Dostinex

Patient Information Leaflet

Warning! Keep this leaflet! Information on the immediate packaging in a foreign language.
DOSTINEX, 0.5 mg, tablets
Cabergoline
Please read carefully the entire leaflet before using the medicine, as it contains
important information for the patient.

• Keep this leaflet for possible future reference.
• If you have any doubts, consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm someone else, even if their symptoms are identical.
• If you experience any adverse effects, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of Contents

1. What Dostinex is and what it is used for
2. Important information before taking Dostinex
3. How to take Dostinex
4. Possible side effects
5. How to store Dostinex
6. Contents of the pack and other information

1. What Dostinex is and what it is used for

Dostinex is an ergoline derivative with dopaminergic activity, which strongly and long-lastingly reduces prolactin levels. It acts by directly stimulating dopamine D₂ receptors on cells of the anterior pituitary gland, thereby inhibiting prolactin secretion. Dostinex is indicated:

• to suppress lactation immediately after childbirth or to stop milk production;
• in the treatment of disorders associated with excessive prolactin secretion (hyperprolactinemia), including menstrual disorders (absent, scanty, or irregular menstruation), anovulation, and galactorrhea;
• in the treatment of pituitary adenoma, idiopathic hyperprolactinemia, or empty sella syndrome associated with hyperprolactinemia.

2. Important information before using Dostinex

When not to use Dostinex:

• if the patient is allergic to cabergoline or any of the other ingredients of this medicine (listed in section 6);
• if the patient is allergic to other ergot derivatives;
• if the patient currently has or has previously had fibrotic (scarring) disorders affecting the heart, lungs, or abdomen;
• if the patient is to receive long-term treatment with Dostinex and has current or past history of fibrotic (scarring) reactions of the heart muscle.

Warnings and precautions
Before starting treatment with Dostinex, discuss the following with your doctor:

• in patients with severe cardiovascular disorders;
• in patients with Raynaud's syndrome;
• in patients with peptic ulcer disease or gastrointestinal bleeding;
• in patients with a history of serious psychiatric disorders, particularly psychosis;
• in patients with severe hepatic insufficiency – lower doses of the drug should be considered;
• when concomitantly using antihypertensive drugs, as orthostatic hypotension may occur after administration of cabergoline (especially during the first days of treatment);
• in patients who have symptoms of respiratory or cardiovascular disorders related to fibrotic processes or a history suggestive of such disorders;
• in patients with Parkinson's disease, episodes of sudden sleep onset may occur – dose reduction or discontinuation of treatment should be considered;
• if the patient has current or past history of fibrotic (scarring) reactions of the heart muscle, lungs, or abdominal organs. In patients receiving long-term treatment with Dostinex, the doctor will check before starting treatment whether heart, lung, and kidney function are normal. Echocardiographic examinations (ultrasound of the heart) will be performed before starting treatment and at regular intervals during treatment. If fibrotic reactions occur, treatment will be discontinued;
• inform your doctor if you or your family members notice unusual behaviors due to irresistible impulses, compulsions, or obsessive performance of certain actions that may be harmful to the patient or others. These behaviors are known as impulse control disorders and may include gambling addiction, compulsive or binge eating, increased sex drive, or intense sexual thoughts and feelings. The doctor may decide to adjust the treatment or discontinue the medicine.

Women in the immediate postpartum period may be more susceptible to certain adverse events,
including high blood pressure, heart attack, seizures, stroke, and psychiatric disorders. For this
reason, the doctor will need to monitor blood pressure regularly during treatment. If a woman
experiences high blood pressure, chest pain, or an unusually severe or persistent headache (with or
without visual disturbances), she should inform her doctor immediately.
The medicine should not be used in women with pregnancy-induced hypertension, pre-eclampsia,
or postpartum hypertension, unless the potential benefits outweigh the risks.
To avoid orthostatic hypotension, the single dose of Dostinex should not exceed 0.25 mg when
suppressing established lactation in breastfeeding women.
Before starting treatment with Dostinex, a detailed assessment of pituitary function is recommended.
Since Dostinex restores ovulation and fertility in women with hypogonadism due to hyperprolactinemia,
a pregnancy test should be performed at least every 4 weeks before menstruation resumes, and thereafter
whenever menstrual bleeding is delayed by more than 3 days. Women who wish to avoid pregnancy
should use mechanical contraceptive methods during treatment with Dostinex and after discontinuation
of the drug until ovulation ceases again. Pregnant women should be monitored for symptoms of
pituitary enlargement, as pre-existing pituitary tumors may grow during pregnancy.
In patients treated with dopamine agonists, including cabergoline, pathological gambling behavior,
increased libido, and hypersexuality have been observed. These symptoms were usually reversible
upon dose reduction or discontinuation of the drug.
Consult your doctor, even if the above warnings relate to conditions that occurred in the past.

Dostinex and other medicines
Inform your doctor about all medicines you are currently taking, including those available without
a prescription.

• There is no information on interactions between cabergoline and other ergot alkaloids; therefore, concomitant use of these drugs is not recommended during long-term treatment with Dostinex.
• Dostinex should not be taken together with phenothiazines, butyrophenones, thioxanthenes (antipsychotic drugs), or metoclopramide (a drug used for upper gastrointestinal motility disorders), as these drugs may reduce the therapeutic effect of Dostinex.
• Dostinex, like other ergot derivatives, should not be used concomitantly with macrolide antibiotics (e.g., erythromycin) due to increased bioavailability of cabergoline.
• Dostinex may cause orthostatic hypotension in patients taking antihypertensive drugs.

Dostinex with food and drink
Tolerance of dopaminergic drugs is improved when taken with food; therefore, it is recommended to take Dostinex with meals.

Pregnancy, breastfeeding, and fertility
If you are pregnant, breastfeeding, think you may be pregnant, or are planning to have a baby, you should consult your doctor or pharmacist before using this medicine.
Before starting treatment with Dostinex, pregnancy must be excluded. Additionally, measures to prevent pregnancy should be taken for at least one month after stopping treatment with Dostinex.
There are no clinical data on the use of Dostinex in pregnant women. Animal studies have shown reduced fertility and potential fetal toxicity.
Dostinex should be used during pregnancy only if clearly indicated and after careful assessment of the benefit-risk ratio.
Due to the long half-life of the drug and limited data on fetal exposure, women planning to become pregnant should discontinue Dostinex one month before the planned conception. If conception occurs during treatment, therapy should be discontinued immediately upon confirmation of pregnancy to minimize fetal exposure to the drug.
Considering the mechanism of action of Dostinex, inhibition or suppression of lactation is expected during treatment. Women taking Dostinex must not breastfeed.

Driving and using machines
Patients should exercise caution when performing activities requiring rapid and accurate responses at the beginning of treatment with Dostinex.
Patients taking Dostinex who experience somnolence and/or sudden onset of sleep attacks must not drive or perform activities where impaired alertness could put themselves or others at risk of serious injury or death (e.g., operating machinery) until somnolence and/or sudden sleep attacks have resolved.

Dostinex contains lactose. If you have been previously diagnosed with intolerance to certain sugars, you should consult your doctor before taking this medicine.

3. How to use Dostinex

This medicine should always be used exactly as prescribed by your doctor. If in doubt, consult your
doctor or pharmacist.
Dostinex is intended for oral administration. It is recommended to take Dostinex with food.
In patients who are intolerant to dopaminergic drugs, the doctor may decide to initiate treatment
with a reduced dose (e.g. 0.25 mg once weekly), gradually increasing the dose until the therapeutic
dose is reached, in order to reduce the likelihood of adverse reactions.
If persistent or severe adverse reactions occur, the doctor may decide to temporarily reduce the
dose to improve drug tolerance, then return to the therapeutic dose by gradually increasing it (e.g.
0.25 mg weekly, every two weeks).

Inhibition of lactation
The recommended dose is: 1 mg of cabergoline (2 tablets of 0.5 mg) on the first day after delivery.

Cessation of milk secretion
The recommended dose is: 0.25 mg (half a tablet) every 12 hours for two days.

Treatment of disorders associated with excessive prolactin secretion
The recommended initial dose is 0.5 mg per week, administered as a single dose (1 tablet of 0.5 mg)
or in two doses (twice weekly, half a tablet each time, e.g. on Monday and Thursday).
The weekly dose should be gradually increased, preferably by 0.5 mg per week at monthly
intervals, until optimal therapeutic effect is achieved. The therapeutic dose ranges from 0.25 mg
to 2 mg per week, with an average of 1 mg per week. Doses up to 4.5 mg weekly have been used
in patients with hyperprolactinemia.
The doctor will decide on the appropriate administration schedule of the weekly dose—either as a
single dose or divided into two or more doses—depending on drug tolerance.
The doctor will determine the lowest effective dose that achieves the therapeutic effect. After the
therapeutic dose is established, the doctor will decide on appropriate monitoring of serum
prolactin levels.
Normalization of prolactin levels is usually achieved within 2–4 weeks.
After discontinuation of Dostinex therapy, hyperprolactinemia usually recurs. However, in some
patients, a sustained reduction in prolactin levels has been observed for several months. In most
women, ovulatory cycles occurred for at least 6 months after treatment ended.

Use in children and adolescents
The safety and efficacy of Dostinex have not been established in patients under 16 years of age.

Use in patients with hepatic impairment
In patients with severe liver dysfunction, dose reduction of Dostinex should be considered (see
section: When to be cautious with Dostinex).

Use in elderly patients
There have been no systematic studies on the use of Dostinex in elderly patients with disorders
related to excessive prolactin secretion.

Use of a higher than recommended dose of Dostinex
If an overdose of Dostinex is taken, contact a doctor immediately. Symptoms of overdose are
presumably similar to those associated with excessive stimulation of dopamine receptors, such as
nausea, vomiting, gastrointestinal disturbances, orthostatic hypotension, confusion, and/or
psychosis or hallucinations.
If necessary, the doctor will employ supportive measures to remove unabsorbed drug and stabilize
blood pressure. Additionally, the doctor may administer dopamine antagonists as treatment.

Missed dose of Dostinex
If a patient forgets to take Dostinex, they should take it as soon as possible, unless it is almost time
for the next dose. In that case, the patient should take the next dose at the scheduled time. A
double dose should not be taken to make up for a missed dose.

Discontinuation of Dostinex
The decision to discontinue treatment must be made by the doctor.
If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
Adverse reactions observed during the use of the medicine to suppress lactation:
The adverse reactions are listed according to frequency of occurrence. They reflect data from clinical trials using Dostinex administered at a dose of 1 mg, and in breastfeeding women receiving Dostinex at a dose of 0.25 mg every 12 hours to suppress lactation.
Reported adverse reactions were mostly transient and mild to moderate in intensity.
During the first 3–4 days after delivery, asymptomatic decreases in blood pressure (≥20 mmHg systolic and ≥10 mmHg diastolic) may occur.

Adverse reactions observed during the use of the medicine in the treatment of disorders associated with excessive prolactin secretion:
The adverse reactions are listed according to frequency of occurrence. They reflect data from 6-month clinical trials using Dostinex at weekly doses of 1 to 2 mg (administered in two weekly doses). Reported adverse reactions were mostly mild to moderate in intensity and occurred mainly during the first two weeks of treatment. Most of them resolved during continued treatment or within a few days after discontinuation of the medicine.

General information:
Adverse reactions are mainly dose-dependent.
Dostinex, when used long-term, may cause lowering of blood pressure, although orthostatic hypotension or fainting have been reported rarely.
Dostinex is an ergot derivative and therefore may have vasoconstrictive effects. With long-term use, abnormal results in standard laboratory tests are unlikely; in amenorrheic women, a decrease in hemoglobin has been observed within the first few months after resumption of menstruation.

The following adverse reactions may occur:

• inability to resist an impulse, urge, or compulsion to perform actions that may be harmful to the patient or others; this includes:
  • strong impulse or uncontrollable gambling, despite serious personal or family consequences,
  • altered or increased sexual interests and behaviors of significant concern to the patient or others, e.g., activities related to increased sexual drive,
  • compulsive, uncontrolled spending or shopping,
  • binge eating (consuming larger amounts of food than normal and more than needed to satisfy hunger).

Patients should inform their doctor if they exhibit any of these behaviors, so that ways of managing or reducing these symptoms can be discussed.
Adverse reactions are listed according to frequency of occurrence.

Very common (affects more than 1 in 10 people)

• heart valve disorders (including regurgitation) and associated conditions (pericarditis, pericardial effusion)
• headache*, central and/or peripheral dizziness*
• nausea*, dyspepsia, gastritis*, abdominal pain*
• asthenia***, fatigue

Common (affects more than 1 in 100 but less than 1 in 10 people)

• somnolence
• depression
• decreased blood pressure in patients undergoing long-term treatment; orthostatic hypotension, hot flushes**
• constipation, vomiting**
• breast pain
• asymptomatic decreases in blood pressure (systolic ≥20 mmHg and diastolic ≥10 mmHg)

Uncommon (affects more than 1 in 1,000 but less than 1 in 100 people)

• palpitations
• dyspnea, pleural effusion, fibrosis (including pulmonary fibrosis), epistaxis
• hypersensitivity reactions
• transient hemianopia, fainting, paresthesia
• increased libido
• digital vasoconstriction
• edema, peripheral edema
• rash, alopecia
• muscle cramps in lower limbs
• in amenorrheic women, decreased hemoglobin concentration has been observed during the first few months after resumption of menstruation

Rare (affects more than 1 in 10,000 but less than 1 in 1,000 people)

• epigastric pain

Very rare (affects less than 1 in 10,000 people)

• pleural fibrosis

Not known: frequency cannot be estimated from the available data

• painful angina
• respiratory disorders, respiratory failure, pleuritis, chest pain
• sudden sleep attacks, tremor
• visual disturbances
• liver function disorders
• increased blood creatine phosphokinase concentration, abnormal liver function tests

* Very common in patients treated for hyperprolactinemia; Common in women treated to suppress and/or inhibit lactation
** Common in patients treated for hyperprolactinemia; Uncommon in women treated to suppress and/or inhibit lactation
*** Very common in patients treated for hyperprolactinemia; Very common in women treated to suppress and/or inhibit lactation

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, patients should inform their doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring of Adverse Drug Reactions at the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl.
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store Dostinex

Store below 25°C, in the original packaging.
Keep the medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging.
The expiry date refers to the last day of the stated month.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What Dostinex contains

• The active substance is cabergoline. One tablet contains 0.5 mg of cabergoline.
• The other ingredients are: leucine, lactose.

What Dostinex looks like and contents of the pack
Dostinex is a white, flat, oblong tablet, embossed with the mark "PU" on one side and a breakline, and the mark "700" with a fine notch above and below the central "0" on the other side.
The tablets are contained in a brown glass bottle with an aluminium cap or in an HDPE bottle closed with a PP cap, equipped with a child-resistant closure system. The bottle is placed in a cardboard box.
The pack contains 2 or 8 tablets.
For more detailed information, please contact the Marketing Authorisation Holder or the parallel importer.
Marketing Authorisation Holder in Romania, the country of export:
PFIZER EUROPE MA EEIG
Boulevard de la Plaine 17
1050 Brussels, Belgium
Manufacturer:
Pfizer Italia S.r.l.
Località Marino del Tronto
63100 Ascoli Piceno (AP)
Italy
Parallel importer:
InPharm Sp. z o.o.
ul. Strumykowa 28/11
03-138 Warsaw, Poland
Repackaged in:
InPharm Sp. z o.o. Services sp. k.
ul. Chełmżyńska 249
04-458 Warsaw, Poland
Marketing Authorisation number in Romania, the country of export: 11765/2019/01
11765/2019/02
11765/2019/03
11765/2019/04
Parallel import licence number: 67/18