Mannitol (Page 2 of 4)

5.4 Fluid and Electrolyte Imbalances, Hyperosmolarity

​ Depending on dosage and duration, administration of Mannitol Injection may result in hypervolemia leading to or exacerbating existing congestive heart failure. Accumulation of mannitol due to insufficient renal excretion increases the risk of hypervolemia. Mannitol-induced osmotic diuresis may cause or worsen dehydration/hypovolemia and hemoconcentration. Administration of Mannitol Injection may also cause hyperosmolarity [see Description (11)].

​ Depending on dosage and duration of administration, electrolyte and acid/base imbalances may also result from transcellular shifts in water and electrolytes, osmotic diuresis, and/or other mechanisms. Such imbalances may be severe and potentially fatal.

​ Imbalances that may result from administration of Mannitol Injection include:

• ​ Hypernatremia, dehydration, and hemoconcentration
• ​ Hyponatremia, which can lead to headache, nausea, seizures, lethargy, coma, cerebral edema, and death. Acute symptomatic hyponatremic encephalopathy is considered a medical emergency.
• ​ Hypo/hyperkalemia. The development of electrolyte imbalances (e.g., hyperkalemia, hypokalemia) associated with mannitol administration may result in cardiac adverse reactions in patients receiving drugs that are sensitive to such imbalances (e.g., digoxin, agents that may cause QT prolongation, neuromuscular blocking agents) [see Drug Interactions (7.4)].
• ​ Other electrolyte disturbances
• ​ Metabolic acidosis/alkalosis

​ Pediatric patients less than two years of age, particularly preterm and term neonates, may be at higher risk for fluid and electrolyte abnormalities following administration of Mannitol Injection due to decreased glomerular filtration rate and limited ability to concentrate urine [see Use in Specific Populations (8.4)].

​ During and following infusion of Mannitol Injection for the reduction in intracranial pressure, monitor fluid and electrolyte status and discontinue Mannitol Injection if imbalances occur [see Warnings and Precautions (5.5)].

5.5 Monitoring/Laboratory Tests

​ During and following infusion of Mannitol Injection for the reduction in intracranial pressure, monitor:

• ​ serum osmolarity, serum electrolytes (including sodium, potassium, calcium and phosphate) and acid/base balance,
• ​ the osmol gap
• ​ signs of hypo- or hypervolemia, including urine output
• ​ renal, cardiac, and pulmonary function
• ​ intracranial pressure

​ Discontinue Mannitol Injection if renal, cardiac, or pulmonary status worsens or CNS toxicity develops [see Contraindications (4)].

5.6 Infusion Site Reactions

​ The infusion of hypertonic solutions through a peripheral vein, including Mannitol Injection, may result in peripheral venous irritation, including phlebitis. Other severe infusion site reactions, such as compartment syndrome and swelling associated with extravasation, can occur with administration of Mannitol Injection [see Adverse Reactions (6)]. Mannitol Injection is preferably administered through a central venous catheter [see Dosage and Administration (2.1)].

5.7 Interference with Laboratory Tests

​ High concentrations of mannitol can cause false low results for inorganic phosphorus blood concentrations [see Drug Interactions (7.6)].

​ Mannitol may produce false positive results in tests for blood ethylene glycol concentrations [see Drug Interactions (7.6)].

6 ADVERSE REACTIONS

The following adverse reactions associated with the use mannitol were identified in clinical studies or postmarketing reports. Because some of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Hypersensitivity reactions:	Cardiac arrest, anaphylaxis, hypotension, dyspnea, hypertension, pyrexia, chills, sweating, cough, musculoskeletal stiffness, myalgia, urticaria/rash, pruritus, generalized pain, discomfort, nausea, vomiting, headache [see Warnings and Precautions (5.1)]
Renal failure:	Acute kidney injury, osmotic nephrosis, anuria, oliguria, urinary retention [see Warnings and Precautions (5.2)]
CNS toxicity:	Coma, seizures, confusion, lethargy, rebound increase in intracranial pressure, headache, dizziness [see Warnings and Precautions (5.3)]
Fluid and electrolyte imbalances:	Metabolic acidosis, dehydration (hypovolemia), hypervolemia, hyponatremia, hypernatremia, hyperkalemia, hypokalemia [see Warnings and Precautions (5.4)]
Infusion site reactions:	Venous thrombosis, thrombophlebitis extending from the site of injection, compartment syndrome and swelling associated with extravasation [see Warnings and Precautions 5.6)]
Cardiac and respiratory disorders:	Tachycardia, angina-like chest pain, congestive heart failure, pulmonary congestion, hypotension, edema, rhinitis
Gastrointestinal disorders:	Dryness of mouth, nausea, vomiting
General disorders:	Thirst

7 DRUG INTERACTIONS

7.1 Nephrotoxic Drugs

Concomitant administration of nephrotoxic drugs (e.g., cyclosporine, aminoglycosides) increases the risk of renal failure following administration of mannitol. Avoid use of nephrotoxic drugs with Mannitol Injection, if possible [see Warnings and Precautions (5.2)].

7.2 Diuretics

Concomitant administration of other diuretics may potentiate the renal toxicity of mannitol. Avoid concomitant administration of other diuretics with Mannitol Injection, if possible [see Warnings and Precautions (5.2)].

7.3 Neurotoxic Drugs

Concomitant administration of systemic neurotoxic drugs (e.g., aminoglycosides) with Mannitol Injection may potentiate the CNS toxicity of mannitol. Avoid use of systemic neurotoxic drugs with Mannitol Injection, if possible [see Warnings and Precautions (5.3)].

7.4 Drugs Affected by Electrolyte Imbalances

The development of electrolyte imbalances (e.g., hyperkalemia, hypokalemia) associated with mannitol administration may result in cardiac adverse reactions in patients receiving drugs that are sensitive to such imbalances (e.g., digoxin, drugs that prolong the QT interval, neuromuscular blocking agents) [see Warnings and Precautions (5.4)]. During and following infusion of Mannitol Injection, monitor serum electrolytes and discontinue Mannitol Injection if cardiac status worsens [ see Warnings and Precautions (5.5)].