Drug Catalog - Product Detail
Carbidopa-Levodopa-Entacapone Tabs 25-100-200 MG 100 EA
| NDC | Mfr | Size | Str | Form |
|---|---|---|---|---|
| 00781-5637-01 | SANDOZ | 100 | 25-100-200MG | TABLET |
PACKAGE FILES
Generic Name
CARBIDOPA, LEVODOPA, AND ENTACAPONE
Substance Name
CARBIDOPA
Product Type
HUMAN PRESCRIPTION DRUG
Route
ORAL
Application Number
NDA021485
Description
11 DESCRIPTION Carbidopa, levodopa and entacapone tablets are a combination of carbidopa, levodopa, and entacapone for the treatment of Parkinson's disease. Carbidopa, an inhibitor of aromatic amino acid decarboxylation, is a white, crystalline compound, slightly soluble in water, with a molecular weight of 244.3. It is designated chemically as (-)-L-(α-hydrazino-(α-methyl-β-(3,4-dihydroxybenzene) propanoic acid monohydrate. Its empirical formula is C 10 H 14 N 2 O 4 •H 2 O, and its structural formula is: Tablet content is expressed in terms of anhydrous carbidopa, which has a molecular weight of 226.3. Levodopa, an aromatic amino acid, is a white, crystalline compound, slightly soluble in water, with a molecular weight of 197.2. It is designated chemically as (-)-L-α-amino-β-(3,4-dihydroxybenzene) propanoic acid. Its empirical formula is C 9 H 11 NO 4 , and its structural formula is: Entacapone, a COMT inhibitor, is a nitro-catechol-structured compound with a molecular weight of 305.3. The chemical name of entacapone is (E)-2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)-N,N-diethyl-2-propenamide. Its empirical formula is C 14 H 15 N 3 O 5 and its structural formula is: Carbidopa, Levodopa and Entacapone Tablets are supplied as tablets in 6 strengths: Carbidopa, Levodopa and Entacapone Tablets: 12.5 mg of carbidopa, 50 mg of levodopa and 200 mg of entacapone Carbidopa, Levodopa and Entacapone Tablets: 18.75 mg of carbidopa, 75 mg of levodopa and 200 mg of entacapone Carbidopa, Levodopa and Entacapone Tablets: 25 mg of carbidopa, 100 mg of levodopa and 200 mg of entacapone Carbidopa, Levodopa and Entacapone Tablets: 31.25 mg of carbidopa, 125 mg of levodopa and 200 mg of entacapone Carbidopa, Levodopa and Entacapone Tablets: 37.5 mg of carbidopa, 150 mg of levodopa and 200 mg of entacapone Carbidopa, Levodopa and Entacapone Tablets: 50 mg of carbidopa, 200 mg of levodopa and 200 mg of entacapone Inactive Ingredients: corn starch, croscarmellose sodium, glycerol 85%, hypromellose, magnesium stearate, mannitol, polysorbate 80, povidone, sucrose, red iron oxide, and titanium dioxide. Tablets containing 12.5 mg of carbidopa, 50 mg of levodopa and 200 mg of entacapone, tablets containing 25 mg of carbidopa, 100 mg of levodopa and 200 mg of entacapone, and tablets containing 37.5 mg of carbidopa, 150 mg of levodopa and 200 mg of entacapone also contain yellow iron oxide. carbidopa_chemstructure levodopa_chemstructure entacapone_chemstructure
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING Carbidopa, levodopa and entacapone tablets are supplied as film-coated tablets for oral administration in the following six strengths: Carbidopa, levodopa and entacapone film-coated tablets containing 12.5 mg of carbidopa, 50 mg of levodopa, and 200 mg of entacapone. The round, bi-convex shaped tablets are brownish- or greyish-red, unscored, and embossed “LCE 50” on one side. NDC 0781-5613-01 HDPE bottle of 100 tablets Carbidopa, levodopa and entacapone film-coated tablets containing 18.75 mg of carbidopa, 75 mg of levodopa, and 200 mg of entacapone. The oval-shaped tablets are light brownish red, unscored and embossed with code “LCE 75” on one side. NDC 0781-5625-01 HDPE bottle of 100 tablets Carbidopa, levodopa and entacapone film-coated tablets containing 25 mg of carbidopa, 100 mg of levodopa, and 200 mg of entacapone. The oval-shaped tablets are brownish- or greyish-red, unscored, and embossed “LCE 100” on one side. NDC 0781-5637-01 HDPE bottle of 100 tablets Carbidopa, levodopa and entacapone film-coated tablets containing 31.25 mg of carbidopa, 125 mg of levodopa, and 200 mg of entacapone. The oval-shaped tablets are light brownish red, unscored and embossed with code “LCE 125” on one side. NDC 0781-5641-01 HDPE bottle of 100 tablets Carbidopa, levodopa and entacapone film-coated tablets containing 37.5 mg of carbidopa, 150 mg of levodopa, and 200 mg of entacapone. The elongated-ellipse shaped tablets are brownish- or greyish-red, unscored, and embossed “LCE 150” on one side. NDC 0781-5654-01 HDPE bottle of 100 tablets Carbidopa, levodopa and entacapone film-coated tablets containing 50 mg of carbidopa, 200 mg of levodopa, and 200 mg of entacapone. The oval shaped tablets are dark brownish red, unscored, and embossed “LCE 200” on one side. NDC 0781-5669-01 HDPE bottle of 100 tablets Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). [See USP Controlled Room Temperature.] Dispense in tight container (USP).
Indications & Usage
1 INDICATIONS AND USAGE Carbidopa, levodopa and entacapone tablets, a combination drug consisting of levodopa, carbidopa (dopa decarboxylase inhibitor), and entacapone (catechol-O-methyltransferase-COMT inhibitor) are indicated for the treatment of Parkinson's disease. Carbidopa, levodopa and entacapone tablets can be used: • To substitute (with equivalent strengths of each of the three components) carbidopa/levodopa and entacapone previously administered as individual products. • To replace carbidopa/levodopa therapy (without entacapone) when patients experience the signs and symptoms of end-of-dose “wearing-off” and when they have been taking a total daily dose of levodopa of 600 mg or less and have not been experiencing dyskinesias. Carbidopa, levodopa and entacapone tablets, a combination drug consisting of levodopa (aromatic amino acid), carbidopa (aromatic amino acid decarboxylation inhibitor), and entacapone (catechol-O-methyltransferase (COMT) inhibitor) are indicated for the treatment of Parkinson's disease. Carbidopa, levodopa and entacapone tablets are to be used: • To substitute (with equivalent strengths of each of the three components) for carbidopa/levodopa and entacapone previously administered as individual products ( 1 ) • To replace carbidopa/levodopa therapy (without entacapone) when patients experience the signs and symptoms of end-of-dose “wearing-off” and when they have been taking a total daily dose of levodopa of 600 mg or less and have not been experiencing dyskinesias ( 1 )
Dosage and Administration
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. • The optimum daily dosage of carbidopa, levodopa and entacapone tablets must be determined by careful titration in each patient ( 2.1 ) • Individual tablets should not be split or fractionated. Administer only one tablet at each dosing interval ( 2.6 ) 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 of carbidopa, levodopa and entacapone tablets 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 per 50 mg per 200 mg 8 18.75 mg per 75 mg per 200 mg 25 mg per 100 mg per 200 mg 31.25 mg per 125 mg per 200 mg 37.5 mg per 150 mg per 200 mg 50 mg per 200 mg per 200 mg 6 2.2 Converting Patients from Carbidopa, Levodopa, and Entacapone Products 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 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 tablets. 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 tablets may be required. 2.5 Decrease or Interruption of Dosing Avoid interruption of carbidopa, levodopa and entacapone tablets dosing 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) ] .