openFDA text is shown for search and cross-checking; DailyMed SPL is canonical.
Adverse reactions sections page 1 of 2 · 5 matching rows.
adverse reactions
6 ADVERSE REACTIONS The following clinically significant adverse reactions are described below and elsewhere in the labeling: • Application Site Skin Reactions [ see Warnings and Precautions (5.1) ] • Cardiovascular Conditions [ see Warnings and Precautions (5.3) ] • Nausea and Vomiting [ see Warnings and Precautions (5.4) ] • Peptic Ulcer Disease and GI Bleeding [ see Warnings and Precautions (5.5) ] • Genitourinary Conditions [ see Warnings and Precautions (5.6) ] • Neurological Conditions: Seizures [ see Warnings and Precautions (5.7) ] • Pulmonary Conditions [ see Warnings and Precautions (5.8) ] Most common adverse reactions (greater than 5% with donepezil tablets and twice the placebo rate) are nausea, diarrhea, insomnia, vomiting, muscle cramps, fatigue, and anorexia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Corium, Inc. at 1-800-910-8432 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 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 and may not reflect the rates observed in practice. Donepezil Tablet Studies [see Clinical Studies (14.1 , 14.2) ] Donepezil tablets have been administered to over 1,700 individuals during clinical trials worldwide. Approximately 1,200 of these patients have been treated for at least 3 months and more than 1,000 patients have been treated for at least 6 months. Controlled and uncontrolled trials in the United States included approximately 900 patients. In regard to the highest dose of 10 mg/day, this population includes 650 patients treated for 3 months, 475 patients treated for 6 months, and 116 patients treated for over 1 year. The range of patient exposure is from 1 to 1,214 days. Mild to Moderate Alzheimer’s Disease Adverse Reactions Leading to Discontinuation The rates of discontinuation from controlled clinical trials of donepezil tablets due to adverse reactions for the donepezil 5 mg/day treatment groups were comparable to those of placebo treatment groups at approximately 5%. The rate of discontinuation of patients who received 7-day escalations of donepezil tablets from 5 mg/day to 10 mg/day was higher at 13%. The most common adverse reactions leading to discontinuation, defined as those occurring in at least 2% of patients and at twice or more the incidence seen in placebo patients, are shown in Table 2. Table 2. Most Common Adverse Reactions Leading to Discontinuation in Patients with Mild to Moderate Alzheimer’s Disease Adverse Reaction Placebo (n=355) % 5 mg/day donepezil tablet (n=350) % 10 mg/day donepezil tablet (n=315) % Nausea 1 1 3 Diarrhea 0 <1 3 Vomiting <1 <1 2 Most Common Adverse Reactions The most common adverse reactions, defined as those occurring at a frequency of at least 5% in patients receiving donepezil tablets 10 mg/day and twice the placebo rate, are nausea, diarrhea, insomnia, vomiting, muscle cramp, fatigue, and anorexia. These adverse reactions were often transient, resolving during continued donepezil treatment without the need for dose modification. There is evidence to suggest that the frequency of these common adverse reactions may be affected by the rate of titration. An open-label study was conducted with 269 patients who received placebo in the 15- and 30-week studies. These patients were titrated to a dose of 10 mg/day over a 6-week period. The rates of common adverse reactions were lower than those seen in patients titrated to donepezil tablets 10 mg/day over one week in the controlled clinical trials and were comparable to those seen in patients on 5 mg/day. See Table 3 for a comparison of the most common adverse reactions following one- and six-week titration regimens. Table 3. Comparison of Rates of Adverse Reactions in Mild to Moderate Patients Titrated to 10 mg/day over 1 and 6 Weeks No titration One week titration Six-week titration Adverse Reaction Placebo (n=315) % 5 mg/day donepezil tablet (n=311) % 10 mg/day donepezil tablet (n=315) % 10 mg/day donepezil tablet (n=269) % Nausea 6 5 19 6 Diarrhea 5 8 15 9 Insomnia 6 6 14 6 Fatigue 3 4 8 3 Vomiting 3 3 8 5 Muscle cramps 2 6 8 3 Anorexia 2 3 7 3 Table 4 lists adverse reactions that occurred in at least 2% of patients in pooled placebo-controlled trials who received either donepezil tablets 5 mg or 10 mg and for which the rate of occurrence was greater for patients treated with donepezil than with placebo. In general, adverse reactions occurred more frequently in female patients and with advancing age. Table 4. Adverse Reactions in Pooled Placebo-Controlled Clinical Trials in Mild to Moderate Alzheimer’s Disease Adverse Reaction Placebo (n=355) % Donepezil Tablet (n=747) % Percent of Patients with any Adverse Reaction 72 74 Nausea 6 11 Diarrhea 5 10 Headache 9 10 Insomnia 6 9 Pain, various locations 8 9 Dizziness 6 8 Accident 6 7 Muscle Cramps 2 6 Fatigue 3 5 Vomiting 3 5 Anorexia 2 4 Ecchymosis 3 4 Abnormal Dreams 0 3 Depression <1 3 Weight Loss 1 3 Arthritis 1 2 Frequent Urination 1 2 Somnolence <1 2 Syncope 1 2 Severe Alzheimer’s Disease (Donepezil Tablets 5 mg/day and 10 mg/day) Donepezil tablets have been administered to over 600 patients with severe Alzheimer’s disease during clinical trials of at least 6 months duration, including three double-blind, placebo-controlled trials, two of which had an open label extension. Adverse Reactions Leading to Discontinuation The rates of discontinuation from controlled clinical trials of donepezil tablets due to adverse reactions for the donepezil patients were approximately 12% compared to 7% for placebo patients. The most common adverse reactions leading to discontinuation, defined as those occurring in at least 2% of donepezil patients and at twice or more the incidence seen in placebo, were anorexia (2% vs. 1% placebo), nausea (2% vs. <1% placebo), diarrhea (2% vs. 0% placebo), and urinary tract infection (2% vs. 1% placebo). Most Common Adverse Reactions The most common adverse reactions, defined as those occurring at a frequency of at least 5% in patients receiving donepezil tablets and at twice or more the placebo rate, are diarrhea, anorexia, vomiting, nausea, and ecchymosis. These adverse reactions were often transient, resolving during continued donepezil treatment without the need for dose modification. Table 5 lists adverse reactions that occurred in at least 2% of patients in pooled placebo-controlled trials who received donepezil tablets 5 mg or 10 mg and for which the rate of occurrence was greater for patients treated with donepezil than with placebo. Table 5. Adverse Reactions in Pooled Controlled Clinical Trials in Severe Alzheimer’s Disease Adverse Reaction Placebo (n=392) % Donepezil Tablet (n=501) % Percent of Patients with any Adverse Reaction 73 81 Accident 12 13 Infection 9 11 Diarrhea 4 10 Anorexia 4 8 Vomiting 4 8 Nausea 2 6 Insomnia 4 5 Ecchymosis 2 5 Headache 3 4 Hypertension 2 3 Pain 2 3 Back Pain 2 3 Eczema 2 3 Hallucinations 1 3 Hostility 2 3 Increase in Creatine Phosphokinase 1 3 Nervousness 2 3 Fever 1 2 Chest Pain <1 2 Confusion 1 2 Dehydration 1 2 Depression 1 2 Dizziness 1 2 Emotional Lability 1 2 Hemorrhage 1 2 Hyperlipemia <1 2 Personality Disorder 1 2 Somnolence 1 2 Syncope 1 2 Urinary Incontinence 1 2 ADLARITY Transdermal System Study The ADLARITY clinical development program included an open-label study in 60 healthy subjects who received ADLARITY 5 mg/day for 5 weeks in Period 1 as a titration dose. In Periods 2 and 3, the subjects received either ADLARITY 10 mg/day for 5 weeks or oral donepezil tablet 10 mg/day for 5 weeks in a randomized, crossover fashion. The most common adverse reactions (incidence >3%) occurring in healthy subjects receiving ADLARITY 10 mg/day were headache (15%), application site pruritus (9%), muscle spasms (9%), insomnia (7%), abdominal pain (6%), application site dermatitis (6%), constipation (6%), diarrhea (4%), application site pain (4%), dizziness (4%), abnormal dreams (4%), and skin laceration (4%). Overall, the adverse reactions reported by healthy volunteers receiving the ADLARITY transdermal system were consistent with those reported by Alzheimer’s patients receiving oral donepezil tablets in clinical trials. Application Site Reactions Cases of skin irritation were captured after ADLARITY removal on an investigator-rated skin irritation scale. Skin irritation was observed, including erythema (64.6%), papules (16.0%), and edema (0.4%), following removal of 268 ADLARITY 10 mg/day transdermal systems; none of the ADLARITY transdermal systems were discontinued because of skin irritation. All application site adverse reactions were reported as mild. In a clinical study investigating the skin sensitizing potential of ADLARITY in 229 healthy subjects, 4 cases of potential sensitization were observed [ see Warnings and Precautions (5.1) ]. 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of donepezil. 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. Blood and Lymphatic System Disorders : hemolytic anemia Cardiac Disorders : heart block (all types), QTc prolongation, and torsade de pointes Gastrointestinal Disorders : abdominal pain Hepatobiliary Disorders : cholecystitis, hepatitis, pancreatitis Metabolism and Nutritional Disorders : hyponatremia Musculoskeletal and Connective Tissue Disorders : rhabdomyolysis Nervous System Disorders : convulsions, neuroleptic malignant syndrome Psychiatric Disorder : agitation, aggression, confusion, hallucinations Skin and Subcutaneous Tissue Disorders : rash