MIRAPEXIN 0.35 mg TABLETS

2. What you need to know before you take MIRAPEXIN

Do not take MIRAPEXIN

• if you are allergic to pramipexole or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Tell your doctor before you start taking MIRAPEXIN. Inform your doctor if you have or have had any disease or symptoms, especially any of the following:

• Kidney disease.

• Hallucinations (seeing, hearing or feeling things that are not there). Most hallucinations are visual.
• Dyskinesia (e.g. abnormal involuntary movements of the limbs). If you have advanced Parkinson's disease and are also taking levodopa, you may experience dyskinesia during the gradual increase in MIRAPEXIN dose.
• Dystonia (inability to keep the trunk and neck straight and upright [axial dystonia]). In particular, you may experience forward bending of the head and neck (also called antecollis), forward bending of the lumbar region (also called camptocormia) or sideways bending of the back (also called pleurothotonus or Pisa syndrome).
• Somnolence and sudden episodes of sleep.
• Psychosis (e.g. similar to symptoms of schizophrenia).
• Visual impairment. You should have regular eye examinations during treatment with MIRAPEXIN.
• Severe heart or blood vessel disease. You should have regular blood pressure checks, especially at the start of treatment, to avoid postural hypotension (a drop in blood pressure when standing up).
• Increased restless legs syndrome. If you experience that the symptoms start earlier than usual at night (or even in the afternoon), are more intense or affect larger areas of the affected limbs or affect other limbs. Your doctor may reduce your dose or stop treatment.

Tell your doctor if you, your family or caregivers notice that you are developing impulses or cravings to behave in an unusual way for you and that you cannot resist the impulse, instinct or temptation to carry out certain activities that may harm you or others. This is called impulse control disorder and may include behaviors such as addiction to gambling, excessive eating or spending, abnormally high sexual urges or interests. Your doctor may need to adjust your dose or stop treatment.

Tell your doctor if you, your family or caregivers notice that you are developing mania (agitation, feeling elated or overexcited) or delirium (decreased consciousness, confusion or loss of contact with reality). Your doctor may need to adjust your dose or stop treatment.

Tell your doctor if you notice symptoms such as depression, apathy, anxiety, fatigue, sweating or pain when stopping or reducing treatment with MIRAPEXIN. If the problems persist for more than a few weeks, your doctor may need to adjust your treatment.

Tell your doctor if you notice inability to keep the trunk and neck straight and upright (axial dystonia). In this case, your doctor may decide to adjust or modify your treatment.

Children and adolescents

MIRAPEXIN is not recommended for use in children or adolescents under 18 years of age.

Other medicines and MIRAPEXIN

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. This includes medicines, herbal remedies, natural products or nutritional supplements that you have obtained without a prescription.

You should avoid using MIRAPEXIN with antipsychotic medicines.

Be cautious if you are using the following medicines:

• cimetidine (for the treatment of excess acid and stomach ulcers)
• amantadine (which may be used in the treatment of Parkinson's disease)
• mexiletine (for the treatment of irregular heartbeats, a disorder known as ventricular arrhythmia)
• zidovudine (which may be used to treat acquired immune deficiency syndrome [AIDS], a disease of the human immune system)
• cisplatin (to treat various types of cancer)
• quinine (which may be used to prevent painful leg cramps that occur at night and to treat a type of malaria known as falciparum malaria [malignant malaria])
• procainamide (to treat irregular heartbeat)

If you are taking levodopa, it is recommended to reduce the levodopa dose when starting treatment with MIRAPEXIN.

Be cautious if you are using sedative medicines (with a sedative effect) or if you drink alcohol. In these cases, MIRAPEXIN may affect your ability to drive and operate machinery.

Taking MIRAPEXIN with food, drinks and alcohol

You should be cautious if you drink alcohol during treatment with MIRAPEXIN.

You can take MIRAPEXIN with or without food.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine. Your doctor will tell you if you should continue treatment with MIRAPEXIN.

The effect of MIRAPEXIN on the fetus is not known. Therefore, do not take MIRAPEXIN if you are pregnant unless your doctor tells you to.

MIRAPEXIN should not be used during breast-feeding. MIRAPEXIN may decrease milk production. Additionally, it may pass into breast milk and reach your baby. If the use of MIRAPEXIN is essential, breast-feeding should be discontinued.

Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines

MIRAPEXIN may cause hallucinations (seeing, hearing or feeling things that are not there). If this happens, do not drive or use machines.

MIRAPEXIN has been associated with somnolence and sudden episodes of sleep, especially in patients with Parkinson's disease. If you experience these side effects, do not drive or operate machinery. Tell your doctor if this happens to you.

3. How to take MIRAPEXIN

Take this medicine exactly as your doctor has told you. If you are not sure, ask your doctor again. Your doctor will tell you the correct dose.

You can take MIRAPEXIN with or without food. The tablets should be swallowed with water.

Parkinson's disease

The daily dose should be taken divided into 3 equal doses.

During the first week, the usual dose is 1 tablet of MIRAPEXIN 0.088 mg three times a day (equivalent to 0.264 mg daily):

This dose will be increased every 5-7 days according to your doctor's instructions until your symptoms are controlled (maintenance dose).

The usual maintenance dose is 1.1 mg per day. However, it may be necessary to increase your dose further. If necessary, your doctor may increase your tablet dose up to a maximum of 3.3 mg of pramipexole per day. It is also possible to reduce the maintenance dose to three tablets of MIRAPEXIN 0.088 mg per day.

Patient with kidney disease

If you have moderate or severe kidney disease, your doctor will prescribe a lower dose. In this case, you should take the tablets only once or twice a day. If you have moderate kidney impairment, the usual starting dose is 1 tablet of MIRAPEXIN 0.088 mg twice a day. If you have severe kidney impairment, the usual starting dose is 1 tablet of MIRAPEXIN 0.088 mg per day.

Restless legs syndrome

The dose is usually given once a day, in the evening, 2-3 hours before bedtime.

During the first week, the usual dose is 1 tablet of MIRAPEXIN 0.088 mg once a day (equivalent to 0.088 mg per day):

This dose will be increased every 4-7 days according to your doctor's instructions until your symptoms are controlled (maintenance dose).

The daily dose should not exceed 6 tablets of MIRAPEXIN 0.088 mg or a dose of 0.54 mg (0.75 mg of pramipexole salt).

If you stop taking your tablets for a few days and want to start treatment again, you should start again with the smallest dose and then gradually increase the dose as you did the first time. Ask your doctor if you have any doubts.

Your doctor will assess your treatment after 3 months to decide whether to continue or not with the treatment.

Patient with kidney disease

If you have severe kidney disease, MIRAPEXIN may not be a suitable treatment for you.

If you take more MIRAPEXIN than you should

If you accidentally take too many tablets,

• contact your doctor or the nearest hospital emergency department immediately.
• you may experience vomiting, restlessness or any of the side effects described in section 4, "Possible side effects".

If you forget to take MIRAPEXIN

Do not worry. Omit that dose completely and take the next dose at the correct time. Do not take a double dose to make up for forgotten doses.

If you stop taking MIRAPEXIN

Do not stop your treatment with MIRAPEXIN without consulting your doctor first. If you need to stop your treatment with this medicine, your doctor will reduce your dose gradually. This reduces the risk of worsening symptoms.

If you have Parkinson's disease, do not stop your treatment with MIRAPEXIN abruptly. Sudden interruption can cause a condition called neuroleptic malignant syndrome, which can be a serious risk to your health. The symptoms include:

• akinesia (loss of muscle movement)
• muscle rigidity
• fever
• unstable blood pressure
• tachycardia (increased heart rate)
• confusion
• decreased level of consciousness (e.g. coma)

If you stop treatment or reduce the dose of MIRAPEXIN, you may also experience a medical condition called dopamine agonist withdrawal syndrome. The symptoms include depression, apathy, anxiety, fatigue, sweating or pain. If you experience these symptoms, you should contact your doctor.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them. The classification of adverse effects is based on the following frequencies:

If you have Parkinson's disease, you may experience the following adverse effects:

Very Common:

• Dyskinesia (e.g., abnormal involuntary movements of the limbs)
• Somnolence
• Dizziness
• Nausea

Common:

• Need to behave in an unusual way
• Hallucinations (seeing, hearing, or feeling things that are not present)
• Confusion
• Fatigue
• Insomnia
• Excess fluid, usually in the legs (peripheral edema)
• Headache
• Hypotension (low blood pressure)
• Abnormal dreams
• Constipation
• Visual disturbance
• Vomiting
• Weight loss, including loss of appetite

Uncommon:

• Paranoia (e.g., excessive concern for one's health)
• Delusion
• Excessive daytime somnolence and sudden episodes of sleep
• Amnesia (memory impairment)
• Hyperkinesia (increased movement and inability to remain still)
• Weight gain
• Allergic reactions (e.g., skin rash, itching, hypersensitivity)
• Fainting
• Heart failure (heart problems that can cause shortness of breath or swelling of the ankles)*
• Inadequate secretion of antidiuretic hormone*
• Restlessness
• Dyspnea (difficulty breathing)
• Hiccup
• Pneumonia (lung infection)
• Inability to resist the impulse, instinct, or temptation to perform an action that may be harmful to oneself or others, including:

• Strong impulse to gamble excessively despite serious personal or family consequences.
• Altered or increased sexual interest and behavior that is concerning to you or others, for example, increased sexual desire.
• Uncontrollable excessive shopping or spending.
• Binge eating (consuming large amounts of food in a short period) or compulsive eating (consuming more food than normal and more than needed to satisfy hunger).*
• Delirium (decreased consciousness, confusion, loss of contact with reality)

Rare:

• Mania (agitation, feeling elated or overexcited)

Frequency Not Known:

• After stopping or reducing treatment with MIRAPEXIN: depression, apathy, anxiety, fatigue, sweating, or pain (known as dopamine agonist withdrawal syndrome or DAWS) may occur.

Tell your doctor if you experience any of these behaviors; he will explain how to manage or reduce the symptoms.

For the adverse effects marked with *, it is not possible to provide a precise estimate of the frequency, as these adverse effects were not observed in clinical trials among 2,762 patients treated with pramipexole. The frequency category is probably no higher than "uncommon".

If you have restless legs syndrome, you may experience the following adverse effects:

Very Common:

• Nausea
• Symptoms that start earlier than usual, are more intense, or affect other limbs (increase in restless legs syndrome).

Common:

• Changes in sleep patterns, such as insomnia and somnolence
• Fatigue
• Headache
• Abnormal dreams
• Constipation
• Dizziness
• Vomiting

Uncommon:

• Need to behave in an unusual way*
• Heart failure (heart problems that can cause shortness of breath or swelling of the ankles)*
• Inadequate secretion of antidiuretic hormone*
• Dyskinesia (e.g., abnormal involuntary movements of the limbs)
• Hyperkinesia (increased movement and inability to remain still)*
• Paranoia (e.g., excessive concern for one's health)*
• Delusion*
• Amnesia (memory impairment)*
• Hallucinations (seeing, hearing, or feeling things that are not present)
• Confusion
• Excessive daytime somnolence and sudden episodes of sleep
• Weight gain
• Hypotension (low blood pressure)
• Excess fluid, usually in the legs (peripheral edema)
• Allergic reactions (e.g., skin rash, itching, hypersensitivity)
• Fainting
• Restlessness
• Visual disturbance
• Weight loss, including loss of appetite
• Dyspnea (difficulty breathing)
• Hiccup
• Pneumonia (lung infection)*
• Inability to resist the impulse, instinct, or temptation to perform an action that may be harmful to oneself or others, including:

• Strong impulse to gamble excessively despite serious personal or family consequences.*
• Altered or increased sexual interest and behavior that is concerning to you or others, for example, increased sexual desire.*
• Uncontrollable excessive shopping or spending.*
• Binge eating (consuming large amounts of food in a short period) or compulsive eating (consuming more food than normal and more than needed to satisfy hunger).*

• Mania (agitation, feeling elated or overexcited)*
• Delirium (decreased consciousness, confusion, loss of contact with reality)*

Frequency Not Known:

• After stopping or reducing treatment with MIRAPEXIN: depression, apathy, anxiety, fatigue, sweating, or pain (known as dopamine agonist withdrawal syndrome or DAWS) may occur.

Tell your doctor if you experience any of these behaviors; he will explain how to manage or reduce the symptoms.

For the adverse effects marked with *, it is not possible to provide a precise estimate of the frequency, as these adverse effects were not observed in clinical trials among 1,395 patients treated with pramipexole. The frequency category is probably no higher than "uncommon".

Reporting of Adverse Effects

If you experience any adverse effects, consult your doctor or pharmacist, even if they are possible adverse effects that are not listed in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of MIRAPEXIN

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiration date stated on the carton after EXP. The expiration date is the last day of the month indicated.

Do not store above 30°C.

Store in the original packaging to protect from light.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of the packaging and any unused medicine. This will help protect the environment.

6. Package Contents and Additional Information

Composition of MIRAPEXIN

The active ingredient is pramipexole.

Each tablet contains 0.088 mg, 0.18 mg, 0.35 mg, or 0.7 mg of pramipexole as 0.125 mg, 0.25 mg, 0.5 mg, or 1 mg of pramipexole dihydrochloride monohydrate, respectively.

The other ingredients are mannitol, cornstarch, colloidal anhydrous silica, povidone K 25, and magnesium stearate.

Appearance and Packaging of the Product

The MIRAPEXIN 0.088 mg tablets are white, round, flat, and without a score line.

The MIRAPEXIN 0.18 mg and MIRAPEXIN 0.35 mg tablets are white, oval, and flat. The tablets are scored on both sides and can be divided into two equal parts.

The MIRAPEXIN 0.7 mg tablets are white, round, and flat. The tablets are scored on both sides and can be divided into two equal parts.

All tablets have the Boehringer Ingelheim company symbol embossed on one side and the codes P6, P7, P8, or P9 on the other side, representing the tablet strength: 0.088 mg, 0.18 mg, 0.35 mg, and 0.7 mg, respectively.

All strengths of MIRAPEXIN are available in aluminum blister packs of 10 tablets per strip, in boxes of 3 or 10 blister packs (30 or 100 tablets). Not all pack sizes may be marketed.

Marketing Authorization Holder

Boehringer Ingelheim International GmbH

Binger Strasse 173

55216 Ingelheim am Rhein

Germany

Manufacturer

Boehringer Ingelheim Pharma GmbH & Co. KG

Binger Strasse 173

55216 Ingelheim am Rhein

Germany

Rottendorf Pharma GmbH

Ostenfelder Strasse 51 – 61

59320 Ennigerloh

Germany

Boehringer Ingelheim France

100-104 avenue de France

75013 Paris

France

You can obtain more information about this medicine by contacting the local representative of the marketing authorization holder:

Date of Last Revision of this Leaflet:{MM/AAAA}.

Detailed information on this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu.