Carbidopa/levodopa/entacapone

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Carbidopa/levodopa/entacapone
Stalevo.jpg
Combination of
Carbidopa Dopa decarboxylase inhibitor
Levodopa Dopaminergic Precursor
Entacapone COMT inhibitor
Clinical data
Trade names Stalevo
AHFS/Drugs.com Consumer Drug Information
MedlinePlus a601068
Pregnancy
category
  • US: C (Risk not ruled out)
Routes of
administration
Oral
ATC code
Legal status
Legal status
Identifiers
PubChem CID
  (verify)

Carbidopa/levodopa/entacapone, sold under the brand name Stalevo, is an anti-parkinsonian dopaminergic combination medication that contains carbidopa, levodopa, and entacapone for the treatment of Parkinson's disease. It is marketed by Swiss-based Novartis Pharmaceuticals and manufactured by Finnish drugmaker Orion Corporation.

Medical uses[edit]

Carbidopa/levodopa/entacapone was approved by the FDA in June 2003 to treat adults with Parkinson’s disease of unknown cause in two scenarios. First, to substitute with equivalent strength of each of the three components for immediate-release carbidopa/levodopa and entacapone previously administered as individual products. Second, to replace immediate-release carbidopa/levodopa therapy (without entacapone) when people experience the signs and symptoms of end-of-dose "wearing-off" but only for people taking a total daily dose of levodopa of 600 mg or less and not experiencing dyskinesias.[1]

It may help decrease a change of response to Parkinson's medications.[2]

Side effects[edit]

Sometimes a wearing off effect may occur at the end of the dosing interval, where a patient may feel Parkinson's symptoms. Urine, saliva, or sweat may be discolored (dark color such as red, brown, or black) after taking carbidopa/levodopa/entacapone.[3]

Prostate cancer[edit]

On March 31, 2010, the United States Food and Drug Administration stated it is evaluating long-term clinical data from STRIDE-PD which found that a greater number of patients taking Stalevo had prostate cancer compared to those taking carbidopa/levodopa.[4] Other controlled clinical trials evaluating carbidopa/levodopa/entacapone or entacapone did not find an increased risk of prostate cancer. FDA is still reviewing the available information and has not concluded that carbidopa/levodopa/entacapone increases the risk of developing prostate cancer. Healthcare professionals were advised to be aware of this possible risk and follow current guidelines for prostate cancer screening. FDA recommended that healthcare professionals follow the recommendations in the drug label when prescribing carbidopa/levodopa/entacapone and Comtan. Patients were directed to not stop taking their medication unless directed to do so by their healthcare professional.[5]

Cardiovascular risks[edit]

On August 20, 2010, the United States Food and Drug Administration stated meta-analysis of several studies "appeared to show an increase in the risk of heart attack, stroke, and cardiovascular death for people taking the drug" but also stated "findings were not clear."[6] Heart problems are not uncommon in Parkinson's patients and the FDA will investigate the concerns.

Drug interactions[edit]

Carbidopa/levodopa/entacapone is contraindicated in patients taking a class of antidepressant drugs known as non-selective monoamine oxidase (MAO) inhibitors such as phenelzine and tranylcypromine.[7] Combining carbidopa/levodopa/entacapone with these drugs could cause serious—possibly life-threatening—side effects. MAO inhibitors should be stopped at least two weeks before starting therapy with carbidopa/levodopa/entacapone.

Carbidopa/levodopa/entacapone may be combined with the drugs rasagiline or selegiline. These drugs are a different type of MAO inhibitor known as selective MAO inhibitors that are often prescribed for Parkinson's disease.[3] Many drug interactions involving selegiline are theoretical, primarily based on interactions with non-selective MAO inhibitors; at oral doses the risk of these interactions may be very low. However, transdermal selegiline, known by its trade name Emsam, is still contraindicated.[7] Transdermal selegiline results in higher plasma levels at which it behaves like a non-selective MAO inhibitor. Concominant use of entacapone, a component of carbidopa/levodopa/entacapone, with MAO inhibitors may increase toxicity of MAO inhibitors. Levodopa, also a component of carbidopa/levodopa/entacapone, in combination with MAO inhibitors may result in hypertensive reactions.[8]

Dosing[edit]

carbidopa/levodopa/entacapone is supplied as tablets in six strengths:[9]

Stalevo Dosing Forums
Carbidopa Levodopa Entacapone
Stalevo 50 12.5 50 200
Stalevo 75 18.75 75 200
Stalevo 100 25 100 200
Stalevo 125 31.25 125 200
Stalevo 150 37.5 150 200
Stalevo 200 50 200 200

Adult dosing[edit]

Parkinson's disease, idiopathic[edit]

Maximum 1 tablet per dose, 8 tablets per day (all but the highest strength tablets), 6 tablets per day (Stalevo 200). Tablets are not to be cut, crushed, or chewed.[10]

Renal dosing[edit]

Not defined. In severe impairment caution is advised.

Hepatic dosing[edit]

Not defined. In severe impairment caution is advised.

Pediatric dosing[edit]

Pediatric dosing is currently unavailable and/or not applicable.[11]

Mechanism of action[edit]

Main articles: Levodopa, Carbidopa, and Entacapone

Levodopa is the immediate precursor to dopamine. Entacapone is a selective, reversible catechol-O-methyltransferase (COMT) inhibitor that increases the bioavailability of levodopa. Entacapone does not cross the blood–brain barrier. Carbidopa is a peripheral aromatic L-amino acid decarboxylase (AADC) inhibitor. Carbidopa, which also does not cross the blood–brain barrier, is combined with levodopa to prevent its conversion to dopamine in the periphery.[1]

Society and culture[edit]

Extension[edit]

As of 2010 Applications for extending the indication of carbidopa/levodopa/entacapone to people requiring initiation of levodopa therapy have been under review by the European Medicines Agency (EMEA) and the U.S. Food and Drug Administration (FDA), based on the favourable results from FIRST-STEP, a study conducted in North America and Europe by Novartis from 2005 to 2007 (see below).[12]

See also[edit]

References[edit]

  1. ^ a b Drug Reference for FDA Approved Parkinson's Disease Drugs Retrieved 2010-4-1
  2. ^ Salat, D; Tolosa, E (1 January 2013). "Levodopa in the treatment of Parkinson's disease: current status and new developments.". Journal of Parkinson's disease. 3 (3): 255–69. doi:10.3233/JPD-130186. PMID 23948989. 
  3. ^ a b Stalevo patient advice including side effects - Drugs.com Retrieved 2010-4-2
  4. ^ FDA evaluating cancer link in Parkinson's drug Retrieved 2010-3-31
  5. ^ Stalevo (entacapone/carbidopa/levodopa): Ongoing Safety Review Retrieved on 2010-4-2
  6. ^ FDA to review heart risks of Parkinson's drug Retrieved 2010-8-20
  7. ^ a b Stalevo Drug Interactions - ePocrates Online Retrieved 2010-4-2
  8. ^ Leikin, Jerrold B. & Paloucek, Frank P. (2007). Poisoning and toxicology handbook (4th ed.). Informa Health Care. p. 610. ISBN 1-4200-4479-6. Google Book Search. Retrieved on April 2, 2010.
  9. ^ Novartis Stalevo Insert Retrieved 2010-4-1
  10. ^ Stalevo Adult Dosing - ePocrates Online Retrieved 2010-4-2
  11. ^ Stalevo Pediatric Dosing - ePocrates Online Retrieved 2010-4-2
  12. ^ Orion: Primary objective of STRIDE-PD study was not achieved Retrieved 2010-3-31

External links[edit]