Parkinson disease

To the Editor: I have the following comments and questions regarding the excellent Medical Grand Rounds article on Parkinson disease by Dr. Fernandez in your January 2012 issue.¹

The author mentions that when “cost may be of concern, levodopa is the preferred starting drug.”¹ Generic versions of pramipexole and ropinirole are now available and have made these medications more affordable. For example, the cash price of generic ropinirole 5 mg was recently $66 for 100 tablets, comparable with generic carbidopa/levodopa (25/100 mg priced at $46 for 100 tablets.² And even though the price of generic pramipexole was $240 for 90 tablets, seniors with Medicare Part D drug coverage can usually get any generic medication for a low copay.

When choosing a dopamine agonist, how does Dr. Fernandez decide between ropinirole and pramipexole (aside from the price difference noted above)? Pramipexole has a longer elimination half-life (8 to 12 hours) compared with ropinirole (6 hours).³ Does this imply a significantly longer effective dosing interval for pramipexole? Are there other significant clinical differences between these agents?

Isradipine (DynaCirc CR), a dihydropyridine calcium channel blocker, has shown promise as a neuroprotective agent for slowing the progression of Parkinson disease in epidemiologic and laboratory studies, as noted by the author. In addition, immediate-release isradipine, with its relatively short elimination half-life of 8 hours,³ may be well suited for treating Parkinson patients whose essential hypertension is complicated by episodes of orthostatic hypotension. It should be noted that dihydropyridines that do not cross the blood-brain barrier (such as amlodipine [Norvasc]) have shown no evidence of neuroprotection.

Ibuprofen is another drug that has fairly strong epidemiologic and laboratory evidence that it might be neuroprotective,⁴ although the other nonsteroidal anti-inflammatory drugs (NSAIDs) have proven disappointing as a class.⁵ Lacking any prospective randomized trials, the evidence is not strong enough to recommend ibuprofen solely for neuroprotection. Does Dr. Fernandez, however, consider it reasonable to suggest ibuprofen to Parkinson patients who need to take an NSAID for an approved indication (such as pain)?

Dexpramipexole has recently demonstrated great promise in a phase 3 clinical trial as a neuroprotective agent in amyotrophic lateral sclerosis.⁶ How does this compound relate to pramipexole, and does the author believe it may offer neuroprotection in other neurodegenerative diseases like Parkinson disease?

The author discusses the use of catechol-O-methyltransferase (COMT) inhibitors (such as Comtan and Tasmar) and the monoamine oxidase (MAO) type-B inhibitors rasagiline (Azilect) and selegiline (Eldepryl, Zelapar) for prolonging the effects of levodopa by slowing the breakdown of dopamine. However, it is important to note that it is contraindicated to prescribe both a COMT inhibitor and an MAO-B inhibitor, because these agents also inhibit the breakdown of other catecholamines and can lead to adrenergic crisis when taken concomitantly.

To the Editor: I have the following comments and questions regarding the excellent Medical Grand Rounds article on Parkinson disease by Dr. Fernandez in your January 2012 issue.¹

The author mentions that when “cost may be of concern, levodopa is the preferred starting drug.”¹ Generic versions of pramipexole and ropinirole are now available and have made these medications more affordable. For example, the cash price of generic ropinirole 5 mg was recently $66 for 100 tablets, comparable with generic carbidopa/levodopa (25/100 mg priced at $46 for 100 tablets.² And even though the price of generic pramipexole was $240 for 90 tablets, seniors with Medicare Part D drug coverage can usually get any generic medication for a low copay.

When choosing a dopamine agonist, how does Dr. Fernandez decide between ropinirole and pramipexole (aside from the price difference noted above)? Pramipexole has a longer elimination half-life (8 to 12 hours) compared with ropinirole (6 hours).³ Does this imply a significantly longer effective dosing interval for pramipexole? Are there other significant clinical differences between these agents?

Isradipine (DynaCirc CR), a dihydropyridine calcium channel blocker, has shown promise as a neuroprotective agent for slowing the progression of Parkinson disease in epidemiologic and laboratory studies, as noted by the author. In addition, immediate-release isradipine, with its relatively short elimination half-life of 8 hours,³ may be well suited for treating Parkinson patients whose essential hypertension is complicated by episodes of orthostatic hypotension. It should be noted that dihydropyridines that do not cross the blood-brain barrier (such as amlodipine [Norvasc]) have shown no evidence of neuroprotection.

Ibuprofen is another drug that has fairly strong epidemiologic and laboratory evidence that it might be neuroprotective,⁴ although the other nonsteroidal anti-inflammatory drugs (NSAIDs) have proven disappointing as a class.⁵ Lacking any prospective randomized trials, the evidence is not strong enough to recommend ibuprofen solely for neuroprotection. Does Dr. Fernandez, however, consider it reasonable to suggest ibuprofen to Parkinson patients who need to take an NSAID for an approved indication (such as pain)?

Dexpramipexole has recently demonstrated great promise in a phase 3 clinical trial as a neuroprotective agent in amyotrophic lateral sclerosis.⁶ How does this compound relate to pramipexole, and does the author believe it may offer neuroprotection in other neurodegenerative diseases like Parkinson disease?

The author discusses the use of catechol-O-methyltransferase (COMT) inhibitors (such as Comtan and Tasmar) and the monoamine oxidase (MAO) type-B inhibitors rasagiline (Azilect) and selegiline (Eldepryl, Zelapar) for prolonging the effects of levodopa by slowing the breakdown of dopamine. However, it is important to note that it is contraindicated to prescribe both a COMT inhibitor and an MAO-B inhibitor, because these agents also inhibit the breakdown of other catecholamines and can lead to adrenergic crisis when taken concomitantly.

To the Editor: I have the following comments and questions regarding the excellent Medical Grand Rounds article on Parkinson disease by Dr. Fernandez in your January 2012 issue.¹

The author mentions that when “cost may be of concern, levodopa is the preferred starting drug.”¹ Generic versions of pramipexole and ropinirole are now available and have made these medications more affordable. For example, the cash price of generic ropinirole 5 mg was recently $66 for 100 tablets, comparable with generic carbidopa/levodopa (25/100 mg priced at $46 for 100 tablets.² And even though the price of generic pramipexole was $240 for 90 tablets, seniors with Medicare Part D drug coverage can usually get any generic medication for a low copay.

When choosing a dopamine agonist, how does Dr. Fernandez decide between ropinirole and pramipexole (aside from the price difference noted above)? Pramipexole has a longer elimination half-life (8 to 12 hours) compared with ropinirole (6 hours).³ Does this imply a significantly longer effective dosing interval for pramipexole? Are there other significant clinical differences between these agents?

Isradipine (DynaCirc CR), a dihydropyridine calcium channel blocker, has shown promise as a neuroprotective agent for slowing the progression of Parkinson disease in epidemiologic and laboratory studies, as noted by the author. In addition, immediate-release isradipine, with its relatively short elimination half-life of 8 hours,³ may be well suited for treating Parkinson patients whose essential hypertension is complicated by episodes of orthostatic hypotension. It should be noted that dihydropyridines that do not cross the blood-brain barrier (such as amlodipine [Norvasc]) have shown no evidence of neuroprotection.

Ibuprofen is another drug that has fairly strong epidemiologic and laboratory evidence that it might be neuroprotective,⁴ although the other nonsteroidal anti-inflammatory drugs (NSAIDs) have proven disappointing as a class.⁵ Lacking any prospective randomized trials, the evidence is not strong enough to recommend ibuprofen solely for neuroprotection. Does Dr. Fernandez, however, consider it reasonable to suggest ibuprofen to Parkinson patients who need to take an NSAID for an approved indication (such as pain)?

Dexpramipexole has recently demonstrated great promise in a phase 3 clinical trial as a neuroprotective agent in amyotrophic lateral sclerosis.⁶ How does this compound relate to pramipexole, and does the author believe it may offer neuroprotection in other neurodegenerative diseases like Parkinson disease?

The author discusses the use of catechol-O-methyltransferase (COMT) inhibitors (such as Comtan and Tasmar) and the monoamine oxidase (MAO) type-B inhibitors rasagiline (Azilect) and selegiline (Eldepryl, Zelapar) for prolonging the effects of levodopa by slowing the breakdown of dopamine. However, it is important to note that it is contraindicated to prescribe both a COMT inhibitor and an MAO-B inhibitor, because these agents also inhibit the breakdown of other catecholamines and can lead to adrenergic crisis when taken concomitantly.