Stalevo (carbidopa, levodopa, and entacapone) for Parkinson’s disease

What is Stalevo for Parkinson’s disease?

Stalevo (carbidopa, levodopa, and entacapone) is an approved oral combination therapy used to treat the symptoms of Parkinson’s disease. It can be used as a substitute for other products with the same active ingredients, or as a therapy replacement for certain people experiencing symptom fluctuations between doses of carbidopa and levodopa (off episodes).

The death of nerve cells that produce the chemical messenger dopamine causes Parkinson’s. Without enough dopamine to fulfill vital brain functions, the disease’s characteristic motor and nonmotor symptoms develop.

A standard treatment is levodopa, a precursor molecule that can be converted to dopamine in the brain. Levodopa is often combined with other medications that help more of it reach the brain, including carbidopa and entacapone (sold as Comtan and generics).

Stalevo contains all three of these medications in a single pill, offering more convenience than regimens that involve taking carbidopa-levodopa and entacapone as separate pills.

Orion Pharma developed the medication, which is distributed by Almatica Pharma in the U.S. Generics of Stalevo are also available.

Therapy snapshot

Who can take Stalevo?

In the U.S., Stalevo is approved for the treatment of Parkinson’s disease. It can be used as:

• a substitute for separate carbidopa-levodopa and entacapone pills, with equal dosage strengths of each active ingredient
• a replacement for oral carbidopa-levodopa in patients who are still having off episodes and have been taking a levodopa dose of no more than 600 mg daily without experiencing dyskinesia (uncontrolled, involuntary movements)

Stalevo is similarly approved elsewhere, including the European Union and Canada.

Stalevo’s prescribing information notes that the medication is contraindicated, meaning it should not be used, in people who:

• have narrow-angle glaucoma, a type of eye disease
• are taking nonselective monoamine oxidase (MAO) inhibitors, or have taken them within the past two weeks, because the combination can increase blood pressure

A class of Parkinson’s medications, MAO-B inhibitors, is related to nonselective MAO inhibitors but is generally safe for use with Stalevo.

How is Stalevo administered?

Stalevo is available as film-coated oral tablets, typically taken multiple times per day.

Several Stalevo dosage strengths are available — selecting the optimal dose for each individual usually requires careful titration under medical guidance. The maximum number of tablets per day is six to eight, depending on the tablet strength.

The tablets should be swallowed whole and not split, crushed, or chewed. They can be taken with or without food, but high-fat, high-calorie meals may delay levodopa absorption by about two hours.

Vitamin B6 levels should be checked before starting Stalevo and periodically during treatment. If levels are too low, vitamin B6 supplements may be recommended and can be taken while continuing Stalevo.

Stalevo in clinical trials

The use of Stalevo for off episodes was supported by three clinical trials that tested the efficacy of entacapone (Comtan) as an add-on to carbidopa-levodopa tablets among people with Parkinson’s disease, most of whom were experiencing motor fluctuations.

In all three trials — NOMECOMT, SEESAW, and CELOMEN — participants took entacapone (200 mg) or a placebo with levodopa and carbidopa (or a similar medication), up to ten times daily for six months. Overall, results generally showed that, compared with the control group, the combination led to:

• significant increases in daily on-time, when motor symptoms are effectively controlled
• proportional decreases in daily off time
• reductions in average daily levodopa dose
• reductions in motor symptoms and improved ability to participate in daily activities

Other trials later tested Stalevo vs. Sinemet, an oral formulation of carbidopa and levodopa, among people with early Parkinson’s disease.

• The Phase 3 FIRST-STEP trial (NCT00134966) found significantly greater improvement on a combined measure of motor symptoms and activities of daily living with Stalevo compared with Sinemet.
• The Phase 3 STRIDE-PD trial (NCT00099268) demonstrated that the Stalevo-treated participants had a greater likelihood of developing dyskinesia and developed it earlier, on average, than participants taking Sinemet.

Stalevo side effects