A Double-Blind Placebo-Controlled Crossover Trial of Intravenous Magnesium Sulfate for Foscarnet-Induced Ionized Hypocalcemia and Hypomagnesemia in Patients with AIDS and Cytomegalovirus Infection

Abstract

Foscarnet (trisodium phosphonoformate hexahydrate) is an antiviral agent used to treat cytomegalovirus disease in immunocompromised patients. One common side effect is acute ionized hypocalcemia and hypomagnesemia following intravenous administration. Foscarnet-induced ionized hypomagnesemia might contribute to ionized hypocalcemia by impairing excretion of preformed parathyroid hormone (PTH) or by producing target organ resistance. Prevention of ionized hypomagnesemia following foscarnet administration could blunt the development of ionized hypocalcemia. To determine whether intravenous magnesium ameliorates the decline in ionized calcium and/or magnesium following foscarnet infusions, MgSO 4 at doses of 1, 2, and 3 g was administered in a double-blind, placebo-controlled, randomized, crossover trial to 12 patients with AIDS and cytomegalovirus disease. Overall, increasing doses of MgSO 4 reduced or eliminated foscarnetinduced acute ionized hypomagnesemia. Supplementation, however, had no discernible effect on foscarnetinduced ionized hypocalcemia despite significant increases in serum PTH levels. No dose-related, clinically significant adverse events were found, suggesting that intravenous supplementation with up to 3 g of MgSO 4 was safe in this chronically ill population. Since parenteral MgSO 4 did not alter foscarnet-induced ionized hypocalcemia or symptoms associated with foscarnet, routine intravenous supplementation for patients with normal serum magnesium levels is not recommended during treatment with foscarnet.

Review of the Refeeding Syndrome

“…Suggestions for empiric IV dosing of magnesium (for patients with normal renal function) are listed in Table 5. 39,41,[75][76][77][78][79][80][81][82][83] Because magnesium distribution and equilibration between serum and intracellular spaces and tissues are slow 32,84 but renal elimination is rapid (with up to 50% of an IV dose of magnesium excreted in the urine), 31,32,[75][76][77]80,82 infusion time of IV magnesium is important. In nonemergent situations, we recommend infusing doses of Յ6 g of magnesium sulfate over 6 -12 hours and infusing higher doses over 12-24 hours, with a maximum of 1 g magnesium sulfate (ϳ8.1 mEq elemental magnesium) over 1 hour.…”

“…The patient should be monitored closely for further signs and symptoms of RS. Table 5 Treatment of hypomagnesemia 39,41,[75][76][77][78][79][80][81][82][83]…”

Magnesium in Man: Implications for Health and Disease

“…Patients also suffer from hypocalcemia and hypokalemia, which may be secondary to the Mg 2ϩ disturbances (253,369). Until now, no studies have examined the effect of forscarnet on the expression of renal ion transporters.…”

Treatment of electrolyte disorders in adult patients in the intensive care unit

“…dosing regimens for the treatment and repletion of hypomagnesemia have been suggested. 46,[166][167][168][169][170][171][172] Magnesium deficiency has been associated with a total body magnesium deficiency of 1.0-2.0 meq/kg. 169 Magnesium distributes into tissues slowly, but renal elimination is rapid, with up to 50% of an i.v.…”