Adult Dosing

Idiopathic parkinson disease

• 1 tab PO
• Max: 1 tab/dose, 8 tabs/day (defined by the maximum daily dose of entacapone), 6 tabs/day (50/200/200 mg tabs)

• Do not cut/crush/chew the tablet
• Use as a substitute for patients already stabilized on equivalent doses of carbidopa-levodopa and entacapone
• Determine optimum dose by careful titration in individual patient
• Not more than one stalevo should be taken at each dosing administration

Transferring patients to Stalevo

• Transferring patients taking carbidopa-levodopa preparations and Comtan (entacapone) tablets to Stalevo
• Safety and efficacy is not established for transferring patients currently treated with carbidopa -levodopa formulations other than immediate-release carbidopa-levodopa with a 1:4 ratio (controlled-release formulations, or standard-release presentations with a 1:10 ratio of carbidopa-levodopa) and entacapone to Stalevo
• Directly switch patients currently treated with Comtan 200 mg tablet with each dose of standard-release carbidopa-levodopa to the corresponding strength of Stalevo containing the same amounts of levodopa and carbidopa

• Transfer patients not currently treated with Comtan (entacapone) tablets from carbidopa-levodopa to Stalevo(carbidopa, levodopa and entacapone) tablets
• Patients experiencing wear off effects with a history of moderate or severe dyskinesias or taking >600 mg/day of levodopa are likely to require a reduction in daily levodopa dose when entacapone is added to their treatment
• Titrate patients with a carbidopa-levodopa product (ratio 1:4) and an entacapone product, and then transferred to a corresponding dose of Stalevo once the patient’s status has stabilized
• Transfer patients without dyskinesias consuming a total daily levodopa dose up to 600 mg to the corresponding daily dose of Stalevo
• Individualized therapy and adjust if necessary according to the desired therapeutic response

Maintenance of Stalevo treatment

• Individualized therapy and adjust if necessary according to the desired therapeutic response
• On requiring less levodopa reduce the total daily dosage of carbidopa-levodopa by either decreasing the strength of Stalevo during each administration of dose or by decreasing the frequency of administration by extending the time between doses
• On requiring more levodopa take the next higher strength of Stalevo and/or the frequency of doses should be increased, up to a maximum of 8 times daily of Stalevo 50, Stalevo 75, Stalevo 100, Stalevo 125 and Stalevo 150, and maximum of 6 times daily of Stalevo 200

Pediatric Dosing

• Safety and effectiveness in pediatric patients have not been established

[Outline]

• Adult Dosing
• Pediatric Dosing

• Idiopathic parkinson disease
• Substitute for immediate-release carbidopa/levodopa and entacapone previously administered as individual products
• Replacement of immediate-release carbidopa/levodopa therapy (without entacapone) in patients experiencing the signs and symptoms of end-of-dose "wearing-off''(only for patients consuming a daily dose of levodopa of 600 mg or less and not experiencing dyskinesias)

• Hypersensitivity to any of the ingredients of the product
• Use of nonselective monoamine oxidase (MAO) inhibitors within 14 days
• Narrow-angle glaucoma
• Suspicious, undiagnosed skin lesions
• History of melanoma
• Abrupt withdrawal

• 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

• Dyskinesias have occurred at lower dosages; appropriately modify dose
• Due to increased brain dopamine, mental disturbances have occurred; carefully observe patients for development of depression with concomitant suicidal tendencies
• During the period of initial dose titration carefully monitor cardiac function in patients with a history of MI having have residual atrial, nodal, or ventricular arrhythmias at facilities with provisions for intensive cardiac care
• Upper gastrointestinal hemorrhage in patients with a history of peptic ulcer have occurred
• Sporadic cases of a symptom complex resembling NMS have occurred. Carefully monitor patients on abrupt reduction of dosages or discontinuation of therapy. Avoid abrupt withdrawal
• Fatal neuroleptic malignant syndrome (NMS) have occurred; provide intensive symptomatic treatment and monitor the patient
• Increased heart rates, possibly arrhythmias, and excessive changes in blood pressure have occurred on concomitant use of drugs known to be metabolized by Catechol-O-Methyltransferase (COMT)
• Hypotension/syncope associated with therapy have occurred
• Diarrhea and colitis ranging from mild to moderate in severity have occurred; discontinue therapy and consider appropriate medical therapy. On persistence of diarrhea after discontinuation of therapy consider colonoscopy and biopsies
• Hallucinations leading to hospitalization have occurred
• Exacerbation of preexisting dyskinesia have occurred due to potentiating of the dopaminergic side effects of levodopa
• Severe rhabdomyolysis has occurred
• Closely monitor the patient and adjust other dopaminergic treatments while considering discontinuation of therapy
• Increased risk of melanoma exists. Periodic skin examinations should be performed by dermatologists
• Monitor Cr, CBC, LFTs on prolonged therapy
• Monitor patients for changes in intraocular pressure
• On prolonged therapy perform periodic evaluations of hepatic, hematopoietic, cardiovascular, and renal function
• Monitor cardiovascular status on history of cardiovascular disease
• Monitor for symptoms of orthostatic hypotension
• Cases of retroperitoneal fibrosis, pulmonary infiltrates, pleural effusion, and pleural thickening have been reported; may resolve when the drug is discontinued, but complete resolution may not always occur

Cautions: Use cautiously in

• Renal impairment
• Hepatic impairment
• History or current psychoses
• Severe cardiovascular disease
• Pulmonary disease
• Bronchial asthma
• Endocrine disease
• History of myocardial infarction who have residual atrial, nodal, or ventricular arrhythmias
• History of peptic ulcer
• Chronic wide-angle glaucoma
• Biliary obstruction
• GI bleeding

Supplemental Patient Information

• Instruct patients to strictly follow prescribed dosage regimen and to avoid any additional antiparkinsonian medications without consulting the physician
• Instruct patients to report to physician if wearing-off occurs at the end of the dosing interval
• Rare occasions of dark color may appear in saliva, urine, or sweat after ingestion
• Inform patients that consuming high protein food content might delay the absorption of levodopa
• 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
• Instruct patients to avoid engaging in activities requiring mental alertness such as operating hazardous machinery or operating a car
• Advise patients to consume adequate amount of fluids to maintain adequate hydration during diarrhea
• Advise patients to notify their physicians if they become pregnant or having any intention to become pregnant 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 13 December 2010). According to manufacturer’s data, caution is advised as excretion of entacapone/carbidopa/levodopa in human milk is unknown.

• CNS: Syncope, dizziness, somnolence, confusion
• NEURO: Dyskinesia, bradykinesia, neuroleptic malignant syndrome, hypokinesia/hyperkinesia
• PSYCHIATRY: Depression, suicidal ideation, hallucinations, psychosis, compulsive behaviors, anxiety, agitation, changes in mood
• CV: Severe hypertension, MI, arrhythmias, orthostatic hypotension
• DERM: Malignant melanoma, dark sweat, increased sweating
• GI: Severe diarrhea, GI bleeding, nausea, vomiting, diarrhea, dark saliva, abdominal pain, constipation, dry mouth, flatulence, dyspepsia
• HEMA: Blood dyscrasias
• RESP: Fibrotic complications, dyspnea
• MUSC: Rhabdomyolysis, back pain
• GU: Dark urine
• MISC: Fatigue

Carbidopa

• Antiparkinson; prevents peripheral decarboxylation of levodopa, making more levodopa available for transport to brain and serves as dopamine precursor
• Metabolized by liver; CYP450: Unknown
• Renally excreted: 30% unchanged
• Half-life: 1.6-2 hrs

Levodopa

• Dopamine precursor; crosses the blood-brain barrier, and converted to dopamine in the brain
• Rapidly absorbed
• Metabolized by liver, GI tract, kidney; CYP450: Unknown
• Excreted in urine
• Half life: 1.7 hrs

Entacapone

• Antiparkinson; precise mechanism of action unknown; inhibits the COMT enzyme in peripheral tissues leading to more levels of levodopa
• Rapid absorption
• Metabolized by liver; CYP450: Unknown
• Excreted in feces (90%), urine (10%) unchanged (0.2%)
• Half life: 0.8-1 hrs

US Trade Name(s)

• Stalevo 50
• Stalevo 75
• Stalevo 100
• Stalevo 125
• Stalevo 150
• Stalevo 200

US Availability

carbidopa/entacapone/levodopa (generic)

• TABS: 25 mg/200 mg/100 mg
• TABS: 37.5 mg/200 mg/150 mg
• TABS: 12.5 mg/200 mg/50 mg
• TABS: 18.75 mg/200 mg/75 mg
• TABS: 31.25 mg/200 mg/125 mg
• TABS: 50 mg/200 mg/200 mg

Stalevo 50 (carbidopa/entacapone/levodopa)

• TABS: 12.5 mg/200 mg/50 mg

Stalevo 75 (carbidopa/entacapone/levodopa)

• TABS: 18.75 mg/200 mg/75 mg

Stalevo 100 (carbidopa/entacapone/levodopa)

• TABS: 25 mg/200 mg/100 mg

Stalevo 125 (carbidopa/entacapone/levodopa)

• TABS: 31.25 mg/200 mg/125 mg

Stalevo 150 (carbidopa/entacapone/levodopa)

• TABS: 37.5 mg/200 mg/150 mg

Stalevo 200 (carbidopa/entacapone/levodopa)

• TABS: 50 mg/200 mg/200 mg

Canadian Trade Name(s)

• Stalevo

Canadian Availability

Stalevo (levodopa/carbidopa/entacapone)

• TABS:
• 50 mg/12.5 mg/200 mg
• 75 mg/18.75 mg/200 mg
• 100 mg/25 mg/200 mg
• 125 mg/31.25 mg/200 mg

UK Trade Name(s)

• Stalevo

UK Availability

Stalevo (levodopa/carbidopa/entacapone)

• TABS:
• 50 mg/12.5 mg/200 mg
• 75 mg/18.75 mg/200 mg
• 100 mg/25 mg/200 mg
• 125 mg/31.25 mg/200 mg
• 150 mg/37.5 mg/200 mg
• 200 mg/50 mg/200 mg

Australian Trade Name(s)

• Stalevo

Australian Availability

Stalevo (levodopa/carbidopa/entacapone)

• TABS:
• 50 mg/12.5 mg/200 mg
• 75 mg/18.75 mg/200 mg
• 100 mg/25 mg/200 mg
• 125 mg/31.25 mg/200 mg
• 150 mg/37.5 mg/200 mg
• 200 mg/50 mg/200 mg

[Outline]

Neurologic

Antiparkinson Agents

Dopaminergic Agents

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

• Stalevo 200 50-200-200 MG TABS [Bottle] (NOVARTIS)
  100 mg = $363.99
  300 mg = $1043.97
• Stalevo 100 25-100-200 MG TABS [Bottle] (NOVARTIS)
  90 mg = $339.98
  270 mg = $969.99
• Stalevo 50 12.5-50-200 MG TABS [Bottle] (NOVARTIS)
  30 mg = $112.99
  90 mg = $329.98
• Stalevo 150 37.5-150-200 MG TABS [Bottle] (NOVARTIS)
  30 mg = $112.99
  90 mg = $329.98

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.