Mannitol - Warnings and Precautions

5 WARNINGS AND PRECAUTIONS • Hypersensitivity Reactions, including anaphylaxis : Stop infusion immediately if hypersensitivity reactions develop. • Renal Complications Including Renal Failure : Risk factors include pre-existing renal failure, concomitant use of nephrotoxic drugs or other diuretics.

Avoid use of nephrotoxic drugs.

Discontinue OSMITROL if renal function worsens. ( 5.2 , 8.6 ) • Central Nervous System (CNS) Toxicity : Confusion, lethargy and coma may occur during or after infusion.

Concomitant neurotoxic drugs may potentiate toxicity.

Avoid use of neurotoxic drugs.

Discontinue OSMITROL if CNS toxicity develops. • Fluid and Electrolyte Imbalances, Hyperosmolarity : Hypervolemia may exacerbate congestive heart failure, hyponatremia can lead to encephalopathy; hypo/hyperkalemia can result in cardiac adverse reactions in sensitive patients.

Discontinue OSMITROL if fluid and/or electrolyte imbalances occur. • Monitoring/Laboratory Tests : Monitor fluid and electrolytes, serum osmolarity and renal, cardiac and pulmonary function.

Discontinue if toxicity develops. • Infusion Site Reactions : May include irritation and inflammation, as well as severe reactions (compartment syndrome) when associated with extravasation. • Interference with Laboratory Tests : High concentrations of mannitol may cause false low results of inorganic phosphorus blood concentrations.

Mannitol may produce false positive results for blood ethylene glycol. ( 5.7 , 7.6 ) 5.1 Hypersensitivity Reactions Serious hypersensitivity reactions, including anaphylaxis, hypotension and dyspnea resulting in cardiac arrest and death have been reported with OSMITROL [see Adverse Reactions ].

Stop the infusion immediately if signs or symptoms of a suspected hypersensitivity reaction develop.

Initiate appropriate therapeutic countermeasures as clinically indicated.

5.2 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 large intravenous doses of mannitol.

Although the osmotic nephrosis associated with mannitol administration is in principle reversible, osmotic nephrosis in general is known to potentially proceed chronic or even end-stage renal failure.

Monitor renal function closely, including signs of urine output reduction, during OSMITROL infusion.

Patients with pre-existing renal disease, patients with conditions that put them at high risk for renal failure, or those receiving potentially nephrotoxic drugs or other diuretics, are at increased risk of renal failure following administration of OSMITROL.

Avoid concomitant administration of nephrotoxic drugs (e.g., aminoglycosides) or, other diuretics with OSMITROL, if possible [see Drug Interactions (7.1 , 7.2 )].

Patients with oliguric AKI who subsequently develop anuria while receiving mannitol are at risk of congestive heart failure, pulmonary edema, hypertensive crisis, coma and death.

During and following OSMITROL infusion for the reduction in intracranial pressure, monitor the patient clinically and laboratory tests for changes in fluid and electrolyte status.

Discontinue OSMITROL if renal function worsens. [see Warnings and Precautions ].

5.3 Central Nervous System (CNS) Toxicity CNS toxicity manifested by, e.g., confusion, lethargy, coma has been reported in patients treated with mannitol, some resulting in death, in particular in the presence of impaired renal function CNS toxicity may result from high serum mannitol concentrations, serum hyperosmolarity resulting in intracellular dehydration within CNS, hyponatremia or other disturbances of electrolyte and acid/base balance secondary to mannitol administration [see Warnings and Precautions ].

At high concentrations, mannitol may cross the blood brain barrier and interfere with the ability of the brain to maintain the pH of the cerebrospinal fluid especially in the presence of acidosis.

In patients with preexisting compromise of the blood brain barrier, the risk of increasing cerebral edema (general and focal) associated with repeated or continued use of OSMITROL must be individually weighed against the expected benefits.

A rebound increase of intracranial pressure may occur several hours after the infusion.

Patients with a compromised blood brain barrier are at increased risk.