Recommended dose antacids and severe hypercalcaemia

We would like to highlight a serious complication of a nonprescription medication take in accordance with the manufacturer's instructions, illustrated by the following case.

A 27 year-old man presented with a 3 month history of increasing clumsiness, vomiting, dizziness and confusion. For the preceding 5 years he had suffered from persistent epigastric discomfort. An oesophago-gastro-duodenoscopy arranged by his general practitioner had been normal. His discomfort was eased by omeprazole 20 mg once a day. In addition, for many years he had also consumed 10 Tums (SmithKline Beecham) or 6 Rennie (Roche) antacid tablets a day. He drank little milk and had no recent sun exposure.

His admission blood results revealed urea 22.4 mmol l⁻¹, creatinine 489 µmol l⁻¹, calcium 4.1 mmol l⁻¹, phosphate 0.95 mmol l⁻¹, albumin 41 g l⁻¹, alkaline phosphatase 104 IU l⁻¹, bicarbonate 63 mmol l⁻¹ and parathyroid hormone (PTH) 10 ng l⁻¹ (normal range 10–65). Immunoglobulins, 24 h urinary calcium, serum angiotensin converting enzyme and parathyroid hormone-related protein levels were all normal.

A repeat oesophago-gastro-duodenoscopy and a whole body CT scan were normal.

He was vigorously rehydrated using intravenous 0.9% saline with potassium supplements. Within 12 h his symptoms ceased and his renal function began to improve. After 3 days of hydration, because his calcium remained elevated at 3.02 mm l⁻¹, 60 mg of disodium pamidronate was given intravenously. The following day the patient revealed that he had continued to take Rennie in the hospital without informing the medical or nursing staff, having not considered antacids as ‘medication’. His antacids were discontinued at that point. A week later he developed symptomatic hypocalcaemia (calcium 0.87 mmol l⁻¹) requiring calcium supplementation before normalizing.

On discharge he was advised to avoid antacids containing calcium carbonate. When reviewed 6 months later he was asymptomatic, with normal blood results and requiring no medication.

The milk–alkali syndrome is a triad of hypercalcaemia, alkalosis and renal impairment resulting from the ingestion of calcium and absorbable alkali [1]. Calcium carbonate, present in the majority of nonprescription antacids, acts as a common source of both. A self-perpetuating environment is thought to develop within the kidney whereby the calcium and alkali limit the excretion of each other [1]. Renal impairment, secondary to hypercalcaemia and dehydration, exacerbates the situation.

The amount of calcium carbonate required to provoke the milk–alkali syndrome is controversial. The antacid regimens used before the development of H₂-receptor antagonists and proton-pump inhibitors employed 20–60 g calcium carbonate per day and up to 35% patients developed toxic symptoms [1]. Such high levels of calcium carbonate are no longer used therapeutically and the syndrome has become correspondingly rare. Only seven patients presented with the milk–alkali syndrome during an 8 year period in one American teaching hospital. In these patients calcium carbonate was implicated at doses as low as 4–12 g day⁻¹ [2]. Similarly, our patient only took 4–5 g calcium carbonate a day, which was within the maximum recommended by the antacid's manufacturer.

The recommended dosages for nonprescription antacids available in the UK allow for daily calcium carbonate loads ranging from 7.2 g (Andrew's Antacid, SmithKline Beecham) to 10.8 g (Rennie's, Roche). Indeed, one antacid product, Bisodol Indigestion Relief (Whitehall Laboratories) states no recommended maximum dosage, but only that one or two tablets (each containing 522 mg calcium carbonate) be ‘taken as required’.

We feel that certain individuals are clearly susceptible to developing the milk–alkali syndrome at doses of calcium carbonate less than many antacid manufacturer's recommended daily limits. Individual variations in the fraction of any calcium carbonate load absorbed, or in its metabolism may be responsible.

Our case exemplifies the importance of nonprescription medications in a full drug history, and raises concerns about the printed advice given to users of calcium carbonate containing antacids. If dyspeptic symptoms are controlled, antacid packaging that only states ‘consult your doctor if symptoms persist', may not deter chronic ingestion. Such advice inevitably increases the risk of severe hypercalcaemia from nonprescription antacids even when taken at or below the recommended daily dose.