4.1. Therapeutic indications

Magnesium 4mmol Chewable Tablets are indicated as oral magnesium supplements for the treatment of patients with chronic magnesium loss or hypomagnesaemia as diagnosed by a doctor.

Magnesium 4mmol Chewable Tablets are also indicated for adult patients with hypomagnesaemia due to the concomitant administration of loop and thiazide diuretics or other drugs which cause hypomagnesaemia.

4.2. Posology and method of administration

Posology

Patients with severe, symptomatic hypomagnesaemia should receive intravenous magnesium repletion for acute recovery of magnesium levels prior to receiving Magnesium 4mmol Chewable Tablets.

It is recommended that serum magnesium levels should be monitored at regular intervals (e.g. every 3-6 months), particularly in children and in patients with renal impairment.

Adults (> 18 years): The dosage regimen should be adjusted according to the serum total magnesium level of the individual patient. Starting doses for adult patients are recommended as 4-8 mmol (1-2 tablets) administered 3 times a day. This equates to a total dose of 12 to 24 mmol per day taken in divided doses.

Elderly: No dose adjustment is necessary.

Paediatric population

Magnesium 4mmol Chewable Tablets should only be used if the benefits of treatment outweigh any potential risks and under the supervision of physicians experienced in the management of children with hypomagnesaemia.

Children: below 4 years: Not recommended as there is insufficient information regarding the use of Magnesium 4mmol Chewable Tablets in this age group.

Children: 4 to 12 years: The dosage regimen should be adjusted according to the serum total magnesium level of the individual patient. A starting dose for children 4 to 12 years is recommended as 4 mmol (1 tablet) administered 2 times a day. This equates to a total dose of 8 mmol per day taken in divided doses.

Children: 12 to 18 years: The dosage regimen should be adjusted according to the serum total magnesium level of the individual patient. A starting dose for children 12 to 18 years is recommended as 4 mmol (1 tablet) administered 3 times a day. This equates to a total dose of 12 mmol per day taken in divided doses.

Patients with Renal Impairment: Magnesium 4mmol Chewable Tablets is contraindicated in patients with severe renal impairment (see Section 4.3). There is no dose adjustment necessary in patients with mild to moderate renal impairment.

Method of administration

For oral use.

The tablet should be chewed.

Co-Administration of Potassium and Calcium Supplements: Administration of potassium and calcium together with magnesium may be necessary since associated loss of these cations is common in severe magnesium deficiency.

4.3. Contraindications

Magnesium 4mmol Chewable Tablets is contraindicated in patients with severe renal impairment (glomerular filtration rate <30ml/min).

Magnesium 4mmol Chewable Tablets should not be administered to patients with hyperphosphataemia as Magnesium 4mmol Chewable Tablets contain phosphate.

Do not administer Magnesium 4mmol Chewable Tablets if there is evidence of hypersensitivity to any of the constituents.

4.4. Special warnings and precautions for use

The principle sites of absorption of magnesium in the gastrointestinal tract are the jejunum and ileum, therefore, in patients who have undergone extensive bowel resection the absorption of magnesium may be reduced.

In the case of confirmed magnesium deficiency, concomitant hypocalcaemia and hypokalaemia should be suspected and corrected if confirmed, since magnesium deficiency is frequently secondary to those conditions.

This medicinal product contains sorbitol, sucrose and sodium.

This medicine contains 25 mg sorbitol in each chewable tablet.

The additive effect of concomitantly administered products containing sorbitol (or fructose) and dietary intake of sorbitol (or fructose) should be taken into account. The content of sorbitol in medicinal products for oral use may affect the bioavailability of other medicinal products for oral use administered concomitantly.

Patients with hereditary fructose intolerance (HFI) should not take/be given this medicinal product.

This medicinal product contains 12.64 mg sodium per chewable tablet, equivalent to 0.6 % of the WHO recommended maximum daily intake of 2 g sodium for an adult.

This medicine contains sucrose. Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine. Sucrose included in this medicinal product may be harmful to the teeth.

4.5. Interaction with other medicinal products and other forms of interaction

Cardiovascular drugs: Digoxin and loop diuretics are magnesiuretic drugs and may affect magnesium balance. Magnesium deficiency may enhance digoxin toxicity.

As magnesium and other medicinal products may mutually influence each other's absorption, a time interval of 2 to 3 hours should generally be respected if possible.

This specifically applies to:

• Cellulose sodium phosphate; edetate disodium: concurrent use with magnesium supplements may result in binding of magnesium; patients should be advised not to take magnesium supplements within 1 hour of cellulose sodium phosphate or edetate disodium.

• Fluorides and tetracycline: if they must be used, the doses must be separated by 2 to 3 hours or more to prevent their admixture in the gut.

• Aminoquinolines, quinidine and quinidine derivatives, nitrofurantoin, penicillamine, iron, bisphosphonates (such as alendronate and risedronate), eltrombopag, nitroxoline: to avoid impairment of absorption, magnesium preparations should be taken 3 to 4 hours before or after the administration of those drugs.

Because of increased magnesium losses, a dose adjustment of magnesium may be necessary when taking the following substances:

• Aminoglycoside antibiotics, cisplatinum and ciclosporin A

• Diuretics (such as thiazide and furosemide),

• EGF-receptor antagonists (such as cetuximab and erlotinib),

• proton pump inhibitors (such as omeprazole and pantoprazole) and

• viral DNA polymerases-inhibiting foscarnet, pentamidine, rapamycin and amphotericin B

In addition, other electrolyte disturbances, such as hypokalaemia and hypocalcaemia, should be looked for in these patients with hypomagnesaemia.

For further information on mechanisms of drug interactions see section 5.2.

4.6. Fertility, pregnancy and lactation

Pregnancy

The effectiveness and safety of Magnesium 4mmol Chewable Tablets has not been established in pregnant women. Magnesium 4mmol Chewable Tablets should only be used in pregnancy if the benefits of the treatment outweigh any potential risks. However, long-term data available from treatment of pre-eclampsia do not indicate malformative or feto/neonatal toxicity of magnesium.

Administration of aminoglycoside antibiotics should be avoided during this period, as there are indications of interactions (see Section 4.5).

Breast-feeding

Magnesium 4mmol Chewable Tablets can be used during breast-feeding.

Magnesium glycerophosphate/ its metabolites are excreted in human milk, but at therapeutic doses of Magnesium 4mmol Chewable Tablets no effects on the breastfed newborns/infants are anticipated.

Fertility

Based on long-term experience, no effects of magnesium on male and female fertility are anticipated.

4.7. Effects on ability to drive and use machines

Magnesium 4mmol Chewable Tablets has no or negligible influence on the ability to drive and use machines.

4.8. Undesirable effects

As with other magnesium salt preparations, Magnesium 4mmol Chewable Tablets may cause diarrhoea, which is usually dose dependant. If diarrhoea occurs, the daily dose should be reduced and gradually increased later if needed.

Hypermagnesaemia is possible with higher doses and with impaired renal function.

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 Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9. Overdose

Symptoms: Hypermagnesaemia characterised by flushing, thirst, hypotension, drowsiness, nausea, vomiting, confusion, loss of tendon reflexes due to neuromuscular blockade, muscle weakness, respiratory depression, cardiac arrhythmias, coma and cardiac arrest.

Treatment of Iatrogenic Hypermagnesaemia and Overdose: When hypermagnesaemia is found, magnesium therapy should be withdrawn and this is all that is needed in most patients with mild to moderate hypermagnesaemia. In patients with symptomatic hypermagnesaemia, serum magnesium should be lowered and the effects of hypermagnesaemia antagonised. Calcium antagonises the toxic effects of magnesium and therefore patients with severe magnesium intoxication should be given intravenous calcium gluconate as a bolus followed by an infusion. Administration of glucose and insulin may also help to promote magnesium entry into cells. If renal function is normal adequate fluids should be given to assist removal of magnesium from the body. If the patient is in renal failure, peritoneal or haemodialysis against a low magnesium dialysis fluid will rapidly and effectively lower the serum magnesium concentration.