| Drug Name |
CREXONT® (carbidopa and levodopa) |
| Active Ingredient |
carbidopa and levodopa |
| Date of Approval |
August 7, 2024 |
| Manufacturer |
Amneal Pharmaceuticals LLC |
| Approval Pathways and Indications |
Approval Pathway: NDA
Indication: CREXONT® is indicated for the treatment of Parkinson’s disease, post-encephalitic parkinsonism, and parkinsonism that may follow carbon monoxide intoxication or manganese intoxication in adults. |
| Therapeutic Class |
Parkinson's agent |
| Formulation |
Extended-Release Capsules: Carbidopa and Levodopa 35 mg / 140 mg, 52.5 mg / 210 mg, 70 mg / 280 mg, 87. 5 mg / 350 mg |
| MoA |
CREXONT® is a combination of carbidopa and levodopa.
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 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 treats symptoms of Parkinson's disease. |
| Dosing and Administration |
Levodopa-naïve patients: Start with 35 mg carbidopa / 140 mg levodopa taken orally twice daily for the first 3 days. Gradually increase the dosage as needed starting on the fourth day.
Switching from immediate-release carbidopa/levodopa: Dosages are not directly substitutable.
For daily doses less than 500 mg:
For a single dose of 100 mg, start with 280 mg CREXONT® twice daily.
For a single dose of 150 mg, start with 420 mg twice daily.
For a single dose of 200 mg, start with 560 mg twice daily.
For daily doses of 500 mg or more:
For a single dose of 100 mg, start with 280 mg CREXONT® three times daily.
For a single dose of 150 mg, start with 420 mg three times daily.
For a single dose of 200 mg, start with 560 mg three times daily.
For a single dose greater than 200 mg, start with 700 mg three times daily.
Maximum daily dosage: 525 mg carbidopa / 2100 mg levodopa.
Administration: CREXONT® can be taken with or without food. It should not be chewed, divided, or crushed. Patients should avoid alcohol when on this medication. |
| Administered by self or by HCP |
Administered by self |
| Place in Therapy |
CREXONT® is a novel formulation combining immediate-release granules with carbidopa and levodopa for rapid onset, and extended-release pellets with levodopa for prolonged effect. Unlike RYTARY® extended-release capsules, CREXONT® dual-component formulation enhances its duration of effectiveness and reduces "OFF" time, which is when Parkinson's symptoms return between doses. Research indicates that CREXONT® provides about 30 more minutes of "good on" time per day compared to immediate-release formulations. It offers more sustained "good on" time with fewer doses compared to traditional short-acting oral carbidopa/levodopa products. CREXONT® should not be used with nonselective monoamine oxidase inhibitors. |
| Expected Market Launch Date |
September 2024 |
| New Molecular Entity (NME) or Existing Formulation |
Existing Formulation |
| Expected Cost |
Data Unavailable |
| Product Discontinuation |
N/A |
| Clinical Trials |
The effectiveness of CREXONT® in treating Parkinson’s disease was demonstrated in a 20-week, active-controlled, multicenter clinical trial (Study 1; NCT03670953). The trial included a 3-week dose adjustment of immediate-release carbidopa-levodopa, followed by a 4-week conversion to CREXONT®, and a 13-week double-blind period comparing CREXONT® to immediate-release carbidopa-levodopa. Enrolling 630 patients who were stable on at least 400 mg of levodopa daily and experienced at least 2.5 hours of "Off" time per day, the study assessed patients with a mean age of 67 years and a mean disease duration of 9 years. Most patients (96%) were white, and 63% were male.
At baseline, 73% of the CREXONT® group and 63% of the immediate-release carbidopa-levodopa group were on additional Parkinson’s medications. The study allowed for the continuation of certain stable medications but excluded several others. Most patients (75%) required two or fewer dose adjustments to reach a stable dose of CREXONT®, with a mean daily levodopa dosage of 1487 mg.
The primary efficacy measure was the mean change from baseline in “On” time without troublesome dyskinesia, as recorded in the patients' diaries. CREXONT® showed a statistically significant improvement in “On” time without troublesome dyskinesia (p=0.019) and a reduction in “Off” time (p=0.025) compared to immediate-release carbidopa-levodopa. |
| Sources |
Amneal Pharmaceuticals. Amneal Receives U.S. FDA Approval for IPX203 for Treatment of Parkinson’s Disease to Be Launched as CREXONT Carbidopa and Levodopa Extended Release Capsules. Accessed August 13, 2024. Available from: https://investors.amneal.com/news/press-releases/press-release-details/2024/Amneal-Receives-U.S.-FDA-Approval-for-IPX203-for-Treatment-of-Parkinsons-Disease-to-Be-Launched-as-CREXONT-Carbidopa-and-Levodopa-Extended-Release-Capsules/ |