Version May 2024
Note: Resectisol has been discontinued in the United States for >1 year.
Intracranial pressure reduction (eg, due to cerebral edema, trauma, intracerebral hemorrhage, acute ischemic stroke, hepatic encephalopathy, transtentorial herniation syndrome) (off-label dosing):
IV (using 20% solution): 0.5 to 2 g/kg once; may repeat 0.25 to 1 g/kg per dose every 4 to 6 hours based on response and clinical status (Ref).
Intraocular pressure reduction:
Presurgical dosing: IV: 1.5 to 2 g/kg administered over 30 to 60 minutes 1 to 1.5 hours prior to surgery.
Traumatic hyphema: IV: 1.5 g/kg administered over 45 minutes twice daily for IOP >35 mm Hg; may administer every 8 hours in patients with extremely high pressure (Ref).
Kidney transplant, intraoperative volume optimization (off label): Note: Concentrated mannitol (ie, 20%) is preferred to optimize intravascular volume status (Ref).
IV: 12.5 to 25 g at kidney revascularization (Ref); doses up to 50 g have been studied (Ref). Some experts utilize 1 g/kg (maximum dose: 75 g); however, many centers utilize fixed dosing (Ref).
Transurethral irrigation: Use 5% urogenital solution as required for irrigation.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Contraindicated in severe kidney impairment. Use caution in patients with underlying kidney disease. May be used to reduce the incidence of acute kidney injury when administered prior to revascularization during kidney transplantation.
No dosage adjustment necessary.
Refer to adult dosing. Consider initiation at lower end of dosing range.
(For additional information see "Mannitol (systemic): Pediatric drug information")
Intracranial pressure (ICP) reduction: Infants, Children, and Adolescents: IV: Usual range: 0.25 to 1 g/kg/dose infused over 20 to 30 minutes; repeat as needed to maintain serum osmolality <320 mOsm/kg (Ref).
Intraocular pressure (IOP) reduction: Infants, Children, and Adolescents: IV: 1.5 to 2 g/kg/dose infused over ≥30 minutes. Note: When used preoperatively, administer 60 to 90 minutes prior to surgery.
Traumatic hyphema, intraocular pressure (IOP) reduction: Infants, Children, and Adolescents: IV: 1.5 g/kg/dose infused over 45 minutes twice daily for IOP >35 mm Hg; may administer every 8 hours in patients with extremely high pressure (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling for kidney impairment. Use with caution in patients with underlying renal disease, with conditions that put them at high risk for developing kidney failure, or receiving potentially nephrotoxic drugs. Use is contraindicated in patients with anuria.
There are no dosage adjustments provided in the manufacturer's labeling.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
Frequency not defined:
Cardiovascular: Cardiac failure, chest pain, edema, hypertension, localized phlebitis, palpitations, peripheral edema, tachycardia, thrombophlebitis
Central nervous system: Chills, coma, confusion, dizziness, headache, increased intracranial pressure (rebound), lethargy, malaise, pain, seizure
Dermatologic: Diaphoresis, localized erythema, localized rash, pruritus, skin necrosis, skin rash, urticaria
Endocrine & metabolic: Dehydration, fluid and electrolyte disturbance, hyperkalemia, hypernatremia, hypervolemia, hypokalemia, hyponatremia, hypovolemia, increased thirst, metabolic acidosis, metabolic alkalosis
Gastrointestinal: Nausea, vomiting, xerostomia
Genitourinary: Anuria, azotemia, diuresis, hematuria, oliguria, osmotic nephrosis, urinary retention
Hematologic & oncologic: Hemoconcentration
Local: Local inflammation, local pain, local pruritus
Neuromuscular & skeletal: Arm and/or wrist pain, asthenia, muscle rigidity, myalgia
Ophthalmic: Blurred vision
Renal: Polyuria
Respiratory: Cough, pulmonary congestion, pulmonary edema, rhinitis
Miscellaneous: Fever
Postmarketing: Acute renal failure, anaphylaxis, central nervous system toxicity, dyspnea, hypersensitivity reaction, hypotension
Injection: Hypersensitivity to mannitol or any component of the formulation; anuria; severe hypovolemia; active intracranial bleeding except during craniotomy; preexisting severe pulmonary vascular congestion or pulmonary edema.
Genitourinary irrigation solution: Anuria.
Concerns related to adverse effects:
• Extravasation: Vesicant (at concentrations >5%); ensure proper catheter or needle position prior to and during IV infusion. Avoid extravasation of IV infusions; may cause compartment syndrome. Administration into a large central vein is recommended.
• Fluid/electrolyte imbalance: May cause hypervolemia and electrolyte disturbances; monitor for new onset or worsening cardiac or pulmonary congestion. Also may cause profound diuresis with fluid and electrolyte loss; close medical supervision and dose evaluation are required. Correct electrolyte disturbances; adjust dose to avoid dehydration.
• Hypersensitivity: Serious hypersensitivity reactions (eg, anaphylaxis), including fatalities, have been reported. Discontinue mannitol immediately if hypersensitivity reaction develops and treat accordingly.
• Nephrotoxicity: May cause kidney dysfunction, especially with high doses; use caution in patients taking other nephrotoxic agents, with sepsis, or preexisting kidney disease. To minimize adverse kidney effects, monitor serum osmolality or osmolar gap (NCCS [Cook 2020]). Discontinue mannitol if acute kidney injury develops.
Disease-related concerns:
• Administration: Do not administer mannitol solutions simultaneously with blood due to the possibility of pseudoagglutination or hemolysis.
• Cardiac and pulmonary: Mannitol may initially worsen pulmonary edema or heart failure by causing hypervolemia before diuresis ensues. Do not administer large volumes of mannitol to patients with preexisting severe pulmonary edema or heart failure. Discontinue mannitol if cardiac or pulmonary status worsens.
• 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. If hypotension occurs, monitor cerebral perfusion pressure; reassess dose and mannitol therapy if there is a decrease in cerebral perfusion pressure.
• CNS effects: CNS toxicity (eg, coma, confusion, lethargy) may occur; risk may be increased in patients with impaired kidney function or with concomitant use of neurotoxic drugs. Discontinue mannitol if CNS toxicity develops.
• Kidney impairment: Use with caution. In patients with severe impairment; do not use until adequacy of kidney function and urine flow is established.
Mannitol may increase cerebral blood flow, increase the risk of postoperative bleeding in neurosurgical patients, and worsen intracranial hypertension in children who develop generalized cerebral hyperemia during the first 24 to 48 hours after traumatic brain injury.
Resectisol has been discontinued in the United States for >1 year.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Intravenous:
Osmitrol: 5% (1000 mL [DSC]); 10% (500 mL); 15% (500 mL [DSC]); 20% (250 mL, 500 mL)
Generic: 20% (500 mL); 25% (50 mL)
Solution, Intravenous [preservative free]:
Generic: 20% (250 mL, 500 mL)
Solution, Irrigation:
Resectisol: 5% (2000 mL [DSC])
Yes
Solution (Mannitol Intravenous)
20% (per mL): $0.05 - $0.12
25% (per mL): $0.07 - $0.13
Solution (Osmitrol Intravenous)
10% (per mL): $0.12
20% (per mL): $0.24
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Intravenous:
Osmitrol: 10% (1000 mL); 20% (500 mL)
Generic: 20% (500 mL); 25% (50 mL)
Solution, Irrigation:
Resectisol: 5% ([DSC])
IV: Concentration and rate of administration depends on indication/severity. Use of an administration set with a final in-line filter (eg, ≤5 micron) is recommended (Ref). For cerebral edema or elevated intracranial pressure, administer over 10 to 30 minutes; for patients with high risk for cerebral herniation, use faster administration rates (over ~10 minutes) (Ref). Inspect for crystals prior to administration. If crystals are present, redissolve by warming solution. Do not place mannitol 25% injection in PVC bags; a white flocculent precipitate may form from contact with PVC surfaces. Do not administer simultaneously with blood due to the possibility of pseudoagglutination or hemolysis. If coadministration with blood is essential, at least 20 mEq sodium chloride should be added to each liter of mannitol.
Vesicant (at concentrations >5%); ensure proper catheter or needle position prior to and during IV infusion. Avoid extravasation of IV infusions. Administration into a large central vein is recommended.
Extravasation management: If extravasation occurs, stop infusion immediately; leave needle/cannula in place temporarily but do NOT flush the line; gently aspirate extravasated solution then remove needle/cannula; elevate extremity; apply dry warm compresses; initiate hyaluronidase antidote (Ref).
Hyaluronidase: Intradermal or SUBQ: Inject a total of 1 mL (15 units/mL) as 5 separate 0.2 mL injections (using a tuberculin syringe) around the site of extravasation; if IV catheter remains in place, administer IV through the infiltrated catheter; may repeat in 30 to 60 minutes if no resolution (Ref).
Irrigation: Administer using only the appropriate transurethral urologic instrumentation.
Parenteral: Administer IV only; do not administer IM or SUBQ. Central line preferred. Use of an inline filter set (≤5 microns) is recommended (Ref). Inspect for crystals prior to administration; if crystals are present, redissolve by warming solution; see manufacturer labeling for details. Inspect for particulates or discoloration; if particulates or discoloration, discard bag. Do not place mannitol 25% injection in PVC bags; a white flocculent precipitate may form from contact with PVC surfaces. Do not administer with blood; pseudoagglutination or hemolysis of red blood cells may occur. Infusion rate is dependent upon indication:
Cerebral edema or increased intracranial pressure: Administer over 20 to 30 minutes (Ref).
Increased intraocular pressure: Administer over ≥30 minutes.
Traumatic hyphema: Administer over 45 minutes (Ref).
Vesicant (at concentrations >5%); ensure proper catheter or needle position prior to and during IV infusion. Avoid extravasation of IV infusions. If extravasation occurs, stop infusion immediately and disconnect (leave needle/cannula in place); gently aspirate extravasated solution (do NOT flush the line); initiate hyaluronidase antidote (see Management of Drug Extravasations for more details); remove needle/cannula; apply cold compresses (Ref); elevate extremity.
Injection: Reduction of increased intracranial pressure (associated with cerebral edema and/or brain mass); reduction of increased intraocular pressure
Genitourinary irrigation solution: Irrigation in transurethral prostatic resection or other transurethral surgical procedures
Kidney transplant, intraoperative volume optimization
Osmitrol may be confused with esmolol
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Amikacin Liposome (Oral Inhalation): May enhance the nephrotoxic effect of Mannitol (Systemic). Risk X: Avoid combination
Aminoglycosides: Mannitol (Systemic) may enhance the nephrotoxic effect of Aminoglycosides. Risk X: Avoid combination
Arsenic Trioxide: Osmotic Diuretics may enhance the QTc-prolonging effect of Arsenic Trioxide. Management: When possible, avoid concurrent use of arsenic trioxide with drugs that can cause electrolyte abnormalities, such as the osmotic diuretics. Risk D: Consider therapy modification
Desmopressin: Hyponatremia-Associated Agents may enhance the hyponatremic effect of Desmopressin. Risk C: Monitor therapy
Diacerein: May enhance the therapeutic effect of Diuretics. Specifically, the risk for dehydration or hypokalemia may be increased. Risk C: Monitor therapy
Lithium: Osmotic Diuretics may decrease the serum concentration of Lithium. Management: Consider temporarily discontinuing use of osmotic diuretics during coadministration with lithium. If coadministration is required, monitor lithium concentrations and for signs of lithium toxicity frequently. Risk D: Consider therapy modification
Mivacurium: Mannitol (Systemic) may enhance the therapeutic effect of Mivacurium. Risk C: Monitor therapy
Opioid Agonists: May enhance the adverse/toxic effect of Diuretics. Opioid Agonists may diminish the therapeutic effect of Diuretics. Risk C: Monitor therapy
Polyethylene Glycol-Electrolyte Solution: Diuretics may enhance the nephrotoxic effect of Polyethylene Glycol-Electrolyte Solution. Risk C: Monitor therapy
Sodium Phosphates: Diuretics may enhance the nephrotoxic effect of Sodium Phosphates. Specifically, the risk of acute phosphate nephropathy may be enhanced. Risk C: Monitor therapy
Tobramycin (Oral Inhalation): Mannitol (Systemic) may enhance the nephrotoxic effect of Tobramycin (Oral Inhalation). Risk X: Avoid combination
Mannitol crosses the placenta.
Outcome information following surgical use in pregnancy is limited; amniotic fluid volume may be decreased (Handlogten 2015; Kazemi 2014).
It is not known if mannitol is present in breast milk.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother. Other sources consider mannitol to be compatible with breastfeeding (WHO 2002).
Kidney function; cardiac and pulmonary function; urine output; intravascular volume status; serum electrolytes, serum osmolality (measured); osmolar gap; acid-base status; serum glucose; intracranial pressure (if applicable). Monitor infusion site.
For treatment of cerebral edema and intracranial pressure, some suggest monitoring osmolar gap as a surrogate marker for mannitol accumulation to evaluate for the risk of acute kidney injury (NCCS [Cook 2020]). Others suggest maintaining serum osmolality <320 mOsm/kg due to the potential risk of acute kidney injury; however, this threshold may be exceeded if clinically necessary (Grape 2012; Rabenstein 2006).
Produces an osmotic diuresis by increasing the osmotic pressure of glomerular filtrate, which inhibits tubular reabsorption of water and electrolytes and increases urinary output . Mechanism of action in reduction of intracranial pressure (ICP) is less clear. However, it is thought that mannitol reduces ICP by reducing blood viscosity which transiently increases cerebral blood flow and oxygen transport and constricts pial arterioles. This in turn reduces cerebral blood volume and ICP. Furthermore, mannitol reduces ICP by withdrawing water from the brain parenchyma and excretes water in the urine (Allen 1998; BTF [Carney 2017]).
Onset of action: Diuresis: 1 to 3 hours; Reduction in intracranial pressure: ~15 to 30 minutes.
Duration: Reduction in intracranial pressure: 1.5 to 6 hours.
Distribution: 17 L; 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: 0.5 to 2.5 hours; ~36 hours in acute kidney injury and end-stage kidney failure.
Excretion: Urine (~80% as unchanged drug).
Altered kidney function: Elimination half-life is ~36 hours in patients with acute kidney injury and end-stage kidney failure. In patients with kidney impairment receiving hemodialysis, half-life elimination reduced to ~6 hours; in patients receiving peritoneal dialysis, half-life elimination reduced to ~21 hours.
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