• In section 2 (qualitative and quantitative composition), the phrase 'Excipient' has been updated to 'Excipient(s) with known effect'
• In section 4.3 (contraindications), the sentence 'Hypersensitivity to any of the ingredients of the product, refer to section 6.1.' has been updated to 'Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.'
• In section 5.1 (pharmacodynamics properties), the ATC code for Calcium carbonate has been corrected from 'A01ACA1' to 'A01AC01'.
• Date of renewal has been added to section 9

4.8 Undesirable effects

…

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, Earlsfort Terrace, IRL - Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. Website: www.hpra.ie; E-mail: medsafety@hpra.ie.

10. DATE OF (PARTIAL) REVISION OF THE TEXT

May 2013March 2015

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Section 2: Qualitative and Quantitative Composition

Each chewable tablet contains:

Calcium carbonate                              680.0  mg (272 mg elemental calcium)

Heavy Magnesium Carbonate             80.0  mg

Excipient:

Sucrose                                                475.0  mg

For full list of excipients, see section 6.1

Section 4.3: Contra-indications

Rennie ICE should not be administered in the following cases:

·         Hypersensitivity to any of the ingredients of the product, refer to section 6.1.

·         Hypercalcaemia, hypercalciuria and/or conditions resulting in hypercalcaemia e.g sarcoidosis

·         Nephrocalcinosis Nephrolithiasis due to calculi containing calcium deposits

·         Severe renal failure (creatinine clearance below 30 ml/min) insufficiency

·         Hypophosphatemia

Section 4.4: Special warnings and special precautions for use

Prolonged use should be avoided. Do not exceed the stated dose and if symptoms persist, after 7 days, further medical advice should be sought.

Rennie ICE should be used with caution in the following cases:

Caution should generally be excercised in the case of patients with impaired renal function. If Rennie ICE is to be used in these patients, plasma calcium, phosphate and magnesium levels should be regularly monitored.

Prolonged use should be avoided.

As with other antacids, Rennie ICE tablets may mask a malignancy in the stomach.

Do not exceed the stated dose and if symptoms persist after 7 days consult your doctor.

Long term uses at high doses can result in undesirable effects such as hypercalcaemia, hypermagnesaemia and milk-alkali syndrome, especially in patients with renal insufficency.  The product should not be taken with large amounts of milk or dairy products. Prolonged use possibly enhances the risk for the development of kidney stones.

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

Magnesium salts may cause central nervous system depression in the presence of renal insufficiency.

Section 4.5: Interactions with other medicinal products and other forms of interactions

Changes in gastric acidity, e.g. during treatment with antacids, may impair the rate and degree of absorption of other drugs, if taken concomitantly.

·         It has been shown that antacids containing calcium and magnesium may form complexes with certain substances, e.g. antibiotics (tetracyclines, quinoloines), and cardiac glycosides, e.g. digoxin, levothyroxine and eltrombopag,  resulting in decreased absorption. This should be borne in mind when concomitant administration is considered.

·         Thiazide diuretics reduce the urinary excretion of calcium and increase the serum calcium. Due to an increased risk of hypercalcaemia, serum calcium should be regularly monitored during concomitant use of thiazide diuretics.

·       Calcium and magnesium salts can also impede the absorption of phosphates, fluorides, and iron containing products.

Therefore it is preferable to administer Rennie ICE separately from other drugs, allowing a 1-2 hours interval.

Section 4.6: Fertility, pregnancy and lactation

Up to now, Nno increased risk of congenital defects has been observed after the use of calcium carbonate and magnesium carbonate during pregnancy.  In case of high or prolonged doses or renal insufficiency, the risk for hypercalcaemia and/or hypermagnaesaemia can not be completely excluded. Rennie ICE tablets can be used during pregnancy if taken as instructed but prolonged intake of high dosages should be avoided. Rennie ICE tablets can be used during lactation if taken as instructed.

During pregnancy and lactation, it has to be taken into account that Rennie ICE tablets provide a substantial amount of calcium in addition to dietary calcium intake. For this reason, pregnant women should strictly limit their use of Rennie ICE chewable tablets to the maximum recommended daily dose (see section 4.2) and avoid concomitant, excessive intake of milk and dairy products. This warning is to prevent calcium overload which might result in milk alkali syndrome.

Section 4.8: Undesirable effects

The following sentence was displayed in bold formal:

“Undesirable effects only occurring in the context of milk-alkali syndrome (see Section 4.9):”

5.1 Pharmacodynamic properties

ATC code:

Magnesium carbonate: A02AA01

Calcium carbonate:  A02AC01

Calcium carbonate and magnesium carbonate:

Calcium and magnesium carbonates function as antacids reacting with excess hydrochloric acid in the gastric medium to produce soluble chlorides.

CaCO₃ + 2HCl => CaCl₂ + H₂O + CO₂

MgCO₃ + 2HCl => MgCl₂ + H₂O + CO₂

Each Rennie ICE tablet neutralises 15.5 mEq H⁺

Pharmacotherapeutic group: Antacids, other combinations; ATC Code: A02AX

ATC Code: Calcium carbonate A01ACA1, magnesium carbonate: A02AA01

Rennie ICE is a combination of two antacids, calcium carbonate and magnesium carbonate. The mode of action of calcium carbonate & magnesium carbonate is local, based on the neutralisation of gastric acid, and is not dependant on systemic absorption. Calcium carbonate has a rapid, long lasting and powerful neutralising action. This effect is increased by the addition magnesium carbonate which also has a strong neutralising action. In vitro, the total neutralising capacity of the product is 15.5 mEq H+ (titration to endpoint pH 2.5)

5.2 Pharmacokinetic properties

Calcium carbonate and magnesium carbonate:

A small amount of calcium and magnesium may be absorbed, but in healthy subjects it is usually rapidly excreted by the kidney.

The soluble chlorides produced by the reaction of calcium and magnesium with gastric acid react, in turn, with intestinal, biliary and pancreatic secretions to form insoluble salts, which are excreted in the faeces.

In the stomach, calcium carbonate and magnesium carbonate react with the acid in the gastric juice, forming water and soluble mineral salts.

CaCO₃ + 2HCl => CaCl₂ + H₂O + CO₂

MgCO₃ + 2HCl => MgCl₂ + H₂O + CO₂

Calcium and magnesium can be absorbed from these soluble salts. However, the degree of absorption is dependant on the subject and the dose. Less than 10% calcium and 15-20% magnesium is absorbed.

The small quantities of calcium and magnesium absorbed are usually excreted rapidly via the kidneys in healthy individuals. In the case of impaired renal function, plasma concentrations of calcium and magnesium may be increased.

Due to the effects of various digestive juices outside the stomach, the soluble salts are converted to insoluble salts in the intestinal canal and then excreted with the faeces.

Section 10: Date of revision of the text:

December 2012 May 2013