Carbidopa, with levodopa

Carbidopa/levodopa - There is no experience in transferring patients currently treated with formulation of carbidopa/levodopa 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 carbidopa, levodopa, and entacapone combination. 

Chap. 31), and during lactation. Levodopa is used cautiously in patients with cardiovascular disease, bronchial asthma, emphysema, peptic ulcer disease, renal or hepatic disease and psychosis. Levodopa and combination antiparkinsonism drugs (eg, carbidopa/levodopa) are classified as Pregnancy Category C and are used with caution during pregnancy and lactation. 

Patients with severe dyskinesias and off periods may achieve more constant blood concentrations (lower peak and higher trough concentrations) by taking a liquid formulation of levodopa with carbidopa. Each day patients make a 1 mg/mL levodopa... 

Patients currently treated with conventional carbidopa/levodopa preparations Substitute dosage with extended-release tablets at an amount that provides about 10% more levodopa per day, although this may need to be increased to a dosage that provides up to 30% more levodopa per day. Use intervals of 4 to 8 hours while awake. 

CNS effects Certain adverse CNS effects (eg, dyskinesias) will occur at lower dosages and sooner during therapy with levodopa and carbidopa than with levodopa alone. 

Parkinson disease To treat patients with idiopathic Parkinson disease to substitute (with equivalent strength of each of the 3 components) for immediate release carbidopa/levodopa and entacapone previously administered as individual products to replace immediate release carbidopa/levodopa therapy (without entacapone) when patients experience the signs and symptoms of end-of-dose wearing-off (only for patients taking a total daily dose of levodopa of 600 mg or less and not experiencing dyskinesias). 

Use carbidopa, levodopa, and entacapone combination as a substitute for patients already stabilized on equivalent doses of carbidopa/levodopa and entacapone. Some patients who have been stabilized on a given dose of carbidopa/levodopa may be treated with carbidopa, levodopa, and entacapone combination if a decision has been made to add entacapone. 

The optimum daily dosage of carbidopa, levodopa, and entacapone combination must be determined by careful titration in each patient. Carbidopa, levodopa, and entacapone combination tablets are available in 3 strengths, each in a 1 4 ratio of carbidopa to levodopa and combined with 200 mg of entacapone in a standard... 

Clinical experience with daily doses above 1600 mg of entacapone is limited. It is recommended that no more than 1 carbidopa, levodopa, and entacapone combination tablet be taken at each dosing administration. Thus, the maximum recommended daily dose of carbidopa, levodopa, and entacapone combination is 8 tablets/day. 

Transferring patients currently treated with carbidopa/levodopa and entacapone to carbidopa, levodopa, and entacapone combination tablet ... 

Entacapone - Patients who are currently treated with entacapone 200 mg tablet with each dose of standard release carbidopa/levodopa, can be directly switched to the corresponding strength of carbidopa, levodopa, and entacapone combination containing the same amounts of levodopa and carbidopa. 

Transferring patients not currently treated with entacapone tablets from carbidopa/levodopa to carbidopa, levodopa, and entacapone combination tablets In patients with Parkinson disease who experience the signs and symptoms of end-of-dose wearing-off on their current standard release carbidopa/levodopa treatment, clinical experience shows that patients with a history of moderate or severe dyskinesias or taking more than 600 mg/day of levodopa are likely to require a reduction in daily levodopa dose when entacapone is added to their treatment. Maintenance therapy Individualize therapy and adjust for each patient according to the desired therapeutic response. 

Levodopa, the metabolic precursor of dopamine, is the most effective agent in the treatment of Parkinson s disease but not for drug-induced Parkinsonism. Oral levodopa is absorbed by an active transport system for aromatic amino acids. Levodopa has a short elimination half-life of 1-3 hours. Transport over the blood-brain barrier is also mediated by an active process. In the brain levodopa is converted to dopamine by decarboxylation and both its therapeutic and adverse effects are mediated by dopamine. Either re-uptake of dopamine takes place or it is metabolized, mainly by monoamine oxidases. The isoenzyme monoamine oxidase B (MAO-B) is responsible for the majority of oxidative metabolism of dopamine in the striatum. As considerable peripheral conversion of levodopa to dopamine takes place large doses of the drug are needed if given alone. Such doses are associated with a high rate of side effects, especially nausea and vomiting but also cardiovascular adverse reactions. Peripheral dopa decarboxylase inhibitors like carbidopa or benserazide do not cross the blood-brain barrier and therefore only interfere with levodopa decarboxylation in the periphery. The combined treatment with levodopa with a peripheral decarboxylase inhibitor considerably decreases oral levodopa doses. However it should be realized that neuropsychiatric complications are not prevented by decarboxylase inhibitors as even with lower doses relatively more levodopa becomes available in the brain. 

If levodopa is administered alone, it is extensively metabolized by L-aromatic amino acid decarboxylase in the liver, kidney, and gastrointestinal tract. To prevent this peripheral metabolism, levodopa is coadministered with carbidopa (Sinemet), a peripheral decarboxylase inhibitor. The combination of levodopa with carbidopa lowers the necessary dose of levodopa and reduces peripheral side effects associated with its administration. 

Carbidopa (used with levodopa 25 mg carbidopa + 100 mg levodopa TIDOMET PLUS) 20-100 mg/day... 

A commercial preparation named Stalevo consists of a combination of levodopa with both carbidopa and entacapone. It is available in three strengths Stalevo 50 (50 mg levodopa plus 12.5 mg carbidopa and 200 mg entacapone), Stalevo 100 (100 mg, 25 mg, and 200 mg, respectively), and Stalevo 150 (150 mg, 37.5 mg, and 200 mg). Use of this preparation simplifies the drug regimen and requires the consumption of a lesser number of tablets than otherwise. Stalevo is priced at or below the price of its individual components. 

Dopamine precursors are considered first-line in adults. Side effects include orthostatic hypotension, insomnia, daytime fatigue, and somnolence nausea, and augmentation may occur. Levodopa with benserazide or carbidopa (Sinemet) 100-125 mg or 200-250 mg at bedtime and additional doses may be needed. Dopamine agonists are becoming more popular because of the fewer side effects, and less augmentation. These are used to treat RLS and PLMD. Their side effects include nausea, orthostatic hypotension, insomnia, and somnolence also, the potential for tolerance exists. 

Later, the disease does not respond to the drug and doses are required to be given in combination with carbidopa. Levodopa is effective in relieving bradykinesia and other disorderly voluntary movements. Parkinson s disease is not a hereditary disease. Drugs such as levodopa, carbidopa, benserazide, bromocriptine, pergolide, selegiline, and amantadine are used as therapeutic agents.61... 

Minimisation of unwanted effects. Combining levodopa with benserazide (Madopar) or with carbidopa (Sinemet) slows its metabolism outside the central nervous system so that smaller amounts of levodopa can be used this reduces adverse effects. 

Enzyme inhibitors compete with the active drug for the enzyme and, thereby, reduce the degradation of the drug and deliver it more efficiently to the systemic circulation. An example is the carbidopa-levodopa combination. Carbidopa competes for levodopa decarboxylase, thereby reducing the levodopa degradation and improving the low bioavailability of levodopa. 

CD is a 70-year-old man who resides in a nursing home. His PMH is significant for Parkinson s disease and COPD. His medications include carbidopa/levodopa, and amantadine, as well as ipratropium, albuterol, and triamcinolone inhalers. One of the residents is diagnosed with influenza A and all the residents now require prophylaxis for influenza A with rimantadine. Which of the following would be the most appropriate therapy for prevention of influenza A in CD ... 

Papavasiliou, P.S. Cotzias, G. Rosal, V.L.F. Miller, S.T. (1978) Treatment of parkinsonism with N-//-propyl norapomorphine and Levodopa (with or without Carbidopa). Arch. Neurol. 35, 787-791. 

The form and severity of dyskinesias due to levodopa may vary widely in different patients. Dyskinesias occur in up to 80% of patients receiving levodopa for long periods. With continued treatment, dyskinesias may develop at a dose of levodopa that was previously well tolerated. They occur more commonly in patients treated with levodopa in combination with carbidopa or with other dopamine receptor agonists. Muscarinic receptor blockers do not prevent their occurrence. The answer is (B). 

The elderly client diagnosed with Parkinson s disease (PD) has been prescribed carbidopa/levodopa (Sinemet). Which data indicates the medication has been effective ... 

A study in 2 patients taking levodopa with carbidopa found that concurrent treatment with clonidine (up to 1.5 mg daily for 10 to 24 days) caused a worsening of the parkinsonism (an exacerbation of rigidity and akinesia). The eoncurrent use of antimuscarinic drugs reduced the effects of this interaction. ... 

Methyldopa can increase the effects of levodopa and permit a reduction in the dosage in some patients taking levodopa alone, but it can aiso worsen dyskinesias in others. This interaction would not be expected to be significant in a patient taking levodopa with benserazide or carbidopa but this does not appear to have been studied. A small increase in the hypotensive actions of methyldopa may also occur. 

A woman with long-standing parkinsonism, well controlled on levodopa (with the later addition of carbidopa), began to show a steady worsening of her parkinsonism within a week of additionally starting papaverine 100 mg daily for cerebral vascular insufficiency. The deterioration continued until the papaverine was withdrawn. The normal response to levodopa returned within a week. Four other patients had a similar response. Two other similar cases have been described in another report. ... 

Barone P, Lang AE, Olanow CW. Initiating levodopa/carbidopa therapy with and without entacapone in early Parkinson disease the STRIDE-PD study. Ann Neurol... 

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