Renocal Plus Tablet

This is indicated in the treatment of hyperphosphatemia associated with chronic renal insufficiency in patients undergoing dialysis (haemodialysis, peritoneal dialysis). This is indicated in adults.

Each film-coated tablet contains:

• Calcium acetate, 435 mg equivalent to 110 mg calcium and
• Magnesium carbonate, heavy 235 mg equivalent to 60 mg magnesium.

As calcium acetate and magnesium carbonate are phosphate-binding compounds, they lead together with the phosphate contained in food to the formation of low solubility calcium and magnesium phosphate-salts in the gut, which then will be excreted with the faeces. Calcium acetate reaches its maximal phosphate-binding capacity at a pH of 6-8. Therefore, this tablet is also suitable for phosphate binding in patients with hypo- or anacidity of the stomach.

Adults: 3 to 10 film-coated tablets per day, depending on the serum phosphate level. The daily dose should be subdivided according to the number of meals per the day (usually 3 a day). The recommended starting dose is 3 tablets daily. If necessary, the dosage may be raised to maximally 12 film-coated tablets per day.

Pediatric population: The safety and efficacy of this tablet in children and adolescence have not been established. Therefore, the administration of this tablet is not recommended in children and adolescents below 18 years of age.

Method of administration:To achieve the maximum phosphate binding effect, this tablet must be taken together with the meal and should not be crushed or chewed. For easy swallowing, the tablets should be taken together with some liquid. In case the tablets are too large to be swallowed by the patient, the tablets should be broken along the score line immediately before swallowing in order to avoid the development of taste of acetic acid. Because the rate and/or extent of absorption of other defined medicinal products may vary when used concomitantly with this tablet, none of the oral medicinal products should be taken within the period 2 hours before and 3 hours after administration of this tablet. This can be applied long-term.

To prevent an interaction between this tablet and other defined medicinal products when taken concomitantly, none of the oral medicinal products listed in this section should be taken within the period 2 hours before and 3 hours after administration of this tablet.

This tablet affects the absorption of antibiotics (such as tetracyclines, doxycycline, norfloxacin, some cephalosporins like cefpodoxime, cefuroxime, and some quinolones (gyrase inhibitors) like ciprofloxacin), biphosphonates, fluorides, ketokonazole, estramustin-preparation, anticholinergics, zinc, urso- and chenodesoxychol acid, halofantrine.

In case of an additional treatment with oral iron preparations, attention has to be paid to the fact that simultaneous intake of magnesium may influence iron absorption.

Magnesium salts may adsorb digoxin in the gastrointestinal tract, decreasing its bioavailability.

Adsorption of nitrofurantoin may occur, decreasing the bioavailability and possibly the anti-infective effect of this medicinal product.

Further, the gastrointestinal absorption of penicillamine may be decreased, possibly decreasing its pharmacological effects.

A combination of magnesium carbonate, hydroxide and aluminium hydroxide with levothyroxine may cause an increased absorption of levothyroxine.

Vitamin D and derivatives increase the absorption of calcium. Thiazide diuretics reduce the renal elimination of calcium. In case of a simultaneous administration of this tablet and thiazides or vitamin D derivatives it is therefore necessary to control the serum calcium level.

Concurrent use of oestrogens with this tablet may increase calcium absorption.

The sensitivity for glycosides and therefore the risk for arrhythmia is increased by elevated serum calcium levels.

The administration of adrenalin in patients with increased serum calcium levels may lead to severe arrhythmia.

The effect of calcium antagonists may be reduced.

This is contraindicated in patients with:

• Hypophosphataemia
• Hypercalcaemia with or without clinical symptoms, e.g. as a result of an overdose of vitamin D, a paraneoplastic syndrome (bronchial carcinoma, breast cancer, renal cell carcinoma, plasmacytoma), bone metastases, sarcoidosis or immobilisation osteoporosis
• Elevated serum magnesium levels of more than 2 mmol/l, and/or symptoms of hypermagnesaemia
• AV-block III°
• Myasthenia gravis
• Hypersensitivity to the active substances or to any of the excipients.

Gastrointestinal disorders: Soft stools, gastrointestinal irritation like nausea, anorexia, sensation of fullness, belching and constipation, diarrhoea.

Metabolism and nutrition disorders: Hypercalcaemia either asymptomatic or symptomatic, asymptomatic hypermagnesaemia.

There are no or limited amount of data from the use of this tablet in pregnant women. Animal studies are insufficient with respect to reproductive toxicity. This tablet should not be used during pregnancy unless the clinical condition of the woman requires treatment with calcium acetate and magnesium carbonate. Calcium acetate and magnesium carbonate are excreted in human milk to such an extent that effects on the breastfed newborns/infants are likely. Breast-feeding is not recommended during treatment with this tablet.

The use of phosphate binders should be preceded by a dietary consultation with the patient concerning phosphate uptake, and may depend on the kind of dialysis treatment the patient is receiving. This tablet should only be administered with caution (only with continuous monitoring of serum calcium, magnesium and phosphate) in case of severe hyperphosphataemia with a calcium-phosphate-product of more than 5.3 mmol 2/l2 if

• refractory to therapy,
• refractory hyperkalaemia,
• clinical relevant bradycardia or AV-block II° with bradycardia.

Continuous monitoring of serum phosphate, serum magnesium, serum calcium and the calcium-phosphate-product should be performed, especially in case of simultaneous intake of vitamin D preparations and thiazide diuretics.

High doses and long-term administration of this tablet may result in hypermagnesaemia. Hypermagnesaemia is mostly asymptomatic, but in some cases systemic effects may be seen.

For symptoms and management of hypermagnesaemia and hypercalcaemia please see section 4.9.

Patients should be advised to seek medical advice before taking antacids containing calcium or magnesium salts to avoid adding to the calcium or magnesium load.

If patients with a chronic renal insufficiency receive this tablet they may develop hypercalcaemic episodes, especially in combination with the administration of metabolites of vitamin D.

Patients should be warned of the possible symptoms of hypercalcaemia.

During a long-term therapy with this tablet attention must be paid to the progression or the appearance of vascular and soft tissue calcifications. The risk decreases by lowering the calcium-phosphate-product to < 4.5 mmol2/l2.

In patients receiving digitalis glycosides, this tablet should only be administered under ECG control and monitoring of the serum calcium level.

Increased intake of calcium salts may result in the precipitation of fatty acids and bile acid as calcium soap. This may lead to constipation. In case of diarrhoea the dosage of this tablet should be reduced.

this tablet contains sucrose. Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

This tablet contains sodium. This has to be taken in consideration by patients on a controlled sodium diet.

Paediatric population

The safety and efficacy of this tablet in children and adolescence have not been established. Therefore, the administration of this tablet is not recommended in children and adolescents below 18 years of age.

n acute hypermagnesaemia (either asymptomatic or with acute systemic toxicity) suppresses both the central and the peripheral neural activity by inhibiting acetylcholine release. Systemic toxicity is to be expected from a serum concentration of 2.5 mmol/l, severe neurotoxic side effects appear from 3 mmol/l and above. With concentrations of 2.5-5.0 mmol/l gastrointestinal disturbances (nausea, anorexia, constipation), cystospasm, muscle weakness, lethargy, missing deep-tendon reflexes and disturbed AV-conduction and ventricular stimulus conduction has been observed.

In case of serum magnesium levels of 5-10 mmol/l, arterial hypotension induced by vasodilatation, paralytic ileus, flaccid paralysis and coma have been observed. At a level of more than 10 mmol/l respiratory arrest and cardiac arrest occur.

Symptoms of hypercalcaemia are initially muscle weakness and gastrointestinal disturbances (abdominal pain, constipation, nausea and vomiting). Severe hypercalcaemia is characterised by disturbances of consciousness (e.g. lethargy,disorientation, stupor, in extreme cases also coma). In patients with a serum calcium level of more than 3.5 mmol/l a hypercalcaemic crisis is possible with the symptoms of:

• Polyuria, polydipsia
• Nausea, anorexia, constipation, pancreatitis (infrequent)
• Arrhythmia, shortening of the QT-interval, adynamia, hypertension
• Muscle weakness up to pseudo paralysis
• Psychosis, somnolence up to coma.

Long-term overdosing may lead to the development of an adynamic osteopathy.

Emergency treatment: In addition to symptomatic treatment, the therapy of hypermagnesaemia consists in lowering the magnesium-concentration of the dialysate and in a reduction of the dose of this tablet.

Specific mineral preparations

Keep below 30°C temperature, away from light & moisture. Keep out of the reach of children.