Sucrose suspected in cases of IVIG-associated renal failures
Study instigated during product shortage
The U.S. Food and Drug Administration has issued an alert concerning the growing number of cases of acute renal failure in patients receiving IVIG. The alert coincides with an assessment by the FDA’s Center for Biologics Evaluation and Research that the shortage of IVIG product dating to mid-1998 is expected to continue indefinitely. (See "IVIG shortage brings federal oversight," Drug Utilization Review, September 1998, p. 156.)
The agency is not linking the adverse reactions to the shortage but is saying 88% of the renal failure reports have been associated with IVIG that contains sucrose. "The hyperosmolality of some reconstituted products and differences in stabilizer sugar choice and content are factors," says Jay Epstein, director of the office of blood research and review. Along with compiling MedWatch cases matched to IVIG manufacturers, distributors, and approved uses (see tables, below and on p. 30), the FDA had identified which products contain sucrose. They are Sandoglobulin and Pangloglo bulin, distributed by Novartis and the American Red Cross, respectively, and both manufactured by the Swiss Red Cross; and the Centeon-manufactured products Gammar P.I.V. and Gammar I.V.
The FDA also has found that 55% of renal failures occurred in patients being treated for idiopathic thrombocytopenia purpura (ITP), while just 5% of the reports concerned primary immune deficiency (PID) treatment. "This may relate to the fact that higher and consecutive doses are used for ITP" than for PID, Epstein notes.
Revise prescribing information
As those details are sorted out, the agency is directing manufacturers to revise prescribing information with new package inserts warning of acute renal failure reports, which also will include new dosage and administration recommendations currently being investigated.
In the meantime, the agency advocates current recommendations along with renal function (urine output, blood urea nitrogen/serum creatinine) testing and advises against reduced doses simply because no data exist to support them.
Specifically, for the IVIGs containing sucrose, the FDA recommends a maximum infusion rate of 3 mg sucrose/kg/min (2 mg Ig/kg/min for Sandoglobulin and Pangloglobulin; 3 mg Ig/kg/min for Gammar P.I.V.).
In terms of the IVIG shortage, the agency says overseas manufacturers using American plasma sources are seeking approval to market the product domestically, which should help meet demand and build reserves this year.
For more information, contact Jay Epstein in the FDA’s office of blood research and review, (301) 594-6758. Or call the FDA’s MedWatch program toll-free at (800) FDA-1088.
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