Magnesium

Magnesium/Nutrient Depletion:

  • ACE inhibitorsACE inhibitors: Deray et al. published a report on the treatment of cardiac failure with angiotensin-converting enzyme inhibitors and diuretics (184). The authors also discussed the prevention of the secondary effects of diuretics and ACE inhibitors on renal function, serum sodium, and potassium and magnesium concentrations. Further details are lacking.
  • AminoglycosidesAminoglycosides: Concurrent use of magnesium and aminoglycosides may result in neuromuscular weakness (188). According to secondary sources, nephrotoxicity caused by aminoglycosides (e.g., streptomycin and tobramycin) may lead to increased urinary loss of various electrolytes, including magnesium. Aminoglycosides include amikacin (Amikin?), gentamicin (Garamycin?), kanamycin (Kantrex?), streptomycin, and tobramycin (Nebcin?).
  • Amphotericin-BAmphotericin-B: According to human and animal studies, electrolyte disturbances, including low serum magnesium levels, developed in a large proportion of patients receiving amphotericin-B (189; 190; 191). Lipid-based formulations such as Abelcet? and Anphotec? may have a lesser effect than conventional formulations (191). This disturbance has been association with nephrotoxicity and may necessitate discontinuing the drug and administering intravenous electrolyte replacement.
  • Antineoplastics, alkylating agentsAntineoplastics, alkylating agents: According to a review, cisplatin alters magnesium handling by the body (205). Carboplatin and cisplatin may cause hypomagnesemia due to renal tubular damage, which increases urinary magnesium losses. With carboplatin, hypomagnesemia is rarely symptomatic and usually does not require magnesium supplements. Hypomagnesemia is usually more severe with cisplatin and worsens with progressive courses of treatment. Most patients who receive cumulative doses of cisplatin above 400mg/m2 will develop hypomagnesemia. Intravenous or oral magnesium supplements counteract this hypomagnesemia.
  • AntineoplasticsAntineoplastics: According to a systematic review, cetuximab or panitumumab use resulted in an increased risk of hypomagnesemia (223; 224). The addition of anti-EGFR monoclonal antibodies to this anti-neoplastic regimen further increased the risk of hypomagnesemia.
  • Beta-agonistsBeta-agonists: Clinically, magnesium is often used as an adjunct to treatment with beta-2 agonists (33; 34; 35; 36; 168; 39; 40; 199; 37; 200; 172; 201; 173; 202; 203; 225; 169; 204). Beta-2 agonists promote movement of magnesium from the extracellular to the intracellular space, and increase magnesium excretion in the urine. Reduced serum magnesium levels have been shown to occur after a single dose of albuterol or terbutaline orally, or by intravenous infusion, SC injection, or inhalation. The reductions are generally small (about 0.04-0.06mmol/L); it is unlikely that individuals receiving regular doses of beta-2 agonists will need magnesium supplementation unless they have other factors contributing to magnesium deficiency.
  • CalciumCalcium: According to a systematic review, use of magnesium increased hypocalcemia (54)
  • Cetuximab (Erbitux?)Cetuximab (Erbitux?): In human research, cetuximab increased renal magnesium excretion, resulting in lowered magnesium levels in patients (237; 238; 239; 240).
  • Cholestyramine (Questran?)Cholestyramine (Questran?): Preliminary evidence suggests that cholestyramine may slightly increase urinary magnesium excretion, possibly by binding vitamin D and leading to reduced magnesium absorption (241). However, evidence of clinically significant magnesium deficiency is currently lacking, and the necessity for magnesium supplementation may be unlikely.
  • CorticosteroidsCorticosteroids: According to human research, chronic use of corticosteroids increased urinary magnesium excretion (242). Magnesium-containing antacids have also been found to reduce the bioavailability of corticosteroids, such as prednisone (243).
  • DiureticsDiuretics: In human research and clinical review, diuretics interfered with the kidney's ability to regulate magnesium concentrations (131; 132). Long-term use of loop diuretics or thiazide diuretics may impair the magnesium-conserving ability of the kidneys and lead to hypomagnesemia (133; 134). Conversely, long-term use of potassium-sparing diuretics has been found to increase renal tubular reabsorption of magnesium, which may cause hypermagnesemia in patients also receiving magnesium supplements, especially in patients with renal insufficiency (244). Deray et al. published a report on the treatment of cardiac failure with angiotensin-converting enzyme inhibitors and diuretics (184). The authors also discussed the prevention of the secondary effects of diuretics and ACE inhibitors on renal function, serum sodium, and potassium and magnesium concentrations. Further details are lacking.
  • ElectrolytesElectrolytes: According to a systematic review, electrolyte disturbance has been reported (53).
  • EstrogensEstrogens: According to human research and clinical review, estrogens may enhance magnesium uptake by soft tissues and bones, thus lowering serum levels (248; 249). An inverse relationship between estrogen levels and magnesium serum levels has been reported.
  • Foscarnet (Foscavir?)Foscarnet (Foscavir?): In case reports, foscarnet caused various electrolyte disturbances, including symptomatic hypomagnesemia (250; 251). This may be due to chelation of magnesium and increased elimination.
  • GlucoseGlucose: In clinical research, oral magnesium has been reported to improve glycemic control in type 2 diabetes (45; 46; 49; 105; 106). Concurrent use of magnesium with agents, particularly sulfonylureas (e.g., glipizide), may increase the risk of hypoglycemic by increased rate of absorption (103; 104).
  • Interleukin-2Interleukin-2: Asymptomatic hypomagnesemia may occur with aldesleukin therapy, possibly due to an intracellular shift of magnesium (185). Urinary magnesium did not increase, and serum levels normalized a few days after the drug was discontinued.
  • OleanderOleander: According to a review, magnesium concentrations are not highly likely to be affected in yellow oleander poisoning (273).
  • Panitumumab (Vectibix?)Panitumumab (Vectibix?): According to secondary sources, panitumumab increased renal magnesium excretion, leading to lowered magnesium levels.
  • Pentamidine (NebuPent?, Pentacarinat?, Pentam 300?)Pentamidine (NebuPent?, Pentacarinat?, Pentam 300?): According to case reports, symptomatic hypomagnesemia may occur with pentamidine, particularly if given intravenously (257; 258; 259). This is likely due to renal tubular injury, leading to increased urinary losses of magnesium. Hypomagnesemia usually requires treatment with intravenous, followed by oral, magnesium supplements.
  • PhosphatesPhosphates: Concomitant use of oral preparations in conjunction with magnesium compounds, such as antacids containing magnesium (e.g., magnesium carbonate, magnesium hydroxide), may bind phosphate in the stomach and reduce its absorption (145; 146; 147; 148).
  • Proton pump inhibitors (PPIs)Proton pump inhibitors (PPIs): In clinical research, case studies, and reviews, use of proton pump inhibitors has been associated with decreased magnesium levels (261; 262; 263; 264; 265; 266; 267; 268; 269); severe hypomagnesemia has been reported in some cases (262; 263; 268).
  • Tacrolimus (FK506, Prograf?)Tacrolimus (FK506, Prograf?): In human research, tacrolimus reduced renal tubular reabsorption of magnesium, resulting in increased excretion (270). This has been reported to result in hypomagnesemia in a significant proportion of people treated with tacrolimus.
  • Vitamin DVitamin D: According to a review, large (pharmacological) doses of vitamin D increase the absorption of vitamin D in animal models; however, vitamin D may also increase urinary excretion of magnesium (274).