warnings and cautions
5 WARNINGS AND PRECAUTIONS 5.1 Renal Complications Including Renal Failure Renal complications, including irreversible renal failure have been reported in patients receiving mannitol. Reversible, oliguric acute kidney injury (AKI) has occurred in patients with normal pretreatment renal function who received mannitol. Osmotic nephrosis, a reversible vacuolization of the tubules of no known clinical significance, may proceed to severe irreversible nephrosis, so that the renal function must be closely monitored during mannitol infusion. Patients with pre-existing renal disease, patients with conditions that put them at risk for renal failure, or those receiving potentially nephrotoxic drugs or other diuretics, are at increased risk for renal failure. Avoid concomitant administration of nephrotoxic drugs (e.g., aminoglycosides) or other diuretics with mannitol [see Drug Interactions (7) ]. If urine output declines during mannitol infusion, the patient's clinical status should be closely reviewed and mannitol infusion suspended if necessary. 5.2 Fluid and Electrolyte Imbalances The obligatory diuretic response following rapid infusion of 25% mannitol may further aggravate pre-existing hemoconcentration. Excessive loss of water and electrolytes may lead to serious imbalances. With continued administration of mannitol, loss of water in excess of electrolytes can cause hypernatremia. Electrolyte measurements, including sodium and potassium are therefore of vital importance in monitoring the infusion of mannitol. The shift of sodium-free intracellular fluid into the extracellular compartment following mannitol infusion may lower serum sodium concentration and aggravate pre-existing hyponatremia. By sustaining diuresis, mannitol administration may obscure and intensify inadequate hydration or hypovolemia. Accumulation of mannitol may result in overexpansion of the extracellular fluid which may intensify existing or latent congestive heart failure. The cardiovascular status of the patient should be carefully evaluated before rapidly administering mannitol since sudden expansion of the extracellular fluid may lead to fulminating congestive heart failure. 5.3 Central Nervous System (CNS) Toxicity Mannitol injection may increase cerebral blood flow and the risk of postoperative bleeding in neurosurgical patients. Mannitol may increase cerebral blood flow and worsen intracranial hypertension in children who develop generalized cerebral hyperemia during the first 24 to 48 hours post injury. 5.4 Monitoring Serum sodium and potassium should be carefully monitored during mannitol administration. If an adverse reaction does occur, discontinue the infusion, evaluate the patient, institute appropriate therapeutic counter measures and save the remainder of the fluid for examination if deemed necessary. Electrolyte-free mannitol solutions should not be given conjointly with blood. If it is essential that blood be given simultaneously, at least 20 mEq of sodium chloride should be added to each liter of mannitol solution to avoid pseudoagglutination. When exposed to low temperatures, solutions of mannitol may crystallize. If crystals are observed, the container should be warmed to redissolve, then cooled to body temperature before administering [see How Supplied/Storage and Handling (16) ]. When infusing 25% mannitol, the administration set should include a filter. Do not infuse mannitol solution if crystals are present.