Renal Complication of IVIg

Source: Letter from the FDA, September 29, 1999.

The fda has alerted physicians to the risk of acute renal failure associated with the administration of intravenously administered immune globulin (IVIg). A total of 114 cases of renal dysfunction and acute renal failure have been reported in association with infusion of IVIg; although most patients recovered with supportive care, 17 cases were fatal. Most of the patients were older or had severe underlying disease. Just over half the cases occurred in patients with ITP, who often receive multiple sequential infusions at higher dosages compared with other recipients.

Histopathology available in 15 cases demonstrated acute tubular necrosis, vacuolar degeneration, and osmotic nephrosis—suggestive of osmotic injury to the proximal tubules. Indeed, 88% of U.S. cases of renal toxicity occurred in patients receiving sucrose-containing products, which are hyperosmolar. Available sucrose-containing products include those manufactured by the Central Laboratory, Swiss Red Cross (distributed by Novaritis Pharmaceuticals as Sandoglobulin® and the American Red Cross as Panglobulin®), which are responsible for 69% of reported cases, and Gammar® products, which are responsible for another 22% of reported cases. An additional 9% of cases have been associated with nonsucrose-containing products.

The FDA stressed that caution should be used when administering these products to patients who are elderly, have diabetes, pre-existing renal disease, paraproteinemia, evidence of volume depletion, or hypotension. Patients should be adequately hydrated before receiving these products. While the duration of infusion time has not been analyzed as a factor, these products should be administered as slowly as is practical (no more than 3 mg sucrose/kg/min or approximately 2 mg/kg/min for Sandoglobulin® and Panglobulin® and 1 mg/kg/min for Gammar® -P.I.V. products). You might want to check with your pharmacist for assistance when calculating the timing of an infusion. Patients should be advised of the potential risk of kidney damage and instructed to report any symptoms associated with fluid overload or decreased urine output.

Chronic Leg Ulcers Due to Hydroxyurea

Source: Sirieix ME, et al. Arch Derm 1999;135:818-820.

Hydroxyurea (hu) has been widely used in the suppression of chronic myeloproliferative disorders, as well as, more recently, in the treatment of HIV. A lesser known side effect of this agent is the development of chronic lower extremity ulcerations, which occurs in up to 8.5% of patients with myeloproliferative disorders receiving continuous HU therapy.

Sirieix and colleagues reviewed a total of 41 cases of chronic lower extremity ulcerations in patients receiving chronic maintenance therapy with HU for hematologic malignancy (mean duration of therapy, 5 years). Most of the patients were elderly and had poor wound healing, although there was no evidence of vascular compromise. The ulcerations promptly resolved in 80% of patients when HU was withheld. While the cause is not known, it has been suggested that the ulcerations may be the result of stasis changes from megaloblastic red cells, similar to that seen in hereditary blood dyscrasias, such as thalasemia, sickle cell disease, and spherocytosis. Interestingly, similar lower extremity ulcerations have not been described in patients with HIV infection, although macroerythrocytosis commonly occurs in those receiving zidovudine and HU. Topical GM-CSF has also been described as of potential benefit in the promotion of wound healing in some cases.

Moxifloxacin Penetrates Inflamed Skin

Source:Muller M, et al. Antimicrob Agents Chemother 1999;43:2345-2349.

Moxifloxacin is a promising new quinolone antibiotic with activity similar to trovafloxacin. To investigate the concentration of drug achieved in different body compartments in people, 12 healthy volunteers received a single oral dose of 400 mg or a single intravenous bolus of 400 mg over one hour. Concentrations of drug were measured in cantharides-induced skin blisters, saliva, and capillary plasma. Concentrations of free unbound drug in plasma rapidly equilibrated with the interstitial compartment. While the levels of moxifloxacin in capillary plasma and saliva were similar to that in plasma, the concentration of drug in skin blisters was 50% greater. These data suggest that moxifloxacin has excellent penetration of inflammatory interstitial fluid and damaged soft tissues.