Other reasons for aggressive replacement in patients with grade 3/4 hypomagnesemia include the risk of cardiac arrhythmias. Indeed, cases of sudden death have been reported on some studies of cetuximab(Drug information on cetuximab) and radiation therapy. Whether death in these cases was related to hypomagnesemia is unclear.
Magnesium replacement in patients with severe, grade 3/4 hypomagnesemia can be very challenging. Weekly intravenous replacement is typically inadequate, as serum magnesium levels tend to fall back to the low baseline level within 3 to 4 days. Our experience suggests that these patients require about 6 to 10 g of magnesium sulfate(Drug information on magnesium sulfate) daily to twice weekly, dependent on the patient. An initial strategy of IV replacement and every-other-day serum magnesium monitoring is helpful to guide the frequency of replacement until a steady state is reached. In some patients, magnesium wasting worsens despite ongoing replacement. We have treated a case of ongoing grade 4 hypomagnesemia despite daily 10-g magnesium sulfate replacement.
It is important to note that an aggressive replacement strategy may be associated with significant patient inconvenience. For example, a magnesium sulfate dose of 8 g will require an infusion time of 4 hours, which can be socially limiting when administered on a daily basis. Furthermore, frequent intravenous infusions will require central venous accessing, which may increase the risk of infections.An alternative strategy for patients requiring frequent magnesium sulfate infusion, if they do not have a large tumor burden, may be to consider a stop-and-go approach to anti-EGFR monoclonal antibody therapy. Usually, serum magnesium levels correct within 6 weeks of stopping cetuximab. The rechallenge of patients with cetuximab after reversal of magnesium wasting (4–8 weeks after a cetuximab break) usually does not result in reoccurrence of grade 3/4 hypomagnesemia before another 6 to 8 weeks. Thus, a 2-month stop-and-go approach may decrease or eliminate the need of magnesium replacement in patients with severe cetuximab-induced hypomagnesemia. We have found this approach to be successful in several patients with grade 4 hypomagnesemia.
—Marwan Fakih, MD