What is Stalevo?
Stalevo is a drug composed of three active ingredients: levodopa, carbidopa and entacapone. It is available in a range of brown oval tablets in six formulations containing 50 to 200 mg of levodopa and 12.5 to 50 mg of carbidopa. All tablets contain 200 mg of entacapone.
What is Stalevo used for?
Stalevo is indicated for the treatment of adults with Parkinson's disease. Parkinson's disease is a progressive mental disorder that causes tremor, slowness of movement and muscle stiffness.
Stalevo is used in patients treated with a treatment based on levodopa and a dopa decarboxylase inhibitor (two standard therapies for the treatment of Parkinson's disease) that present "fluctuations" towards the end of the time interval between the administration of two doses. Fluctuations occur when the effects of the drug are reduced and symptoms reappear. The fluctuations are linked to a reduction in the effects of levodopa, whereby the patient is subjected to sudden changes between the "on" state, in which he is able to move, and the "off" state, in which he has difficulty in movement. Stalevo is used when it is not possible to cure such fluctuations with the standard combination only.
The medicine can only be obtained with a prescription.
How is Stalevo used?
Each Stalevo tablet contains a full dose of levodopa, in six formulations, with corresponding amounts of carbidopa and entacapone which improve its effectiveness. The Stalevo formulation that the patient must take depends on the amount of levodopa needed to control the symptoms. Further information on how to switch to Stalevo therapy and the correct dose adjustment during treatment is contained in the Summary of Product Characteristics (also part of the EPAR).
The maximum dose of Stalevo is 10 tablets per day, except for tablets containing 200 mg of levodopa and 50 mg of carbidopa, in which case the maximum dose is seven tablets per day.
Stalevo tablets should be given whole and can be taken with or without food.
Stalevo should be used with caution in patients with mild to moderate problems with the liver or severe kidney problems. It must also not be given to patients with severe liver problems.
How does Stalevo work?
In patients with Parkinson's disease, the brain cells that produce the dopamine neutralizer begin to die, resulting in a decrease in the concentration of this substance in the brain. Patients therefore lose the ability to control their movements reliably. All the active ingredients present in Stalevo help to restore dopamine levels in the areas of the brain responsible for controlling movement and coordination.
Levodopa turns into dopamine in the brain. Carbidopa and entacapone block some of the enzymes involved in the breakdown of levodopa in the body: carbidopa blocks the enzyme dopa decarboxylase, while entacapone blocks the enzyme catechol-O-methyl transferase (COMT). As a result, levodopa remains active longer, helping to improve the symptoms of Parkinson's disease, such as stiffness and slowness in movement.
Entacapone has been authorized in the European Union (EU) as Comtess / Comtan since 1998.
The use of combinations of levodopa and carbidopa is well established and dates back to the mid-1970s. Thanks to the combination of all three active ingredients in a single tablet, the number of tablets to be taken decreases and this can help patients comply with the treatment regimen.
What studies have been carried out on Stalevo?
The company used some data referring to Comtess / Comtan to support the use of Stalevo and presented data from the published literature on levodopa and carbidopa.
The company also carried out "bioequivalence" studies to show that taking Stalevo produces the same concentrations of levodopa, carbidopa and entacapone in the blood compared to taking separate tablets containing entacapone and a combination of levodopa and carbidopa.
What benefit has Stalevo shown during the studies?
Studies have shown that Stalevo is bioequivalent to separate tablets.
What is the risk associated with Stalevo?
The most common side effects with Comtess (seen in 1 patient in 10) are dyskinesia (involuntary movements), aggravated parkinsonism (worsening of Parkinson's disease), nausea and harmless urine discoloration. For the full list of all side effects reported with Stalevo, see the Package Leaflet.
Stalevo should not be used in people who may be hypersensitive (allergic) to levodopa, carbidopa, entacapone or any of the other substances. Stalevo should not be given to patients:
• suffering from severe liver disease;
• suffering from uncontrolled angle-closure glaucoma (increase in eye pressure);
• suffering from pheochromocytoma (a tumor of the adrenal gland);
• with a history of neuroleptic malignant syndrome (a serious nervous disorder caused
normally from antipsychotic drugs) or rhabdomyolysis (rupture of muscle fibers).
Stalevo should not be used simultaneously with other drugs belonging to the group of "monoamine oxidase inhibitors" (a type of antidepressant). For more details, see the summary of product characteristics (also included with the EPAR).
Why was Stalevo approved?
The Committee for Medicinal Products for Human Use (CHMP) has determined that Stalevo's benefits are greater than its risks for the treatment of patients with Parkinson's disease who experience "fine dose" daily motor fluctuations that are not stabilized by treatment with based on levodopa / dopa decarboxylase inhibitors. The committee recommended that Stalevo be given marketing authorization.
More information on Stalevo
On 17 October 2003, the European Commission issued a marketing authorization for Stalevo, valid throughout the European Union. The marketing authorization holder is Orion Corporation. The marketing authorization was renewed on 17 October 2008.
The full EPAR for Stalevo can be found here.
Last update of this summary: 03-2009.
