Immediate-release Pramipexole Research Articles

Efficacy and safety of non-ergot dopamine-receptor agonists as an adjunct to levodopa in advanced Parkinson's disease: Anetwork meta-analysis.

Non-ergot dopamine agonists (NEDAs) have been used as an adjunct therapy to levodopa in advanced Parkinson's disease (PD) for many years. However, there is no strong evidence that a given NEDA is more potent than another. To compare and rank the efficacy, tolerability, and safety of six commonly used NEDAs as an adjunct to levodopa in advanced PD, which includes long-acting and standard formulations, a network meta-analysis was performed. The MEDLINE, Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, and Wanfang databases were searched from January 1996 to June 2022 for eligible randomized controlled trials (RCTs). Six NEDAs, including rotigotine transdermal patch, ropinirole immediate-release (IR)/prolonged-release (PR), pramipexole IR/extended-release (ER), and piribedil, were investigated. A total of 34 RCTs (7868 patients) were included in the current study. The surface under the cumulative ranking curve indicated that ropinirole PR was associated with the best improvement in Unified Parkinson's Disease Rating Scale (UPDRS)-II, UPDRS-III, and UPDRS-II + III (0.811, 0.742, and 0.827). For OFF time reduction, pramipexole IR ranked first (0.979), and ropinirole PR ranked first in OFF time responder rate (0.927). Pramipexole ER ranked first in overall withdrawals, and rotigotine transdermal patch ranked first in the incidence of adverse events (≥1 AEs). This network meta-analysis suggests six commonly used NEDAs are effective as an adjunct to levodopa in advanced PD. In comprehensive consideration of better symptomatic management, ropinirole PR may be a better choice than other NEDAs in advanced PD. Six NEDAs showed different profiles of AEs.

Efficacy and Safety of Pramipexole Sustained Release versus Immediate Release Formulation for Nocturnal Symptoms in Chinese Patients with Advanced Parkinson's Disease: A Pilot Study.

Objective To explore the efficacy and safety of pramipexole sustained release (SR) versus pramipexole immediate release (IR) in treating nocturnal symptoms in levodopa-treated Chinese patients with advanced Parkinson's disease (PD) and sleep disturbances. Method SUSTAIN was an open-label, randomised, active-controlled parallel group exploratory pilot study (NCT03521635). A total of 98 patients were randomly allocated (1 : 1) to either pramipexole SR (n = 49) or pramipexole IR (n = 49) groups. The primary endpoint was a change from baseline in PD Sleep Scale 2nd version (PDSS-2) total score at 18 weeks. A reduction in score represents improvement. Secondary endpoints included Nocturnal Hypokinesia Questionnaire, Scales for Outcomes in PD Sleep Scale, Early Morning Off (EMO), Epworth Sleepiness Scale, PD Questionnaire-8, and responder rates as measured by PDSS-2 total score (<18), EMO scores (≥1 point change), Clinical Global Impression Improvement scale, and Patient Global Impression-Improvement scale. Other endpoints included motor complications (MDS-UPDRS part IV) score. Adverse events were evaluated for each group. Results The mean pramipexole dose for both groups was 1.5 mg/day at week 18, and the mean changes in PDSS-2 total score for pramipexole SR and IR were –13.7 (95% CI –16.0 to –11.4) and –14.4 (–16.8 to –12.0) (difference of 0.7; p=0.688). Change from baseline for both groups achieved the minimal clinical important difference threshold (MCID = –3.44). No significant difference was observed in change from baseline for other measures of sleep-related disturbances or responder rates. For motor complications, a greater improvement in MDS-UPDRS part IV score was observed in pramipexole SR over IR (–3.4 vs –2.3; treatment group difference: –1.1; p=0.036). Both groups had comparable safety profiles. Conclusion In Chinese patients with advanced PD and sleep disturbances, pramipexole SR and IR have similar benefits in the treatment of nocturnal symptoms and safety, and an improvement from baseline in nocturnal symptoms was observed regardless of pramipexole formulation.

Switch from Immediate-release Pramipexole to Extended-release Pramipexole: The Safety and Efficacy Characteristics of Sixty-eight Patients

Objective: To evaluate the safety and efficacy of switching from immediate-release pramipexole (pex) to extended-release pramipexole (pex-ER). Materials and Methods: Pex-ER became available in Turkey about a year ago, since then we documented satisfactory information on patients (26 women; 38%) who were switched from pex to pex-ER. We recorded preand post-switch pex and levodopa, equivalent doses of other anti-parkinsonian medication, and analyzed the frequency and nature of reported adverse effects. Results: The mean age of the patients was 63.3 years (range, 44-88 years), and the mean disease duration was 7.1 years (range, 1-27 years). The other drugs were levodopa (57 patients, 82.6%), entacapone (24 patients, 34.58%), rasagiline (20 patients, 29%), amantadine (18 patients, 26.1%), and apomorphine (six patients, 8.7%). Switch from pex to pex-ER was uneventful in 62 (91.2%) patients. Adverse events were reported in six (8.8%) patients: ankle swelling (two patients), nausea (one patient), dyskinesia (one patient), hypersexuality (one patient), and psychosis (one patient). Problems resolved with further medication change in two patients. Four patients preferred to return to pex. Conclusion: The great majority of patients (91.2%) switched from three times daily pex to once daily pex-ER uneventfully. A slight increase in pex daily dose, which was tailored according to patients’ symptomatic needs, resulted in an increase in post-switch levodopa equivalent doses. Our experience is compatible with previously reported studies.

Ophthalmologic Baseline Characteristics and 2-Year Ophthalmologic Safety Profile of Pramipexole IR Compared with Ropinirole IR in Patients with Early Parkinson's Disease.

Background. Parkinson's disease (PD) progressively affects dopaminergic neurotransmission and may affect retinal dopaminergic functions and structures. Objective. This 2-year randomized, open-label, parallel-group, flexible-dose study, NCT00144300, evaluated ophthalmologic safety profiles of immediate-release (IR) pramipexole and ropinirole in patients with early idiopathic PD with ≤6 months' prior dopamine agonist exposure and without preexisting major eye disorders. Methods. Patients received labeled IR regimens of pramipexole (n = 121) or ropinirole (n = 125) for 2 years. Comprehensive ophthalmologic assessments (COA) included corrected acuity, Roth 28-color test, slit-lamp biomicroscopy, intraocular pressure, computerized visual field test, fundus photography, and electroretinography. Results. At baseline, we observed retinal pigmentary epithelium (RPE) hypopigmentation not previously reported in PD patients. The estimated relative risk of 2-year COA worsening with pramipexole versus ropinirole was 1.07 (95% CI: 0.71–1.60). Mean changes from baseline in Unified Parkinson's Disease Rating System parts II+III total scores (pramipexole: 1 year, −4.1 ± 8.9, and 2 years, −0.7 ± 10.1, and ropinirole: 1 year, −3.7 ± 8.2, and 2 years, −1.7 ± 10.5) and Hoehn–Yahr stage distribution showed therapeutic effects on PD symptoms. Safety profiles were consistent with labeling. Conclusions. The risk of retinal deterioration did not differ in early idiopathic PD patients receiving pramipexole versus ropinirole. RPE hypopigmentation at baseline was not previously reported in this population. This trial is registered with NCT00144300.

Pramipexole extended-release: a review of its use in patients with Parkinson's disease.

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.

The efficacy and safety of pramipexole ER versus IR in Chinese patients with Parkinson's disease: a randomized, double-blind, double-dummy, parallel-group study.

ObjectiveTo evaluate the non-inferiority of pramipexole extended-release (ER) versus immediate-release (IR) in Chinese patients with Parkinson’s disease (PD) in a double-blind, randomized, parallel-group study.MethodsSubjects were Chinese patients with idiopathic PD with diagnosis ≥ 2 years prior to trial, age ≥ 30 years old at diagnosis, and Modified Hoehn and Yahr score 2-4 during ‘on’-time. Subjects received treatment with pramipexole ER (n=234) or IR (n=239). Non-inferiority was based on the primary endpoint, the change from baseline to end of maintenance (week 18) in the UPDRS (Parts II + III) total score.ResultsFor the primary endpoint, the adjusted mean changes (standard error) of UPDRS Parts II + III at week 18 were -13.81 (0.655) and -13.05 (0.643) for ER and IR formulations, respectively, using ANCOVA adjusted for treatment and centre (fixed effect) and baseline (covariate). The adjusted mean between group difference was 0.8 for the 2-sided 95% CI (-1.047, 2.566). Since the lower limit of the 2-sided 95% CI (-1.047) for treatment difference was higher than the non-inferiority margin of -4, non-inferiority between pramipexole ER and IR was demonstrated. The incidence of adverse events (AEs) was 68.8% in the ER arm and 73.6% in the IR arm with few severe AEs (ER: 2.1%; IR: 3.8%).ConclusionBased on the UPDRS II + III score, pramipexole ER was non-inferior to pramipexole IR. The safety profiles of pramipexole ER and IR were similar. These results were based on comparable mean daily doses and durations of treatment for both formulations.

Minimal clinically important difference in Parkinson's disease as assessed in pivotal trials of pramipexole extended release.

Background. The minimal clinically important difference (MCID) is the smallest change in an outcome measure that is meaningful for patients. Objectives. To calculate the MCID for Unified Parkinson's Disease Rating Scale (UPDRS) scores in early Parkinson's disease (EPD) and for UPDRS scores and “OFF” time in advanced Parkinson's disease (APD). Methods. We analyzed data from two pivotal, double-blind, parallel-group trials of pramipexole ER that included pramipexole immediate release (IR) as an active comparator. We calculated MCID as the mean change in subjects who received active treatment and rated themselves “a little better” on patient global impression of improvement (PGI-I) minus the mean change in subjects who received placebo and rated themselves unchanged. Results. MCIDs in EPD (pramipexole ER, pramipexole IR) for UPDRS II were −1.8 and −2.0, for UPDRS III −6.2 and −6.1, and for UPDRS II + III −8.0 and −8.1. MCIDs in APD for UPDRS II were −1.8 and −2.3, for UPDRS III −5.2 and −6.5, and for UPDRS II + III −7.1 and −8.8. MCID for “OFF” time (pramipexole ER, pramipexole IR) was −1.0 and −1.3 hours. Conclusions. A range of MCIDs is emerging in the PD literature that provides the basis for power calculations and interpretation of clinical trials.

PND17 - Budget Impact of Switching Pramipexole Immediate Release to Pramipexole Extended Release in Treatment of Parkinson’s Disease; Perspective of the Social Security Institution

Budget impact analysis of switching Pramipexole Immediate Release (IR) to Pramipexole Extended Release (ER) in treatment of Parkinson’s Disease in the Turkish health care setting from a Social Security Institution’s (SSI) perspective. Based upon a literature review demonstrating that, Pramipexole ER is similar to Pramipexole IR in efficacy and safety in treatment of Parkinson’s Disease (non-inferiority), budget impact analyses were performed using Microsoft Excel (2007). The switch from IR to ER was analyzed for the following formulations 0.75MG /1.50MG /3.00MG /4.50MG per day and patient. The daily pill burden per patient was reduced from 3 to 1 and 6 to 1 for 0,75MG /1,5MG /3,0MG and 4,5MG respectively. The total annual treatment cost per patient was reduced by 2.91%, 6.25%, 1.74% and 3.30% for 0.75MG, 1.50MG, 3.00MG and 4.50MG respectively. The findings of this study indicate that, switching Parkinson’s Patients from Pramipexole IR to ER will not result in an additional budget impact for the Turkish health care system from a SSI perspective. However, further research needs to be conducted in order to explore the potential implications of compliance benefits and if they can be translated into long-term savings. No local effectiveness data was available at the time this analysis was performed. Potential benefits in patients’ adherence were not considered.

Does pramipexole treatment improve headache in patients with concomitant migraine and restless legs syndrome?

Recent studies have suggested a strong link between migraines and restless legs syndrome (RLS). It is possible that these disorders share a dopaminergic dysfunction in the hypothalamic A11 nucleus that contributes to this association. However, there have been no clinical studies to evaluate the effect of dopaminergic treatment on migraine symptoms in patients with concomitant migraines and RLS. We present an illustrative patient with concomitant RLS and migraine who showed improvement in her headache frequency and RLS symptoms following immediate-release pramipexole (P-IR) treatment and provide review results from the medical records of patients who experienced both migraines and RLS in our previous cross-sectional study. Ten patients (nine patients from the previously completed single-center study) received P-IR treatment were included in the study. RLS symptoms improved markedly in all of the subjects. Five out of the 10 patients (50%) reported improvement in migraine headaches. Of these five patients, four (80%) had reported morning headaches before P-IR treatment. Our results indicate that the identification of RLS in migraine patients is clinically significant and that dopaminergic treatment may improve both migraines, particularly morning headache (80% improvement in this study), and RLS symptoms. However, further clinical studies are warranted to verify our results.

Success rate, efficacy, and safety/tolerability of overnight switching from immediate‐ to extended‐release pramipexole in advanced Parkinson's disease

For Parkinson's disease (PD), an extended-release (ER) pramipexole formulation taken once daily, has shown efficacy, safety, and tolerability resembling those of immediate-release (IR) pramipexole taken three times daily. The present study assessed, in advanced PD, the success of an overnight switch from adjunctive IR to ER. Levodopa users experiencing motor fluctuations were randomized to adjunctive double-blind (DB) placebo, IR, or ER. Amongst completers of ≥18weeks, ER recipients were kept on DB ER, whilst IR recipients were switched overnight to DB ER at unchanged daily dosage. After a DB week, switch success was assessed. During the next 5weeks, all patients underwent ER titration to optimal open-label maintenance dosage. One week post-switch, 86.2% of 123 IR-to-ER and 83.8% of 105 ER-to-ER patients had ≤15% (or ≤3-point, for pre-switch scores ≤20) increase on UPDRS Parts II+III, and 77.9% (of 122) and 70.2% (of 104) had ≤1-h increase in daily OFF-time. At 32weeks, the groups showed comparable improvements from DB baseline (pramipexole inception), including, on UPDRS II+III, adjusted mean (SE) changes of -14.8 (1.5) for IR-to-ER and -13.3 (1.6) for ER-to-ER. Rates of premature discontinuation owing to adverse events were 6.5% for IR-to-ER and 4.9% for ER-to-ER. By OFF-time and UPDRS criteria, majorities of patients with advanced PD were successfully switched overnight from pramipexole IR to ER at unchanged daily dosage. During subsequent maintenance, pramipexole showed sustained efficacy, safety, and tolerability, regardless of formulation (IR or ER) in the preceding DB trial.

Efficacy and Safety of Extended- Versus Immediate-Release Pramipexole in Japanese Patients With Advanced and L-dopa–Undertreated Parkinson Disease

To compare the efficacy, safety, tolerability, and trough plasma levels of pramipexole extended-release (ER) and pramipexole immediate-release (IR), and to assess the effects of overnight switching from an IR to an ER formulation, in L-dopa-treated patients with Parkinson disease (PD). After a 1- to 4-week screening/enrollment, 112 patients who had exhibited L-dopa-related problems or were receiving suboptimal L-dopa dosage were randomized in double-blind, double-dummy, 1:1 fashion to pramipexole ER once daily or pramipexole IR 2 to 3 times daily for 12 weeks, both titrated to a maximum daily dose of 4.5 mg. Successful completers of double-blind treatment were switched to open-label pramipexole ER, beginning with a 4-week dose-adjustment phase. Among the double-blind treatment patients (n = 56 in each group), Unified Parkinson's Disease Rating Scale Parts II+III total scores decreased significantly from baseline and to a similar degree with pramipexole ER and IR formulations. In each group, 47 double-blind patients (83.9%) reported adverse events (AEs), requiring withdrawal of 3 ER patients (5.4%) and 2 IR patients (3.6%). Trough plasma levels at steady state (at the same doses and dose-normalized concentrations) were also similar with both formulations. Among open-label treatment patients (n = 53 from IR to ER), 83% were successfully switched (no worsening of PD symptoms) to pramipexole ER. In L-dopa-treated patients, pramipexole ER and pramipexole IR demonstrated similar efficacy, safety, tolerability, and trough plasma levels. Patients can be safely switched overnight from pramipexole IR to pramipexole ER with no impact on efficacy.

Pramipexole extended release in Parkinson’s disease

Pramipexole extended release (ER) is a new once-daily formulation of pramipexole, a nonergot dopamine agonist, which is available in five dosage strengths: 0.26 (0.375) mg, 0.52 (0.75) mg, 1.05 (1.5) mg, 2.1 (3) mg and 3.15 (4.5) mg (all doses are expressed in terms of pramipexole base and the corresponding dose strengths of pramipexole salt are given in brackets). Pramipexole ER is currently approved as monotherapy in early Parkinson’s disease (PD), as well as an adjunct therapy to levodopa in advanced PD. Compared with the immediate release (IR) formulation, the ER formulation offers several advantages, including the potential for improved compliance owing to its simple once-daily dosing regimen and steadier plasma levels over 24 h. Double-blind, randomized, placebo and active comparator controlled trials in early, as well as advanced PD, established the superiority of both pramipexole ER and IR over placebo. The overnight switch from pramipexole IR three times a day to ER once-daily in early PD has been shown to be successful in more than 80% of patients. Pramipexole ER is well tolerated, with a similar adverse event profile to pramipexole IR. The aim of this article is to provide a short review of the most relevant pharmacological and clinical data on pramipexole ER.

Extended-release pramipexole in advanced Parkinson disease

In advanced Parkinson disease (PD), immediate-release pramipexole, taken 3 times daily, improves symptoms and quality of life. A once-daily extended-release formulation may be an effective and simple alternative therapy. For a multicenter randomized, double-blind, parallel trial of extended- and immediate-release pramipexole vs placebo, patients experiencing motor fluctuations while taking levodopa underwent flexible study drug titration and then maintenance at optimized dosage (0.375-4.5 mg/day). The primary endpoint was a change in the Unified Parkinson's Disease Rating Scale (UPDRS) part II+III score at 18 weeks, with further assessments at 33 weeks in a subset of patients. Adverse events were recorded throughout. Among 507 patients in the 18-week analyses, UPDRS II+III scores decreased (from baseline means of 40.0-41.7) by an adjusted mean of -11.0 for extended-release pramipexole and -12.8 for immediate-release pramipexole vs -6.1 for placebo (p = 0.0001 and p < 0.0001) and off-time decreased (from baseline means of 5.8-6.0 hours/day) by an adjusted mean of -2.1 and -2.5 vs -1.4 hours/day (p = 0.0199 and p < 0.0001). Other outcomes were largely corroborative, including a significant improvement in early morning off symptoms. Among 249 pramipexole patients completing 33 weeks, UPDRS II+III and off-time findings showed ≤10.1% change from 18-week values. Both formulations were well-tolerated. Extended-release pramipexole significantly improved UPDRS score and off-time compared with placebo, with similar efficacy, tolerability, and safety of immediate-release pramipexole compared with placebo. This study provides Class I evidence that the extended-release form of pramipexole, taken once daily, is efficacious as an adjunct to levodopa in advanced PD.

Extended-release pramipexole in early Parkinson disease

To assess the clinical efficacy of a novel once-daily extended-release (ER) formulation of the dopamine agonist pramipexole as monotherapy in patients with early Parkinson disease (PD) and establish its noninferiority vs standard immediate-release (IR) pramipexole. This was a multicenter, double-blind, parallel study of patients with early PD not receiving levodopa or dopamine agonists, randomly assigned to pramipexole IR, pramipexole ER, or placebo. Seven-week flexible titration was followed by 26-week maintenance, with levodopa permitted as rescue medication. The primary analysis was to test pramipexole ER noninferiority to pramipexole IR based on a change in the Unified Parkinson's Disease Rating Scale (UPDRS) part II+III score at 33 weeks, with noninferiority predefined as a treatment group difference for which the lower bound of the 95% confidence interval (CI) did not exceed -3 points. Among 213 ER and 207 IR recipients, the adjusted mean 33-week UPDRS II+III change (excluding levodopa rescue effects) was -8.2 for ER and -8.7 for IR, a difference of -0.5 with a 95% CI of -2.3 to 1.3. Compared with placebo (n = 103), pramipexole ER and pramipexole IR were significantly superior on UPDRS II+III score, all key secondary outcomes, and almost all other endpoints. On the 39-item Parkinson Disease Questionnaire, superiority of pramipexole ER failed to reach statistical significance. Both formulations were equally safe and well-tolerated. As monotherapy for early PD, pramipexole ER was noninferior to pramipexole IR and significantly more effective than placebo. Tolerability and safety did not differ between the formulations. This study provides Class I evidence that pramipexole ER is not inferior to pramipexole IR in patients with early PD.

Pramipexole for the treatment of early Parkinson’s disease

Pramipexole is a nonergolinic dopamine agonist, with high affinity for the D2 subfamily of dopamine receptors. Pramipexole is efficacious for the symptomatic treatment of early Parkinson’s Disease (PD) and its early use, before that of levodopa can delay the emergence of levodopa-related motor complication. Dosage should be increased gradually from a starting dose of 0.375 mg/day up to a maximum of 4.5 mg/day in equally divided doses taken three times per day with pramipexole immediate-release or equivalent daily dosages once-daily with pramipexole extended-release. Pramipexole can also improve depressive symptoms and possibly health-related quality of life in PD. Nonetheless, its use is not devoid of tolerability problems. While peripheral adverse drug reactions, such as nausea, vomiting or orthostatic hypotension, can be effectively treated and usually pose few problems to most patients, neuropsychiatric events can seriously limit the use of pramipexole in some cases. Indeed, excessive daytime somnolence, impulse-control disorders, hallucinations or delusions can severely affect patients, causing important personal or social handicap. Patients should be informed about the risk of such neuropsychiatric complications and their presence should be actively detected at each consultation. More effort will have to be put into further studying the risk–benefit ratio of pramipexole and other dopamine agonists in the treatment of early PD.

Randomized, double‐blind, multicenter evaluation of pramipexole extended release once daily in early Parkinson's disease

The objective of this study was to evaluate the efficacy and safety of pramipexole extended release (ER) administered once daily in early Parkinson's disease (PD). Pramipexole immediate release (IR) administered three times daily (TID) is an efficacious and generally well-tolerated treatment for PD. A pramipexole ER formulation is now available. We performed a randomized, double-blind, placebo and active comparator-controlled trial in subjects with early PD. The primary efficacy and safety evaluation of pramipexole ER compared with placebo took place at week 18. Two hundred fifty-nine subjects were randomized 2:2:1 to treatment with pramipexole ER once daily, pramipexole IR TID, or placebo. Levodopa rescue was required by 7 subjects in the placebo group (14%), 3 subjects in the pramipexole ER group (2.9%, P = 0.0160), and 1 subject in the pramipexole IR group (1.0%, P = 0.0017). Adjusted mean [standard error (SE)] change in Unified Parkinson Disease Rating Scale (UPDRS) II [activities of daily living (ADL)] + III (motor) scores from baseline to week 18, including post-levodopa rescue evaluations, was -5.1 (1.3) in the placebo group, -8.1 (1.1) in the pramipexole ER group (P = 0.0282), and -8.4 (1.1) in the pramipexole IR group (P = 0.0153). Adjusted mean (SE) change in UPDRS ADL + motor scores, censoring post-levodopa rescue data, was -2.7 (1.3) in the placebo group, -7.4 (1.1) in the pramipexole ER group (P = 0.0010), and -7.5 (1.1) in the pramipexole IR group (P = 0.0006). Adverse events more common with pramipexole ER than placebo included somnolence, nausea, constipation, and fatigue. Pramipexole ER administered once daily was demonstrated to be efficacious compared with placebo and provided similar efficacy and tolerability as pramipexole IR administered TID.

Efficacy, safety, and tolerability of overnight switching from immediate‐ to once daily extended‐release pramipexole in early Parkinson's disease

The aim of this article is to test the feasibility, in early Parkinson's disease (PD), of an overnight switch from immediate-release (IR) pramipexole to a new once-daily extended-release (ER) formulation. Nonfluctuating patients on pramipexole IR three-times daily, alone or with levodopa, for early PD were randomly switched overnight to double-blind IR three-times daily (N = 52) or ER once-daily (N = 104) at initially unchanged daily dosage. Successful switching (defined as no worsening >15% of baseline UPDRS II+III score and no drug-related adverse event withdrawal) was assessed at 9 weeks, after optional dosage adjustments (primary endpoint), and at 4 weeks, before adjustment. Other secondary endpoints included adjusted mean changes from baseline in UPDRS scores and proportion of responders based on Clinical or Patient Global Impression (CGI/PGI). Absolute difference between percentage of successful switch to ER versus IR was tested for ER noninferiority, defined as a 95% confidence-interval lower bound not exceeding -15%. At 9 weeks, 84.5% of the ER group had been successfully switched, versus 94.2% for IR. Noninferiority was not demonstrated, with a difference of -9.76% (95% CI: [-18.81%, +1.66%]). At 4 weeks, 81.6% of the ER group had been successfully switched, versus 92.3% for IR, a difference of -10.75% (95% CI: [-20.51%, +1.48%]). UPDRS changes and CGI/PGI analyses showed no differences between the groups. Both formulations were safe and well tolerated. Pramipexole ER was not equivalent to IR, but the difference was marginal. The fact that >80% of the patients successfully switched overnight at unchanged dosage shows that this practice was feasible in most patients.

Pramipexole extended-release (once-daily formulation) for the treatment of Parkinson's disease

Importance of the field: Immediate-release pramipexole (P-IR) is indicated three times daily for the symptomatic treatment of early and advanced Parkinson's disease (PD). An extended-release formulation of pramipexole (P-ER) has been developed to allow a once-daily formulation and to provide more stable dopaminergic stimulation.Areas covered in this review: This review summarizes clinical pharmacology and pharmacokinetics of P-ER for the treatment of early and advanced PD. The advantages and disadvantages of the strategies available at present for achieving continuous dopaminergic stimulation in the treatment of PD are discussed first. The pharmacological properties are then summarized. Finally, the clinical pharmacology and pharmacokinetics of P-ER are described.What the reader will gain: The reader will gain knowledge of the development of P-ER, its current place in the pharmacotherapy of PD, and future directions.Take home message: P-ER has been shown to be efficacious in early and advanced PD and it has the same clinical profile when administered once daily as P-IR administered three times daily. An overnight switching of P-IR to dose-equivalent P-ER is successful in 80% of patients with early PD.

Pramipexole Extended Release

Pramipexole extended release (ER) is a non-ergolinic dopamine receptor agonist available for use as a once-daily oral treatment for the signs and symptoms of early and advanced idiopathic Parkinson's disease. Once-daily pramipexole ER and three times-daily pramipexole immediate release (IR) have similar exposure over 24 hours. The ER formulation is associated with fewer fluctuations in plasma pramipexole concentrations over this period. Pramipexole ER improved the symptoms of Parkinson's disease in three well designed trials in adults with early or advanced disease, as measured by changes from baseline in the sum of the Unified Parkinson's Disease Rating Scale (UPDRS) parts II and III subtotal scores. In a 9-week study, the majority of patients with early Parkinson's disease who were receiving stable pramipexole IR treatment were successfully switched to pramipexole ER. Relative to placebo at week 18, pramipexole ER 0.375-4.5 mg (of the salt) once daily significantly decreased the sum of the UPDRS parts II and III subtotal scores from baseline in two trials in patients with early or advanced Parkinson's disease, and also reduced the percentage of off-time during waking hours in patients with advanced disease. The efficacy of pramipexole ER was maintained after 33 weeks of treatment in the trials in patients with early or advanced Parkinson's disease. Pramipexole ER was generally well tolerated in patients with Parkinson's disease, with the rate of adverse events being generally similar to that with pramipexole IR.

Pramipexole extended release: a novel treatment option in Parkinson's disease.

Pramipexole, the most commonly prescribed dopamine agonist worldwide, meanwhile serves as a reference substance for evaluation of new drugs. Based on numerous clinical data and vast experiences, efficacy and safety profiles of this non-ergoline dopamine agonist are well characterized. Since October 2009, an extended-release formulation of pramipexole has been available for symptomatic treatment of Parkinson's disease. Pramipexole administration can be cut down from three times to once a day due to the newly developed extended-release formulation. This is considerable progress in regard to minimizing pill burden and enhancing compliance. Moreover, the 24 h continuous drug release of the once-daily extended-release formulation results in fewer fluctuations in plasma concentrations over time compared to immediate-release pramipexole, given three times daily. The present study summarizes pharmacokinetics and all essential pharmacological and clinical characteristics of the extended-release formulation. In addition, it provides all study data, available so far, with regard to transition and de-novo administration of extended-release formulation for patients with Parkinson's disease. It further compares efficacy and safety data of immediate-release pramipexole with the extended-release formulation of pramipexole.