NEODOSE

Pediatric FDA Approved Indications

Intravenous •Reduction of intracranial pressure and treatment of cerebral edema . •Reduction of high intraocular pressure Administration Injection: •For IV infusion, preferably into a central vein . •Do not administer simultaneously with blood products through the same administration set because of the possibility of pseudoagglutination or hemolysis . •Use administration sets with a final in-line filter because of potential for crystals to form . •Use a non-vented infusion set or close the vent on a vented set, avoid multiple connections, and do not connect flexible containers in series to prevent air embolism •Fully evacuate residual gas in the container prior to administration and do not pressurize the flexible container to increase flow rates to prevent air embolism •If administration is controlled by a pumping device, turn off pump before the container runs dry to prevent air embolism •For single use only. Discard unused portion .

Contraindications

IV formulation [1] Anuria Severe hypovolemia Active intracranial bleeding, except during craniotomy Preexisting severe pulmonary vascular congestion or pulmonary edema

Precautions

Intravenous Administration: Peripheral venous irritation, including phlebitis, can occur when concentrations of 10% or greater are used Administration: Severe infusion site reactions (eg, compartment syndrome and swelling associated with extravasation) can occur Cardiovascular: Hypervolemia may occur and can lead to or exacerbate existing congestive heart failure; increased risk with accumulation of mannitol due to insufficient renal excretion Cardiovascular: Osmotic diuresis due to mannitol may cause or worsen dehydration/hypovolemia and hemoconcentration; hyperosmolarity may also occur Cardiovascular: Fluid and electrolyte imbalance (eg, hypernatremia, hyponatremia, hypokalemia, hyperkalemia, and metabolic acidosis/alkalosis), including severe and potentially fatal imbalances, may occur; increased risk in pediatric patients younger than 2 years, particularly preterm and term neonates; monitoring recommended and discontinuation may be required Concomitant use: with neurotoxic and nephrotoxic drugs (eg, aminoglycosides) or other diuretics should be avoided, if possible Endocrine and metabolic: Hyponatremia, new-onset or exacerbation, may occur Immunologic: Serious hypersensitivity reactions, including anaphylaxis, hypotension, and dyspnea resulting in cardiac arrest and death, have been reported with mannitol injection; if hypersensitivity reaction occurs, stop infusion immediately Neurological: CNS toxicity (eg, confusion, lethargy, coma) has been reported with some cases resulting in fatalities; monitoring recommended and discontinuation of therapy may be necessary Neurologic: 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 Neurologic: Preexisting compromise of the blood brain barrier; increased risk of increasing cerebral edema (general and focal) associated with repeated or continued use Neurologic: Rebound increase in intracranial pressure may occur several hours after infusion; increased risk in patients with compromised blood brain barrier Renal: Renal complications, including irreversible renal failure, have been reported; discontinuation may be required

Renal: Reversible, oliguric acute kidney injury (AKI) has occurred in patients with normal renal function who received large IV doses; patients with oliguric AKI who develop anuria during therapy have increased risk of congestive heart failure, pulmonary edema, hypertensive crisis, coma, and death; monitor during and following administration; discontinuation may be required Renal: Osmotic nephrosis can occur with potential to lead to chronic or end-stage renal failure; increased risk with preexisting renal disease or concomitant use of nephrotoxic agents and other diuretics; monitoring recommended Renal: Urine output, inadequate; during infusion could lead to water intoxication or congestive heart failure; monitoring recommended and infusion suspension may be necessary.

Adverse Effects

Common: Hypersensitivity reactions, renal failure, CNS toxicity, hypo/hypervolemia, hypo/hypernatremia, hypo/hyperkalemia, and infusion site reactions .

Monitoring

Intravenous: •Monitor for hypersensitivity reactions during and following infusion, including laboratory tests for changes in fluid and electrolyte status . •Closely monitor renal function, especially in patients with renal disease, conditions that put them at high risk for renal failure, or those receiving potentially nephrotoxic drugs or other diuretics . Monitor during and after reduction of Intracranial pressure: Serum osmolarity Fluid and serum electrolytes, including sodium, potassium, calcium, and phosphate Acid base balance Osmol gap Signs of hypovolemia and hypervolemia, including urine output Renal function Cardiac function Pulmonary function Intracranial pressure