Riva-Magnesium Oxide, Citric Acid and Sodium Picosulfate Product Monograph

SUMMARY PRODUCT INFORMATION

General

The active components of RIVA-MAGNESIUM OXIDE, CITRIC ACID AND SODIUM PICOSULFATE are sodium picosulfate and magnesium citrate.

Picosulfate (a pro-drug) is a stimulant cathartic active locally in the colon.

Magnesium citrate (magnesium oxide and citric acid) acts as an osmotic laxative by retaining moisture in the colon. The action is of a powerful “washing out” effect combined with peristaltic stimulation to clear the bowel prior to radiography, colonoscopy or surgery. Full doses of the saline cathartics (15 g of magnesium sulfate or its equivalent) produces a semi- fluid or watery evacuation within 3-6 hours or less.

The product is not intended for routine use as a laxative.

Some absorption of the component ions of the saline cathartics does occur, and in certain instances they may produce systemic toxicity. This is especially true for magnesium salts, since 20% or more of the administered cation is absorbed. If renal function is normal, the absorbed magnesium is rapidly excreted. However, if a magnesium cation is given to an individual with impaired renal function, the accumulation of magnesium ion in the body fluids may be sufficient to cause magnesium intoxication.

In most instances, salts that gain access to the systemic circulation are rapidly excreted by the kidneys.

INDICATIONS AND CLINICAL USE

RIVA-MAGNESIUM OXIDE, CITRIC ACID AND SODIUM PICOSULFATE is indicated for clearance of the bowel prior to x-ray examination, endoscopy or surgery.

CONTRAINDICATIONS

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.

Use with caution in patients on drugs that might affect water and/or electrolyte balance e.g. diuretics, corticosteroids, lithium [see Drug Interactions and Adverse Reactions].

RIVA-MAGNESIUM OXIDE, CITRIC ACID AND SODIUM PICOSULFATE may modify the absorption of regularly prescribed oral medication and should be used with caution e.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. Constipating drugs (e.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 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. Seizures were associated with electrolyte abnormalities (e.g. hyponatremia, hypokalemia, hypocalcemia and hypomagnesemia) and low serum osmolality. Neurologic abnormalities resolved with correction of fluid and electrolyte abnormalities.

Use caution when prescribing RIVA-MAGNESIUM OXIDE, CITRIC ACID AND SODIUM PICOSULFATE 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 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. Use caution when prescribing RIVA-MAGNESIUM OXIDE, CITRIC ACID AND SODIUM PICOSULFATE 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).

Colonic Mucosal Ulceration, Ischemic Colitis and Ulcerative Colitis

Osmotic laxatives may produce colonic mucosal aphthous ulceration and there have been reports of more serious cases of ischemic colitis requiring hospitalization. Concurrent use of additional stimulant laxatives with RIVA-MAGNESIUM OXIDE, CITRIC ACID AND SODIUM PICOSULFATE may increase this risk. The potential for mucosal ulceration should be considered when interpreting colonoscopy findings in patients with known or suspected inflammatory bowel disease [see Adverse Reactions].

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 RIVA-MAGNESIUM OXIDE, CITRIC ACID AND SODIUM PICOSULFATE. Use with caution in patients with severe active ulcerative colitis.

Aspiration

Patients with an impaired gag reflex and patients prone to regurgitation or aspiration should be observed during the administration of RIVA-MAGNESIUM OXIDE, CITRIC ACID AND SODIUM PICOSULFATE. Use with caution in these patients.

Not for Direct Ingestion

Each packet must be dissolved in 150 mL (5 oz) of cold water and administered at separate times according to the dosing regimen. Direct ingestion of the undissolved powder may increase the risk of nausea, vomiting, dehydration, and electrolyte disturbances.

Pregnancy and Lactation

Reproduction studies with sodium picosulfate performed in animals have revealed no evidence of a harmful action on the fetus. However, clinical experience of the use of RIVA-MAGNESIUM OXIDE, CITRIC ACID AND SODIUM PICOSULFATE during pregnancy is limited and caution should be observed, particularly during the first trimester.

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when RIVA-MAGNESIUM OXIDE, CITRIC ACID AND SODIUM PICOSULFATE is administered to a nursing woman.

Geriatrics (≥ 65 years of age)

In controlled clinical trials of bowel preparations like magnesium oxide, citric acid and sodium picosulfate powder for oral solution, 215 of 1201 (18%) patients were 65 years of age or older. The overall incidence of treatment-emergent adverse events was similar among patients ≥65 years of age (73%) and patients <65 years of age (71%).

ADVERSE REACTIONS

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.

DRUG INTERACTIONS

As a purgative, RIVA-MAGNESIUM OXIDE, CITRIC ACID AND SODIUM PICOSULFATE increases the gastrointestinal transit rate therefore the absorption of other orally administered medicines (e.g. anti-epileptics, contraceptives, anti- diabetics, antibiotics) may be modified during the treatment period (see Warnings and Precautions for Use).

The efficacy of RIVA-MAGNESIUM OXIDE, CITRIC ACID AND SODIUM PICOSULFATE is lowered by bulk-forming laxatives.

Drugs That May Increase Risks of Fluid and Electrolyte Abnormalities

Use caution when prescribing RIVA-MAGNESIUM OXIDE, CITRIC ACID AND SODIUM PICOSULFATE for patients with conditions or who are using medications that increase the risk for fluid and electrolyte disturbances, or may increase the risk of seizure, arrhythmias, and prolonged QT in the setting of fluid and electrolyte abnormalities. This includes patients receiving drugs which may be associated with hypokalemia (such as diuretics or corticosteroids, or drugs where hypokalemia is a particular risk, such as cardiac glycosides) or hyponatremia. Use caution when RIVA-MAGNESIUM OXIDE, CITRIC ACID AND SODIUM PICOSULFATE is used in patients on non-steroidal anti-inflammatory drugs (NSAIDS) or drugs known to induce Antidiuretic Hormone Secretion (SIADH), such as tricyclic antidepressants, selective serotonin re-uptake inhibitors, antipsychotic drugs and carbamazepine, as these drugs may increase the risk of water retention and/or electrolyte imbalance. Consider additional patient evaluations as appropriate [see Adverse Reactions].

Potential for Altered Drug Absorption

Oral medication administered within one hour of the start of administration of RIVA-MAGNESIUM OXIDE, CITRIC ACID AND SODIUM PICOSULFATE solution may be flushed from the GI tract and the medication may not be absorbed.

Tetracycline and fluoroquinolone antibiotics, digoxin, chlorpromazine and penicillamine, should be taken at least 2 hours before and not less than 6 hours after administration of RIVA-MAGNESIUM OXIDE, CITRIC ACID AND SODIUM PICOSULFATE to avoid chelation with magnesium.

DOSAGE AND ADMINISTRATION

PRE-DOSING INSTRUCTIONS:

• At least 3 days prior to the patients procedure, advise the patient to not consume seeds or nuts due to digestive residue or fresh fruits or raw vegetables (i.e. no salads) and no multigrain bread

ADULT DOSING INSTRUCTIONS:

Fill a mug with 150 ml (5 oz) of cold water. Empty contents of one sachet in the mug (rarely, mixture may heat up - allow to cool before drinking). Stir for 2 -3 minutes until completely dissolved. The solution should now become an off-white, cloudy liquid. Following each dose, advise the patient to drink 1.5 to 2 Litres of a variety of clear fluids over 4 hours.

Advise the patient TO NOT DRINK JUST WATER ALONE. Patients should also drink a balanced electrolyte solution. Drinking only water to replace the fluid losses may lead to electrolyte imbalance, particularly to hyponatremia and possibly seizures.

Recommended clear fluids include Gatorade^†, fruit juices, clear both, tea or coffee (black, sweetened to taste, no milk, cream or soy), clear sodas (e.g. ginger ale), plain Jell-O^† (not red or purple), Popsicles^† (not red or purple) and water.

Diabetics can use a fibre-free supplement/meal replacement.

One day before the procedure the patient should have clear fluids ONLY and no solid food.

Morning colonoscopy - before 12:00 pm (noon);

One day before procedure: Take 1 sachet (first dose) at 5:00 pm followed by 1.5 to 2 Litres of a variety of clear fluids.

Six (6) hours prior to procedure: Take 1 sachet (second dose) followed by 1.5 to 2 Litres of a variety of clear fluids.

No fluid should be taken at least 2 hours prior to the procedure.

Afternoon colonoscopy - 12:00 pm (noon) or later:

One day before procedure: Take 1 sachet (first dose) at 7:00 pm followed by 1.5 to 2 Litres of a variety of clear fluids.

On the same day as procedure: Take 1 sachet (second dose) in the morning, 6 hours prior to procedure (time to be confirmed by the physician), followed by 1.5 to 2 Litres of a variety of clear fluids.

In order to replace fluid lost from the body, advise patients to drink plenty of clear fluids throughout the treatment with RIVA-MAGNESIUM OXIDE, CITRIC ACID AND SODIUM PICOSULFATE until bowel movements have ceased.

No fluid should be taken at least 2 hours prior to the procedure.

PEDIATRIC DOSING INSTRUCTIONS:

Fill a mug with 150 ml (5 oz) of cold water. Empty contents of one sachet in the mug (rarely, mixture may heat up - allow to cool before drinking). Stir until completely dissolved.

It is recommended that RIVA-MAGNESIUM OXIDE, CITRIC ACID AND SODIUM PICOSULFATE should be given at least 5-6 hours before bedtime to avoid interference with sleep. Splitting the dose over two days is recommended as follows:

(1 to 6 years old): One day before procedure: Take ¼ of the prepared solution as per DOSING INSTRUCTIONS (first dose) at 6:00 pm followed by one cup of clear liquid (250 mL, 8 oz) every hour while the child is awake. No solid food should be taken after 6:00 PM.

On the same day as procedure: Take ¼ of the prepared solution as per DOSING INSTRUCTIONS (second dose) at 8:00 am, followed by one cup of clear liquid (250 mL, 8 oz) every hour up to 2 hours prior to the child’s procedure.

(6-12 years old): One day before procedure: Take ½ of the prepared solution as per DOSING INSTRUCTIONS (first dose) at 6:00 pm followed by one cup of clear liquid (250 mL, 8 oz) every hour while the child is awake. No solid food should be taken after 6:00 PM.

On the same day as procedure: Take ½ of the prepared solution as per DOSING INSTRUCTIONS (second dose) at 8:00 am, followed by one cup of clear liquid (250 mL, 8 oz) every hour up to 2 hours prior to the child’s procedure.

In order to replace fluid lost from the body, it is important to drink plenty of clear fluids throughout the treatment with RIVA-MAGNESIUM OXIDE, CITRIC ACID AND SODIUM PICOSULFATE until bowel movements have ceased. In general, patients should drink about 250 mL of water or clear fluid and/or a balanced electrolyte solution (e.g.: Gastrolyte^®, Pedialyte^®) every hour while they feel the effects of RIVA-MAGNESIUM OXIDE, CITRIC ACID AND SODIUM PICOSULFATE.

No fluid should be taken at least 2 hours prior to the procedure.

OVERDOSAGE

For the most recent information in the management of a suspected drug overdose, contact your regional poison control centre or Health Canada's toll-free number, 1-844 POISON-X (1-844-764-7669).

Overdose would lead to profuse diarrhoea. Treatment is by general supportive measures and correction of fluid and electrolyte balance.

ACTION AND CLINICAL PHARMACOLOGY

Picosulfate (a pro-drug) is a stimulant cathartic active locally in the colon.

Magnesium citrate (magnesium oxide and citric acid) acts as an osmotic laxative by retaining moisture in the colon. The action is of a powerful “washing out” effect combined with peristaltic stimulation to clear the bowel prior to radiography, colonoscopy or surgery. Full doses of the saline cathartics (15 g of magnesium sulfate or its equivalent) produces a semi-fluid of watery evacuation within 3-6 hours or less.

The product is not intended for routine use as a laxative.

Some absorption of the component ions of the saline cathartics does occur, and in certain instances they may produce systemic toxicity. This is especially true for magnesium salts, since 20% or more of the administered cation is absorbed. If renal function is normal, the absorbed magnesium is rapidly excreted. However, if a magnesium cation is given to an individual with impaired renal function, the accumulation of magnesium ion in the body fluids may be sufficient to cause magnesium intoxication.

In most instances, salts that gain access to the systemic circulation are rapidly excreted by the kidneys.

STORAGE AND STABILITY

Store at 15 °C - 30 °C.

Keep out of the reach of children.

DOSAGE FORMS, COMPOSITION AND PACKAGING

RIVA-MAGNESIUM OXIDE, CITRIC ACID AND SODIUM PICOSULFATE is supplied in a carton containing 2 sachets, each holding 16.1 grams of powder for oral solution. Each packet contains 10 mg sodium picosulfate, 3.5 g magnesium oxide and 12 g anhydrous citric acid. The excipients include lactose anhydrous, potassium bicarbonate, sodium saccharin, orange flavour.

REFERENCES

1. 1. Prescribing Information for PICO-SALAX^®, Ferring Pharmaceuticals, Control No. 288383, Date of revision: DEC 18, 2024.