Mannitol
Indications: Edema, cerebral; Hypertension, ocular; Poisoning, adjunct; Renal failure, acute
DESCRIPTION:
Composition - Each 100 ml contains:
TABLE 1
Solution
Mannitol USP
Calculated Osmolarity mOsmol/liter pH
pH
5% Mannitol Injection USP
5.0 g
275
5.3 (4.5-7.0)
10% Mannitol Injection USP
10.0 g
550
5.3 (4.5-7.0)
15% Mannitol Injection USP
15.0 g
825
5.3 (4.5-7.0)
20% Mannitol Injection USP
20.0 g
1100
5.3 (4.5-7.0)
Water for Injection USP qs
Mannitol injections USP function as osmotic diuretics. They are sterile and nonpyrogenic solutions of mannitol in water for injection. Mannitol is a 6-carbon sugar alcohol prepared commercially by the reduction of dextrose. Although inert metabolically in humans, it occurs naturally in fruits and vegetables.
Molecular Weight: 182.17
The plastic container is made from a multilayered film specifically developed for parenteral drugs. It contains no plasticizers. The solution contact layer is a rubberized copolymer of ethylene and propylene. Solutions in contact with the plastic container may leach out certain chemical components from the plastic in very small amounts; however, biological testing was supportive of the safety of the plastic container materials. The container-solution unit is a closed system and is not dependent upon entry of external air during administration. The container is overwrapped to provide protection from the physical environment and to provide an additional moisture barrier when necessary. Exposure to temperatures above 25Β°C/77Β°F during transport and storage will lead to minor losses in moisture content. Higher temperatures lead to greater losses. It is unlikely that these minor losses will lead to clinically significant changes within the expiration period.
The closure system has two ports; the one for the administration set has a tamper evident plastic protector and the other is a medication addition site. Refer to the Directions for Use of the container.
CLINICAL PHARMACOLOGY:
Mannitol is an obligatory osmotic diuretic. When administered parenterally, mannitol is confined to the extracellular space, only slightly metabolized, and rapidly excreted by the kidney. Approximately 80 percent of a typical dose appears in the urine within 3 hours. Mannitol is freely filtered by the glomeruli with less than 10 percent tubular reabsorption; it is not secreted by tubular cells. It induces diuresis by elevating the osmolarity of the glomerular filtrate and thereby hindering tubular reabsorption of water. Excretion of sodium and chloride is also enhanced.
INDICATIONS AND USAGE:
Mannitol injections USP are indicated for:
Reduction of diuresis in the prevention and/or treatment of the oliguric phase of acute renal failure before irreversible renal failure becomes established.
Reduction of intracranial pressure and treatment of cerebral edema by reducing brain mass.
Reduction of elevated intraocular pressure when the pressure cannot be lowered by other means.
Promotion of urinary excretion of toxins.
CONTRAINDICATIONS:
Mannitol injections are contraindicated in:
Well established anuria due to severe renal disease.
Severe pulmonary congestion or frank pulmonary edema.
Active intracranial bleeding except during craniotomy.
Severe dehydration.
Progressive renal damage or dysfunction after institution of mannitol therapy, including increasing oliguria and azotemia.
Progressive heart failure or pulmonary congestion after institution of mannitol therapy.
WARNINGS:
A test dose should be utilized in patients with severe impairment of renal function. A second test dose may be tried if there is an inadequate response, but no more than two test doses should be attempted.
If urine output continues to decline during mannitol infusion, the patient's clinical status should be closely reviewed and mannitol infusion suspended if necessary. Accumulation of mannitol may result in overexpansion of the extracellular fluid which may intensify existing or latent congestive heart failure.
Excessive loss of water and electrolytes may lead to serious imbalances. With rapid or prolonged administration of mannitol, loss of water in excess of electrolytes can cause hypernatremia. Electrolyte measurements including sodium and potassium are therefore of vital importance in monitoring the infusion of mannitol.
Osmotic nephrosis, a reversible vacuolization of the tubules of no known clinical significance, may proceed to severe irreversible nephrosis, requiring close monitoring during mannitol infusion.
Electrolyte-free mannitol solutions should not be given conjointly with blood.
PRECAUTIONS:
General
Clinical evaluation and periodic laboratory determinations are necessary to monitor changes in fluid balance, electrolyte concentrations, and acid-base balance during parenteral therapy with mannitol solutions.
These solutions should be used with care in patients with hypervolemia, renal insufficiency, urinary tract obstruction, or impending or frank cardiac decompensation.
The cardiovascular status of the patient should be carefully evaluated before rapidly administering mannitol since sudden expansion of the extracellular fluid may lead to fulminating congestive heart failure.
Shifting of sodium-free intracellular fluid into the extracellular compartment following mannitol infusion may lower serum sodium concentration and aggravate preexisting hyponatremia.
Mannitol administration may obscure and intensify inadequate hydration or hypovolemia by sustaining diuresis.
If it is essential that blood be given simultaneously, at least 20 mEq of sodium chloride should be added per liter of mannitol solution to avoid agglomeration of erythrocytes. In no other instance should additions be made to Mannitol Injections USP. The addition of sodium chloride to 20% mannitol solutions may result in precipitation of mannitol. The final infusate should therefore be inspected for cloudiness or precipitation immediately after mixing, prior to administration, and periodically during administration.
Solutions of mannitol may crystallize when exposed to low temperatures.
Concentrations greater than 15% have a greater tendency to crystallization. If crystals are observed, the container should be warmed by appropriate means to not greater than 60Β°C, shaken, then cooled to body temperature before administering. If all crystals cannot be completely redissolved, the container must be rejected.
Do not use plastic container in series connection.
If administration is controlled by a pumping device, care must be taken to discontinue pumping action before the container runs dry or air embolism may result.
These solutions are intended for intravenous administration using sterile equipment. It is recommended that intravenous administration apparatus be replaced at least once every 24 hours.
Use only if solution is clear and container and seals are intact.
Carcinogenesis, Mutagenesis, and Impairment of Fertility
Long term studies in animals to evaluate the carcinogenic and mutagenic potential or the effect on fertility of mannitol injection USP have not been conducted.
Pregnancy Category C
Animal reproduction studies have not been conducted with mannitol injections USP. It is also not known whether mannitol injections USP can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Mannitol injections USP should be given to a pregnant woman 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 injections USP are administered to a nursing mother.
Pediatric Use
Safety and effectiveness in children below the age of 12 years have not been established.
ADVERSE REACTIONS:
Reactions which may occur because of the solution or the technique of administration include febrile response, infection at the site of injection, venous thrombosis or phlebitis extending from the site of injection, extravasation and hypervolemia.
Isolated cases of adverse reactions, such as pulmonary congestion, fluid and electrolyte imbalance, acidosis, electrolyte loss, dryness of mouth, thirst, marked diuresis, urinary retention, edema, headache, blurred vision, convulsions, nausea, vomiting, rhinitis, arm pain, skin necrosis, thrombophlebitis, chills, dizziness, urticaria, dehydration, hypotension, tachycardia, fever and angina-like chest pains have been reported during or following mannitol infusion.
Too rapid infusion of hypertonic solutions may cause local pain and venous irritation. Rate of administration should be adjusted according to tolerance. Use of the largest peripheral vein and a small bore needle is recommended. (See DOSAGE AND ADMINISTRATION.)
The physician should also be alert to the possibility of adverse reactions to drug additives. Prescribing information for drug additives to be administered in this manner should be consulted.
If an adverse reaction does occur, discontinue the infusion, evaluate the patient, institute appropriate therapeutic countermeasures and save the remainder of the fluid for examination if deemed necessary.
OVERDOSAGE:
In the event of a fluid or solute overload during parenteral therapy, reevaluate the patient's condition, and institute appropriate corrective treatment.
Larger doses than recommended may result in increased electrolyte excretion, particularly sodium, chloride, and potassium. Sodium depletion can result in orthostatic tachycardia and/or hypotension and decreased central venous pressure. Chloride metabolism closely follows that of sodium. Potassium deficit can impair neuromuscular function and cause intestinal dilation and ileus.
Mannitol may cause pulmonary edema or water intoxication if urine flow is inadequate. See WARNINGS.
DOSAGE AND ADMINISTRATION:
These solutions are for intravenous use only.
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. The usual adult dosage ranges from 50 to 200 g in a 24-hour period, but in most cases an adequate response will be achieved at a dosage of approximately 100 g/24 hours. The rate of administration is usually adjusted to maintain a urine flow of at least 30 to 50 ml/hr. This outline of dosage and administration is only a general guide to therapy.
Dosage requirements for patients 12 years of age and under have not been established. As with adults, dose is dependent on weight, clinical condition, and laboratory results. Follow recommendations of appropriate pediatric reference text.
Test Dose
A test dose of mannitol should be given prior to instituting therapy for patients with marked oliguria or those believed to have inadequate renal function. Such test doses may be approximately 0.2 g/kg of body weight (about 75 ml of a 20% solution, or 100 ml of a 15% solution) infused in a period of 3 to 5 minutes to produce a urine flow of at least 30 to 50 ml/hr. If urine flow does not increase, a second test dose may be given; but if there is an inadequate response, the patient should be reevaluated.
Prevention of Acute Renal Failure (Oliguria)
When used during cardiovascular and other types of surgery, 50 to 100 g of mannitol as a 5%, 10% or 15% solution may be given. The concentration will depend upon the fluid requirements of the patient. Generally, a concentrated solution is given initially followed by a 5% or 10% solution.
Treatment of Oliguria
The usual dose for treatment of oliguria is 100 g administered as a 15% or 20% solution.
Reduction of Intracranial and Intraocular Pressure
A dose of 1.5 to 2 g/kg as a 20% solution (7.5 to 10 ml/kg) or as a 15% solution (10 to 13 ml/kg) may be given over a period as short as 30 minutes in order to obtain a prompt and maximal effect. When used preoperatively, the dose should be given one to one and one-half hours before surgery to achieve maximal reduction of pressure before operation.
Adjunctive Therapy for Intoxications
As an agent to promote diuresis in intoxications, 5%, 10%, 15% or 20% mannitol is indicated. The concentration will depend upon the fluid requirement and the urinary output of the patient. Generally, a bolus dose of 15% or 20% mannitol is given followed by a slower infusion of 5% mannitol (with electrolytes) to maintain urine output at the desired level.
It is recommended that 20% mannitol injection USP be administered through a blood filter set to ensure against infusion of mannitol crystals.
When a hypertonic solution is to be administered peripherally, it should be slowly infused through a small bore needle, placed well within the lumen of a large vein to minimize venous irritation. Carefully avoid infiltration.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Directions for Use of Excel Container
Do not admix with other drugs.
Caution: Do not use plastic container in series connection.
To Open
Tear overwrap down at notch and remove solution container. Check for minute leaks by squeezing solution container firmly. If leaks are found, discard solution as sterility may be impaired.
Note: Before use, perform the following checks:
Inspect each container. Read the label. Ensure solution is the one ordered and is within the expiration date.
Invert container and carefully inspect the solution in good light for cloudiness, haze, or particulate matter. Any container which is suspect should not be used.
Use only if solution is clear and container and seals are intact.
Preparation for Administration
1. Remove plastic protector from sterile set port at bottom of container.
2. Attach administration set. Refer to complete directions accompanying set.