THERAPEUTICS

Brands

• Mirapex, Mirapex ER, Mirapexin Generic?

• Yes

Class

• Antiparkinson agent

Commonly Prescribed for

(FDA approved in bold)

• Parkinson’s disease (PD)

• Restless legs syndrome (RLS) (not for Mirapex ER)

• Fibromyalgia

How the Drug Works

• Dopamine agonist, with high affinity for presynaptic and postsynaptic D2, D3, D4 receptors (greater affinity for D3), inhibiting dopamine synthesis and release. The antiparkinson action is likely due to D2 agonism within the caudate-putamen. High affinity for D3 receptors might affect impulse control and dyskinesia. The mechanism of action for RLS is probably related to D2 or D3 receptor agonism

• It expresses neuroprotective effects in disease models (e.g., antioxidant, neurotrophic stimulation, attenuates programmed cell death, etc)

• It also has affinity for α2-adrenergic receptors

How Long Until It Works

• PD: weeks

• RLS: days to weeks

If It Works

• PD: may require dose adjustments over time or augmentation with other agents. Most PD patients will eventually require carbidopa-levodopa to manage their symptoms

• RLS: safe for long-term use with dose adjustments

If It Doesn’t Work

• PD: bradykinesia, gait, and tremor should improve. Non-motor symptoms including autonomic symptoms such as postural hypotension, depression, and bladder dysfunction do not improve. If the patient has significantly impaired functioning, add carbidopa-levodopa with or without pramipexole

• RLS: rule out peripheral neuropathy, iron deficiency, thyroid disease. Change to another drug such as a benzodiazepine. Gabapentin enacarbil (not gabapentin) may also be beneficial. In severe cases consider opioids

Best Augmenting Combos for Partial Response or Treatment-Resistance

• For suboptimal effectiveness add carbidopa-levodopa with or without a catechol-O-methyltransferase (COMT) inhibitor. Monoamine oxidase (MAO)-B inhibitors may also be beneficial

• For severe motor fluctuations and/or dyskinesias with good “on” time, functional neurosurgery is an option

• For RLS, can change to a different dopamine agonist (ropinirole, carbidopa-levodopa) or add clonazepam. Gabapentin enacarbil may be beneficial. In severe cases consider opioix1ds