MIRAPEX- pramipexole dihydrochloride tablet
Boehringer Ingelheim Pharmaceuticals, Inc.
1 INDICATIONS AND USAGE
1.1 Parkinson's Disease
MIRAPEX tablets are indicated for the treatment of Parkinson's disease.
1.2 Restless Legs Syndrome
MIRAPEX tablets are indicated for the treatment of moderate-to-severe primary Restless Legs Syndrome (RLS).
2 DOSAGE AND ADMINISTRATION
2.1 General Dosing Considerations
MIRAPEX tablets are taken orally, with or without food.
If a significant interruption in therapy with MIRAPEX tablets has occurred, re-titration of therapy may be warranted.
2.2 Dosing for Parkinson's Disease
In all clinical studies, dosage was initiated at a subtherapeutic level to avoid intolerable adverse effects and orthostatic hypotension. MIRAPEX tablets should be titrated gradually in all patients. The dose should be increased to achieve a maximum therapeutic effect, balanced against the principal side effects of dyskinesia, hallucinations, somnolence, and dry mouth.
DESCRIPTION
MIRAPEX tablets contain pramipexole, a nonergot dopamine agonist. The chemical name of pramipexole dihydrochloride is (S)-2-amino-4,5,6,7-tetrahydro-6-(propylamino)benzothiazole dihydrochloride monohydrate. Its empirical formula is C10 H17 N3 S � 2HCl � H2 O, and its molecular weight is 302.26.
CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Pramipexole is a non-ergot dopamine agonist with high relative in vitro specificity and full intrinsic activity at the D2 subfamily of dopamine receptors, binding with higher affinity to D3 than to D2 or D4 receptor subtypes.
Parkinson's Disease
The precise mechanism of action of pramipexole as a treatment for Parkinson's disease is unknown, although it is believed to be related to its ability to stimulate dopamine receptors in the striatum. This conclusion is supported by electrophysiologic studies in animals that have demonstrated that pramipexole influences striatal neuronal firing rates via activation of dopamine receptors in the striatum and the substantia nigra, the site of neurons that send projections to the striatum. The relevance of D3 receptor binding in Parkinson's disease is unknown.
Restless Legs Syndrome (RLS)
The precise mechanism of action of MIRAPEX tablets as a treatment for RLS is unknown. Although the pathophysiology of RLS is largely unknown, neuropharmacological evidence suggests primary dopaminergic system involvement. Positron Emission Tomographic (PET) studies suggest that a mild striatal presynaptic dopaminergic dysfunction may be involved in the pathogenesis of RLS.
WARNINGS AND PRECAUTIONS
5.1 Falling Asleep During Activities of Daily Living and Somnolence
Patients treated with pramipexole have reported falling asleep while engaged in activities of daily living, including the operation of motor vehicles which sometimes resulted in accidents. Although many of these patients reported somnolence while on pramipexole tablets, some perceived that they had no warning signs (sleep attack) such as excessive drowsiness, and believed that they were alert immediately prior to the event. Some of these events had been reported as late as one year after the initiation of treatment.
