STALEVO 75 mg/18.75 mg/200 mg FILM-COATED TABLETS

2. What you need to know before you take Stalevo

Do not take Stalevo if:

• you are allergic to levodopa, carbidopa or entacapone, or any of the other ingredients of this medicine (listed in section 6)
  • you have narrow-angle glaucoma (a condition where the pressure in the eye is increased)
  • you have a tumor of the adrenal gland
  • you are taking certain medicines for depression (combinations of selective MAO-A and MAO-B inhibitors, or non-selective MAO inhibitors)
  • you have ever had neuroleptic malignant syndrome (NMS - a rare reaction to medicines used to treat severe mental disorders)
  • you have ever had non-traumatic rhabdomyolysis (a rare muscle disorder)
  • you have severe liver disease.

Warnings and precautions

Tell your doctor or pharmacist before you start taking Stalevo if you have or have had:

• a heart attack or any other heart disease, including arrhythmias, or blood vessel disease
• asthma or any other lung disease
• a liver problem, as you may need to have your dose adjusted
• any kidney disease or hormone-related disease
• stomach ulcer or convulsions
• prolonged diarrhea. Check with your doctor as it may be a sign of colon inflammation
• any severe mental disorder, such as psychosis
• open-angle glaucoma, as your dose may need to be adjusted and your eye pressure monitored.

Tell your doctor if you are taking:

• antipsychotics (medicines for treating psychosis)
• any medicine that may cause a drop in blood pressure when standing up from a chair or bed. You should be aware that Stalevo may worsen these reactions.

Tell your doctor if, while taking Stalevo, you:

• notice great stiffness in your muscles or that they contract violently, or if you suffer from tremors, agitation, confusion, fever, rapid pulse or large fluctuations in blood pressure. If any of these occur, contact your doctor immediately
• feel depressed, have suicidal thoughts or notice unusual changes in your behavior
• find that you suddenly fall asleep, or feel very drowsy. If this happens, do not drive or use tools or machines (see also section "Driving and using machines")
• notice that you have uncontrolled movements or that they get worse. If this happens, your doctor may need to adjust your dose of medication
• suffer from diarrhea; it is recommended to monitor your weight to avoid excessive weight loss
• suffer from progressive loss of appetite, asthenia (weakness, exhaustion) and weight loss over a relatively short period of time. In these cases, a complete medical evaluation should be considered, including a liver function test
• consider that you need to stop taking Stalevo; see the section "If you stop taking Stalevo".

Tell your doctor if you, or your family member/caregiver, notice that you are developing symptoms similar to addiction, which lead to a desire for high doses of Stalevo and other medicines used to treat Parkinson's disease.

Tell your doctor if you, or your family member/caregiver, notice that you are developing desires or tendencies to behave in ways that are unusual for you or that you cannot resist the impulse, determination or temptation to perform certain activities that may harm you or others. These behaviors are known as impulse control disorders and may include addiction to gambling, food or excessive spending, and an abnormally high sexual drive or preoccupation with sexual thoughts and feelings. Your doctor may need to review your treatment.

During prolonged treatment with Stalevo, your doctor may perform regular blood tests.

If you need to undergo surgery, tell your doctor that you are taking Stalevo.

Stalevo is not recommended for the treatment of extrapyramidal symptoms (e.g. involuntary movements, agitation, muscle rigidity and muscle contractions) caused by other medicines.

Children and adolescents

Experience with the use of Stalevo in patients under 18 years is limited. Therefore, it is not recommended for use in children or adolescents.

Taking Stalevo with other medicines

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.

Do not take Stalevo if you are taking certain medicines for depression (combinations of selective MAO-A and MAO-B inhibitors, or non-selective MAO inhibitors).

Stalevo may increase the effect, and also the side effects, of certain medicines. These include:

• medicines used to treat depression, such as moclobemide, amitriptyline, desipramine, maprotiline, venlafaxine and paroxetine
• ritodrine and isoprenaline, used to treat respiratory diseases
• adrenaline, used for severe allergic reactions
• noradrenaline, dopamine and dobutamine, used to treat heart diseases and low blood pressure
• alpha-methyldopa, used to treat high blood pressure
• apomorphine, used to treat Parkinson's disease.

Certain medicines may reduce the effect of Stalevo. These medicines are:

• dopamine antagonists used to treat mental disorders, nausea and vomiting
• phenytoin, used to prevent convulsions
• papaverine, used to relax muscles.

Stalevo may reduce the absorption of iron from the gut. Therefore, do not take Stalevo at the same time as iron supplements. If you take either, wait at least 2 or 3 hours before taking the other.

Taking Stalevo with food and drink

• Stalevo can be taken with or without food.
• It is possible that in some patients Stalevo may not be absorbed as well if taken with protein-rich foods (meat, fish, dairy products, cereals and nuts) or shortly after eating them. Check with your doctor if you think this applies to you.

Pregnancy, breast-feeding and fertility

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

You should not breast-feed while taking Stalevo.

Driving and using machines

Stalevo may lower your blood pressure, which may cause dizziness or fainting. Therefore, be careful when using tools or machines.

If you feel very tired or notice that you suddenly fall asleep, wait until you feel fully awake before driving or doing anything that requires you to be alert. Otherwise, you may put yourself and others at risk of serious accident or even death.

Stalevo contains sucrose

Stalevo contains sucrose (1.4 mg/tablet). If your doctor has told you that you have an intolerance to some sugars, check with them before taking this medicine.

3. How to take Stalevo

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

Adults and the elderly:

• Your doctor will tell you exactly how many Stalevo tablets to take each day.
  • The tablets must not be broken or divided into smaller pieces.
  • Take only one tablet at a time.
  • Depending on how you respond to treatment, your doctor may ask you to increase or decrease the dose.
  • If you are taking Stalevo 50 mg/12.5 mg/200 mg, 75 mg/18.75 mg/200 mg, 100 mg/25 mg/200 mg, 125 mg/31.25 mg/200 mg or 150 mg/37.5 mg/200 mg tablets, do not take more than 10 tablets per day.

Talk to your doctor or pharmacist if you think the effect of Stalevo is too strong or too weak, or if you experience possible side effects.

If you take more Stalevo than you should

If you accidentally take more Stalevo tablets than you should, talk to your doctor or pharmacist immediately. In case of overdose, you may feel dizzy or agitated, your heart rate may be slower or faster than normal, or your skin, tongue, eyes or urine may change color.

If you forget to take Stalevo

Do not take a double dose to make up for forgotten doses.

If it is more than 1 hour until your next dose:

Take a tablet as soon as you remember, and the next one at the usual time.

If it is less than 1 hour until your next dose:

Take a tablet as soon as you remember, wait 1 hour and take another tablet then. Then continue as usual.

There should always be an interval of 1 hour between Stalevo tablets to avoid possible side effects.

If you stop taking Stalevo

Do not stop taking Stalevo unless your doctor tells you to. If your doctor tells you to stop taking Stalevo, they may need to adjust the dose of your other Parkinson's medicines, especially levodopa, to control your symptoms. If you stop taking Stalevo and other Parkinson's medicines suddenly, you may experience unwanted side effects.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. Many can be relieved by adjusting the dose.

If you experience any of these symptoms while taking Stalevo, contact your doctor immediately:

• Great stiffness or violent contractions of the muscles, tremors, agitation, confusion, fever, rapid pulse or large fluctuations in blood pressure. These may be symptoms of neuroleptic malignant syndrome (NMS - a rare and serious reaction to medicines used to treat disorders of the central nervous system) or rhabdomyolysis (a rare and serious muscle disorder).
• An allergic reaction characterized by signs such as hives, itching, rash and swelling of the face, lips, tongue or throat. This reaction may cause difficulty breathing or swallowing.

Very common (may affect more than 1 in 10 people):

• uncontrolled movements (dyskinesias)
• feeling sick (nausea)
• brownish discoloration of urine (harmless)
• muscle pain
• diarrhea

Common (may affect up to 1 in 10 people):

• fainting or fainting due to low blood pressure, high blood pressure
• worsening of parkinsonian symptoms, dizziness, drowsiness
• vomiting; abdominal pain and discomfort; heartburn; dry mouth; constipation
• difficulty sleeping; hallucinations; confusion; abnormal dreams (with nightmares); fatigue
• changes in mental state, including memory problems, anxiety and depression (possibly with suicidal thoughts)
• heart or blood vessel disease (e.g. chest pain), irregular heartbeats
• more frequent falls
• breathlessness
• increased sweating, rash
• muscle cramps, swelling of the legs
• blurred vision
• anemia
• decreased appetite, weight loss
• headache, joint pain
• urinary tract infections

Uncommon (may affect up to 1 in 100 people):

• heart attack
• intestinal bleeding
• changes in blood cell counts that may cause bleeding; abnormalities in liver function tests
• seizures
• feeling agitated
• psychotic symptoms
• colitis (inflammation of the colon)
• changes in skin color different from those of urine (e.g. skin, nails, hair, sweat)
• difficulty swallowing
• inability to urinate

Frequency not known (cannot be estimated from the available data):

Dopamine dysregulation syndrome, characterized by an excessive desire for high doses of Stalevo, beyond those required to control motor symptoms. Some patients experience severe abnormal involuntary movements (dyskinesias), mood changes or other side effects after taking high doses of Stalevo.

The following side effects have also been reported:

• hepatitis (inflammation of the liver)
• itching

You may experience the following side effects:

• Inability to resist the impulse to perform an action that could be harmful, which may include:
• • a strong impulse to gamble excessively despite severe personal or family consequences
  • an increased or altered interest in sex and a disturbing behavior for you or others, such as an increased sexual drive
  • excessive or uncontrolled shopping or spending
  • eating excessively (eating large amounts of food in short periods) or compulsively (eating more food than usual and more than needed to satisfy hunger).

Tell your doctor if you experience any of these behaviors: they will discuss how to manage or reduce these symptoms.

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storing Stalevo

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

Do not use this medicine after the expiry date which is stated on the carton after EXP. The expiry date refers to the last day of the month stated.

No special storage conditions are required.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Package Contents and Additional Information

Stalevo Composition

• The active ingredients of Stalevo are levodopa, carbidopa, and entacapone.
• Each Stalevo 75 mg/18.75 mg/200 mg tablet contains 75 mg of levodopa, 18.75 mg of carbidopa, and 200 mg of entacapone.
• The other components of the tablet core are sodium croscarmellose, magnesium stearate, corn starch, mannitol (E 421), and povidone (E 1201)
• The components of the film coating are glycerol 85 percent (E 422), hypromellose, magnesium stearate, polysorbate 80, red iron oxide (E 172), sucrose, and titanium dioxide (E 171).

Product Appearance and Package Contents

Stalevo 75 mg/18.75 mg/200 mg: light reddish-brown, oval tablets with “LCE 75” engraved on one side.

There are five different package sizes of Stalevo 75 mg/18.75 mg/200 mg (10, 30, 100, 130, or 175 tablets). Not all package sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Orion Corporation

Orionintie 1

FI-02200 Espoo

Finland

You can request more information about this medication from the local representative of the marketing authorization holder.

Date of Last Revision of this Prospectus:

Other Sources of Information

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