2 DOSAGE AND ADMINISTRATION

Carbidopa, levodopa and entacapone tablets should be used as a substitute for patients already stabilized on equivalent doses of carbidopa/levodopa and entacapone. However, some patients who have been stabilized on a given dose of carbidopa/levodopa may be treated with carbidopa, levodopa and entacapone tablets if a decision has been made to add entacapone (see below). Therapy should be individualized and adjusted according to the desired therapeutic response.

2.1 Dosing Information

The optimum daily dosage of carbidopa, levodopa and entacapone tablets must be determined by careful titration in each patient.

Clinical experience with daily doses above 1,600 mg of entacapone is limited. The maximum recommended daily dose of carbidopa, levodopa and entacapone tablets depends on the strength used. The maximum number of tablets to be used in a 24-hour period is less with the highest strength (carbidopa, levodopa and entacapone tablets 50 mg/200 mg/200 mg) than with lower strengths (see Table 1). Studies show that peripheral dopa decarboxylase is saturated by carbidopa at approximately 70 mg per day to 100 mg per day. Patients receiving less than this amount of carbidopa are more likely to experience nausea and vomiting.

Table 1: Maximum Recommended Dose of Carbidopa, Levodopa and Entacapone Tablets in a 24 hour Period

Carbidopa, Levodopa and Entacapone Tablets Dosage Strength	Maximum Number of Tablets in a 24‑hour Period
12.5 mg/50 mg/200 mg 18.75 mg/75 mg/200 mg 25 mg/100 mg/200 mg 31.25 mg/125 mg/200 mg 37.5 mg/150 mg/200 mg	8
50 mg/200 mg/200 mg	6

2.2 Converting Patients from Carbidopa, Levodopa, and Entacapone to

Carbidopa, Levodopa and Entacapone Tablets

Patients currently treated with entacapone 200 mg with each dose of non- extended release carbidopa/levodopa tablet, can switch to the corresponding strength of carbidopa, levodopa and entacapone tablets containing the same amounts of levodopa and carbidopa. For example, patients receiving one tablet of carbidopa/levodopa 25 mg/100 mg and one tablet of entacapone 200 mg at each administration can switch to a single carbidopa, levodopa and entacapone tablet 25 mg/100 mg/200 mg (containing 25 mg of carbidopa, 100 mg of levodopa and 200 mg of entacapone).

2.3 Converting Patients from Carbidopa and Levodopa Products to Carbidopa,

Levodopa and Entacapone Tablets

There is no experience in transferring patients currently treated with extended release formulations of carbidopa/levodopa, or carbidopa/levodopa products that are not combined in a 1:4 ratio of carbidopa to levodopa.

Patients with a history of moderate or severe dyskinesias or taking more than 600 mg of the levodopa component per day are likely to require a reduction in their daily levodopa dose when entacapone is added. Because dose adjustment of the individual carbidopa or levodopa component is not possible with fixed-dose products, initially titrate patients to a dose that is tolerated and that meets their individual therapeutic need using a separate carbidopa/levodopa tablet (1:4 ratio) plus an entacapone tablet. Once the patient’s individual dose of carbidopa/levodopa plus entacapone dose has been established using two separate tablets; switch the patient to a corresponding single tablet of carbidopa, levodopa and entacapone.

When less levodopa is required, reduce the total daily dosage of carbidopa/levodopa either by decreasing the strength of carbidopa, levodopa and entacapone tablets at each administration or by decreasing the frequency of administration by extending the time between doses.

2.4 Concomitant Use with Other Anti-Parkinson's Disease Drugs

Anticholinergic agents, dopamine agonists, monoamine oxidase (MAO) - B inhibitors, amantadine, and other standard drugs for Parkinson's disease may be used concomitantly while carbidopa, levodopa and entacapone tablets are being administered; however, dosage adjustments of the concomitant medication or carbidopa, levodopa and entacapone tabletsmay be required.

2.5 Decrease or Interruption of Dosing

Avoid interruption of carbidopa, levodopa and entacapone tabletsdosing because hyperpyrexia has been reported in patients who suddenly discontinue or reduce their use of levodopa [see Warnings and Precautions (5.7)].

2.6 Important Administration Instructions

Do not split, crush or chew carbidopa, levodopa and entacapone tablets. Administer only one tablet at each dosing interval. All strengths of carbidopa, levodopa and entacapone tablets contain 200 mg of entacapone. Combining multiple tablets or portions of tablets to achieve a higher levodopa dose may lead to an overdose of entacapone.

Administer carbidopa, levodopa and entacapone tablets with or without food. However, a high-fat, high-calorie meal may delay the absorption of levodopa by about 2 hours[see Clinical Pharmacology (12.3)].