For Intravenous Injection: Mannitol Injection, USP is indicated for:

1. Promotion of diuresis, in the prevention and/or treatment of the oliguric phase of acute renal failure before irreversible renal failure becomes established.
2. Reduction of intracranial pressure and treatment of cerebral edema by reducing brain mass.
3. Reduction of elevated intraocular pressure when it cannot be lowered by other means.
4. Promotion of urinary excretion of toxic substances.

For Urologic Irrigation: Mannitol solution, 2.5 percent, is indicated for irrigation in transurethral prostatic resection or other transurethral surgical procedures.

General: If crystals are present in mannitol, 25 percent solution, dissolve only by one of two methods: 1. Heat water bath to 80°C. Remove it from heat source then immerse vial (15-20 minutes), or, 2. Autoclave for 20 minutes at 120°C (15 psi). As soon as cool enough to handle, shake gently several times. The heat treatment can be repeated as often as necessary if the crystals have not completely dissolved or have reformed. Allow to cool to body temperature before use. Do not use vial if crystals are present.

NOTE: Use of other methods to heat the vial may result in its explosion.

The cardiovascular status should be carefully evaluated before use of mannitol rapidly intravenously or before and during transurethral resection since expansion of extracellular fluid may lead to fulminating congestive heart failure.

By sustaining diuresis, mannitol may obscure and intensify inadequate hydration or hypovolemia.

Unless it is essential, electrolyte-free mannitol solutions should not be combined with blood. When it is essential to give the combination, at least 20 mEq of sodium chloride should be added to each liter of mannitol solution to avoid pseudoagglutination.

Carcinogenesis, Mutagenesis, Impairment of Fertility: In an early study of 1, 5 or 10 percent mannitol, given for 94 weeks in the diet of Wistar rats, a low incidence of benign thymomas occurred in females which was apparently treatment related. A subsequent life-time study at similar dose levels in Spraque-Dawley, Fischer, and Wistar rats revealed no carcinogenic effect in the thymus.

Mannitol had no mutagenic activity in a series of in vitro and in vivo test systems.

Adequate studies measuring the effects of mannitol on fertility have not been done.

Pregnancy: Pregnancy Category B: Teratogenic studies in the mouse, rat, and rabbit at oral doses up to 1600 mg/kg did not reveal harm to the fetus or adverse effects on reproduction due to mannitol. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Nursing Mothers: It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when mannitol is given to a nursing mother.

Pediatric Use: Dosage requirements in children below the age of 12 years have not been established.

For Intravenous Injection: General Recommendations – Give mannitol injection only intravenously. The total dosage, concentration and rate of administration should be governed by the nature and severity of the condition being treated, fluid requirement and urinary output.

Usual adult dosage ranges from 50 to 200 g in 24 hours but in most instances an adequate response will be achieved at a dosage of approximately 100 g in 24 hours. The rate is usually adjusted to maintain an adequate urine flow (at least 30 to 50 mL an hour).

Test Dose – In marked oliguria or inadequate renal function a test dose of mannitol should be given. The test dose may be approximately 0.2 g/kg (about 50 mL of a 25% solution) infused in 3 to 5 minutes to produce an adequate urine flow (at least 30 to 50 mL/hr). If urine flow does not increase within 2 or 3 hours a second test dose may be given. If there is an inadequate response the patient should be re-evaluated.

Prevention of Acute Renal Failure (Oliguria): When used during surgery, immediately postoperatively or following trauma, 50 to 100 g of mannitol as a 5 to 25 percent solution may be given. The concentration and amount will depend upon the fluid requirements of the patient. Following suspected or actual hemolytic transfusion reactions 20 g of mannitol may be given intravenously over a 5 minute period to provoke diuresis. If diuresis does not occur the 20 g dose may be repeated. If there is an adequate urine flow (30 to 50 mL an hour) then intravenous fluids containing not more than 50 to 75 mEq of sodium per liter should be given in sufficient volume to match the desired urine flow (100 mL/hr) until fluids can be taken orally.

Treatment of Oliguria: The usual dose for treatment of oliguria is 50 to 100 g as a 15 to 25 percent solution.

Reduction of intracranial pressure, cerebral edema or intraocular pressure: A 25 percent solution of mannitol is recommended since its effectiveness depends on establishing intravascular hyperosmolarity. When used before or after surgery, a total dose of 1.5 to 2 g/kg can be given over a period of 30 to 60 minutes. Careful evaluation must be made of the circulatory and renal reserve prior to and during use of mannitol at this relatively high dose and rapid infusion rate. Careful attention must be paid to fluid and electrolyte balance, body weight, and total input and output before and after infusion of mannitol. Evidence of reduced cerebral spinal fluid pressure may be observed within 15 minutes after starting infusion.

Maximal reduction of intraocular pressure occurs 30 to 60 minutes after injection.

Urinary excretion of toxic substances: Mannitol in 5 to 25 percent solutions is used as an infusion as long as indicated if the level of urinary output remains high. The concentration will depend upon the fluid requirement and urinary output. Intravenous water and electrolytes must be given to replace the loss of these substances in the urine, sweat and expired air. If benefits are not observed after 200 g of mannitol are given discontinue it.

PREPARATION OF SOLUTION for intravenous injection: