Granisetronside effects

The following are serious or otherwise clinically significant adverse reactions reported in other sections of labeling: Progressive ileus and gastric distention Serotonin syndrome Skin reactions Increased drug exposure with use of external heat sources Phototoxicity with ultraviolet light exposure [se Warnings and Precautions ] The most common adverse reaction (≥ 3%) is constipation. To report SUSPECTED ADVERSE REACTIONS, contact Cumberland Pharmaceuticals Inc. at 1-877-484-2700 (X 225) 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 clinical practice. The safety of SANCUSO was evaluated in a total of 404 patients undergoing chemotherapy who participated in two double-blind, comparator studies with transdermal system treatment durations of up to 7 days. The control groups included a total of 406 patients who received a daily dose of 2 mg oral granisetron, for 1 to 5 days. Adverse reactions occurred in 9% (35/404) of patients receiving SANCUSO and 7% (29/406) of patients receiving oral granisetron. The most common adverse reaction was constipation that occurred in 5% of patients in the SANCUSO group and 3% of patients in the oral granisetron group. Table 1 lists the adverse reactions that occurred in at least 3% of patients treated with SANCUSO or oral granisetron.

Table 1: Incidence of Adverse Reactions in Double-Blind, Active Comparator Controlled Studies in Cancer Patients Receiving Chemotherapy (³ 3% in either group) SANCUSO Transdermal System Oral granisetron Body System N=404 N=406 Preferred Term (%) (%) Gastrointestinal disorders Constipation 5 3 Nervous system disorders Headache 1 3 5-HT 3 receptor antagonists, such as granisetron, may be associated with arrhythmias or ECG abnormalities. Three ECGs were performed on 588 patients in a randomized, parallel group, double-blind, double-dummy study: at baseline before treatment, the first day of chemotherapy, and 5 to 7 days after starting chemotherapy. QTcF prolongation greater than 450 milliseconds was seen in a total of 11 (1.9%) patients after receiving granisetron, 8 (2.7%) on oral granisetron, and 3 (1.1%) on the transdermal system. No new QTcF prolongation greater than 480 milliseconds was observed in any patient in this study. No arrhythmias were detected in this study. Adverse reactions reported in clinical trials with other formulations of granisetron include the following: Gastrointestinal: abdominal pain, diarrhea, constipation, elevation of ALT and AST levels, nausea and vomiting Cardiovascular: hypertension, hypotension, angina pectoris, atrial fibrillation and syncope have been observed rarely Central Nervous System: dizziness, insomnia, headache, anxiety, somnolence and asthenia Hypersensitivity: rare cases of hypersensitivity reactions, sometimes severe (e.g. anaphylaxis, shortness of breath, hypotension, urticaria) have been reported Other: fever; events often associated with chemotherapy have also been reported: leucopenia, decreased appetite, anemia, alopecia, thrombocytopenia.

6.2 Postmarketing

Experience The following adverse reactions have been identified during post approval use of SANCUSO. 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. General Disorders and Administration Site Conditions: Application site reactions (pain, pruritus, erythema, rash, irritation, vesicles, burn, discoloration, urticaria); transdermal system non-adhesion.

Cardiac Disorders: bradycardia, chest pain, palpitations, sick sinus syndrome