Carbidopadosage

Evaluate vitamin B6 levels prior to starting treatment with carbidopa/levodopa therapies. Levodopa-naïve patients: Starting dose is 23.75 mg/95 mg three times daily; may increase to 36.25 mg/145 mg three times daily on the fourth day of treatment. See Table 1 for instructions for converting patients taking immediate-release carbidopa-levodopa to an initial dose of RYTARY. Dosages of RYTARY are not interchangeable with other carbidopa-levodopa products. The maximum recommended daily dose of RYTARY is 612.5 mg/2,450 mg. RYTARY may be taken with or without food; do not chew, divide or crush.

2.1 Management of

Vitamin B6 Levels Evaluate vitamin B6 levels prior to initiating carbidopa/levodopa therapies, including RYTARY, periodically during treatment, and as clinically indicated. If vitamin B6 levels are low, supplement to sufficient levels per standard of care. Patients may initiate and continue treatment with RYTARY while supplementing vitamin B6.

2.2 Dosage in

Patients Naïve to Levodopa Therapy The recommended starting dosage of RYTARY 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. Maintain patients on the lowest dosage required to achieve symptomatic control and to minimize adverse reactions such as dyskinesia and nausea. The maximum recommended daily dose of RYTARY is 612.5 mg/2,450 mg.

2.3 Converting from

Immediate-Release Carbidopa-Levodopa to RYTARY The dosages of other carbidopa and levodopa products are not interchangeable on a 1:1 basis with the dosages of RYTARY. To convert patients from immediate-release carbidopa-levodopa to RYTARY, first calculate the patient’s current total daily dose of levodopa. The starting total daily dose of RYTARY is as recommended in Table 1. After conversion, any combination of the four RYTARY dosage strengths can be used to achieve an optimal dosing. Adjust the dose and dosing frequency as necessary to maintain patient tolerance and sufficient symptomatic control. Administration of concomitant Parkinson’s disease medications should remain stable while adjusting the RYTARY dose. In clinical trials, RYTARY was administered in divided doses of three to five times a day. The maximum recommended total daily dose of RYTARY is 612.5 mg/2,450 mg. For patients currently treated with carbidopa and levodopa plus a catechol-O-methyl transferase (COMT) inhibitor (such as entacapone), the initial total daily dose of levodopa in RYTARY described in Table 1 may need to be increased. Use of RYTARY in combination with other levodopa products has not been studied.

Table 1: Conversion from Immediate-Release Carbidopa-Levodopa to RYTARY Total Daily Dose of Levodopa in Immediate-Release Carbidopa-Levodopa Recommended Starting Dosage of RYTARY Total Daily Dose of Levodopa in RYTARY RYTARY Dosing Regimen 400 mg to 549 mg 855 mg 3 capsules RYTARY 23.75 mg/95 mg taken TID a 550 mg to 749 mg 1,140 mg 4 capsules RYTARY 23.75 mg/95 mg taken TID 750 mg to 949 mg 1,305 mg 3 capsules RYTARY 36.25 mg/145 mg taken TID 950 mg to 1,249 mg 1,755 mg 3 capsules RYTARY 48.75 mg/195 mg taken TID Equal to or greater than 1,250 mg 2,340 mg or 4 capsules RYTARY 48.75 mg/195 mg taken TID or 2,205 mg 3 capsules RYTARY 61.25 mg/245 mg taken TID a TID: three times a day

2.4 Discontinuation of RYTARY

Avoid sudden discontinuation or rapid dose reduction of RYTARY. The daily dose of RYTARY should be tapered at the time of treatment discontinuation.

2.5 Administration

Information Swallow RYTARY whole with or without food. A high-fat, high-calorie meal may delay the absorption of levodopa by about 2 hours. Do not chew, divide or crush RYTARY capsules. For patients who have difficulty swallowing intact capsules, administer RYTARY by carefully twisting apart both halves of the capsule. Sprinkle the entire contents of both halves of the capsule on a small amount of applesauce (1 to 2 tablespoons) and consume the mixture immediately. Do not store the drug/food mixture for future use.