Mirapex ER

SIDE EFFECTS

The following adverse reactions are discussed in greater detail in other sections of the labeling:

• Falling Asleep During Activities of Daily Living and Somnolence [see WARNINGS AND PRECAUTIONS]
• Symptomatic Orthostatic Hypotension [see WARNINGS AND PRECAUTIONS]
• Impulse Control/Compulsive Behaviors [see WARNINGS AND PRECAUTIONS]
• Hallucinations and Psychotic-like Behavior [see WARNINGS AND PRECAUTIONS]
• Dyskinesia [see WARNINGS AND PRECAUTIONS]
• Rhabdomyolysis [see WARNINGS AND PRECAUTIONS]
• Retinal Pathology [see WARNINGS AND PRECAUTIONS]
• Events Reported with Dopaminergic Therapy [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug (or of another development program of a different formulation of the same drug) and may not reflect the rates observed in practice.

During the premarketing development of MIRAPEX ER tablets, patients with early Parkinson's disease were treated with MIRAPEX ER tablets, placebo, or immediate-release pramipexole tablets. In addition, a randomized, double-blind, parallel group trial was conducted in 156 early Parkinson's disease patients (Hoehn & Yahr Stages I-III) to assess overnight switching of immediate-release pramipexole tablets to MIRAPEX ER tablets. In this latter study, concomitant treatment with stable doses of levodopa, monoamine oxidase B inhibitor (MAOB-I) drugs, anticholinergics, or amantadine, individually or in combination, was allowed. In a third trial, advanced Parkinson's disease patients received MIRAPEX ER tablets, placebo, or immediate-release pramipexole tablets as adjunctive therapy to levodopa.

Early Parkinson's Disease

The most common adverse reactions ( ≥ 5% and more frequent than placebo) after 33 weeks of treatment with MIRAPEX ER tablets in the trial of early Parkinson's disease patients were somnolence, nausea, constipation, dizziness, fatigue, hallucinations, dry mouth, muscle spasms, and peripheral edema.

Twenty four of 223 (11%) patients treated with MIRAPEX ER tablets for 33 weeks discontinued treatment due to adverse reactions compared to 4 of 103 (4%) patients who received placebo and approximately 20 of 213 (9%) patients who received immediate-release pramipexole tablets. The adverse reaction most commonly causing discontinuation of treatment with MIRAPEX ER tablets was nausea (2%).

Table 1 lists adverse reactions that occurred with a frequency of at least 2% with MIRAPEX ER and were more frequent than with placebo during 33 weeks of treatment in a double-blind, placebo-controlled study in early Parkinson's disease. In this study, patients did not receive concomitant levodopa; however, levodopa was permitted as rescue medication.

Table 1 : Adverse-Reactions in a 33-Week Double-Blind, Placebo-Controlled Trial with MIRAPEX ER in Early Parkinson's Disease

Because this study used a flexible dose titration design, it was not possible to assess the effects of dose on the incidence of adverse reactions.

Adverse reactions can initially occur in either the titration or maintenance phase. Some adverse reactions developed in MIRAPEX ER-treated patients during the titration phase and SHUVLVWHG .7 days) into the maintenance phase (i.e., MIRAPEX ER % -SODFHER WUHDWPHQW GLIIHUHQFH . SHUVLVWHQW DGYHUVH reactions were somnolence, nausea, constipation, fatigue, and dry mouth.

A double-blind, randomized, parallel group trial evaluated the tolerability of an overnight switch from immediate-release pramipexole tablets to MIRAPEX ER tablets at the same daily dose in 156 early Parkinson's disease patients with or without levodopa. One of 104 patients switched from immediate-release pramipexole tablets to MIRAPEX ER tablets discontinued due to adverse reactions (vertigo and nausea).

Advanced Parkinson's Disease

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Eight of 164 (5%) patients treated with MIRAPEX ER tablets for 18 weeks discontinued treatment due to adverse reactions compared to 7 of 178 (4%) patients who received placebo and 8 of 175 (5%) patients who received immediate-release pramipexole tablets. The most common adverse reactions leading to discontinuation of treatment with MIRAPEX ER tablets were nausea (1%) and hallucination (1%).

Table 2 lists adverse reactions that occurred with a frequency of at least 2% with MIRAPEX ER and were more frequent than with placebo during 18 weeks of treatment in patients with advanced Parkinson's disease treated with MIRAPEX ER tablets. In this study, MIRAPEX ER tablets, immediate-release pramipexole tablets, or placebo was administered to patients who were also receiving concomitant levodopa.

Table 2 : Adverse-Reactions in an 18-Week Double-Blind, Placebo-Controlled Trial with MIRAPEX ER in Advanced Parkinson's Disease

Because this flexible dose study used a titration design, it was not possible to assess the effects of dose on the incidence of adverse reactions.

Adverse reactions can initially occur in either the titration or maintenance phase. Some adverse reactions developed in MIRAPEX ER-treated patients during the titration phase and pHUVLVWHG . GD\V LQWR WKH maintenance phase (i.e., MIRAPEX ER % -SODFHER WUHDWPHQW GLIIHUHQFH. SHUVLVWHQW DGYHUVH reactions were dyskinesia and insomnia.

Laboratory Tests

During the development of MIRAPEX ER tablets, no systematic abnormalities on routine laboratory testing were noted.

Other adverse reactions observed during clinical trials of MIRAPEX immediate-release or MIRAPEX ER in early and advanced Parkinson's disease

Other adverse reactions in clinical studies involving MIRAPEX immediate-release or MIRAPEX ER tablets include abnormal dreams, akathisia, amnesia, decreased libido, decreased weight, dyspnea, pneumonia, and vision abnormalities.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of MIRAPEX immediate-release or MIRAPEX ER tablets, primarily in Parkinson's disease patients. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Decisions to include these reactions in labeling are typically based on one or more of the following factors: (1) seriousness of the reaction, (2) frequency of reporting, or (3) strength of causal connection to pramipexole tablets. Similar types of reactions were grouped into a smaller number of standardized categories using the MedDRA terminology: cardiac failure, inappropriate antidiuretic hormone secretion (SIADH), skin reactions (including erythema, rash, pruritus, urticaria), syncope, vomiting, and weight increase.

Read the entire FDA prescribing information for Mirapex ER (Pramipexole Dihydrochloride Extended-Release Tablets)