Problem 8: Counseling on Co-Careldopa Prescription and ADRs

Question 1

Discuss the appropriateness of adding co-careldopa? How does it differ from the co-beneldopa? How do they work?

Answer 1

Co-careldopa: (Sinemet)
Antiparkinsonism medication containing carbidopa and levodopa.
Levodopa is administered most commonly in combination with a peripheral decarboxylase inhibitor (PDI), such as carbidopa, to maximize the amount of levodopa available to enter the brain and to lessen adverse effects (such as nausea, vomiting, and hypotension) caused by the peripheral decarboxylation of levodopa to dopamine.

Co-beneldopa: (Madopar)
Levodopa and benserazide. Benserazide is a peripherally-acting aromatic L-amino acid decarboxylase (AADC) or DOPA decarboxylase inhibitor, which is unable to cross the blood–brain barrier.

However, most levodopa is decarboxylated to dopamine before it reaches the brain, and since dopamine is unable to cross the blood–brain barrier, this translates to little therapeutic gain with strong peripheral side effects.

Benserazide inhibits the aforementioned decarboxylation, and since it itself cannot cross the blood–brain barrier, this allows dopamine to build up solely in the brain instead. Adverse effects caused by peripheral dopamine, such as vasoconstriction, nausea, and arrhythmia, are minimized.

Question 2

State the usual dose of co-careldopa

Answer 2

Initially 25/100 mg 3 times a day, then increased in steps of 12.5/50 mg once daily or on alternate days, alternatively increased in steps of 25/100 mg once daily or on alternate days, dose to be adjusted according to response; dose increased until 800 mg levodopa (with 200 mg carbidopa) daily in divided doses is reached

Question 3

Explain why the dose should be increased slowly

Answer 3

Studies show that peripheral dopa decarboxylase is saturated by carbidopa at approximately 70 to 100 mg a day. Patients receiving less than this amount of carbidopa are more likely to experience nausea and vomiting.

Question 4

Discuss the various points of counseling in relation to co-careldopa

Answer 4

FINISH

Question 5

Nausea and vomiting is associated with co-careldopa. How should this be managed if Mr Li experiences this side effect?

Answer 5

Metoclopramide and prochlorperazine are NOT recommended in nausea and vomitting for PD patients - can cause or exacerbate parkisonism.

Consider prescribing low-dose domperidone, reducing or stopping it when the nausea or vomiting settles. (Avoid in patients with cardiovascular disease as has been associated with increased ventricular tacchyarrhytmias

If domperidone is ineffective or not tolerated, seek specialist advice, as one or more of the following options may be recommended:
An increase in the proportion of decarboxylase inhibitor to levodopa (for people taking co-careldopa specifically).
A slower titration of the anti-parkinsonian drug.
A switch to an alternative anti-parkinsonian drug.
A switch to an alternative anti-emetic drug.