Dostinex

Package leaflet: Information for the user

Warning! Keep this leaflet. The information on the immediate packaging is in a foreign language.
Dostinex, 0.5 mg, tablets
Cabergolinum
Please read all of this leaflet carefully before taking this medicine because it contains
important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, please ask your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm other people, even if their symptoms are the same.
• If you experience any adverse effects, including any not listed in this leaflet, please inform your doctor, pharmacist or nurse. See section 4.

Contents of the leaflet

1. What Dostinex is and what it is used for
2. What you need to know 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 D receptors on the cells of the anterior pituitary gland, thereby inhibiting prolactin secretion.
Dostinex is indicated:

• for the inhibition of lactation immediately after childbirth or for the cessation of milk secretion,
• for the treatment of disorders associated with excessive prolactin secretion (hyperprolactinemia), including menstrual disorders (absent, scanty or irregular menstruation), anovulation, and galactorrhea,
• for 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 had fibrosis (scarring) of the heart, lungs, or abdomen;
• if the patient is to receive long-term treatment with Dostinex and has had current or past 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 medicine should be considered;
• when concomitantly using antihypertensive drugs, as orthostatic hypotension may occur after cabergoline administration (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 may occur – dose reduction or discontinuation of treatment should be considered;
• if the patient has current or past fibrotic (scarring) reactions of the heart muscle, lungs, or abdominal organs. In patients receiving long-term Dostinex treatment, the doctor will check heart, lung, and kidney function before starting treatment. Echocardiographic examinations (ultrasound of the heart) will be performed before treatment initiation 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 caused by 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 sexual drive, or intensified sexual thoughts and feelings. Your doctor may decide to adjust or discontinue treatment.

Women in the immediate postpartum period may be more susceptible to certain adverse events, including high blood pressure, heart attack, seizures, stroke, and psychiatric disturbances. For this reason, your 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.
Dostinex should not be used in women with pregnancy-induced hypertension, pre-eclampsia, or postpartum hypertension unless potential benefits outweigh the risks. To avoid orthostatic hypotension, single doses of Dostinex exceeding 0.25 mg should not be used to suppress ongoing lactation in breastfeeding women.
Before starting Dostinex, a thorough evaluation of pituitary function is recommended.
Since Dostinex restores ovulation and fertility in women with hyperprolactinemia-related hypogonadism, a pregnancy test should be performed at least every 4 weeks during the period 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. Women who become pregnant 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 Dostinex treatment.
• Dostinex should not be taken together with phenothiazines, butyrophenones, thioxanthenes (antipsychotic drugs), or metoclopramide (a drug used for upper gastrointestinal motility disorders), as these 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 medications.

Dostinex with food and drink
Tolerance of dopaminergic drugs is better 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.
Pregnancy must be excluded before starting treatment with Dostinex. Furthermore, 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 benefit versus risk.
Due to the long half-life of the drug and limited data on fetal exposure, women planning pregnancy should discontinue Dostinex one month before the intended conception.
If conception occurs during treatment, therapy should be discontinued immediately after pregnancy is confirmed to minimize fetal exposure to the drug.
Considering the mechanism of action of Dostinex, suppression or reduction of lactation is expected during treatment. Women taking Dostinex must not breastfeed.

Driving and operating machinery
Patients should exercise caution when performing activities requiring rapid and accurate responses at the beginning of Dostinex treatment.
Patients taking Dostinex who experience somnolence and/or sudden sleep attacks must not drive or perform activities where impaired alertness could endanger themselves or others (e.g., operating machinery) until such symptoms resolve.

Dostinex contains lactose. If the patient has previously been diagnosed with intolerance to certain sugars, the patient should consult a doctor before taking this medicine.

3. How to use Dostinex

This medicine should always be taken 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 during meals.
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 effects.
If persistent or severe adverse effects 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 the
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 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 stopping therapy.

Use in children and adolescents
The safety and efficacy of Dostinex have not been evaluated 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: Warnings and precautions).

Use in elderly patients
No formal studies have been conducted 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 your 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 use supportive measures to eliminate any 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 close to the
time for the next dose. In that case, the patient should take the next dose at the scheduled time. Do
not take a double dose to make up for a missed dose.

Discontinuation of Dostinex
The decision to discontinue treatment should 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 effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.
Adverse effects observed during use of the medicine to suppress lactation:
The adverse effects have been listed according to frequency. 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 effects were in most cases transient and mild to moderate in intensity.
During the first 3–4 days after childbirth, asymptomatic decreases in blood pressure (≥20 mmHg systolic and ≥10 mmHg diastolic) may occur.

Adverse effects observed during use of the medicine in the treatment of disorders related to excessive prolactin secretion:
The adverse effects have been listed according to frequency. 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 effects were mostly mild to moderate in intensity and occurred primarily 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 effects are mainly dose-dependent.
Long-term use of Dostinex may cause lowering of blood pressure, although orthostatic hypotension and fainting have been reported rarely. Dostinex is a derivative of ergot, and therefore may have vasoconstrictive properties. With long-term use, abnormal results in standard laboratory tests are unlikely; in non-menstruating women, a decrease in hemoglobin has been observed within the first few months after resumption of menstruation.

The following adverse effects 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 behaviour, despite serious personal or family consequences,
  • Altered or increased sexual interests and behaviours of significance 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 experience any of these behaviours, so that ways of managing or reducing these symptoms can be discussed.
Adverse effects have been listed according to frequency of occurrence.

Very common (occurs in 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*
• Exhaustion***, fatigue

Common (occurs in 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 (occurs in more than 1 in 1,000 but less than 1 in 100 people)

• Palpitations
• Dyspnoea, pleural effusion, fibrosis (including pulmonary fibrosis), epistaxis
• Hypersensitivity reactions
• Transient hemianopia, fainting, paresthesia
• Increased libido
• Vasoconstriction of fingers
• Edema, peripheral edema
• Rash, alopecia
• Muscle cramps in lower limbs
• In non-menstruating women, decreased hemoglobin concentration has been observed during the first few months after resumption of menstruation

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

• Upper abdominal pain

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

• Pleural fibrosis

Not known: frequency cannot be estimated from available data

• Angina pectoris
• Respiratory disorders, respiratory failure, pleuritis, chest pain
• Sudden sleep attacks, tremor
• Visual disturbances
• Liver function disorders
• Increased blood creatine phosphokinase levels, 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 effects
If any adverse effects occur, including any not listed in this leaflet, patients should inform their doctor, pharmacist, or nurse. Adverse effects can be reported directly to the Department of Monitoring of Adverse Drug Reactions, 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 effects 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 the sight and reach of children.
Do not use this medicine after the expiry date stated on the container. The expiry date refers to the last day of the specified 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.
• 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" divided by a score line on one side, and the mark "700" with a small 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 screw cap, equipped with a child-resistant safety closure system, and placed in a cardboard box. The pack contains either 2 or 8 tablets.
For further information, please contact the responsible party or the parallel importer.
Marketing Authorisation Holder in Romania, 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:
Delfarma Sp. z o.o.
ul. Św. Teresy od Dzieciątka Jezus 111
91-222 Łódź, Poland
Repackaged in:
Delfarma Sp. z o.o.
ul. Św. Teresy od Dzieciątka Jezus 111
91-222 Łódź, Poland
Marketing Authorisation numbers in Romania, country of export: 11765/2019/01
11765/2019/02
11765/2019/03
11765/2019/04
Parallel Import Licence Number: 316/18