REQUIP XL SIDE EFFECTS
- Generic Name: ropinirole extended release tablets
- Brand Name: Requip XL
SIDE EFFECTS
The following adverse reactions are described in more detail in other sections of the label:
- Hypersensitivity
- Falling Asleep during Activities of Daily Living and Somnolence
- Syncope
- Hypotension/Orthostatic Hypotension
- Elevation of Blood Pressure and Changes in Heart Rate
- Hallucinations/Psychotic-like Behavior
- Dyskinesia
- Impulse Control/Compulsive Behaviors
- Withdrawal-Emergent Hyperpyrexia and Confusion
- Melanoma
- Fibrotic Complications
- Retinal Pathology
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 with 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 REQUIP XL, patients with advanced Parkinson’s disease received REQUIP XL or placebo as adjunctive therapy with L-dopa in a flexible-dose clinical trial. In a flexible-dose trial, patients with early Parkinson’s disease were treated with REQUIP XL or the immediate-release formulation of REQUIP without L-dopa. In addition, placebo-controlled, fixed-dose, postmarketing trials evaluated the dose response of REQUIP XL in patients with advanced Parkinson’s disease taking L-dopa and in patients with early Parkinson’s disease without concomitant L-dopa.
Advanced Parkinson’s Disease (with L-dopa)
Study 1 was a 24-week, double-blind, placebo-controlled, flexible-dose trial in patients with advanced Parkinson’s disease. In Study 1, the most commonly observed adverse reactions in patients treated with REQUIP XL (incidence at least 5% greater than placebo) were dyskinesia, nausea, dizziness, and hallucinations.
In Study 1, approximately 6% of patients treated with REQUIP XL discontinued treatment due to adverse reactions, compared with 5% of patients who received placebo. The most common adverse reaction in patients treated with REQUIP XL causing discontinuation of treatment with REQUIP XL in Study 1 was hallucination (2%).
Table 1 lists adverse reactions that occurred in at least 2% (and were numerically greater than placebo) of patients with advanced Parkinson’s disease treated with REQUIP XL who participated in Study 1. In this trial, either REQUIP XL or placebo was used as an adjunct to L-dopa.
Table 1: Incidence of Adverse Reactions in a Placebo-Controlled Flexible-Dose Trial in Advanced Stage Parkinson’s Disease in Patients Taking L-dopa (Study 1) (Events ≥ 2% of Patients Treated with REQUIP XL and More Common than on Placebo)a
| Body System/Adverse Reaction | REQUIP XL (n = 202) % |
Placebo (n = 191) % |
| Ear and labyrinth disorders | ||
| Vertigo | 4 | 2 |
| Gastrointestinal disorders | ||
| Nausea | 11 | 4 |
| Abdominal pain/discomfort | 6 | 3 |
| Constipation | 4 | 2 |
| Diarrhea | 3 | 2 |
| Dry mouth | 2 | < 1 |
| General disorders | ||
| Edema peripheral | 4 | 1 |
| Injury, poisoning, and procedural complications | ||
| Fallb | 2 | 1 |
| Musculoskeletal and connective tissue disorders | ||
| Back pain | 3 | 2 |
| Nervous system disorders | ||
| Dyskinesiab | 13 | 3 |
| Dizziness | 8 | 3 |
| Somnolence | 7 | 4 |
| Psychiatric disorders | ||
| Hallucination | 8 | 2 |
| Anxiety | 2 | 1 |
| Vascular disorders | ||
| Orthostatic hypotension | 5 | 1 |
| Hypertensionb | 3 | 2 |
| Hypotension | 2 | 0 |
| a Patients may have reported multiple adverse reactions during the trial or at discontinuation; thus, patients may be included in more than one category. b Dose-related. |
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Although this trial was not designed for optimally characterizing dose-related adverse reactions, there was a suggestion (based upon comparison of incidence of adverse reactions across dose ranges for REQUIP XL and placebo) that the incidence for dyskinesia, hypertension, and fall was dose-related to REQUIP XL.
During the titration phase, the incidence of adverse reactions in descending order of percent treatment difference was dyskinesia, nausea, abdominal pain/discomfort, orthostatic hypotension, dizziness, vertigo, hypertension, peripheral edema, and dry mouth. During the maintenance phase, the most frequently observed adverse reactions were dyskinesia, nausea, dizziness, hallucination, somnolence, fall, hypertension, abnormal dreams, constipation, chest pain, bronchitis, and nasopharyngitis. Some adverse reactions developing in the titration phase persisted ( ≥ 7 days) into the maintenance phase. These “persistent” adverse reactions included dyskinesia, hallucination, orthostatic hypotension, and dry mouth.
The incidence of adverse reactions was similar in women and men.
Study 2 was an 18-week, double-blind, placebo-controlled, fixed-dose, dose-response trial in patients with advanced Parkinson’s disease. In Study 2, approximately 7% of patients treated with any dose of REQUIP XL discontinued prematurely during the titration phase because of adverse reactions, compared with 4% of patients on placebo. The percentage of patients who discontinued from the study because of an adverse reaction was 4% for REQUIP XL 4 mg, 9% for REQUIP XL 8 mg, 8% for REQUIP XL 12 mg, 8% for REQUIP XL 16 mg, and 0% for REQUIP XL 24 mg. Table 2 lists adverse reactions with an incidence of at least 5% of patients in any dose group of REQUIP XL and numerically higher than on placebo in Study 2. The most common adverse reaction (incidence for REQUIP XL all doses at least 5% greater than placebo) was dyskinesia.
Table 2: Incidence of Adverse Reactions in a Placebo-Controlled Fixed-Dose Trial in Advanced Stage Parkinson’s Disease in Patients Taking L-dopa (Study 2) (Events ≥ 5% of Patients Treated with any Dose of REQUIP XL and More Common than on Placebo)
| Adverse Reaction | Placebo N = 74 % |
REQUIP XL | |||||
| 4 mg N = 25 % |
8 mg N = 76 % |
12 mg N = 75 % |
16 mg N = 75 % |
24 mg N = 25 % |
All Doses N = 276 % |
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| Nervous system disorders | |||||||
| Somnolence | 5 | 4 | 5 | 12 | 11 | 0 | 8 |
| Dyskinesia | 1 | 4 | 4 | 7 | 11 | 4 | 7 |
| Dizziness | 3 | 8 | 4 | 8 | 5 | 4 | 6 |
| Sudden onset of sleep | 3 | 8 | 5 | 4 | 1 | 0 | 4 |
| Vascular disorders | |||||||
| Hypertension | 1 | 8 | 1 | 1 | 4 | 8 | 3 |
| Infections and infestations | |||||||
| Nasopharyngitis | 1 | 0 | 3 | 3 | 0 | 8 | 2 |
| Musculoskeletal and connective tissue disorders | |||||||
| Arthralgia | 0 | 0 | 3 | 0 | 3 | 8 | 2 |
| Psychiatric disorders Insomnia | 0 | 0 | 0 | 1 | 5 | 0 | 2 |
Early Parkinson’s Disease (without L-dopa)
Study 3 was a 36-week, flexible-dose crossover trial in patients with early Parkinson’s disease who were first treated with REQUIP XL or the immediate-release formulation of REQUIP and then crossed over to treatment with the other formulation. In Study 3, the most commonly observed adverse reactions ( ≥ 5%) in patients treated with REQUIP XL were nausea (19%), somnolence (11%), abdominal pain/discomfort (7%), dizziness (6%), headache (6%), and constipation (5%).
Study 4 was an 18-week, double-blind, placebo-controlled, fixed-dose, dose-response trial in patients with early Parkinson’s disease. Overall, 7% of patients treated with any dose of REQUIP XL, including 6% during the titration phase, discontinued prematurely from the study because of adverse reactions compared with 5% of patients on placebo. The percentage of patients discontinuing prematurely because of an adverse reaction was 8% for REQUIP XL 2 mg, 5% for REQUIP XL 4 mg, 8% for REQUIP XL 8 mg, 5% for REQUIP XL 12 mg, and 15% for REQUIP XL 24 mg.
Table 3 lists adverse reactions with an incidence of at least 10% of patients in any dose group of REQUIP XL and numerically higher than on placebo in Study 4. The most common adverse reactions (incidence for REQUIP XL all doses at least 5% greater than placebo) were nausea, somnolence, sudden onset of sleep, hypertension, and headache.
Table 3: Incidence of Adverse Reactions in a Double-Blind, Placebo-Controlled, Fixed-Dose, Trial in Early Stage Parkinson’s Disease (Study 4) (Events ≥ 10% of Patients Treated with any Dose of REQUIP XL and Greater % than on Placebo)
| Adverse Reactions | Placebo N = 40 % |
REQUIP XL | |||||
| 2 mg N = 13 % |
4 mg N = 41 % |
8 mg N = 40 % |
12 mg N = 39 % |
24 mg N = 13 % |
All Doses N = 146 % |
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| Gastrointestinal disorders | |||||||
| Nausea | 8 | 8 | 15 | 33 | 10 | 15 | 18 |
| Vomiting | 5 | 0 | 5 | 10 | 0 | 0 | 4 |
| Nervous system disorders | |||||||
| Somnolence | 5 | 15 | 12 | 10 | 8 | 8 | 10 |
| Headache | 3 | 8 | 10 | 8 | 5 | 15 | 8 |
| Dizziness | 5 | 0 | 5 | 10 | 8 | 8 | 7 |
| Sudden onset of sleep | 0 | 0 | 5 | 0 | 10 | 8 | 5 |
| Vascular disorders | |||||||
| Hypertension | 0 | 0 | 5 | 5 | 3 | 15 | 5 |
| Musculoskeletal and connective tissue disorders | |||||||
| Back pain | 3 | 0 | 5 | 3 | 3 | 15 | 4 |
Laboratory Abnormalities
In the fixed-dose trial in advanced Parkinson’s disease (Study 2), 11% of patients on REQUIP XL exhibited a shift in serum creatine phosphokinase (CPK) from normal at baseline to above the normal reference range during treatment, compared with 6% of patients on placebo. There was no clear dose-response for abnormal shifts in CPK levels in patients with early or advanced stage Parkinson’s disease in either fixed-dose trial.
In the fixed-dose trial in early Parkinson’s disease patients (Study 4), serum CPK shifted during treatment from normal to above the normal reference range in 10% of patients on REQUIP XL and in 5% of patients on placebo.
Adverse Reactions Observed During The Clinical Development Of The Immediate-Release Formulation Of REQUIP For Parkinson’s Disease (Advanced and Early)
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with 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.
In patients with advanced Parkinson’s disease who were treated with the immediate-release formulation of REQUIP, the most common adverse reactions ( ≥ 5% treatment difference from placebo presented in order of decreasing treatment difference frequency) were dyskinesia (21%), somnolence (12%), nausea (12%), dizziness (10%), confusion (7%), hallucinations (6%), headache (5%), and increased sweating (5%). In patients with early Parkinson’s disease who were treated with the immediate-release formulation of REQUIP, the most common adverse reactions ( ≥ 5% treatment difference from placebo presented in order of decreasing treatment difference frequency) were nausea (38%), somnolence (34%), dizziness (18%), syncope (11%), asthenic condition (11%), viral infection (8%), leg edema (6%), vomiting (5%), and dyspepsia (5%).
SRC: NLM .