warnings and cautions
5 WARNINGS AND PRECAUTIONS Risk of fluid and electrolyte abnormalities, arrhythmia, seizures, and renal impairment : Encourage adequate hydration, assess concurrent medications, and consider laboratory assessments prior to and after use. ( 5.1 , 5.2 , 5.3 , 5.4 , 7.1 ) Use in patients with renal impairment or taking concomitant medications that affect renal function : Use caution, ensure adequate hydration, and consider testing. ( 4 , 5.3 , 7.1 ) Syncope : Resulted in serious outcomes including falls, head injuries, and fractures; encourage adequate hydration. ( 5.5 ) Mucosal ulcerations : Consider potential for mucosal ulcerations when interpreting colonoscopy findings in patients with known or suspected inflammatory bowel disease. ( 5.6 ) Suspected GI obstruction or perforation : Rule out diagnosis before administration. ( 4 , 5.7 ) Patients at risk for aspiration : Observe during administration. ( 5.8 ) 5.1 Serious Fluid and Electrolyte Abnormalities Advise patients to hydrate adequately before, during, and after the use of CLENPIQ. 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 CLENPIQ, consider performing post-colonoscopy lab tests (electrolytes, creatinine, and BUN) and treat accordingly. Approximately 20% of patients in both arms (sodium picosulfate, magnesium oxide, and anhydrous citric acid, or 2 L of PEG + E plus two × 5-mg bisacodyl tablets) of clinical trials of another oral sodium picosulfate, magnesium oxide, and anhydrous citric acid product had orthostatic changes in blood pressure and/or heart rate on the day of colonoscopy and up to seven days post colonoscopy. In a single study of patients 9 to 16 years of age, approximately 20% of patients who received another oral product of sodium picosulfate, magnesium oxide, and anhydrous citric acid 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, seizures, renal impairment, and syncope [see Warnings and Precautions (5.5) ] . Correct fluid and electrolyte abnormalities before treatment with CLENPIQ. Advise patients to consume a variety of clear liquids (e.g., balanced electrolyte solution), and not only water after each dose of CLENPIQ. In addition, use caution when prescribing CLENPIQ 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 seizure, arrhythmia, and renal impairment [see Drug Interactions (7.1) ] . 5.2 Seizures There have been reports of generalized tonic-clonic seizures and/or loss of consciousness 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 CLENPIQ 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, patients with known or suspected hyponatremia [see Adverse Reactions (6.2) ] . 5.3 Use in Patients with Renal Impairment CLENPIQ is contraindicated in patients with severe renal impairment (creatinine clearance less than 30 mL/min), accumulation of magnesium in plasma may occur. Use caution when prescribing CLENPIQ 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 CLENPIQ. Consider performing baseline and post-colonoscopy laboratory tests (electrolytes, creatinine, and BUN) in these patients. 5.4 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 CLENPIQ 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. 5.5 Syncope Syncope has been reported with CLENPIQ in the postmarketing setting. Some cases were serious events that included falls with associated head injuries or fractures requiring hospitalization. In some cases, electrolyte abnormalities were also present (e.g., hyponatremia and hypokalemia). Cases have been reported after one or two CLENPIQ doses and many of these cases occurred within 12 hours of dosing. Patients should be aware of the risk of syncope during treatment and adequately hydrate before, during, and after the use of CLENPIQ. Advise patients to consume a variety of clear liquids (e.g., balanced electrolyte solution), not only water after each dose of CLENPIQ and to get up gradually from a lying or sitting position [see Warnings and Precautions (5.1) ] . 5.6 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 CLENPIQ may increase this risk. Consider the potential for mucosal ulcerations when interpreting colonoscopy findings in patients with known or suspected inflammatory bowel disease [see Adverse Reactions (6.2) ] . 5.7 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 CLENPIQ [see Contraindications (4) ] . Use with caution in patients with severe active ulcerative colitis. 5.8 Aspiration Patients with impaired gag reflex are at risk for regurgitation or aspiration during the administration of CLENPIQ. Observe these patients during the administration of CLENPIQ.