COLOPREP Tablet Ref.[50583] Active ingredients: Sodium phosphate

In rare cases, this medicine was associated with severe and potentially fatal electrolyte disorders, in elderly patients. The benefit/risk ratio of this medicine must be carefully assessed before use in this population at risk.

Before initiating the treatment, it is necessary to ensure the absence of known contraindications and to stress on the importance of appropriate hydration. For at risk populations, it is important to check serum electrolyte concentrations before and after treatment (see below and section 4.2 and 4.3).

This medicine should be used with caution in patients with:

• a history of renal insufficiency, history of acute phosphate nephropathy, known or suspected electrolyte disorders, arrhythmias, cardiomyopathy, in patients within three months of an acute myocardial infarction or cardiac surgery, including coronary artery bypass graft surgery, patients using diuretics, angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs) or NSAIDs.
• risk factors for electrolyte disorders (e.g., dehydration, gastric retention, inability to drink sufficient quantities of liquids, hypertension or other diseases treated by medicines that can induce dehydration, see below), hypotension with clinical consequences or associated with hypovolemia, or in the elderly or weakened patients. In these patients at risk, serum electrolyte including sodium, potassium, calcium, chloride, bicarbonate, phosphate, urea and creatinine assessment should be performed before and after treatment.
• risk factors for hyponatremia, e.g. SIADH, in adequately treated hypothyroidism, adrenal insufficiency or with risk factors for development of tonic-clonic seizures, e.g. a history of seizures, use of drugs that lower the seizure threshold such as tricyclic antidepressants or withdrawal from alcohol or benzodiazepines.
• intestinal hypomotility, history of gastrointestinal surgery or who have other diseases predisposing to intestinal hypomotility. In patient with colostomy or ileostomy or being on a low salt diet, the medicine must be used with caution becausede hydration, electrolytes or acid-base imbalance may occur.
• in diabetic patients as the recommended liquid diet during the period of administration prior to the procedure may affect blood glucose levels, requiring adjustment of antidiabetic medication or insulin.

Electrolyte disorders

Serum sodium and phosphate may increase and serum calcium and potassium may decrease, therefore, hypernatraemia, hyperphosphataemia, hypocalcaemia, hypokalaemia and acidosis may occur.

Patients should be advised to drink sufficient quantities of clear liquids or water when taking this medicine. Inadequate fluid intake, as with any effective purgative, may lead to dehydration and hypovolemia, which may be exacerbated by vomiting, loss of appetite or the use of diuretics, angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs) and nonsteroidal anti-inflammatory drugs (NSAIDs).

However it is recommended not to drink too much liquid in order to avoid overhydration (water intoxication). If a patient experiences one or more of any of the following symptoms, they must be advised not drink any further liquid and contact a doctor immediately. Signs and/symptoms which might indicate water intoxication in particular are nausea and vomiting, headache, blurred vision, twitching, slowed breathing, change in personality or bizarre behaviour, (hallucinations, and confusion or disorientation). If left untreated, overhydration can lead to dangerously low levels of sodium in the blood (hyponatremia). This can cause more severe symptoms, such as, muscle weakness, spasms or cramps, seizures and unconsciousness.

Renal disease and acute phosphate nephropathy

There have been very rare, but serious reports of acute phosphate nephropathy associated with transient renal failure in patients who received oral sodium phosphate products for colon cleansing prior to colonoscopy. The time of onset is typically within days; however, in some cases, the diagnosis of these events has been delayed up to several months after ingestion of these products. The majority of cases occurred in elderly women taking anti-hypertensive agents and other drugs such as diuretics or NSAIDs which can cause dehydration. Patient hydration should first be assessed by identifying those who are predisposed to dehydration or those taking drugs that may decrease the glomerular filtration rate, such as angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), before using laxative preparations. Patients should be monitored appropriately. When prescribing this medicine, special attention must be paid to the contraindications and adequate hydration of the patient.

Prolonged QT and cardiac arrhytmia

A mild prolongation of the QT interval may rarely occur because of electrolyte imbalance such as hypocalcaemia or hypokalaemia. This medicine should be used with caution in patients who are taking medications known to prolong the QT interval. Electrolyte abnormalities such as hypernatraemia, hyperphosphataemia, hypokalaemia or hypocalcaemia should be corrected before treatment with this medicine.

Seizures

There have been rare reports of generalised tonic-clonic seizures and/or loss of consciousness associated with use of sodium phosphate products in patients with no prior history of seizures. The seizure cases were associated with electrolyte abnormalities (e.g., hyponatremia, hypokaliemia, hypocalcemia, and hypomagnesemia) and low serum osmolality. The neurologic abnormalities resolved with correction of fluid and electrolyte abnormalities.

Colon aphtous ulcerations

Single or multiple aphthous ulcerations, located in the sigmoid or rectum were observed by endoscopy. They consist in either lymphoid follicle or discrete inflammatory in filtrates or epithelial abnormalities observed following the use of the bowel preparation. These anomalies have no clinical relevance and disappear spontaneously. These findings should be considered in patients with known or suspected inflammatory bowel disease.

Risk of ischaemic colitis

Severe cases of ischaemic colitis requiring hospitalisation have been reported. Therefore, this diagnosis should be considered in the event of severe and/or persistent abdominal pain with or without rectal bleeding after the administration of this medicine.

This medicinal product contains 10 016 mg of sodium per course of treatment, equivalent to 500% of the WHO recommended maximum daily intake of 2 g sodium for an adult. A course of treatment consists of 32 tablets of Coloprep. This should be taken into consideration by patients on a controlled sodium diet.

Patients should be advised that they will have frequent and watery stools. This medicine usually acts ½ hour to 6 hours after dosing. Undigested or partially digested medicine may be seen in the watery stool or during colonoscopy. Undigested tablets of other medications may also be seen. When there is no bowel movement increase within 6 hours after taking this medicine, the patient should be aware of the necessity to discontinue the drug and contact a doctor immediately because there is a risk of dehydration.

This medicine should not be used as a treatment for constipation.

No drug interaction studies have been conducted for this medicine.

As with other purgatives the absorption of other orally administered medicines (e.g. oral contraceptives, antibiotics, antidiabetics, antiepileptic drugs) may be delayed or completely prevented.

Phosphate absorption is reduced by concomitant aluminium, calcium or magnesium salts. Phosphate absorption is increased by concomitant administration of vitamin D.

Care should be taken with patients taking calcium channel blockers, diuretics, angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), drugs known to prolong the QT interval, NSAIDs, drugs containing parathyroid hormone, lithium treatment or other medications that might affect electrolyte levels as hyperphosphataemia, hypocalcaemia, hypokalaemia, hypernatraemic dehydration or acidosis may occur.

This medicine must not be used with other laxatives containing sodium phosphate.

No clinical data on exposed pregnancies are available or even data from animal studies on the embryonic/fetal development, childbirth and postnatal development. The potential risk for humans is unknown. This medicine should not be used during pregnancy unless clearly necessary.

Not knowing if this medicine is excreted in breast milk and also if the sodium phosphate may pass into breast milk, it is advisable to draw the milk and not to use as soon after the first intake of this medicine up to 24 hours after taking the second dose. Therefore, women should not breastfeed their babies within 24 hours after taking the second dose of this medicine.

This medicine may cause dizziness, probably due to dehydration, and this may have a minor or moderate influence on the ability to drive and use machines.

The side effects listed below have been reported at frequencies corresponding to: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Cardiac disturbances

Very rare: myocardial infarction, arrhythmias

Rare: mild prolonged QT interval

Gastrointestinal disorders

Very common: abdominal bloating, abdominal pain and nausea

Common: vomiting, abnormalities in colonoscopy (single or multiple aphthous like ulcerations located in the sigmoid and rectum without clinical relevance and disappearing spontaneously without treatment), abnormalities in gastroscopy (erythematous gastritis like lesions and/or superficial gastric ulcerations with necrotizing base, most often asymptomatic and spontaneously regressive).

General disorders and administration site conditions

Very common: chills, asthenia

Common: chest pain

Immune system disorders

Rare: hypersensitivity reactions such as rash, pruritus, urticaria, throat tightness, bronchospasm, dyspnea, pharyngeal oedema, dysphagia, paresthesia and swelling of the lips and tongue and facial swelling, anaphylaxis

Very rare: allergic dermatitis

Metabolism and nutrition disorders

Uncommon: dehydration

Rare: hypomagnesaemia

Very rare: dysnatraemia, hypocalcaemia, hypokalaemia, hyperphosphataemia, metabolic acidosis, tetany

Musculoskeletal and connective tissue disorders

Very rare: muscle cramps

Nervous system disorders

Common: headache and dizziness;

Very rare: generalised tonic-clonic seizures and/or loss of consciousness, paresthesia

Renal and urinary disorders

Very rare: Increased blood urea nitrogen (BUN), increased creatinine, acute renal failure, chronic renal failure, nephrocalcinosis, acute phosphate nephropathy and renal tubular necrosis.

Vascular disorders

Very rare: hypotension

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via: HPRA Pharmacovigilance Website: www.hpra.ie.

Not applicable.