Carbidopa + Entacapone + Levodopa

Carbidopa + Entacapone + Levodopa is a combination of levodopa, carbidopa, and entacapone used for Parkinson's disease. Levodopa is the metabolic precursor of dopamine; it crosses the blood-brain barrier and is converted to dopamine in the brain. Carbidopa is a dopa decarboxylase (DDC) inhibitor that reduces the peripheral metabolism of levodopa, allowing more levodopa to reach the brain. Entacapone is a selective inhibitor of catechol-O-methyltransferase (COMT) that results in greater and more sustained plasma levels of levodopa, leading to greater control of parkinsonism symptoms.

This is indicated for the treatment of adult patients with Parkinson's disease and end-of-dose motor fluctuations not stabilized on levodopa/dopa decarboxylase (DDC) inhibitor treatment.

• Parkinson's disease (with end-of-dose motor fluctuations)

Adults: Each tablet contains levodopa and carbidopa in a 4:1 ratio and entacapone 200 mg (Stalevo 50/75/100/125/150/200).

Initial dose: 1 tablet/day. Titrate dose according to patient's response.

Per dose: Only 1 tablet per dose administration is recommended.

Maximum dose: 8 tablets/day (maximum 2000 mg entacapone/day).

Hepatic impairment: Severe: Contraindicated; Mild-moderate: Caution, dose reduction may be needed.

Renal impairment: Severe (including dialysis): Caution required.

Elderly: No dose adjustment required.

Children: Safety and efficacy not established.

Transfer instructions: Patients on entacapone and levodopa/carbidopa can be transferred to equivalent tablets. Direct switch for patients not on entacapone is not recommended; initiate entacapone separately first.

Common side effects: Dyskinesia (abnormal movements), nausea, hyperkinesia, urine discoloration (red/brown/black), diarrhea, abdominal pain, constipation, headache, dry mouth, insomnia, orthostatic hypotension, anxiety, dizziness, abnormal dreams.

Serious (rare): Diarrhea (sometimes severe, colitis), hallucinations, other mental disturbances, rhabdomyolysis, neuroleptic malignant syndrome (fever, muscle stiffness, confusion), fibrosis, skin cancer.

Urine may become red, brown, or black (harmless).

• May cause dizziness and sleepiness; caution when driving or operating machinery.
• Avoid high-protein meals (meat, poultry, dairy products) as they reduce levodopa absorption.
• Do not stop suddenly (may cause serious syndrome: fever, muscle stiffness, abnormal movements, sweating, confusion).
• Inform your doctor if you develop hallucinations or behavioral changes.
• Periodic evaluation of hepatic, hematopoietic, cardiovascular, and renal function is recommended during extended therapy.
• Caution during pregnancy and lactation; do not breastfeed during treatment.

• Severe hepatic impairment
• Narrow-angle glaucoma
• Pheochromocytoma
• Coadministration with non-selective MAO inhibitors (phenelzine, tranylcypromine)
• History of neuroleptic malignant syndrome
• Hypersensitivity to any ingredient
• Suspicious/undiagnosed skin lesions or history of melanoma

• Antihypertensives: Increased risk of postural hypotension; dose adjustment may be required.
• Dopamine D2 receptor antagonists (some antipsychotics, antiemetics), phenytoin, papaverine: May reduce levodopa efficacy.
• Iron salts: May reduce bioavailability.
• Drugs interfering with biliary excretion: May increase entacapone plasma levels.
• MAOIs: Severe orthostatic hypotension may occur.
• High-protein diet: Reduces levodopa absorption.