Pramipexole Extended-Release: A Review of Its Use in Patients with Parkinson’s Disease

Abstract

Pramipexole, a non-ergolinic, D3-preferring dopamine agonist (DA), is well established as a treatment option for motor symptoms at all stages of Parkinson's disease (PD). It is administered orally and is available as both a three-times daily immediate-release (IR) formulation and a once-daily extended-release (ER) formulation (Mirapex(®) ER, Mirapexin(®) ER; Pexola(®) ER, Sifrol(®) ER). The two formulations are bioequivalent; the majority (>80 %) of patients can be switched overnight from pramipexole IR to ER without the need for dosage adjustment. In terms of improving activities of daily living and motor function in short-term (≤33-week), double-blind studies, pramipexole ER was noninferior to pramipexole IR and significantly more effective than placebo as monotherapy in patients with early PD, and similar to pramipexole IR and significantly more effective than placebo as adjunctive therapy to levodopa in patients with advanced PD. In long-term (80-week) extensions of these trials, open-label treatment with pramipexole ER was associated with sustained symptomatic benefit. Moreover, the majority of extension participants who responded to a simple convenience questionnaire expressed a preference for once-daily over three-times daily dosing. Pramipexole ER was generally well tolerated in clinical trials; no new or unexpected safety signals were identified compared with the IR formulation. Head-to-head trials are needed in order to fully define the role of pramipexole ER relative to other once-daily formulations of DAs (oral ropinirole and transdermal rotigotine). Nonetheless, by reducing the pill burden, the ER formulation of pramipexole provides a more convenient alternative to the IR formulation; studies specifically testing whether this translates into improved patient compliance and symptom control are worthwhile.

Classics in Chemical Neuroscience: Pramipexole

“…1−3 Pramipexole was developed as a nonergot dopamine agonist following the therapeutic findings of ergot-related dopamine agonists, such as bromocriptine (2), pergolide (3), lisuride, and cabergoline, these alongside levodopa (4) had become conventional therapies for the treatment of Parkinson's disease (PD). 3 These ergot derivatives became the most widely tested and used early adjunctive therapies in advanced PD patients, especially for those experiencing adverse motor effects related to levodopa. 3 However, ergot derivatives became phased out of treatment methods due to the risk of fibrotic adverse drug reactions.…”

“…3 These ergot derivatives became the most widely tested and used early adjunctive therapies in advanced PD patients, especially for those experiencing adverse motor effects related to levodopa. 3 However, ergot derivatives became phased out of treatment methods due to the risk of fibrotic adverse drug reactions. 2 Pramipexole's testing in animal models found it efficacious in alleviating Parkinsonian motor signs in monkeys and macaques with N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinsonism.…”

Dissolution-Controlled Salt of Pramipexole for Parenteral Administration: In Vitro Assessment and Mathematical Modeling

“…It helps in the management of motor symptoms in earlier and advanced stage of Parkinson's disease. PRP is a Biopharmaceutics Classification System (BCS) class-I drug, having a highly basic nature (13,14). Pamoic acid is one of the pharmaceutically acceptable excipients for the preparation of poorly water-soluble salts with drugs of basic nature (15).…”

Comparison of nocturnal symptoms in advanced Parkinson’s disease patients with sleep disturbances: pramipexole sustained release versus immediate release formulations

“… 12 In randomized, double-blind, Phase III studies of early and advanced stage PD, PPX SR demonstrated similar efficacy to PPX IR and significantly greater efficacy than placebo, with or without background levodopa. 13 , 14 The adverse event (AE) profiles of both the formulations were similar, mostly of mild or moderate intensity, with no unique safety signals observed in PPX SR. 15 These earlier studies did not assess the treatment effects of different formulations on PD-related sleep problems.…”