Adult Dosing

Parkinsonian syndrome

• Conventional preparation: Start with 25 mg carbidopa/100 mg levodopa tid; increase by 25 mg carbidopa/100 mg levodopa q1-2 days until a total of 8 tablets/day is reached; alternatively start with carbidopa/levodopa 10 mg/100 mg tid or qid, increase by 10 mg carbidopa/100 mg levodopa q1-2 days until a total of 8 tablets/day is reached
• Max 200 mg/2000 mg/day in 3-4 divided doses
• Usual maintenance dose of carbidopa is 70-100 mg daily
• Extended-release preparation: Conventional preparations should be substituted by prolonged-release preparations at an amount that provides approximately 10% more levodopa/day; may be increased to dosage that provides up to 30% more levodopa/day as needed with a dose interval of 4-8 hrs during the waking day
• When switching from levodopa alone to carbidopa combination, begin with 20-25% of previous levodopa dose
• Initial dose of combination extended-release preparation is 50 mg carbidopa/200 mg levodopa bid, should not be given at <6-hour intervals; usual range being 100-400 mg carbidopa/0.4-1.6 g levodopa given at q4-8 hrs intervals while awake
• Dosing of this combination is highly variable depending on disease presentation and therapeutic response
• Note: When shifting patients from levodopa monotherapy to combination therapy, levodopa must be discontinued at least 12 hours prior to starting combination therapy
• Note: Do not crush or chew extended-release preparation
• Note: See package labeling or <I>AHFS 2004</I> for more detailed regimens

Pediatric Dosing

• Safety and effectiveness in pediatric patients have not been established

[Outline]

• Adult Dosing
• Pediatric Dosing

• Treatment of the symptoms of idiopathic Parkinson's disease (paralysis agitans), post-encephalitic parkinsonism, and symptomatic parkinsonism which may follow injury to the nervous system by carbon monoxide intoxication and/or manganese intoxication

• Hypersensitivity to any of the ingredients of the product
• During or within 14 days of nonselective monoamine oxidase (MAO) inhibitors
• Undiagnosed skin lesions
• History of melanoma
• Narrow-angle glaucoma

• N/A

Renal Dose Adjustment

• Severe renal impairment: Use with caution; dose adjustments not defined

Hepatic Dose Adjustment

• Severe hepatic impairment: Use with caution; dose adjustments not defined

See Supplemental Patient Information

• In patients receiving levodopa monotherapy, levodopa must be discontinued at least 12 hrs prior to starting carbidopa/levodopa combination therapy. Combination extended-release preparation must be substituted at a dosage that provides about 25% of the previous levodopa dosage
• Therapy should be individualized to reduce adverse reactions
• Dyskinesias may occur at lower dosages of extended-release tablets; appropriately modify dose
• Due to increased brain dopamine, mental disturbances have occurred; carefully observe patients for development of depression with concomitant suicidal tendencies
• The cardiac functions of patients with a history of MI having residual atrial, nodal, or ventricular arrhythmias should be carefully monitored during the period of initial dose titration at facilities with provisions for intensive cardiac care
• Therapy may be associated with somnolence and occasionally sudden onset of sleep during daily activities and may occur without awareness or warning signs
• Patients with a history of peptic ulcer should be monitored for upper gastrointestinal hemorrhage
• Sporadic cases of a symptom complex resembling neuroleptic malignant syndrome (NMS) have occurred during dose reduction or withdrawal of therapy. Carefully monitor patients during abrupt reduction of dosages or discontinuation of therapy. Avoid abrupt withdrawal
• Exercise caution in patients receiving other CNS depressants or psychoactive agents
• In case of fatal NMS, provide intensive symptomatic treatment and carefully monitor the patients
• Closely monitor the patient and adjust other dopaminergic treatments while considering discontinuation of therapy
• Patients are at an increased risk of developing melanoma. Periodic skin examinations should be performed by dermatologists
• Periodically monitor creatinine, LFTs, hematopoietic, cardiovascular, and renal functions in patients on prolonged therapy
• Monitor patients for changes in intraocular pressure
• Monitor for symptoms of orthostatic hypotension

Cautions: Use cautiously in

• Renal impairment
• Hepatic impairment
• Past or current psychoses
• Suicidal tendencies
• Severe cardiovascular disease
• Pulmonary disease
• Bronchial asthma
• Endocrine disease
• Chronic wide-angle glaucoma
• Biliary obstruction
• GI bleeding
• Elderly patients

Supplemental Patient Information

• Inform patients that consuming high protein foods might delay the absorption of levodopa and may reduce the amount taken up in circulation
• Advise to avoid usage of iron supplements
• Caution patients about rising rapidly after sitting or lying down, especially if they have been doing so for longer periods, and especially at the initiation of treatment
• Patients must be cautioned against performing tasks which require mental alertness (eg, operating machinery or driving)
• Caution patients about the occasional [wearing-off’ effect that may occur at the end of the dosing interval and to inform physicians if it poses a problem to lifestyle
• Advise patients that rarely a dark color (red, brown, or black) may appear in saliva, sweat, or urine after taking this medicine
• Instruct patients to inform their physicians if they experience new or increased gambling or sexual urges, or other intense urges during therapy

Pregnancy Category:C

Breastfeeding: Levodopa is poorly excreted into breastmilk. Sustained-release tablets may result in a smaller amount of drug transferred to the breastfed infant than the immediate-release tablets. Safety unknown for prolonged use of levodopa. This information is based on LactMed database (available at http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT last accessed 25 February 2011). According to manufacturer’s data, caution should be exercised when administered to nursing women.

• CNS/PSYCHIATRY: Dyskinesias, dystonia, asthenia, fatigue, psychotic episodes including depression, delusions, hallucinations, paranoid ideation, neuroleptic malignant syndrome, bradykinetic episodes ("on-off" phenomenon), confusion, anxiety, agitation, dizziness, somnolence, dream abnormalities including nightmares, insomnia, paresthesia, headache, suicidal tendencies, dementia, pathological gambling, mood changes, increased libido including hypersexuality, compulsive behavior
• CV: Chest pain, cardiac irregularities, hypotension, orthostatic hypotension, hypertension, arrhythmias, syncope, phlebitis, palpitation, myocardial infarction
• GI: Dark saliva, GI bleeding, development of duodenal ulcer, anorexia, nausea, vomiting, diarrhea, constipation, dyspepsia, dry mouth, taste alterations
• HEMA: Agranulocytosis, hemolytic and non-hemolytic anemia, thrombocytopenia, leukopenia
• HYPERSENSITIVITY: Angioedema, urticaria, pruritus, Henoch-Schonlein purpura, bullous lesions
• MUSC: Back pain, shoulder pain, muscle cramps
• RESP: Dyspnea, upper respiratory infection
• DERM: Rash, increased sweating, alopecia, dark sweat, malignant melanoma
• GU: Urinary tract infection, urinary frequency, dark urine
• LABTESTS: Decreased hemoglobin and hematocrit; abnormalities in alkaline phosphatase, SGOT (AST), SGPT (ALT), lactic dehydrogenase, bilirubin, blood urea nitrogen (BUN), Coombs test; elevated serum glucose; white blood cells, bacteria, and blood in urine

Levodopa

• Dopamine precursor; crosses the blood-brain barrier and is converted to dopamine in the brain
• Rapidly absorbed from the GI tract
• Metabolized in the lumen of the stomach and intestines, liver, kidney
• Excreted in urine
• Half-life: 50 minutes without carbidopa and about 1.5 hours with carbidopa

Carbidopa

• Antiparkinson; prevents decarboxylation of peripheral levodopa making more levodopa available for transport to brain and also reduces peripheral adverse effects of levodopa
• Not extensively metabolized
• Renally excreted: 30% unchanged
• Half-life: 1-2 hrs

US Trade Name(s)

• Parcopa
• Sinemet
• Sinemet CR

US Availability

carbidopa/levodopa (generic)

• TABS:
• 10 mg/100 mg
• 25 mg/100 mg
• 25 mg/250 mg

• ETABS:
• 25 mg/100mg
• 50 mg/200 mg

• ODT:
• 10 mg/100 mg
• 25 mg/100 mg
• 25 mg/250 mg

Parcopa (carbidopa/levodopa)

• ODT:
• 10 mg/100 mg
• 25 mg/100 mg
• 25 mg/250 mg

Sinemet (carbidopa/levodopa)

• TABS:
• 10 mg/100 mg
• 25 mg/100 mg
• 25 mg/250 mg

Sinemet CR (carbidopa/levodopa)

• ETABS:
• 25 mg/100mg
• 50 mg/200 mg

Canadian Trade Name(s)

• Apo-Levocarb
• Levocarb CR
• NU-Levocarb
• Pro-Levocarb
• Sinemet
• Sinemet CR

Canadian Availability

carbidopa/levodopa (generic)

• TABS:
• 10 mg/100 mg
• 25 mg/100 mg
• 25 mg/250 mg

Apo-Levocarb (carbidopa/levodopa)

• TABS:
• 10 mg/100 mg
• 25 mg/100 mg
• 25 mg/250 mg

Levocarb CR (carbidopa/levodopa)

• ETABS:
• 25 mg/100 mg
• 50 mg/200 mg

NU-Levocarb (carbidopa/levodopa)

• TABS:
• 10 mg/100 mg
• 25 mg/100 mg
• 25 mg/250 mg

Pro-Levocarb (carbidopa/levodopa)

• TABS:
• 10 mg/100 mg
• 25 mg/100 mg
• 25 mg/250 mg

Sinemet (carbidopa/levodopa)

• TABS:
• 10 mg/100 mg
• 25 mg/100 mg
• 50 mg/200 mg

Sinemet CR (carbidopa/levodopa)

• ETABS:
• 25 mg/100 mg
• 25 mg/250 mg

UK Trade Name(s)

• Co-careldopa
• Caramet CR
• Half Sinemet CR
• Lecado
• Sinemet
• Sinemet CR

UK Availability

Co-careldopa (carbidopa/levodopa)

• TABS:
• 10 mg/100 mg
• 25 mg/100 mg
• 25 mg/250 mg

Sinemet (carbidopa/levodopa)

• TABS:
• 12.5 mg/50 mg
• 10 mg/100 mg
• 25 mg/100 mg
• 25 mg/250 mg

Caramet CR (carbidopa/levodopa)

• ETABS:
• 25 mg/100 mg
• 50 mg/200 mg

Half Sinemet CR (carbidopa/levodopa)

• ETABS: 25 mg/100 mg

Sinemet CR (carbidopa/levodopa)

• ETABS: 50 mg/200 mg

Lecado (carbidopa/levodopa)

• ETABS:
• 25 mg/100 mg
• 50 mg/200 mg

Australian Trade Name(s)

• Kinson
• Levohexal
• Sinemet
• Sinemet CR

Australian Availability

Kinson (carbidopa/levodopa)

• TABS: 25 mg/100 mg

Levohexal (carbidopa/levodopa)

• TABS: 25 mg/250 mg

Sinemet (carbidopa/levodopa)

• TABS:
• 25 mg/100 mg
• 25 mg/250 mg

Sinemet CR (carbidopa/levodopa)

• ETABS: 50 mg/200 mg

[Outline]

Neurologic

Antiparkinson Agents

Dopaminergic Agents

Pricing data from www.DrugStore.com in U.S.A.

• Sinemet CR 50-200 MG TBCR [Bottle] (MERCK SHARP & DOHME)
  60 mg = $145.5
  180 mg = $417.26
• Parcopa 25-250 MG TBDP [Bottle] (AZUR PHARMA)
  30 mg = $105.58
  90 mg = $296.96
• Sinemet 10-100 MG TABS [Bottle] (MERCK SHARP & DOHME)
  90 mg = $91.16
  270 mg = $256.57
• Parcopa 25-100 MG TBDP [Bottle] (AZUR PHARMA)
  30 mg = $97.64
  90 mg = $234.33
• Carbidopa-Levodopa 25-250 MG TBDP [Bottle] (SUN PHARMACEUTICAL)
  30 mg = $49.99
  90 mg = $135.99
• Sinemet 25-250 MG TABS [Bottle] (MERCK SHARP & DOHME)
  60 mg = $88.99
  180 mg = $255.97
• Sinemet 25-100 MG TABS [Bottle] (MERCK SHARP & DOHME)
  90 mg = $103.99
  270 mg = $299.97
• Sinemet CR 25-100 MG TBCR [Bottle] (MERCK SHARP & DOHME)
  60 mg = $78.99
  180 mg = $225.96
• Carbidopa-Levodopa 25-250 MG TABS [Bottle] (TEVA PHARMACEUTICALS USA)
  60 mg = $33.99
  180 mg = $82.98

Warning: This pricing information is subject to change at the sole discretion of DS Pharmacy. For the most current and up-to-date pricing information, please visit drugstore.com.

• Carbidopa 10 MG / Levodopa 100 MG Disintegrating Tablet (Sun Pharmaceutical Industries Limited)
• Carbidopa 10 MG / Levodopa 100 MG Oral Tablet (Apotex Corp.)
• Carbidopa 10 MG / Levodopa 100 MG Oral Tablet (McKesson Packaging Services Business Unit of McKesson Corporation)
• Carbidopa 10 MG / Levodopa 100 MG Oral Tablet (Mylan Pharmaceuticals Inc.)
• Carbidopa 10 MG / Levodopa 100 MG Oral Tablet (Physicians Total Care, Inc.)
• Carbidopa 10 MG / Levodopa 100 MG Oral Tablet (Sun Pharmaceutical Industries Limited)
• Carbidopa 10 MG / Levodopa 100 MG Oral Tablet (TEVA Pharmaceuticals USA Inc)
• Carbidopa 10 MG / Levodopa 100 MG Oral Tablet (UDL Laboratories, Inc.)
• Carbidopa 25 MG / Levodopa 100 MG Disintegrating Tablet (Sun Pharmaceutical Industries Limited)
• Carbidopa 25 MG / Levodopa 100 MG Extended Release Tablet (Mylan Pharmaceuticals Inc.)
• Carbidopa 25 MG / Levodopa 100 MG Extended Release Tablet (Physicians Total Care, Inc.)
• Carbidopa 25 MG / Levodopa 100 MG Extended Release Tablet (SUN PHARMACEUTICAL INDUSTRIES LIMITED)
• Carbidopa 25 MG / Levodopa 100 MG Oral Tablet (Apotex Corp.)
• Carbidopa 25 MG / Levodopa 100 MG Oral Tablet (Caremark L.L.C.)
• Carbidopa 25 MG / Levodopa 100 MG Oral Tablet (Goldline Laboratories, Inc.)
• Carbidopa 25 MG / Levodopa 100 MG Oral Tablet (McKesson Packaging Services Business Unit of McKesson Corporation)
• Carbidopa 25 MG / Levodopa 100 MG Oral Tablet (Mylan Pharmaceuticals Inc.)
• Carbidopa 25 MG / Levodopa 100 MG Oral Tablet (Physicians Total Care, Inc.)
• Carbidopa 25 MG / Levodopa 100 MG Oral Tablet (Sun Pharmaceutical Industries Limited)
• Carbidopa 25 MG / Levodopa 100 MG Oral Tablet (TEVA Pharmaceuticals USA Inc)
• Carbidopa 25 MG / Levodopa 100 MG Oral Tablet (UDL Laboratories, Inc.)
• Carbidopa 25 MG / Levodopa 100 MG Oral Tablet [Sinemet 25-100] (Bristol-Myers Squibb)
• Carbidopa 25 MG / Levodopa 250 MG Disintegrating Tablet (Sun Pharmaceutical Industries Limited)
• Carbidopa 25 MG / Levodopa 250 MG Oral Tablet (Apotex Corp.)
• Carbidopa 25 MG / Levodopa 250 MG Oral Tablet (Mylan Pharmaceuticals Inc.)
• Carbidopa 25 MG / Levodopa 250 MG Oral Tablet (Physicians Total Care, Inc.)
• Carbidopa 25 MG / Levodopa 250 MG Oral Tablet (Sun Pharmaceutical Industries Limited)
• Carbidopa 25 MG / Levodopa 250 MG Oral Tablet (TEVA Pharmaceuticals USA Inc)
• Carbidopa 25 MG / Levodopa 250 MG Oral Tablet (UDL Laboratories, Inc.)
• Carbidopa 50 MG / Levodopa 200 MG Extended Release Tablet (ETHEX)
• Carbidopa 50 MG / Levodopa 200 MG Extended Release Tablet (Mylan Pharmaceuticals Inc.)
• Carbidopa 50 MG / Levodopa 200 MG Extended Release Tablet (Physicians Total Care, Inc.)
• Carbidopa 50 MG / Levodopa 200 MG Extended Release Tablet (SUN PHARMACEUTICAL INDUSTRIES LIMITED)
• Parcopa 10/100 Disintegrating Tablet (Azur Pharma Inc.)
• Parcopa 10/100 Disintegrating Tablet (Schwarz Pharma)
• Parcopa 25/100 Disintegrating Tablet (Azur Pharma Inc.)
• Parcopa 25/100 Disintegrating Tablet (Schwarz Pharma)
• Parcopa 25/250 Disintegrating Tablet (Azur Pharma Inc.)
• Parcopa 25/250 Disintegrating Tablet (Schwarz Pharma)
• Sinemet 10/100 Oral Tablet (Bristol-Myers Squibb)
• Sinemet 25/250 Oral Tablet (Bristol-Myers Squibb)
• Sinemet CR (carbidopa 25 MG / levodopa 100 MG) Extended Release Tablet (Bristol-Myers Squibb Pharma Company)
• Sinemet CR 50-200 Extended Release Tablet (Bristol-Myers Squibb Pharma Company)