Risk of hypercalcemia in blacks taking hydrochlorothiazide and vitamin D

Am J Med. 2014 Aug;127(8):772-8. doi: 10.1016/j.amjmed.2014.02.044. Epub 2014 Mar 20.

Abstract

Introduction: Hydrochlorothiazide, an effective antihypertensive medication commonly prescribed to blacks, decreases urinary calcium excretion. Blacks have significantly higher rates of hypertension and lower levels of 25-hydroxyvitamin D. Thus, they are more likely to be exposed to vitamin D supplementation and thiazide diuretics. The risk for hypercalcemia among blacks using vitamin D and hydrochlorothiazide is undefined.

Methods: We assessed the frequency of hypercalcemia in hydrochlorothiazide users in a post hoc analysis of a randomized, double-blind, dose-finding trial of 328 blacks (median age 51 years) assigned to either placebo, or 1000, 2000, or 4000 international units of cholecalciferol (vitamin D3) daily for 3 months during the winter (2007-2010).

Results: Of the 328 participants, 84 reported hydrochlorothiazide use and had serum calcium levels assessed. Additionally, a comparison convenience group of 44 enrolled participants who were not taking hydrochlorothiazide had serum calcium measurements at 3 months, but not at baseline. At 3 months, hydrochlorothiazide participants had higher calcium levels (0.2 mg/dL, P <.001) than nonhydrochlorothiazide participants, but only one participant in the hydrochlorothiazide group had hypercalcemia. In contrast, none of the nonhydrochlorothiazide participants had hypercalcemia. In a linear regression model adjusted for age, sex, 25-hydroxyvitamin D at 3 months, and other covariates, only hydrochlorothiazide use (Estimate [SE]: 0.05 [0.01], P = .01) predicted serum calcium at 3 months.

Conclusion: In summary, vitamin D3 supplementation up to 4000 IU in hydrochlorothiazide users is associated with an increase in serum calcium but a low frequency of hypercalcemia. These findings suggest that participants of this population can use hydrochlorothiazide with up to 4000 IU of vitamin D3 daily and experience a low frequency of hypercalcemia.

Keywords: Black; Hypercalcemia; Hypertension; Thiazide diuretics; Vitamin D.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Black People*
  • Bone Density Conservation Agents / administration & dosage
  • Bone Density Conservation Agents / adverse effects
  • Bone Density Conservation Agents / pharmacokinetics
  • Calcium / blood
  • Diuretics / administration & dosage
  • Diuretics / adverse effects
  • Diuretics / pharmacokinetics
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination / adverse effects
  • Female
  • Humans
  • Hydrochlorothiazide / administration & dosage
  • Hydrochlorothiazide / adverse effects*
  • Hydrochlorothiazide / pharmacokinetics
  • Hypercalcemia / chemically induced*
  • Male
  • Middle Aged
  • Vitamin D / administration & dosage
  • Vitamin D / adverse effects*
  • Vitamin D / pharmacokinetics

Substances

  • Bone Density Conservation Agents
  • Diuretics
  • Hydrochlorothiazide
  • Vitamin D
  • Calcium