RIVA-MAGNESIUM OXIDE, CITRIC ACID AND SODIUM PICOSULFATE

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 clinical trials of another drug and may not reflect the rates observed in practice.

In randomized, multicenter, controlled clinical trials, nausea, headache and vomiting were the most common adverse reactions (>1%) following administration of bowel preparations like magnesium oxide, citric acid and sodium picosulfate powder for oral solution.

The patients were not blinded to the study drug. Since abdominal bloating, distension, pain/cramping and watery diarrhea are known to occur in response to colon cleansing preparations, these effects were documented as adverse events in the clinical trials only if they required medical intervention (such as a change in study drug or led to study discontinuation, therapeutic or diagnostic procedures, met the criteria for a serious adverse event), or showed clinically significant worsening during the study that was not in the frame of the usual clinical course, as determined by the investigator.

Post-marketing Experience The following spontaneous reports have been identified during use of formulations similar to RIVA-MAGNESIUM OXIDE, CITRIC ACID AND SODIUM PICOSULFATE. Because these events 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.

Allergic reactions Cases of hypersensitivity reactions including rash, urticaria and purpura have been reported. Electrolyte abnormalities There have been reports of hypokalemia, hyponatremia and hypermagnesemia with the use of bowel preparations like magnesium oxide, citric acid and sodium picosulfate powder for oral solution for colon preparation prior to colonoscopy.

Gastrointestinal Abdominal pain, diarrhea, fecal incontinence and proctalgia have been reported with the use of bowel preparations like magnesium oxide, citric acid and sodium picosulfate powder for oral solution for colon preparation prior to colonoscopy.

There have been isolated reports of reversible aphthoid ileal ulcers. Ischemic colitis has been reported with the use of bowel preparations like magnesium oxide, citric acid and sodium picosulfate powder for oral solution for colon preparation prior to colonoscopy.

However, a causal relationship between these ischemic colitis cases and the use of bowel preparations like magnesium oxide, citric acid and sodium picosulfate powder for oral solution has not been established. Neurologic There have been reports of generalized tonic-clonic seizures associated with and without hyponatremia in epileptic patients.

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RIVA-MAGNESIUM OXIDE, CITRIC ACID AND SODIUM PICOSULFATE is contraindicated in: • Patients who are hypersensitive to this drug or to any ingredient in the formulation or component of the container. For a complete listing, see the DOSAGE FORMS, COMPOSITION AND PACKAGING section of this document.

• Patients with congestive cardiac failure, gastric retention, gastro-intestinal ulceration, toxic colitis, toxic megacolon, ileus, nausea and vomiting, acute surgical abdominal conditions such as acute appendicitis and known or suspected gastro-intestinal obstruction or perforation.

• Patients with severely reduced renal function, accumulation of magnesium in plasma may occur. Another preparation should be used in such cases. WARNINGS AND PRECAUTIONS General Care should also be taken in patients with recent gastro-intestinal surgery, renal impairment, heart disease or inflammatory bowel disease.

g. diuretics, corticosteroids, lithium [see Drug Interactions and Adverse Reactions]. g. there have been isolated reports of seizures in patients on antiepileptics, with previously controlled epilepsy [see Drug Interactions and Adverse Reactions].

Patients should avoid taking oral iron preparations for a week before colonoscopy. g. cholinergics, opioids) should be suspended for a few days before the procedure, after consulting with your doctor. An inadequate oral intake of water and electrolytes could create clinically significant deficiencies, particularly in less fit patients.

In this regard, the elderly, debilitated individuals and patients at risk of hypokalaemia may need particular attention. Prompt corrective action should be taken to restore fluid/electrolyte balance in patients with signs or symptoms of hyponatraemia.

The period of bowel cleansing should not exceed 24 hours because longer preparation time may increase the risk of water and electrolyte imbalance. Serious Fluid and Serum Chemistry Abnormalities Advise patients to hydrate adequately before, during and after the use of RIVA-MAGNESIUM OXIDE, CITRIC ACID AND SODIUM PICOSULFATE.

Use caution in patients with congestive heart failure when replacing fluids. If a patient develops significant vomiting or signs RIVA-MAGNESIUM OXIDE, CITRIC ACID AND SODIUM PICOSULFATE 5 of 15 of dehydration including signs of orthostatic hypotension after taking RIVA-MAGNESIUM OXIDE, CITRIC ACID AND SODIUM PICOSULFATE, consider performing post- colonoscopy lab tests (electrolytes, creatinine and BUN) and treat accordingly.

Approximately 20% of patients in clinical trials had orthostatic changes (changes in blood pressure and/or heart rate) on the day of colonoscopy; however these changes were not clinically relevant. In clinical trials orthostatic changes were documented out to seven days post colonoscopy [see Adverse Reactions].

Fluid and electrolyte disturbances can lead to serious adverse events including cardiac arrhythmias or seizures and renal impairment. Fluid and electrolyte abnormalities should be corrected before treatment with RIVA-MAGNESIUM OXIDE, CITRIC ACID AND SODIUM PICOSULFATE.

In addition, use caution when prescribing RIVA-MAGNESIUM OXIDE, CITRIC ACID AND SODIUM PICOSULFATE 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.

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. g. hyponatremia, hypokalemia, hypocalcemia and hypomagnesemia) and low serum osmolality.

Neurologic abnormalities resolved with correction of fluid and electrolyte abnormalities. g. tricyclic antidepressants), patients withdraw from alcohol or benzodiazepines, patients with known or suspected hyponatremia. [see Adverse Reactions] Use in Patients with Renal Impairment As in other magnesium containing bowel preparations, use caution when prescribing RIVA- MAGNESIUM OXIDE, CITRIC ACID AND SODIUM PICOSULFATE for patients with impaired renal function 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).

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 RIVA-MAGNESIUM OXIDE, CITRIC ACID AND SODIUM PICOSULFATE. Consider performing baseline and post-colonoscopy laboratory tests (electrolytes, creatinine and BUN) in these patients.

In patients with severely reduced renal function (creatinine clearance < 30 mL/min), accumulation of magnesium in plasma may occur. Cardiac Arrhythmias There have been rare reports of serious arrhythmias associated with the use of ionic osmotic laxative products for bowel preparation.

g. patients with a history of prolonged QT, uncontrolled arrhythmias, recent myocardial infarction, unstable angina, congestive heart failure, or cardiomyopathy). Colonic Mucosal Ulceration, Ischemic Colitis and Ulcerative Colitis Osmotic laxatives may produce colonic mucosal aphthous ulceration […]