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 REVISION OF THE TEXT

 

March 2012March 2015

Section 2:
272mg elemental calcium was added after 680mg for calcium carbonate.

Spelling of simethicone was changed to simeticone.

Section 4.3

'Nephrolithiasis due to calculi containing calcium deposits' replaced nephrocalcinosis.
Severe renal failure (creatinine clearance below 30ml/min) was replaced by 'insufficiency'.

Section 4.4

 

The 2nd paragraph was changed from: "Prolonged use should be avoided. Do not exceed the stated dose and if symptoms persist or only partly disappear, further medical advice should be sought." to "Prolonged use should be avoided. Do not exceed the stated dose and if symptoms persist after 7 days, further medical advice should be sought."

Section 4.5
The following text has been changed from :

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

to :

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

and "Thiazide diuretics reduce the urinary excretion of calcium and increase the serum calcium" has been changed to: "Thiazide diuretics reduce the urinary excretion of calcium."

Section 4.6

"Up to now no increased risk of congenital defects.. "  has been changed to "No Thiazide diuretics reduce the urinary excretion of calcium..."

and "see section 4.2" has been added after  "maximum recommended daily dose".

Section 4.8
The immune system disorders section & metabolism and nutrition sections have been updated.The skin and subcutaneous disorders section has been deleted.

Section 5.1 has been updated to:

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

ATC-Codes: Calcium carbonate A02ACA1, magnesium carbonate A02AA01, silicones A03AX13

 

Rennie Deflatine is a combination of two antacids, calcium carbonate and magnesium carbonate, as well as simeticone, an antifoaming agent.The latter active ingredient causes gas bubbles to coalesce and disperse, thus liberating any trapped gas.

The mode of action of calcium carbonate & magnesium carbonate is local, based on the neutralisation of gastric acid, and is not dependent on systemic absorption. Calcium carbonate has a rapid, long-lasting and powerful neutralising action. This effect is increased by the addition of magnesium carbonate which also has a strong neutralising action. In vitro, the total neutralising capacity of the product is 16 mEq H⁺ (titration to endpoint pH 2.5)

Section 5.2 has been updated to:

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 dependent 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 case of impaired renal function, plasma concentrations of calcium and magnesium may be increased.

Section 4.2 has been changed to reduce the max daily dose to 11 tablets. A warning has also been added for the use of Rennie Deflatine in persons below 18.

 

 

Section 4.3 has been altered to say

“Rennie Deflatine should not be administered in the following cases:

 

·       Hypersensitivity to any of the ingredients of the product

 

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

 

·       Nephrocalcinosis

 

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

 

·       Hypophosphatemia”

 

 

Section 4.4 has been updated to say

“Rennie Deflatine 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 Deflatine is to be used in these patients, plasma calcium, phosphate and magnesium levels should be regularly monitored.

 

Prolonged use should be avoided. Do not exceed the stated dose and if symptoms persist, consult your doctor.

 

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

Long term use at high doses can result in undesirable effects such as hypercalcemia, hypermagnesemia and milk-alkali syndrome, especially in patients with renal insufficiency. 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.”

 

 

Section 4.5 now reads

“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, quinolines), 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 hypercalcemia, 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.”

 

 

Section 4.6 has been updated to say:

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

During pregnancy and lactation, it has to be taken into account that Rennie Deflatine 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 Deflatine 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.”

 

Section 4.8 now reads:

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

 

Immune System Disorders

Hypersensitivity reactions including anaphylaxis have been reported.

 

Metabolism and Nutrition Disorders

Especially in patients with impaired renal function, prolonged use of high doses can result in 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.

 

Skin and Subcutaneous Disorders

Rash, urticaria, and angioedema in context of hypersensitive reactions.

 

Undesirable effects only occurring in the context of milk-alkali syndrome (see 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.”

 

 

Section 4.9 now reads:

“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.”

 

 

Section 10 has been updated to February 2010.

In section 6.3 (Shelf Life), the shelf life has been changed from 5 to 3 years.

In section 6.4 (Special precautions for storage), Storage conditions have been changes from no special requirements to store below 25ºc. 

Section 1: Name updated to:

 

Rennie Deflatine Chewable Tablets

Calcium carbonate 680mg

Magnesium Carbonate 80mg

Simeticone 25mg

Section 2:

'Excipients : Contains Sorbitol (E420) 430mg' has been added.