprolactinemic tumors such as prolactinoma without prior consultation with a physician.
7. Renal impairment: Patients with severe renal impairment should use cabergoline with caution and under medical supervision.

Side effects Dostinex

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 calves.
12. Unusual or unexplained changes in weight.
13. Sexual dysfunction, including decreased libido or erectile problems.
14. Allergic reactions such as itching, hives, or swelling of the face, lips, or tongue.

Overdose

1. Hypotension: A drop in blood pressure to dangerous levels that can lead to fainting or collapse.
2. Psychiatric 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 disorders, changes in appetite.

Interactions with other drugs

1. Drugs acting on dopamine receptors: Since cabergoline is a dopamine receptor agonist, combination with other drugs acting on the dopamine system (e.g. dopamine antagonists) may cause interactions and alter their effectiveness.
2. Drugs Metabolized via CYP3A4: Cabergoline is metabolized primarily via the CYP3A4 isoenzyme in the liver. Therefore, drugs that are inhibitors or inducers of CYP3A4 may alter the blood concentration of cabergoline. 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 change the way both cabergoline and the other drugs work.
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 selective serotonin reuptake inhibitors (SSRIs) or monoamine oxidase inhibitors (MAOIs), which may increase the risk of serotonin hyperstimulation syndrome.