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 IMB HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2; Tel: +353 1 6764971;  Fax: +353 1 6762517. Website: www.imbhpra.ie; eE-mail: imbpharmacovigilance@imb.iemedsafety@hpra.ie.

10.  DATE OF REVISION OF THE TEXT

April 2014March 2015

Update to section 4.8:
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 IMB Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2; Tel: +353 1 6764971;  Fax: +353 1 6762517. Website: www.imb.ie; e-mail: imbpharmacovigilance@imb.ie.

                        6.3       Shelf life

Blisters: 3 years
Roll-wrap: 2 years

6.5 Nature and contents of container
The tablets may also be "roll wrapped" in a laminate to give pack sizes of 12 tablets.

Not all pack sizes may be marketed.

10.       Date of revision of the text

            April 2012 April 2014

In section 4.2 (posology and method of administration), the maximum adult daily dose has been changed from 'sixteen' to 'eleven' tablets. In addition, the following information has also been included: 
    'Children and adolescents: Not recommended for use in children and adolescents below age 18 due to a lack of sufficient data on safety and efficacy.'

In section 4.3 (contraindications), the following changes have been made:

BEFORE: Rennie Sugar Free should not be administered to patients with:

·        Severe renal function impairment.

·        Hypercalcaemia

AFTER: Rennie Sugar Free 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

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

·         Hypophosphatemia

In section 4.4 (special warnings and precautions for use), the following changes have been made:
BEFORE:        Prolonged use should be avoided.

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

Caution should generally be exercised in the case of patients with impaired renal function. If Rennie Sugar Free is used in such patients, plasma calcium and magnesium levels should be regularly monitored.

      Long term use at high doses can result in undersiderable effects such as hypercalcaemia, hypermagnesaemia and milk-alkali syndrome, especially in patients with renal insufficency.  Prolonged use possibly enhances the risk for the development of renal calculi.

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

AFTER:          Rennie Sugar Free should be used with caution in the following case:

·        Caution should generally be exercised in the case of patients with impaired renal function. If Rennie Sugar Free 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 Sugar Free tablets may mask a malignancy in the stomach.

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

Long term uses at high doses can result in undersiderable 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 should not take this medicine.

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

In section 4.5 (interaction with other medicinal products and other forms of interaction), the following changes have been made:
BEFORE:         Changes in gastric acidity, such as that caused by the ingestion of antacids, can affect the rate and degree to which some concurrently administered medicines are absorbed.

This product may form complexes with certain drugs, e.g. antibiotics (tetracyclines and quinolones), digoxin, and vitamins, resulting in decreased absorption.  This should be borne in mind when concomitant administration is considered.

                        Calcium and magnesium salts can also impede the absorption of phosphates.

Because of possible changes in the rates of absorption of concurrently administered medicines, it is recommended that antacids should not be taken concurrently with these medicines, but 1 to 2 hours later.

AFTER:           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 drugs, e.g. antibiotics (tetracyclines, quinolones), and cardiac glycosides, e.g digoxin, 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 the antacid separately from other drugs, allowing a 1-2 hours interval.

In section 4.6 (pregnancy and lactation), the following changes have been made:
BEFORE: Epidemiological studies show no increase in teratogenic and other hazards to the foetus if used at the recommended dosage during pregnancy. As with all medicines it should only be taken during pregnancy or lactation when considered necessary. 

AFTER:  

Up to now, no 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 hypermagnaesia can not be completely excluded.

Rennie Sugar Free tablets can be used during pregnancy if taken as instructed but prolonged intake of high dosages should be avoided. Rennie Sugar Free tablets can be used during lactation if taken as instructed.

During pregnancy and lactation, it has to be taken into account that Rennie Sugar Free 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 Sugar Free chewable tablets to the maximum recommended daily dose and avoid concomitant, excessive intake of milk and dairy products. This warning is to prevent calcium overload which might result in milk alkali syndrome

        
In section 4.8.(Undesirable effects), the following changes have been made:
BEFORE: Very rarely hypersensitivity reactions have been reported.

AFTER         

The listed adverse drug reactions are based on spontaneous reports, thus an organization according to CIOMS III categories of frequency is not pertinent.

            Immune System Disorders

 Hypersensitivity reactions have very rarely been reported. Clinical symptoms may include rash, urticaria, angioedema and anaphylaxis.

            Metabolism and Nutrition Disorders

      Especially in patients with impaired renal function, prolonged use of high doses can result in hypermagnesemia or hypercalcemia and alkalosis which may give rise to gastric symptoms and muscular weakness (see below).

            Gastrointestinal Disorders

                        Nausea, vomiting, stomach discomfort and diarrhea may occur.

            Musculoskeletal and Connective Tissue Disorders

                        Muscular weakness may occur.

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

            Gastrointestinal Disorders

Ageusia may occur in the context of milk-alkali syndrome.

            General Disorders and Administration Site Conditions

                        Calcinosis and asthenia may occur in the context of milk-alkali syndrome.

Nervous System Disorders

Headache may occur in the context of milk-alkali syndrome.

Renal and Urinary Disorders

                       Azotemia may occur in the context of milk-alkali syndrome.

In section 4.9 (Overdose), the following changes have been made:
BEFORE: Prolonged use at high doses may cause renal dysfunction and especially in patients already with impaired renal function, milk alkali syndrome, hypermagnesaemia, hypercalcaemia, alkalosis, nausea, vomiting, constipation or abnormal muscle weakness.
AFTER: Especially in patients with impaired renal function, prolonged use of high doses of calcium carbonate and magnesium carbonate can result in renal insufficiency, hypermagnesemia, hypercalcemia and alkalosis which may give rise to gastrointestinal symptoms (nausea, vomiting, constipation) and muscular weakness. In these cases, the intake of the product should be stopped and adequate fluid intake encouraged. In severe cases of overdosage (e.g. milk-alkali syndrome), a health care professional must be consulted because other measures of rehydration (e.g. infusions) might be necessary.