Pharmacokinetics and safety issues of an accidental overdose of 2,000,000 IU of vitamin D3 in two nursing home patients: a case report

Abstract

BackgroundAdministration of intermittent high doses of vitamin D3 is increasingly used as a strategy for rapid normalization of low 25-hydroxyvitamin D (25(OH)D) blood concentrations in patients with vitamin D deficiency. Here, we describe the pharmacokinetics of an accidental single oral overdose of 2,000,000 IU of vitamin D3 in two elderly nursing home patients and discuss safety issues.Case presentationTwo patients, a Caucasian 90-year old man and a 95-year old woman, were monitored from 1 h up to 3 months after intake for clinical as well as biochemical signs of vitamin D intoxication. Blood vitamin D3 concentrations showed a prompt increase with the highest peak area already hours after the dose, followed by a rapid decrease to undetectable levels after day 14. Peak blood 25(OH)D3 concentrations were observed 8 days after intake (527 and 422 nmol/L, respectively (ref: 50–200 nmol/L)). Remarkably, plasma calcium levels increased only slightly up to 2.68 and 2.73 mmol/L, respectively (ref: 2.20–2.65 mmol/L) between 1 and 14 days after intake, whereas phosphate and creatinine levels remained within the reference range. No adverse clinical symptoms were noted.ConclusionA single massive oral dose of 2,000,000 IU of vitamin D3 does not cause clinically apparent toxicity requiring hospitalization, with only slightly elevated plasma calcium levels in the first 2 weeks. Toxicity in the long term cannot be excluded as annual doses of 500,000 IU of vitamin D3 for several years have shown an increase in the risk of fractures. This means that plasma calcium levels may not be a sensitive measure of vitamin D toxicity in the long term in the case of a single high overdose. To prevent a similar error in the future, the use of multiple-dose bottles need to be replaced by smaller single-unit dose formulations.

A review of the growing risk of vitamin D toxicity from inappropriate practice

“…Inappropriate administration of vitamin D. A single dose of 2 000 000 IU of vitamin D was given in error to two nursing home residents [67], leading to a call to replace multiple use bottles with smaller single-unit dose formulations. At the other extreme of age, most premature infant formulas have high vitamin D levels, which, while safe for short durations, if prolonged feeding is undertaken can result in excessive levels of vitamin D (>100 nmol l -1 ) [68].…”

Plausible ergogenic effects of vitamin D on athletic performance and recovery

“…Although it has been reported that vitamin D toxicity might occur with dosages of ≥10,000 IU/day for an extended period [ 71 , 84 ], producing adverse effects like hypercalcemia, the level of vitamin D causing toxicity is unclear [ 71 , 100 ], and due to ethical reasons, no prospective studies have analyzed the effect of vitamin D intoxication in humans. Recently, an accidental overdose of 2,000,000 IU of vitamin D 3 in two elderly patients did not cause adverse effects and only elevated blood calcium levels slightly [ 101 ]. More importantly, adverse effects have only been reported at serum concentrations of 25(OH)D above 200 nmol/L, which would take daily dosages of 40,000 IU or more of vitamin D to achieve [ 84 ], and serum concentrations of 25(OH)D of <140 nmol/L have not been correlated with hypercalcemia.…”

Vitamin D Toxicity

“… One case report described that a single dose of 2,000,000 IU of vitamin D was given in error to two nursing home residents. 28 This suggests the need to regulate the availability of multiple use bottles with more conventional dose formulations in line with current IOM and other published guidelines. 7 Consideration of vitamin D toxicity or excess should be made in patients presenting with hypercalcemia or hypercalciuria.…”