CARBIDOPA-LEVODOP 61.25-245MG ER CAP 100
Generic: Carbidopa and Levodopa
CARBIDOPA-LEVODOP 61.25-245MG ER CAP 100
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Identification
Carbidopa and Levodopa
Carbidopa and Levodopa
Zydus Pharmaceuticals USA Inc.
HUMAN PRESCRIPTION DRUG
Administration
CAPSULE, EXTENDED RELEASE
ORAL
NDA203312
Active Ingredients
| Ingredient | Strength |
|---|---|
| CARBIDOPA | 61.25 mg/1 |
| LEVODOPA | 245 mg/1 |
Pharmacological Class
Data sourced from openFDA / DailyMed. For full prescribing information, consult the drug label.
Wholesale compliance resources
Drug Resources
Clinical Drug Information
Indications & Usage
1 INDICATIONS AND USAGE Carbidopa and levodopa extended-release capsules are indicated for the treatment of Parkinson's disease, post-encephalitic parkinsonism, and parkinsonism that may follow carbon monoxide intoxication or manganese intoxication. Carbidopa and levodopa extended-release capsule is a combination of carbidopa (an aromatic amino acid decarboxylation inhibitor) and levodopa (an aromatic amino acid) indicated for the treatment of Parkinson's disease, post-encephalitic parkinsonism, and parkinsonism that may follow carbon monoxide intoxication or manganese intoxication ( 1 )
Dosage & Administration
2 DOSAGE AND ADMINISTRATION 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 ( 2.1 ) See Table 1 for instructions for converting patients taking immediate-release carbidopa-levodopa to an initial dose of carbidopa and levodopa extended-release capsules. Dosages of carbidopa and levodopa extended-release capsules are not interchangeable with other carbidopa-levodopa products ( 2.2 ) The maximum recommended daily dose of carbidopa and levodopa extended-release capsules is 612.5 mg/2,450 mg ( 2.1 , 2.2 ) Carbidopa and levodopa extended-release capsules may be taken with or without food; do not chew, divide or crush ( 2.4 , 12.3 ) 2.1 Dosage in Patients Naïve to Levodopa Therapy The recommended starting dosage of carbidopa and levodopa extended-release capsules 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 carbidopa and levodopa extended-release capsules may be increased to 36.25 mg/145 mg taken three times a day. Based upon individual patient clinical response and tolerability, the carbidopa and levodopa extended-release capsules 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 carbidopa and levodopa extended-release capsules is 612.5 mg/2,450 mg. 2.2 Converting from Immediate-Release Carbidopa-Levodopa to Carbidopa and Levodopa Extended-Release Capsules The dosages of other carbidopa and levodopa products are not interchangeable on a 1:1 basis with the dosages of carbidopa and levodopa extended-release capsules. To convert patients from immediate-release carbidopa-levodopa to carbidopa and levodopa extended-release capsules, first calculate the patient's current total daily dose of levodopa. The starting total daily dose of carbidopa and levodopa extended-release capsules is as recommended in Table 1. After conversion, any combination of the four carbidopa and levodopa extended-release capsules 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 carbidopa and levodopa extended-release capsules dose. In clinical trials, carbidopa and levodopa extended-release capsules were administered in divided doses of three to five times a day. The maximum recommended total daily dose of carbidopa and levodopa extended-release capsule 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 carbidopa and levodopa extended-release capsules described in Table 1 may need to be increased. Use of carbidopa and levodopa extended-release capsules in combination with other levodopa products has not been studied. Table 1 Conversion from Immediate-Release Carbidopa-Levodopa to Carbidopa and Levodopa Extended-Release Capsules Total Daily Dose of Levodopa in Immediate-Release Carbidopa- Levodopa Recommended Starting Dosage of Carbidopa and Levodopa Extended-Release Capsules Total Daily Dose of Levodopa in Carbidopa and Levodopa Extended-Release Capsules Carbidopa and Levodopa Extended-Release Capsules Dosing Regimen 400 mg to 549 mg 855 mg 3 capsules carbidopa and levodopa extended-release capsules 23.75 mg/95 mg taken TID a 550 mg to 749 mg 1,140 mg 4 capsules carbidopa and levodopa extended-release capsules 23.75 mg/95 mg taken TID 750 mg to 949 mg 1,305 mg 3 capsules carbidopa and levodopa extended-release capsules 36.25 mg/145 mg taken TID 950 mg to 1,249 mg 1,755 mg 3 capsules carbidopa and levodopa extended-release capsules 48.75 mg/195 mg taken TID Equal to or greater than 1,250 mg 2,340 mg or 4 capsules carbidopa and levodopa extended-release capsules 48.75 mg/195 mg taken TID or 2,205 mg 3 capsules carbidopa and levodopa extended-release capsules 61.25 mg/245 mg taken TID a TID: three times a day 2.3 Discontinuation of Carbidopa And Levodopa Extended-Release Capsules Avoid sudden discontinuation or rapid dose reduction of carbidopa and levodopa extended-release capsules. The daily dose of carbidopa and levodopa extended-release capsules should be tapered at the time of treatment discontinuation [see Warnings and Precautions ( 5.2 )] . 2.4 Administration Information Swallow carbidopa and levodopa extended-release capsules whole with or without food. A high-fat, high-calorie meal may delay the absorption of levodopa by about 2 hours [see Clinical Pharmacology ( 12.3 )]. Do not chew, divide or crush carbidopa and levodopa extended-release capsules. For patients who have difficulty swallowing intact capsules, administer carbidopa and levodopa extended-release capsules 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.
Adverse Reactions
6 ADVERSE REACTIONS The following serious adverse reactions are discussed below and elsewhere in the labeling: Falling Asleep During Activities of Daily Living and Somnolence [see Warnings and Precautions ( 5.1 )] Withdrawal-Emergent Hyperpyrexia and Confusion [see Warnings and Precautions ( 5.2 )] Cardiovascular Ischemic Events [see Warnings and Precautions ( 5.3 )] Hallucinations/Psychosis [see Warnings and Precautions ( 5.4 )] Impulse Control/Compulsive Behaviors [see Warnings and Precautions ( 5.5 )] Dyskinesia [see Warnings and Precautions ( 5.6 )] Peptic Ulcer Disease [see Warnings and Precautions ( 5.7 )] Glaucoma [see Warnings and Precautions ( 5.8 )] Early Parkinson's disease: Most common adverse reactions (incidence ≥ 5% and greater than placebo) are nausea, dizziness, headache, insomnia, abnormal dreams, dry mouth, dyskinesia, anxiety, constipation, vomiting, and orthostatic hypotension ( 6.1 ) Advanced Parkinson's disease: Most common adverse reactions (incidence ≥ 5% and greater than oral immediate-release carbidopa-levodopa) are nausea and headache ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Zydus Pharmaceuticals (USA) Inc. at 1-877-993-8779 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The safety population consisted of a total of 978 Parkinson's disease patients who received at least one dose of carbidopa and levodopa extended-release capsules, and had an average duration of exposure of 40 weeks. Adverse Reactions in Early Parkinson's Disease In a placebo-controlled clinical study in patients with early Parkinson's disease (Study 1), the most common adverse reactions with carbidopa and levodopa extended-release capsules (in at least 5% of patients and more frequently than in placebo) were nausea, dizziness, headache, insomnia, abnormal dreams, dry mouth, dyskinesia, anxiety, constipation, vomiting, and orthostatic hypotension. Table 2 lists adverse reactions occurring in at least 5% of carbidopa and levodopa extended-release capsules-treated patients and at a higher rate than placebo in Study 1. Table 2 Adverse Reactions in Study 1 in Patients with Early Stage Parkinson's Disease Placebo Carbidopa and Levodopa Extended-release Capsules 36.25 mg Carbidopa Carbidopa and Levodopa Extended-release Capsules 61.25 mg Carbidopa Carbidopa and Levodopa Extended-release Capsules 97.5 mg Carbidopa 145 mg Levodopa TID 245 mg Levodopa TID 390 mg Levodopa TID (N=92) (N=87) (N=104) (N=98) % % % % Nausea 9 14 19 20 Dizziness 5 9 19 12 Headache 11 7 13 17 Insomnia 3 2 9 6 Abnormal Dreams 0 2 6 5 Dry Mouth 1 3 2 7 Dyskinesia 0 2 4 5 Anxiety 0 2 3 5 Constipation 1 2 6 2 Vomiting 3 2 2 5 Orthostatic Hypotension 1 1 1 5 Adverse Reactions Leading to Discontinuation in Study 1 In Study 1, 12% of patients discontinued carbidopa and levodopa extended-release capsules early due to adverse reactions; a higher proportion of patients in the 61.25 mg/ 245 mg carbidopa and levodopa extended-release capsules-treated group (14%) and in the 97.5 mg/390 mg carbidopa and levodopa extended-release capsules-treated group (15%) experienced adverse reactions leading to early discontinuation compared to (4%) in the placebo group. The most common adverse reactions resulting in early discontinuation were nausea, dizziness, and vomiting. Adverse Reactions in Advanced Parkinson's Disease In an active-controlled clinical study in patients with advanced Parkinson's disease (Study 2), the most common adverse reactions with carbidopa and levodopa extended-release capsules that occurred during dose conversion or maintenance (in at least 5% of patients and more frequently than on oral immediate-release carbidopa-levodopa) were nausea and headache. Table 3 lists adverse reactions occurring in at least 5% of carbidopa and levodopa extended-release capsules-treated patients and at a higher rate than oral immediate-release carbidopa-levodopa in Study 2. Table 3 Adverse Reactions in Study 2 in Patients with Advanced Parkinson's Disease Carbidopa and Levodopa Extended-release Capsules Immediate-Release Carbidopa-Levodopa (N=201) (N=192) Period Dose Conversion a Maintenance Dose Conversion a Maintenance % % % % Nausea 4 3 6 2 Headache 5 1 3 2 a All patients were converted to carbidopa and levodopa extended-release capsules in the open-label Dose Conversion period and then received randomized treatment during maintenance. Adverse Reactions Leading to Discontinuation in Study 2 In Study 2, 5% of patients discontinued treatment due to adverse reactions during conversion to carbidopa and levodopa extended-release capsules. The common adverse reactions leading to discontinuation during dose conversion were dyskinesia, anxiety, dizziness, and on and off phenomenon. 6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of carbidopa and levodopa extended-release capsules. Because these reactions are reported voluntarily from a population of unknown size, it is not always possible to reliably estimate their frequency or establish causal relationship to carbidopa and levodopa extended-release capsules exposure. Psychiatric : Suicide attempt, suicidal ideation.
Information for Patients
17 PATIENT COUNSELING INFORMATION Dosing Instructions Advise patients to not take other carbidopa-levodopa preparations with carbidopa and levodopa extended-release capsules without consulting their healthcare provider [see Dosage and Administration ( 2.2 )] . Advise patients to call their healthcare provider before stopping carbidopa and levodopa extended-release capsules. Discontinue carbidopa and levodopa extended-release capsules slowly. Tell patients to call their healthcare provider if they develop withdrawal symptoms such as fever, confusion or severe muscle stiffness [see Dosage and Administration ( 2.3 ) and Warnings and Precautions ( 5.2 )]. Advise patients to swallow carbidopa and levodopa extended-release capsules whole, without chewing, dividing, or crushing [see Dosage and Administration ( 2.4 )] . For patients with difficulty swallowing, the entire contents of the carbidopa and levodopa extended-release capsule may be sprinkled on 1 to 2 tablespoons of applesauce and should be taken immediately [see Dosage and Administration ( 2.4 )] . Inform patients that a high fat, high calorie meal may delay the absorption of levodopa and the onset of action by 2 to 3 hours. For this reason, consideration should be given to taking the first dose of the day about 1 to 2 hours before eating [see Dosage and Administration ( 2.4 ) and Clinical Pharmacology ( 12.3 )] . Falling Asleep Advise patients that certain side effects such as sleepiness and dizziness that have been reported with carbidopa and levodopa extended-release capsules may affect some patients' ability to drive and operate machinery safely [see Warnings and Precautions ( 5.1 ) and Adverse Reactions ( 6.1 )] . Suicide Attempt and Suicidal Ideation Instruct patients, family members and caregivers to notify their healthcare provider if suicide attempt and/or suicidal ideation are experienced by patients using carbidopa and levodopa extended-release capsules [see Adverse Reactions ( 6.2 )] . Hallucinations and Psychosis Inform patients that hallucinations can occur with levodopa products [see Warnings and Precautions ( 5.4 )] . Impulse Control Disorder Inform patients of the potential for experiencing intense urges to gamble, increased sexual urges, and other intense urges and the inability to control these urges while taking one or more of the medications that increase central dopaminergic tone, that are generally used for the treatment of Parkinson's disease [see Warnings and Precautions ( 5.5 )] . Dyskinesia Instruct patients to notify their healthcare provider if abnormal involuntary movements appear or get worse during treatment with carbidopa and levodopa extended-release capsules [see Warnings and Precautions ( 5.6 )] . Hypotension and Syncope Advise patients that they may develop orthostatic hypotension with or without symptoms such as dizziness, nausea, syncope, and sweating [see Adverse Reactions ( 6.1 )] . Advise patients to rise slowly after sitting or lying down, especially if they have been doing so for a prolonged period. Advise patients of the possible additive sedative effects when taking other CNS depressants in combination with carbidopa and levodopa extended-release capsules. Pregnancy and Breastfeeding Advise patients to notify their healthcare provider if they become pregnant or intend to become pregnant during carbidopa and levodopa extended-release capsules therapy [see Use in Specific Populations ( 8.1 )] . Advise female patients to notify their physicians if they intend to breastfeed or are breastfeeding an infant [see Use in Specific Populations ( 8.2 )] .
Clinical data sourced from openFDA drug labeling. For complete prescribing information, consult the full drug label.