Rytary (carbidopa and levodopa) extended-release capsules

The following drug information is obtained from various newswires, published medical journal articles, and medical conference presentations.

Company:

Approval Status:

Approved January 2015

Specific Treatments:

Parkinson's disease

Therapeutic Areas

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General Information

Rytary is an extended release formulation of carbidopa and levodopa. Carbidopa is an inhibitor of aromatic amino acid decarboxylation and levodopa is an aromatic amino acid. Carbidopa inhibits the decarboxylation of peripheral levodopa, making more levodopa available for delivery to the brain. 

Rytary is specifically indicated for the treatment of Parkinson’s disease, post-encephalitic parkinsonism, and parkinsonism that may follow carbon monoxide intoxication or manganese intoxication.

Rytary is supplied as a capsule for oral administration. Rytary should be swallowed whole with or without food. A high-fat, high-calorie meal may delay the absorption of levodopa by about 2 hours. The recommended starting dosage in levodopa-naïve patients is 23.75 mg / 95 mg taken orally three times a day for the first 3 days. On the fourth day of treatment, the dosage of Rytary may be increased to 36.25 mg / 145 mg taken three times a day. 

Based upon individual patient clinical response and tolerability, the Rytary dose may be increased up to a maximum recommended dose of 97.5 mg / 390 mg taken three times a day. The dosing frequency may be changed from three times a day to a maximum of five times a day if more frequent dosing is needed and if tolerated. The maximum recommended daily dose of Rytary is 612.5 mg / 2450 mg. Maintain patients on the lowest dosage required to achieve symptomatic control and to minimize adverse reactions. 

For the conversion of patients from immediate-release carbidopa-levodopa to Rytary, please see the drug label.

 

Clinical Results

FDA Approval

The FDA approval of Rytary was based on two trials in patients with advanced Parkinson's disease in the U.S. and in Europe.

Study 1 (APEX-PD)

APEX-PD enrolled and randomized 381 levodopa-naive patients. The study met its primary efficacy endpoint of mean change from baseline in the sum of Unified Parkinson's Disease Rating Scale (UPDRS) Part II (activities of daily living) score and UPDRS Part III (motor skills) score for Rytary versus placebo at Week 30 (or early termination).

Study 2 (ADVANCE-PD)

ADVANCE-PD enrolled 393 patients with advanced Parkinson's disease having "off" time. The results showed treatment with Rytary reduced the percentage of "off" time (36.9% to 23.8%) from baseline versus immediate-release carbidopa-levodopa (36.0% to 29.8%) during waking hours to end of study. Rytary also increased "on" time without troublesome dyskinesia during waking hours versus baseline to end of study by 1.8 hours. Less "off" time was primary related to more "on" time without troublesome dyskinesia.

Side Effects

Adverse effects associated with the use of Rytary may include, but are not limited to, the following:

  • nausea
  • dizziness
  • headache
  • insomnia
  • abnormal dreams
  • dry mouth
  • dyskinesia
  • anxiety
  • constipation
  • vomiting
  • orthostatic hypotension

Mechanism of Action

Rytary is an extended release formulation of carbidopa and levodopa. Carbidopa: When levodopa is administered orally, it is rapidly decarboxylated to dopamine in extracerebral tissues so that only a small portion of a given dose is transported unchanged to the central nervous system. Carbidopa inhibits the decarboxylation of peripheral levodopa, making more levodopa available for delivery to the brain. Levodopa: Levodopa is the metabolic precursor of dopamine, does cross the blood-brain barrier, and presumably is converted to dopamine in the brain. This is thought to be the mechanism whereby levodopa relieves symptoms of Parkinson's disease.

Additional Information

For additional information regarding Rytary or Parkinson's disease, please visit http://www.rytary.com/