carbidopa, levodopa and entacapone
Generic: CARBIDOPA, LEVODOPA AND ENTACAPONE
Basic Information
Manufacturer
Alembic Pharmaceuticals Inc.
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
ORAL
FDA Set ID
9d4e886e-edec-471d-b619-bf4828a6b7ce
Indications & Usage
1 INDICATIONS AND USAGE Carbidopa, levodopa and entacapone tablets 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) is 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 )
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) is 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 )
Adverse Reactions
6 ADVERSE REACTIONS The following adverse reactions are discussed in more detail in the Warnings and Precautions sections of labeling: • Falling Asleep During Activities of Daily Living and Somnolence [see Warnings and Precautions (5.1)] • Hypotension/Orthostatic Hypotension and Syncope [see Warnings and Precautions (5.2)] • Dyskinesia [see Warnings and Precautions (5.3)] • Depression and suicidality [see Warnings and Precautions (5.4)] • Hallucinations/Psychotic-Like Behavior [see Warnings and Precautions (5.5)] • Impulse Control and/or Compulsive Behaviors [see Warnings and Precautions (5.6)] • Withdrawal-Emergent Hyperpyrexia and Confusion [ see Warnings and Precautions (5.7)] • Diarrhea and Colitis [see Warnings and Precautions (5.8)] • Rhabdomyolysis [see Warnings and Precautions (5.9)] • Peptic Ulcer Disease [see Warnings and Precautions (5.13)] The most common adverse reactions (incidence 3% higher than placebo incidence) are dyskinesias, hyperkinesia, diarrhea, nausea, abdominal pain, vomiting, dry mouth, and urine discoloration ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Alembic Pharmaceuticals Limited at 1-866-210-9797 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, the incidence of adverse reactions (number of unique patients experiencing an adverse reaction associated with treatment/total number of patients treated) observed in the clinical trials of a drug cannot be directly compared to the incidence of adverse reactions in the clinical trials of another drug and may not reflect the incidence of adverse reactions observed in clinical practice.
Entacapone The most commonly observed adverse reactions (incidence at least 3% greater than placebo incidence) in the double-blind, carbidopa-levodopa-placebo-controlled trials of entacapone (N=1,003 patients) associated with the use of carbidopa-levodopa-entacapone alone and not seen at an equivalent frequency among the placebo-treated patients were: dyskinesia, diarrhea, nausea, hyperkinesia, abdominal pain, vomiting, dry mouth, and urine discoloration.
The treatment difference incidence for premature study discontinuation for entacapone with levodopa and dopa decarboxylase inhibitor in the double-blind, placebo-controlled trials was 5%.
The treatment difference incidence for the most frequent causes of study discontinuation was 2% for diarrhea, and 1% for other specific adverse reactions including psychiatric reasons, dyskinesia/ hyperkinesia, nausea, or abdominal pain.
Adverse Reaction Incidence in Controlled Clinical Studies of Entacapone Table 2 lists treatment emergent adverse reactions that occurred in at least 1% of patients treated with carbidopa/levodopa and 200 mg of entacapone who participated in the double-blind, placebo-controlled studies, and that were numerically more common in this group than in the carbidopa/levodopa plus placebo group.
In these studies, either entacapone or placebo was added to carbidopa/levodopa (or benserazide/levodopa).
Table 2: Summary of Patients With Adverse Reactions After Start of Trial Drug Administration At Least 1% in Entacapone Group and Greater Than Placebo SYSTEM ORGAN CLASS Carbidopa/levodopa plus Entacapone Carbidopa/levodopa plus Placebo Adverse Reaction (n=603) % of patients (n=400) % of patients SKIN AND APPENDAGES DISORDERS Sweating Increased 2 1 MUSCULOSKELETAL SYSTEM DISORDERS Back Pain 5 3 CENTRAL AND PERIPHERAL NERVOUS SYSTEM DISORDERS Dyskinesia 25 15 Hyperkinesia 10 5 Hypokinesia 9 8 Dizziness 8 6 SPECIAL SENSES, OTHER DISORDERS Taste Perversion 1 0 PSYCHIATRIC DISORDERS Anxiety 2 1 Somnolence 2 0 Agitation 1 0 GASTROINTESTINAL SYSTEM DISORDERS Nausea 14 8 Diarrhea 10 4 Abdominal Pain 8 4 Constipation 6 4 Vomiting 4 1 Mouth Dry 3 0 Dyspepsia 2 1 Flatulence 2 0 Gastritis 1 0 Gastrointestinal Disorders NOS 1 0 RESPIRATORY SYSTEM DISORDERS Dyspnea 3 1 PLATELET, BLEEDING AND CLOTTING DISORDERS Purpura 2 1 URINARY SYSTEM DISORDERS Urine Discoloration 10 0 BODY AS A WHOLE-GENERAL DISORDERS Fatigue 6 4 Asthenia 2 1 RESISTANCE MECHANISM DISORDERS Infection Bacterial 1 0 6.2 Postmarketing Experience The following spontaneous reports of adverse events temporally associated with entacapone or carbidopa, levodopa and entacapone tablets have been identified since market introduction and are not listed in Table 2.
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 entacapone or carbidopa, levodopa and entacapone tablets exposure.
Hepatitis with mainly cholestatic features has been reported.
Effects of Gender and Age on Adverse Reactions No differences were noted in the rate of adverse reactions attributable to entacapone alone by age or gender.
6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, the incidence of adverse reactions (number of unique patients experiencing an adverse reaction associated with treatment/total number of patients treated) observed in the clinical trials of a drug cannot be directly compared to the incidence of adverse reactions in the clinical trials of another drug and may not reflect the incidence of adverse reactions observed in clinical practice.
Entacapone The most commonly observed adverse reactions (incidence at least 3% greater than placebo incidence) in the double-blind, carbidopa-levodopa-placebo-controlled trials of entacapone (N=1,003 patients) associated with the use of carbidopa-levodopa-entacapone alone and not seen at an equivalent frequency among the placebo-treated patients were: dyskinesia, diarrhea, nausea, hyperkinesia, abdominal pain, vomiting, dry mouth, and urine discoloration.
The treatment difference incidence for premature study discontinuation for entacapone with levodopa and dopa decarboxylase inhibitor in the double-blind, placebo-controlled trials was 5%.
The treatment difference incidence for the most frequent causes of study discontinuation was 2% for diarrhea, and 1% for other specific adverse reactions including psychiatric reasons, dyskinesia/ hyperkinesia, nausea, or abdominal pain.
Adverse Reaction Incidence in Controlled Clinical Studies of Entacapone Table 2 lists treatment emergent adverse reactions that occurred in at least 1% of patients treated with carbidopa/levodopa and 200 mg of entacapone who participated in the double-blind, placebo-controlled studies, and that were numerically more common in this group than in the carbidopa/levodopa plus placebo group.
In these studies, either entacapone or placebo was added to carbidopa/levodopa (or benserazide/levodopa).
Table 2: Summary of Patients With Adverse Reactions After Start of Trial Drug Administration At Least 1% in Entacapone Group and Greater Than Placebo SYSTEM ORGAN CLASS Carbidopa/levodopa plus Entacapone Carbidopa/levodopa plus Placebo Adverse Reaction (n=603) % of patients (n=400) % of patients SKIN AND APPENDAGES DISORDERS Sweating Increased 2 1 MUSCULOSKELETAL SYSTEM DISORDERS Back Pain 5 3 CENTRAL AND PERIPHERAL NERVOUS SYSTEM DISORDERS Dyskinesia 25 15 Hyperkinesia 10 5 Hypokinesia 9 8 Dizziness 8 6 SPECIAL SENSES, OTHER DISORDERS Taste Perversion 1 0 PSYCHIATRIC DISORDERS Anxiety 2 1 Somnolence 2 0 Agitation 1 0 GASTROINTESTINAL SYSTEM DISORDERS Nausea 14 8 Diarrhea 10 4 Abdominal Pain 8 4 Constipation 6 4 Vomiting 4 1 Mouth Dry 3 0 Dyspepsia 2 1 Flatulence 2 0 Gastritis 1 0 Gastrointestinal Disorders NOS 1 0 RESPIRATORY SYSTEM DISORDERS Dyspnea 3 1 PLATELET, BLEEDING AND CLOTTING DISORDERS Purpura 2 1 URINARY SYSTEM DISORDERS Urine Discoloration 10 0 BODY AS A WHOLE-GENERAL DISORDERS Fatigue 6 4 Asthenia 2 1 RESISTANCE MECHANISM DISORDERS Infection Bacterial 1 0 6.2 Postmarketing Experience The following spontaneous reports of adverse events temporally associated with entacapone or carbidopa, levodopa and entacapone tablets have been identified since market introduction and are not listed in Table 2.
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 entacapone or carbidopa, levodopa and entacapone tablets exposure.
Hepatitis with mainly cholestatic features has been reported.
Effects of Gender and Age on Adverse Reactions No differences were noted in the rate of adverse reactions attributable to entacapone alone by age or gender.