Mannitol

MANNITOL- mannitol injection, solution
Hospira, Inc.

1 INDICATIONS AND USAGE

​ Mannitol Injection is indicated for the reduction of:

• ​ intracranial pressure and treatment of cerebral edema.
• ​ elevated intraocular pressure.

2 DOSAGE AND ADMINISTRATION

2.1 Important Preparation and Administration Instructions

• Mannitol Injection is for intravenous infusion preferably through a central venous catheter [see Warnings and Precautions (5.6), Description (11)].
• Prior to the administration of Mannitol Injection, evaluate renal, cardiac, and pulmonary status of the patient and correct fluid and electrolyte imbalances [see Dosage and Administration (2.2)].
• Do not administer Mannitol Injection simultaneously with blood products or through the same administration set because of the possibility of pseduoagglutination or hemolysis. 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.
• Do not transfer Mannitol Injection into polyvinylchloride (PVC) bags; a white flocculent precipitate may form from contact with PVC surfaces.
• Administer Mannitol Injection using an administration set with a filter to ensure against infusion of mannitol crystals.

Preparation

1. Visually inspect the container before preparation and again before administration. Do not administer unless solution is clear, the container undamaged, and the fliptop vial seal intact.
2. Crystals may form in Mannitol Injection, especially if the solution is exposed to low temperatures. If crystallization occurs, warm the vial in water at 80°C and periodically shake vigorously to dissolve the crystals. Mannitol Injection may be autoclaved at 121°C for 20 minutes at 15 psi. Cool to body temperature or less before administering. Re-inspect Mannitol Injection for crystals prior to administration. Discard the solution if all the crystals cannot be dissolved.
3. Remove cover from fliptop vial and cleanse stopper with antiseptic before use.
4. Additives may be incompatible. Consult with pharmacist, if available.
5. For single use only; discard unused portion.

2.2 Recommended Dosage

Prior to administration of Mannitol Injection, evaluate renal, cardiac, and pulmonary status of the patient and correct fluid and electrolyte imbalances.

The total dosage, concentration, and rate of administration depend on the age, weight, and condition of the patient being treated, including fluid requirement, electrolyte balance, serum osmolality, urinary output, and concomitant therapy.

The following outline of administration and dosage is only a general guide to therapy.

Reduction of Intracranial Pressure and Treatment of Cerebral Edema

Usually a maximum reduction in intracranial pressure can be achieved with a dose of 0.25 g/kg administered as an intravenous infusion over at least 30 minutes, which may be repeated every six to eight hours. During and following infusion of Mannitol Injection, monitor fluid and electrolytes, serum osmolarity, and renal, cardiac, and pulmonary function. Discontinue Mannitol Injection if renal, cardiac, or pulmonary status worsens or CNS toxicity develops [see Warnings and Precautions (5.2, 5.3, 5.4, 5.5)].

Reduction of Intraocular Pressure

The recommended dosage is 1.5 to 2 g/kg as a single dose administered as an intravenous infusion over at least 30 minutes. When used preoperatively, administer Mannitol Injection 60 to 90 minutes before surgery to achieve maximal reduction of intraocular pressure before operation.

3 DOSAGE FORMS AND STRENGTHS

Mannitol Injection 25%, USP: 12.5 g/50 mL (0.25 g/mL) of mannitol as a clear and colorless solution in a single-dose vial.

4 CONTRAINDICATIONS

​ Mannitol Injection is contraindicated in patients with:

• ​ Known hypersensitivity to mannitol [see Warnings and Precautions (5.1)].
• ​ Anuria [see Warnings and Precautions (5.2)].
• ​ Severe hypovolemia [see Warnings and Precautions (5.4)].
• ​ Pre-existing severe pulmonary vascular congestion or pulmonary edema [see Warnings and Precautions (5.5)].
• ​ Active intracranial bleeding except during craniotomy.

5 WARNINGS AND PRECAUTIONS

5.1 Hypersensitivity Reactions

​ Serious hypersensitivity reactions, including anaphylaxis, hypotension, and dyspnea resulting in cardiac arrest and death have been reported with Mannitol Injection [ see Adverse Reactions (6)]. 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 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 mannitol injection.

​ 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 following administration of Mannitol Injection. Avoid concomitant administration of nephrotoxic drugs (e.g., aminoglycosides) or other diuretics with Mannitol Injection, if possible [see Drug Interactions (7)].

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

​ During and following infusion of Mannitol Injection for the reduction in intracranial pressure, monitor the patient clinically and laboratory tests for changes in fluid and electrolyte status. Discontinue Mannitol Injection if renal function worsens [see Warnings and Precautions (5.5)].

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 (5.4)].

​ 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 pre-existing compromise of the blood brain barrier, the risk of increasing cerebral edema (general and focal) associated with repeated or continued use of Mannitol Injection 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.

​ Concomitant administration of neurotoxic drugs (e.g., aminoglycosides) with Mannitol Injection may potentiate neurotoxicity. Avoid concomitant use of neurotoxic drugs, if possible [see Drug Interactions (7.3)].

​ During and following infusion of Mannitol Injection for the reduction in intracranial pressure, monitor the patient clinically and laboratory tests for changes in fluid and electrolyte status. Discontinue Mannitol Injection if CNS toxicity develops [see Warnings and Precautions (5.5)].