How does it work?

Stalevo tablets contain three active ingredients, levodopa,carbidopa and entacapone. These are all medicines used in Parkinson's diseaseto increase the level of dopamine in the brain.

Dopamine is a substance known as a neurotransmitter.Neurotransmitters are found in the brain and nervous system and are involved intransmitting messages between nerves. These messages allow the normalfunctioning of the body. The neurotransmitter dopamine is known to be reducedor absent in the brains of people with Parkinson's disease, and this is thoughtto be the cause of the disease symptoms.

When you take levodopa, it is converted into dopamine in thebrain. This replaces the lost dopamine and therefore reduces some of thesymptoms of the disease.

Levodopa is also converted into dopamine in the rest of thebody, which can cause unwanted side effects such as nausea and palpitations. Anextra medicine called a dopa-decarboxylase inhibitor is therefore usuallycombined with levodopa treatment to prevent this happening. Dopa-decarboxylaseinhibitors include the medicines carbidopa (found with levodopa in Sinemet) andbenserazide (found with levodopa in Madopar). They block the conversion oflevodopa to dopamine outside the brain and so prevent levodopa side effects onthe rest of the body. (Carbidopa and benserazide cannot pass into the brain andso do not affect the conversion of levodopa to dopamine in the brain.)

Unfortunately levodopa treatment tends to become less effectiveover time, and patients tend to experience 'end-of-dose' deterioration, wherethe duration of benefit after each dose of levodopa becomes progressivelyshorter. Entacapone is used as an add-on treatment for Parkinson's diseasebecause it prolongs the effect of levodopa.

Entacapone works by inhibiting the action of an enzyme in thebody known as COMT. This enzyme normally breaks down levodopa that is left inthe body after a dose so that the body can start to remove it. By stopping theaction of this enzyme, entacapone increases the amount of levodopa that isavailable to pass into the brain with every dose of this medicine.

The three active ingredients have been combined in each tabletof this medicine to treat people with Parkinson's disease whose symptoms arenot controlled by levodopa/carbidopa (Sinemet) or levodopa/benserazide(Madopar) alone, and who therefore need entacapone to increase the length oftime the levodopa controls their symptoms. The medicine should make Parkinson'streatment simpler to remember and take, because all three active ingredientsare contained in one tablet.

What is it used for?

• Parkinson's disease.

Warning!

• You should not suddenly stop taking this medicine unless your doctor tells you otherwise.
• This medicine can occasionally cause your blood pressure to drop when you move from a lying down or sitting position to sitting or standing, especially when you first start taking the medicine. This may make you feel dizzy or unsteady. To avoid this try getting up slowly. If you do feel dizzy, sit or lie down until the symptoms pass.
• As this medicine increases the level of dopamine in your brain more than levodopa alone it may cause abnormal involuntary movements or muscle twitches (dyskinesia). Consult your doctor if you experience these symptoms, as they may indicate that your dose of this medicine needs reducing.
• Consult your doctor if you feel depressed or confused, or have strange or abnormal thoughts while you are taking this medicine.
• You should also let your doctor know if you lose your appetite, lose weight, or feel generally weak during treatment, particularly if this gets progressively worse within a relatively short period of time.
• This medicine can cause sleepiness and on rare occasions people have experienced a sudden onset of sleep during their daily activities. In some cases this occured without any warning signs. Although this is rare, you should exercise caution when driving or performing other potentially hazardous activities. People who have experienced sleepiness or an episode of sudden onset of sleep while taking this medicine should not drive or operate machinary. Caution should be observed when drinking alcohol or taking other medicines that cause drowsiness, as this may increase the risk of drowsiness.
• Pathological gambling, increased sex drive and hypersexuality have been reported in people taking medicines for Parkinson's disease such as this one, that increase dopamine activity in the brain. If you think this medicine is affecting you in this way, you should consult your doctor.
• You should have regular tests to monitor the function of your liver, blood, kidneys and heart while taking this medicine.
• This medicine may affect the results of certain laboratory tests, including those for testing sugar (glucose) levels in blood or urine. If you have diabetes ask your doctor for further information about this. Tell your doctor that you are taking this medicine if you have any blood or urine tests.
• If you have chronic open angle glaucoma you should have regular tests to monitor the pressure within your eye (intraocular pressure) while taking this medicine.
• This medicine may discolour your urine a reddish/brown. This is normal and not harmful.

Use with caution in

• Severely decreased kidney function and people having dialysis for kidney failure.
• Kidney disease.
• Mild to moderately decreased liver function.
• Liver disease.
• Severe lung disease.
• Asthma.
• Severe disease involving the heart and blood vessels (cardiovascular disease).
• People who have an abnormal heart rhythm following a previous heart attack.
• Disorders involving hormone producing glands (endocrine disorders).
• Diabetes.
• History of convulsions, eg epilepsy.
• History of peptic ulcers.
• History of psychiatric illness.
• Open angle glaucoma.

Not to be used in

• Severely decreased liver function.
• Closed angle glaucoma.
• Tumour of the adrenal gland (phaeochromocytoma).
• History of a rare muscle disorder called non-traumatic rhabdomyolysis.
• History of a rare condition called the neuroleptic malignant syndrome.
• People who have taken a monoamine-oxidase inhibitor antidepressant (MAOI) in the last 14 days.
• Breastfeeding.
• Rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency (Stalevo tablets contain sucrose).
• This medicine is not recommended for children and adolescents under 18 years of age, as there is no information regarding its safety and efficacy in this age group.

This medicine should not be used if you are allergic to one orany of its ingredients. Please inform your doctor or pharmacist if you havepreviously experienced such anallergy.If you feel you haveexperienced an allergic reaction, stop using this medicine and inform yourdoctor or pharmacist immediately.

Pregnancy and breastfeeding

Certain medicines should not be used during pregnancy orbreastfeeding. However, other medicines may be safely used in pregnancy orbreastfeeding providing the benefits to the mother outweigh the risks to theunborn baby. Always inform your doctor if you are pregnant or planning apregnancy, before using any medicine.

• The safety of this medicine for use during pregnancy has not been established. It is not recommended for use in pregnancy unless considered essential by your doctor. Seek medical advice from your doctor.
• This medicine passes into breast milk and women taking this medicine should therefore not breastfeed. Seek medical advice from your doctor.

Label warnings

• This medicine should be swallowed whole not chewed.
• This medicine may colour the urine reddish-brown.

Side effects

Medicines and their possible side effects can affect individualpeople in different ways. The following are some of the side effects that areknown to be associated with this medicine. Because a side effect is statedhere, it does not mean that all people using this medicine will experience thator any side effect.

• Difficulty performing voluntary movements, resulting in jerky or involuntary movements or muscle twitches (dyskinesia).
• Disturbances of the gut such as diarrhoea, constipation, nausea, vomiting or abdominal pain.
• Mood changes, strange or abnormal thoughts or depression.
• Confusion.
• Awareness of your heartbeat (palpitations).
• Irregular heart beats.
• Low blood pressure.
• Dizziness.
• Loss of appetite.
• Dry mouth.
• Fatigue.
• Increased sweating.
• Difficulty in sleeping (insomnia).
• Sleepiness (somnolence).
• Suddenly falling asleep.
• False perceptions of things that are not really there (hallucinations).
• Bleeding or ulceration in the stomach or intestines.
• Disturbances in the normal numbers of blood cells in the blood.
• Inability to resist urges to gamble (pathological gambling).
• Increased sex drive (libido) and excessive interest or involvement in sexual activity (hypersexuality).

The side effects listed above may not include all of the sideeffects reported by the drug'smanufacturer.For moreinformation about any other possible risks associated with this medicine,please read the information provided with the medicine or consult your doctoror pharmacist.

How can this medicine affect other medicines?

It is important to tell your doctor or pharmacist what medicinesyou are already taking, including those bought without a prescription andherbal medicines, before you start treatment with this medicine. Similarly,check with your doctor or pharmacist before taking any new medicines whiletaking this one, to ensure that thecombination is safe.

This medicine should not be taken at the same time as, or withintwo weeks of taking non-selective monoamine oxidase inhibitors (MAOIs), forexample the antidepressants phenelzine, isocarboxazid and tranylcypromine, andthe antibiotic linezolid. In addition it should not be taken in combinationwith BOTH a selective MAO-A inhibitor, eg moclobemide, AND a selective MAO-Binhibitor, eg selegiline or rasagiline, though it can be used with either ofthese on their own.

If this medicine is taken in combination with the MAO-Binhibitor selegiline, the daily selegiline dose should not exceed10mg.

There may be an increased risk of dizziness when moving from alying or sitting position to sitting or standing (postural hypotension) if thismedicine is taken with other medicines that can have this effect, for examplemedicines to treat high blood pressure (antihypertensives). Your doctor mayneed to adjust the dose of your blood pressure medicine.

Iron reduces the absorption of this medicine from the gut. Forthis reason, if you are taking iron supplements such as ferrous sulphate, youshould take them two to three hours before or after this medicine.

Entacapone may enhance the effect of warfarin. If you are takingwarfarin your blood clotting time (INR) should be monitored when you start andstop treatment with this medicine.

The following medicines may reduce the effect oflevodopa:

• antipsychotic medicines, eg chlorpromazine, prochlorperazine, haloperidol, flupentixol (equally levodopa may oppose the effect of these medicines)
• benzodiazepines, eg diazepam
• isoniazid
• papaverine
• phenytoin.

Tricyclic antidepressants (eg amitriptyline, imipramine) maydecrease the therapeutic effects of this medicine, and may also rarely increasethe risk of a dangerous rise in blood pressure (hypertensivecrisis).

Anticholinergic medicines, eg procyclidine, atropine, hyoscine,propantheline, orphenadrine, benzhexol, may decrease the absorption of thismedicine from the gut and reduce its therapeutic effect.

This medicine can be used with other medicines forParkinson’s disease, eg anticholinergics, amantadine or dopamineagonists, however both the desired effects and side effects of treatment may beintensified. Your doctor may need to adjust the dose of one or more of yourmedicines to get the correct balance to control your symptoms with minimum sideeffects.

Other medicines containing the same active ingredients

There are currently no other medicines available in the UK thatcontain all three active ingredients that are in Stalevo tablets.

Sinemet containslevodopa and carbidopa alone.

Comtess containsentacapone alone.