MANNITOL- mannitol injection, solution
ICU Medical Inc.
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use MANNITOL INJECTION safely and effectively. See full prescribing information for MANNITOL INJECTION.
MANNITOL injection, for intravenous use
Initial U.S. Approval: 1964
RECENT MAJOR CHANGES
INDICATIONS AND USAGE
DOSAGE AND ADMINISTRATION
Administration Instructions (2.1):
Recommended Dosage (2.2):
DOSAGE FORMS AND STRENGTHS
Injection: 20% (0.2 grams/mL); 20 grams of mannitol, USP per 100 mL in single-dose 250 mL and 500 mL flexible containers (3)
WARNINGS AND PRECAUTIONS
The most common adverse reactions are hypersensitivity reactions, renal failure, CNS toxicity, hypo/hypervolemia, hypo/hypernatremia, hypo/hyperkalemia, and infusion site reactions. (6)
To report SUSPECTED ADVERSE REACTIONS, contact name ICU Medical, Inc. at 1-800-441-4100 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
See 17 for PATIENT COUNSELING INFORMATION.
FULL PRESCRIBING INFORMATION: CONTENTS*
Manitol Injection solutions may crystalize when exposed to low temperatures. Inspect Mannitol Injection for crystals prior to administration. If crystals are visible, re-dissolve by warming the solution up to 70°C with agitation. Heat solution by using a dry-heat cabinet with overwrap intact. The use of a water bath is not recommended. Allow the solution to cool to body temperature or less before administering. Reinspect Mannitol Injection for crystals prior to administration. Discard the solution if all the crystals cannot be dissolved.
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 gram/kg given intravenously as an intravenous infusion over at least 30 minutes, which may be repeated every six to eight hours.
During and following Mannitol Injection infusion, 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.
Injection: 20% (0.2 grams/mL); 20 grams of mannitol, USP per 100 mL as a clear and colorless solution in single-dose 250 mL and 500 mL flexible containers
The following adverse reactions from voluntary reports or clinical studies have been reported with Mannitol Injection. Because many 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.
Concomitant administration of nephrotoxic drugs (e.g., aminoglycosides, cyclosporine) 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)].
Concomitant administration of other diuretics may potentiate the renal toxicity of mannitol. Avoid use of other diuretics with Mannitol Injection, if possible [see Warnings and Precautions (5.2)].
Concomitant administration of systemic neurotoxic drugs (e.g., aminoglycosides) with Mannitol Injection may potentiate the CNS toxicity of mannitol. Avoid concomitant administration of neurotoxic drugs with mannitol [see Warnings and Precautions (5.3)].
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 Mannitol Injection infusion, monitor serum electrolytes and discontinue Mannitol Injection if cardiac status worsens [see Warnings and Precautions (5.5)].
Mannitol may increase the elimination, and decrease the effectiveness of treatment with, drugs that undergo significant renal elimination. Concomitant administration of mannitol with lithium may initially increase the elimination of lithium but may also increase the risk of lithium toxicity in patients who develop hypovolemia or renal impairment. Consider holding lithium therapy during treatment with Mannitol Injection. If lithium therapy cannot be held, monitor serum lithium concentrations frequently for signs of lithium toxicity. Mannitol therapy may increase the elimination of digoxin leading to a potential decrease in effectiveness of the treatment. Monitor digoxin serum concentrations.
High concentrations of mannitol can cause false low results for inorganic phosphorus blood concentrations when an assay based on the conversion of phosphate (orthophosphate) to the phosphomolybdate complex is used [see Warnings and Precautions (5.7)].
Mannitol may produce false positive results in tests for blood ethylene glycol concentrations in which mannitol is initially oxidized to an aldehyde [see Warnings and Precautions (5.7)].
The available case report data with mannitol over decades of use have not identified a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Mannitol crosses the placenta and may cause fluid shifts that could potentially result in adverse effects in the fetus (see Data). No adverse developmental effects from mannitol were reported in published animal studies; however, fluid shifts occurred in fetal ewes in response to maternal infusion of mannitol.
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
There are no data on the presence of mannitol in either human or animal milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Mannitol Injection and any potential adverse effects on the breastfed infant from Injection or from the underlying maternal condition.
Mannitol Injection is approved for use in the pediatric population for the reduction of intracranial and intraocular pressure. Studies have not defined the optimal dose of Mannitol Injection in the pediatric population. The safety profile for mannitol use in pediatric patients is similar to adults at dosages described in labeling. However, pediatric patients less than two years of age, particularly preterm and term neonates, may be at higher risk for fluid and electrolyte abnormalities following Mannitol Injection administration due to decreased glomerular filtration rate and limited ability to concentrate urine [see Warnings and Precautions (5.4)].
Mannitol is known to be substantially excreted by the kidney and the risk of adverse reactions to this drug may be greater in elderly patients with impaired renal function. Evaluate the renal, cardiac, and pulmonary status of the patient and correct fluid and electrolyte imbalances prior to administration of Mannitol Injection [see Warnings and Precautions (5.2, 5.3, 5.4, 5.5)].
Patients with pre-existing renal disease, patients with conditions that put them at high risk of renal failure, or those receiving potentially nephrotoxic drugs or other diuretics, are at increased risk of renal failure with administration of mannitol. Evaluate the renal, cardiac, and pulmonary status of the patient and correct fluid and electrolyte imbalances prior to administration of Mannitol Injection [see Warnings and Precautions (5.2, 5.3, 5.4, 5.5)].
Signs and symptoms of overdose with Mannitol Injection include renal failure and acute kidney injury, hypo/hypervolemia, hyperosmolarity and electrolyte imbalances, CNS toxicity (e.g., coma, seizures), some of which can be fatal [see Warnings and Precautions (5.2, 5.3, 5.4)].
Management of overdosage with Mannitol Injection is symptomatic and supportive. Discontinue the infusion and institute appropriate corrective measures with particular attention to renal, cardiac and pulmonary systems. Correct fluid and electrolyte imbalances.
Mannitol Injection is dialyzable (hemodialysis and peritoneal dialysis), hemodialysis may increase Mannitol Injection elimination.
Mannitol Injection, USP is a sterile, nonpyrogenic solution of mannitol in water for injection available in a concentration of 20% in flexible plastic containers.
The content and characteristics of the available concentration is as follows:
|Concentration (%)||g/100 mL||mOsmol/liter (calc.)||pH*|
|20||20||1098||6.3 (4.5 to 7.0)|
The solution contains no bacteriostat, antimicrobial agent or added buffer (except for pH adjustment) and is intended only as a single-dose injection. When smaller doses are required the unused portion should be discarded.
Mannitol Injection, USP is an osmotic diuretic for intravenous administration.
Mannitol, USP is chemically designated D-mannitol (C6H14O6), a white crystalline powder or free-flowing granules freely soluble in water. It has the following structural formula:
Water for Injection, USP is chemically designated H2O.
The flexible plastic container is fabricated from a specially formulated polyvinylchloride. Water can permeate from inside the container into the overwrap, but not in amounts sufficient to affect the solution significantly. 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. Exposure to temperatures above 25°C/77°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.
Mannitol, when administered intravenously, exerts its osmotic diuretic effect as a solute of relatively small molecular size being largely confined to the extracellular space. Mannitol hinders tubular reabsorption of water and enhances excretion of sodium and chloride by elevating the osmolarity of the glomerular filtrate.
This increase in extracellular osmolarity affected by the intravenous administration of mannitol will induce the movement of intracellular water to the extracellular and vascular spaces. This action underlies the role of mannitol in reducing intracranial pressure, intracranial edema, and intraocular pressure.
Mannitol distributes largely in the extracellular space in 20 to 40 minutes after intravenous administration. The volume of distribution of mannitol is approximately 17 L in adults.
In subjects with normal renal function, the total clearance is 87 to 109 mL/min. The elimination half-life of mannitol is 0.5 to 2.5 hours.
Only relatively small amount of the dose administered is metabolized after intravenous administration of mannitol to healthy subjects.
Mannitol is eliminated primarily via the kidneys in unchanged form. Mannitol is filtered by the glomeruli, exhibits less than 10% of tubular reabsorption, and is not secreted by tubular cells. Following intravenous administration, approximately 80% of an administered dose of mannitol is estimated to be excreted in the urine in three hours with lesser amounts thereafter.
Patients with Renal Impairment
In patients with renal impairment, the elimination half-life of mannitol is prolonged. In a published study, in patients with renal impairment including acute renal failure and end stage renal failure, the elimination half-life of mannitol was estimated at about 36 hours, based on serum osmolarity. In patients with renal impairment on dialysis, the elimination half-life of mannitol was reduced to 6 and 21 hours during hemodialysis and peritoneal dialysis, respectively. [see Use in Specific Populations (8.6), Overdosage (10)].
Mannitol Injection is a clear and colorless solution supplied in single-dose containers as follows:
|Unit of Sale||Concentration||Each|
|ICU Medical is transitioning NDC codes from "0409" to "0990" labeler code. Both NDC codes are expected to be in the market for a period of time.|
Case containing 12
|20% (0.2 g/mL) mannitol, USP||NDC 0409-7715-13
500 mL Flexible Container
Case containing 24
|20% (0.2 g/mL) mannitol, USP||NDC 0409-7715-12
250 mL Flexible Container
Inform patients, caregivers, or home healthcare providers of the following risks of Mannitol Injection:
20% Mannitol Injection,
50 g/250 mL (200 mg/mL)
EACH 100 ML CONTAINS MANNITOL
20 GRAMS. MAY CONTAIN SODIUM
BICARBONATE FOR pH ADJUSTMENT.
1098 mOsmol/LITER (CALC.)
pH 6.3 (4.5 TO 7.0)
ADDITIVES MAY BE INCOMPATIBLE.
CONSULT WITH PHARMACIST, IF
AVAILABLE. WHEN INTRODUCING
ADDITIVES, USE ASEPTIC TECHNIQUE,
MIX THOROUGHLY AND DO NOT STORE.
SINGLE-DOSE CONTAINER. FOR
INTRAVENOUS USE. USUAL DOSAGE:
SEE INSERT. WARNING: SEE INSERT
REGARDING CONTRAINDICATION IN
SEVERE RENAL IMPAIRMENT. WARNING:
IF CRYSTALS FORM, WARM WITH
OVERWRAP INTACT AND AGITATE TO
DISSOLVE. ADMINISTER INTRAVENOUSLY
AT 30° TO 37°C (86° TO 98.6°F). INSPECT
CAREFULLY. DISCARD UNUSED PORTION.
USE ONLY IF SOLUTION IS CLEAR AND
CONTAINER IS UNDAMAGED. MUST NOT
BE USED IN SERIES CONNECTIONS.
ICU Medical, Inc.,
Lake Forest, Illinois, 60045, USA
20% Mannitol Injection,
100 g/500 mL (200 mg/mL)
EACH 100 mL CONTAINS MANNITOL 20 GRAMS. MAY CONTAIN
SODIUM BICARBONATE FOR pH ADJUSTMENT.
1098 mOsmol/LITER (CALC.)
pH 6.3 (4.5 TO 7.0)
ADDITIVES MAY BE INCOMPATIBLE. CONSULT WITH
PHARMACIST, IF AVAILABLE. WHEN INTRODUCING
ADDITIVES, USE ASEPTIC TECHNIQUE, MIX THOROUGHLY
AND DO NOT STORE.
SINGLE-DOSE CONTAINER. FOR INTRAVENOUS USE. USUAL
DOSAGE: SEE INSERT. WARNING: SEE INSERT REGARDING
CONTRAINDICATION IN SEVERE RENAL IMPAIRMENT.
WARNING: IF CRYSTALS FORM, WARM WITH OVERWRAP
INTACT AND AGITATE TO DISSOLVE. ADMINISTER
INTRAVENOUSLY AT 30° TO 37°C (86° TO 98.6°F). INSPECT
CAREFULLY. DISCARD UNUSED PORTION. USE ONLY IF
SOLUTION IS CLEAR AND CONTAINER IS UNDAMAGED. MUST
NOT BE USED IN SERIES CONNECTIONS.
ICU Medical, Inc., Lake Forest, Illinois, 60045, USA
mannitol injection, solution
|Labeler - ICU Medical Inc. (118380146)|