Stalevo

Stalevo is an oral therapy developed by Novartis that contains a combination of three different medicines — carbidopa, levodopa, and entacapone — for Parkinson’s disease. The three work together to boost the amount of dopamine in the brain, thereby relieving the symptoms of Parkinson’s.

How Stalevo works

Levodopa is a precursor of dopamine and can cross the blood-brain barrier and be converted into dopamine in the brain. The blood-brain barrier is a highly selective membrane that protects the central nervous system from circulating toxins and bacteria, and is often an obstacle for therapies that need to reach nerve cells in the brain.

When levodopa is administered orally, it is rapidly broken down by a biological process called decarboxylation that limits its amount reaching the brain. Carbidopa inhibits this process, making more levodopa available for the brain.

Levodopa is also broken down by another process called methylation. This process can be prevented by entacapone, a selective inhibitor of the methylating enzyme called catechol-O-methyltransferase, which causes levodopa to break down.

When entacapone is given in conjunction with levodopa and carbidopa, levels of levodopa in the blood are found to be greater and more sustained than after the administration of levodopa and carbidopa alone.

Stalevo in clinical trials

To get Stavelo approved, Novartis conducted a Phase 3 study (NCT00134966) comparing the efficacy, safety, and tolerability of Stalevo with an immediate-release levodopa/carbidopa therapy (Sinemet IR) in 423 patients with early Parkinson’s. The study, conducted over 39 weeks, found that Stalevo provided greater clinical benefit than Sinemet IR without increasing the development of motor complications.

However, a Phase 3 trial (NCT00099268), called STRIDE-PD, compared the risk of developing dyskinesia (uncontrolled, involuntary movements) in patients who initiated levodopa/carbidopa therapy with or without entacapone. The study enrolled 747 patients with early Parkinson’s, who were treated either with levodopa/carbodopa/entacapone or with an immediate-release carbidopa/levodopa formulation, taken four times daily at 3.5-hour intervals. Results showed that the triple combination therapy failed to delay the time of onset or reduce the frequency of dyskinesia compared to levodopa/carbidopa alone.

The researchers hypothesized that these results could reflect that the treatment protocol used in the study did not provide continuous levodopa availability and the higher levodopa dose equivalents in the Stalevo group.

However, treatment with Stalevo showed a trend toward improved scores in the Unified Parkinson’s Disease Rating Scale — which measures both motor and non-motor symptoms — and reduced the time to wearing off compared to levodopa/carbidopa.

A Phase 4 randomized trial (NCT04952194) is expected to enroll 180 individuals with early Parkinson’s, from 30 to 70 years old. The study seeks to evaluate the efficacy of increasing doses of Stalevo in reducing dyskinesia, compared with treatment with sustained-release carbidopa/levodopa.

Other information

Each tablet of Stalevo contains a 1:4 ratio of carbidopa to levodopa in combination with a fixed 200 mg amount of entacapone. Stalevo tablets are available in six strengths:

  • Stalevo 50 contains 12.5 mg of carbidopa/50 mg of levodopa/200 mg of entacapone.
  • Stalevo 75 contains 18.75 mg/75 mg/200 mg.
  • Stalevo 100 contains 25 mg/100 mg/200 mg.
  • Stalevo 125 contains 31.25 mg/125 mg/200 mg.
  • Stalevo 150 contains 37.5 mg/150 mg/200 mg.
  • Stalevo 200 contains 50 mg/200 mg/200 mg.

The maximum recommended daily dose of Stalevo 50 to 150, defined by the maximum daily dose of entacapone, is eight tablets per day. The maximum for Stalevo 200 is six tablets per day.

Stalevo is contraindicated for patients who have demonstrated unnecessary and undesirable immune reactions (hypersensitivity) in response to any component (carbidopa, levodopa, or entacapone).

The medicine should be administered with caution to patients with biliary obstruction, liver disease, severe cardiovascular or pulmonary disease, bronchial asthma, renal, or endocrine disease. Caution is also advised when prescribing Stalevo to women during pregnancy or while nursing.

Other nonselective monoamine oxidase inhibitors should not be used together with Stalevo. The therapy should also not be used in patients with suspicious, undiagnosed skin lesions or a history of skin cancer (melanoma).

The most common adverse reactions are involuntary movements, urine discoloration, diarrhea, nausea, abdominal pain, vomiting, and dry mouth. Other adverse reactions include daytime drowsiness, low blood pressure, hallucinations, confusion, colitis, skin cancer, and depression with associated suicidal tendencies.

Some medicines may interact with Stalevo such as those used to reduce blood pressure or to treat depression.

Additional information may be found here.

 

Last updated on Jan. 10, 2021, by Teresa Carvalho MSc

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