warnings and cautions
5 WARNINGS AND PRECAUTIONS • Risk of fluid and electrolyte abnormalities: Encourage adequate hydration, assess concurrent medications, and consider laboratory assessments prior to and after use. ( 5.1 , 5.2 , 7.1 ) • Cardiac arrhythmias: Consider pre-dose and post-colonoscopy ECGs in patients at increased risk. ( 5.2 ) • Seizures: Use caution in patients with a history of seizures and patients at increased risk of seizure, including medications that lower the seizure threshold. ( 5.3 , 7.1 ) • Patients with mild to moderate renal impairment or taking concomitant medications that affect renal function: Use caution, ensure adequate hydration and consider testing. ( 4 , 5.4 , 7.1 ) • Mucosal ulcerations: Consider potential for mucosal ulcerations when interpreting colonoscopy findings in patients with known or suspected inflammatory bowel disease. ( 5.5 ) • Suspected GI obstruction or perforation: Rule out diagnosis before administration. ( 4 , 5.6 ) • Patients at risk for aspiration: Observe during administration. ( 5.7 ) • Risk of vomiting and other GI complications with ingestion of undissolved powder: Dissolve each packet in 5 ounces of cold water and administered at separate times according to the dosing regimen. ( 2.3 , 2.4 , 5.8 ) 5.1 Serious Fluid and Electrolyte Abnormalities Advise patients to hydrate adequately before, during, and after the use of sodium picosulfate, magnesium oxide and anhydrous citric acid. Use caution in patients with congestive heart failure when replacing fluids. If a patient develops significant vomiting or signs of dehydration including signs of orthostatic hypotension after taking sodium picosulfate, magnesium oxide and anhydrous citric acid, consider performing post-colonoscopy lab tests (electrolytes, creatinine, and BUN) and treat accordingly. Approximately 20% of adult patients in both arms (sodium picosulfate, magnesium oxide and anhydrous citric acid, 2L of PEG + E plus two x 5 mg bisacodyl tablets) of clinical trials of sodium picosulfate, magnesium oxide and anhydrous citric acid had orthostatic changes (changes in blood pressure and/or heart rate) on the day of colonoscopy. In adult clinical trials orthostatic changes were documented up to seven days post colonoscopy. In a single study of patients 9 to 16 years of age, approximately 20% of patients in sodium picosulfate, magnesium oxide and anhydrous citric acid arms had orthostatic changes (changes in blood pressure and/or heart rate) compared with approximately 7% of those who received the comparator (PEG) [see Clinical Studies ( 14 )]. These changes occurred up to five days post colonoscopy. Fluid and electrolyte disturbances can lead to serious adverse reactions including cardiac arrhythmias or seizures and renal impairment. Correct fluid and electrolyte abnormalities before treatment with sodium picosulfate, magnesium oxide and anhydrous citric acid [see Dosage and Administration ( 2.1 )] . In addition, use caution when prescribing sodium picosulfate, magnesium oxide and anhydrous citric acid for patients who have conditions or who are using medications that increase the risk for fluid and electrolyte disturbances or that may increase the risk of adverse events of seizure, arrhythmia, and renal impairment [see Drug Interactions ( 7.1 )]. 5.2 Cardiac Arrhythmias There have been rare reports of serious arrhythmias associated with the use of ionic osmotic laxative products for bowel preparation. Use caution when prescribing sodium picosulfate, magnesium oxide and anhydrous citric acid for patients at increased risk of arrhythmias (e.g., patients with a history of prolonged QT, uncontrolled arrhythmias, recent myocardial infarction, unstable angina, congestive heart failure, or cardiomyopathy). Consider pre-dose and post-colonoscopy ECGs in patients at increased risk of serious cardiac arrhythmias. 5.3 Seizures There have been reports of generalized tonic-clonic seizures with the use of bowel preparation products in patients with no prior history of seizures. The seizure cases were associated with electrolyte abnormalities (e.g., hyponatremia, hypokalemia, hypocalcemia, and hypomagnesemia) and low serum osmolality. The neurologic abnormalities resolved with correction of fluid and electrolyte abnormalities. Use caution when prescribing sodium picosulfate, magnesium oxide and anhydrous citric acid for patients with a history of seizures and in patients at risk of seizure, such as patients taking medications that lower the seizure threshold (e.g., tricyclic antidepressants), patients withdrawing from alcohol or benzodiazepines, or patients with known or suspected hyponatremia [see Adverse Reactions ( 6.2 )]. 5.4 Use in Patients with Renal Impairment Sodium picosulfate, magnesium oxide and anhydrous citric acid is contraindicated in patients with severe renal impairment (creatinine clearance less than 30 mL/min), accumulation of magnesium in plasma may occur [see Contraindications ( 4 )]. As with other magnesium containing bowel preparations, use caution when prescribing sodium picosulfate, magnesium oxide and anhydrous citric acid for patients with mild to moderate renal impairment or patients taking concomitant medications that may affect renal function (such as diuretics, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, or non-steroidal anti-inflammatory drugs) [see Drug Interactions ( 7.1 )]. These patients may be at increased risk for renal injury. Advise these patients of the importance of adequate hydration before, during and after the use of sodium picosulfate, magnesium oxide and anhydrous citric acid. Consider performing baseline and post-colonoscopy laboratory tests (electrolytes, creatinine, and BUN) in these patients. 5.5 Colonic Mucosal Ulceration, Ischemic Colitis and Ulcerative Colitis Osmotic laxatives may produce colonic mucosal aphthous ulcerations and there have been reports of more serious cases of ischemic colitis requiring hospitalization. Concurrent use of additional stimulant laxatives with sodium picosulfate, magnesium oxide and anhydrous citric acid may increase this risk. The potential for mucosal ulcerations should be considered when interpreting colonoscopy findings in patients with known or suspected inflammatory bowel disease [see Adverse Reactions ( 6.2 )]. 5.6 Use in Patients with Significant Gastrointestinal Disease If gastrointestinal obstruction or perforation is suspected, perform appropriate diagnostic studies to rule out these conditions before administering sodium picosulfate, magnesium oxide and anhydrous citric acid [see Contraindications ( 4 )]. Use with caution in patients with severe active ulcerative colitis. 5.7 Aspiration Patients with impaired gag reflex are at risk for regurgitation or aspiration during the administration of sodium picosulfate, magnesium oxide and anhydrous citric acid. Observe these patients during the administration of sodium picosulfate, magnesium oxide and anhydrous citric acid. Use with caution in these patients. 5.8 Risk of Vomiting and Other Gastrointestinal Complications with Ingestion of Undissolved Powder Each packet must be dissolved in 5 ounces of cold water and administered at separate times according to the dosing regimen [see Dosage and Administration ( 2.3, 2.4 )] . Ingestion of additional water is important to patient tolerance. Direct ingestion of the undissolved powder may increase the risk of nausea, vomiting, dehydration, and electrolyte disturbances.