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Medication Safety Issues
Sound-alike/look-alike issues:
Osmitrol® may be confused with esmolol
Pronunciation
(MAN i tole)
U.S. Brand Names
Index Terms
Generic Available
Yes
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Reduction of increased intracranial pressure associated with cerebral edema; promotion of diuresis in the prevention and/or treatment of oliguria or anuria due to acute renal failure; reduction of increased intraocular pressure; promoting urinary excretion of toxic substances; genitourinary irrigant in transurethral prostatic resection or other transurethral surgical procedures
Pregnancy Risk Factor
C
Pregnancy Considerations
Reproduction studies have not been conducted.
Lactation
Excretion in breast milk unknown/use caution
Contraindications
Hypersensitivity to mannitol or any component or the formulation; severe renal disease (anuria); severe dehydration; active intracranial bleeding except during craniotomy; progressive heart failure, pulmonary congestion, or renal dysfunction after mannitol administration; severe pulmonary edema or congestion
Warnings/Precautions
Concerns related to adverse effects:
• Fluid/electrolyte loss: Excess amounts can lead to profound diuresis with fluid and electrolyte loss; close medical supervision and dose evaluation are required. Watch for and correct electrolyte disturbances; adjust dose to avoid dehydration.
• Nephrotoxicity: May cause renal dysfunction especially with high doses; use caution in patients taking other nephrotoxic agents, with sepsis or pre-existing renal disease. To minimize adverse renal effects, adjust to keep serum osmolality less than 320 mOsm/L. Discontinue if evidence of acute tubular necrosis.
Disease-related concerns:
• Cerebral edema: In patients being treated for cerebral edema, mannitol may accumulate in the brain (causing rebound increases in intracranial pressure) if circulating for long periods of time as with continuous infusion; intermittent boluses preferred. Cardiovascular status should also be evaluated; do not administer electrolyte-free mannitol solutions with blood. If hypotension occurs monitor cerebral perfusion pressure to insure adequate.
Other warnings/precautions:
• Adequate renal function: Should not be administered until adequacy of renal function and urine flow is established; use 1-2 test doses to assess renal response.
Adverse Reactions
Frequency not defined.
Cardiovascular: Chest pain, CHF, circulatory overload, hyper-/hypotension, tachycardia
Central nervous system: Chills, convulsions, dizziness, headache
Dermatologic: Rash, urticaria
Endocrine & metabolic: Fluid and electrolyte imbalance, dehydration and hypovolemia secondary to rapid diuresis, hyperglycemia, hypernatremia, hyponatremia (dilutional), hyperosmolality-induced hyperkalemia, metabolic acidosis (dilutional), osmolar gap increased, water intoxication
Gastrointestinal: Nausea, vomiting, xerostomia
Genitourinary: Dysuria, polyuria
Local: Pain, thrombophlebitis, tissue necrosis
Ocular: Blurred vision
Renal: Acute renal failure, acute tubular necrosis (>200 g/day; serum osmolality >320 mOsm/L)
Respiratory: Pulmonary edema, rhinitis
Miscellaneous: Allergic reactions
Drug Interactions
Amifostine: Antihypertensives may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, antihypertensive medications should be withheld for 24 hours prior to amifostine administration. If antihypertensive therapy can not be withheld, amifostine should not be administered. Risk D: Consider therapy modification
Antihypertensives: May enhance the hypotensive effect of other Antihypertensives. Risk C: Monitor therapy
Diazoxide: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Hypotensive Agents: May enhance the adverse/toxic effect of other Hypotensive Agents. Risk C: Monitor therapy
MAO Inhibitors: May enhance the orthostatic effect of Orthostasis Producing Agents. Risk C: Monitor therapy
Methylphenidate: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Pentoxifylline: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
RiTUXimab: Antihypertensives may enhance the hypotensive effect of RiTUXimab. Risk D: Consider therapy modification
Yohimbine: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Storage
Should be stored at room temperature (15°C to 30°C); do not freeze. Crystallization may occur at low temperatures; do not use solutions that contain crystals. Heating in a hot water bath and vigorous shaking may be utilized for resolubilization. Cool solutions to body temperature before using.
Compatibility
Y-site administration: Compatible: Allopurinol, amifostine, amphotericin B cholesteryl sulfate complex, aztreonam, cisatracurium, cladribine, docetaxel, etoposide, fludarabine, fluorouracil, gatifloxacin, gemcitabine, idarubicin, linezolid, melphalan, ondansetron, paclitaxel, piperacillin/tazobactam, propofol, remifentanil, sargramostim, teniposide, thiotepa, vinorelbine. Incompatible: Cefepime, doxorubicin liposome, filgrastim.
Compatibility when admixed: Compatible: Amikacin, bretylium, cefamandole, cefoxitin, cimetidine, cisplatin, dopamine, fosphenytoin, furosemide, gentamicin, metoclopramide, nizatidine, ofloxacin, ondansetron, sodium bicarbonate, tobramycin, verapamil. Incompatible: Imipenem/cilastatin, meropenem. Variable (consult detailed reference): Etoposide with cisplatin and potassium chloride, potassium chloride.
Mechanism of Action
Increases the osmotic pressure of glomerular filtrate, which inhibits tubular reabsorption of water and electrolytes and increases urinary output
Pharmacodynamics/Kinetics
Onset of action: Diuresis: Injection: 1-3 hours; Reduction in intracranial pressure: ~15-30 minutes
Duration: Reduction in intracranial pressure: 1.5-6 hours
Distribution: Remains confined to extracellular space (except in extreme concentrations); does not penetrate the blood-brain barrier (generally, penetration is low)
Metabolism: Minimally hepatic to glycogen
Half-life elimination: 1.1-1.6 hours
Excretion: Primarily urine (as unchanged drug)
Dosage
Children: I.V.:
Test dose (to assess adequate renal function): 200 mg/kg over 3-5 minutes to produce a urine flow of at least 1 mL/kg for 1-3 hours
Initial: 0.25-1 g/kg
Maintenance: 0.25-0.5 g/kg given every 4-6 hours
Adults:
I.V.:
Test dose (to assess adequate renal function): 12.5 g (200 mg/kg) over 3-5 minutes to produce a urine flow of at least 30-50 mL of urine per hour. If urine flow does not increase, a second test dose may be given. If test dose does not produce an acceptable urine output, then need to reassess management.
Initial: 0.5-1 g/kg
Maintenance: 0.25-0.5 g/kg every 4-6 hours; usual daily dose: 20-200 g/24 hours
Intracranial pressure: Cerebral edema: 0.25-1.5 g/kg/dose I.V. as a 15% to 20% solution over ?30 minutes; maintain serum osmolality 310 to <320 mOsm/kg
Prevention of acute renal failure (oliguria): 50-100 g dose
Treatment of oliguria: 100 g dose
Preoperative for neurosurgery: 1.5-2 g/kg administered 1-1.5 hours prior to surgery
Reduction of intraocular pressure: 1.5-2 g/kg as a 15% to 20% solution; administer over 30 minutes
Topical: Transurethral irrigation: Use urogenital solution as required for irrigation
Elderly: Consider initiation at lower end of dosing range
Dosage adjustment in renal impairment: Contraindicated in severe renal impairment. If test dose does not produce adequate urine output reassess options. Use caution in patients with underlying renal disease.
Dosage adjustment in hepatic impairment: No adjustment required.
Administration: I.V.
Vesicant. Do not administer with blood. Crenation and agglutination of red blood cells may occur if administered with whole blood. Inspect for crystals prior to administration. If crystals present redissolve by warming solution. Use filter-type administration set; in-line 5-micron filter set should always be used for mannitol infusion with concentrations ?20%; administer test dose (for oliguria) I.V. push over 3-5 minutes; avoid extravasation; for cerebral edema or elevated ICP, administer over 20-30 minutes.
Administration: I.V. Detail
Avoid extravasation.
pH: 4.5-7
Monitoring Parameters
Renal function, daily fluid I & O, serum electrolytes, serum and urine osmolality; for treatment of elevated intracranial pressure, maintain serum osmolality 310 to <320 mOsm/kg.
Patient Education
Report immediately any muscle weakness, numbness, tingling, acute headache, nausea, dizziness, blurred vision, eye pain, respiratory difficulty, chest pain, or pain at infusion site. Pregnancy/breast-feeding precautions: Inform prescriber if you are pregnant. Consult prescriber if breast-feeding.
Additional Information
May autoclave or heat to redissolve crystals; mannitol 20% has an approximate osmolarity of 1100 mOsm/L and mannitol 25% has an approximate osmolarity of 1375 mOsm/L
Anesthesia and Critical Care Concerns/Other Considerations
Clinical Pearls/Comments: Other information:
May autoclave or heat mannitol solution to redissolve crystals.
Mannitol 20% has an approximate osmolarity of 1100 mOsm/L.
Mannitol 25% has an approximate osmolarity of 1375 mOsm/L.
Evidence-Based Information:
Management of Intracerebral Hemorrhage (ICH): The 2007 AHA/ASA Guidelines for the Management of Spontaneous Intracerebral Hemorrhage in Adults recommends mannitol as a treatment option to decrease intracranial pressure (ICP) (Class IIa recommendation).
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause dizziness
Mental Health: Effects on Psychiatric Treatment
Has been used to treat lithium toxicity/overdose but its overall effect in lowering serum lithium level is minimum; if toxicity is severe, hemodialysis is the treatment of choice
Nursing: Physical Assessment/Monitoring
Assess for adequate renal function and urine flow prior to administration. Lithium toxicity is increased with concurrent use, and concurrent use of other nephrotic agents may increase potential for renal dysfunction. Infusion site must be closely monitored for extravasation; this is a vesicant. Renal and cardiovascular status should be monitored during infusion. Assess results of laboratory tests, therapeutic effectiveness (according to purpose for use), and adverse response (eg, circulatory overload, CHF, rash, water intoxication). Patient teaching should be appropriate to patient condition.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution: 5% [50 mg/mL] (1000 mL); 10% [100 mg/mL] (500 mL, 1000 mL); 15% [150 mg/mL] (500 mL); 20% [200 mg/mL] (150 mL, 250 mL, 500 mL); 25% [250 mg/mL] (50 mL)
Osmitrol®: 5% [50 mg/mL] (1000 mL); 10% [100 mg/mL] (500 mL, 1000 mL); 15% [150 mg/mL] (500 mL); 20% [200 mg/mL] (250 mL, 500 mL)
Solution, urogenital (Resectisol®): 5% [50 mg/mL] (2000 mL, 4000 mL)
References
Adelson PD, Bratton SL, Carney NA, et al, “Guidelines for the Acute Medical Management of Severe Traumatic Brain Injury in Infants, Children, and Adolescents,” Pediatr Crit Care Med, 2003, 4(3 Suppl):40-4.
Al-Sarraf M, Fletcher W, Oishi N, et al, “Cisplatin Hydration With and Without Mannitol Diuresis in Refractory Disseminated Malignant Melanoma: A Southwest Oncology Group Study,” Cancer Treat Rep, 1982, 66(1):31-5.
Anto HR, Chou SY, Porush JG, et al, “Infusion Intravenous Pyelography and Renal Function. Effect of Hypertonic Mannitol in Patients With Chronic Renal Insufficiency,” Arch Intern Med, 1981, 141(12):1652-6.
Broderick J, Connolly S, Feldmann E, et al, “Guidelines for the Management of Spontaneous Intracerebral Hemorrhage in Adults: 2007 Update: A Guideline From the American Heart Association/American Stroke Association Stroke Council, High Blood Pressure Research Council, and the Quality of Care and Outcomes in Research Interdisciplinary Working Group,” Stroke, 2007, 38(6):2001-23. Available at http://stroke.ahajournals.org/cgi/content/short/STROKEAHA.107.183689.
Gadallah MF, Lynn M, and Work J, “Case Report: Mannitol Nephrotoxicity Syndrome: Role of Hemodialysis and Postulate of Mechanisms,” Am J Med Sci, 1995, 309(4):219-22.
Goodwin WE and Latta H, “Focal Osmotic Nephrosis Due to Therapeutic Use of Mannitol: A Case of Perirenal Hematoma After Renal Biopsy,” J Urol, 1970, 103(1):11-4.
Holdener EE, Park CH, Belt RJ, et al, “Effect of Mannitol and Plasma on the Cytotoxicity of Cisplatin,” Eur J Cancer Clin Oncol, 1983, 19(4):515-8.
Huff JS, “Acute Mannitol Intoxication in a Patient With Normal Renal Function,” Am J Emerg Med, 1990, 8(4):338-9.
Jahns BE, Avula S, Lipscomb JW, et al, “Mannitol for Severe Ciguatera Intoxication,” J Toxicol Clin Toxicol, 1995, 33(5):496.
Moses FM, “Colonic Perforation Due to Oral Mannitol,” JAMA, 1988, 260(5):640.
Ostrow S, Egorin MJ, Hahn D, et al, “High-Dose Cisplatin Therapy Using Mannitol Versus Furosemide Diuresis: Comparative Pharmacokinetics and Toxicity,” Cancer Treat Rep, 1981, 65(1-2):73-8.
Palmquist KL, Quattrocchi FP, and Looney LA, “Compatibility of Furosemide With 20% Mannitol,” Am J Health Syst Pharm, 1995, 52(6):648,50.
Procaccio F, Stocchetti N, Citerio G, et al, “Guidelines for the Treatment of Adults With Severe Head Trauma (Part II). Criteria for Medical Treatment,” J Neurosurg Sci, 2000, 44(1):11-8.
Shapiro WR and Shapiro JR, “Principles of Brain Tumor Chemotherapy,” Semin Oncol, 1986, 13(1):56-69.
Solomon R, Werner C, Mann D, et al, “Effects of Saline, Mannitol, and Furosemide to Prevent Acute Decreases in Renal Function Induced by Radiocontrast Agents,” N Engl J Med, 1994, 331(21):1416-20.
International Brand Names
Lexi-Comp.com
Last full review/revision September 2009
Content last modified September 2009
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