Acute renal failure: IV: 0.5 to 1 g/kg/dose (Andreoli 2004); some experts recommend against routine use due to the risk of IVH in low birth weight neonates (solution is hypertonic) or the precipitation of CHF if a lack of response occurs (Andreoli 2004; Chua 2005)
Note: The manufacturer's labeling recommends a test dose prior to starting IV mannitol therapy in patients with marked oliguria or suspected renal insufficiency.
Acute renal failure (oliguria): Infants, Children, and Adolescents: IV: Initial: 0.5 to 1 g/kg/dose infused over 2 to 6 hours; usual range: 0.25 to 2 g/kg/dose; may repeat dose every 4 to 6 hours; do not repeat dose if oliguria persists. Note: Although FDA-labeled indications, the use of mannitol for the prevention of acute renal failure and/or promotion of diuresis is not routinely recommended (Kellum 2008).
Test dose (to assess adequate renal function): IV: 0.2 g/kg (maximum dose: 12.5 g) over 3 to 5 minutes to produce a urine flow of at least 1 mL/kg/hour for 1 to 3 hours
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 <300 to 320 mOsm/kg (BTF [Carney 2016]; Hegenbarth 2008; Kochanek 2012). Note: The manufacturer's labeling allows for higher single doses up to 2 g/kg/dose.
Intraocular pressure (IOP), reduction: Infants, Children, and Adolescents: IV: 1 to 2 g/kg/dose or 30 to 60 g/m2/dose infused over 30 to 60 minutes administered 1 to 1.5 hours prior to surgery
IOP (traumatic hyphema), 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 (Crouch 1999)
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 renal impairment. Use with caution in patients with underlying renal disease. May be used to reduce the incidence of acute tubular necrosis when administered prior to revascularization during kidney transplantation.
No adjustment required.
(For additional information see "Mannitol (systemic): Drug information")
Intracranial pressure (ICP), cerebral edema, reduction (off-label dosing): IV: 0.25 to 1 g/kg/dose; may repeat every 6 to 8 hours as needed (BTF [Carney 2016]; Grape 2012). Some suggest maintaining serum osmolality <320 mOsm/kg (Rabinstein 2006). However, this value is routinely exceeded without ill effect. A better marker for mannitol toxicity may be the serum osmol gap (or osmolal gap) and the target is <18 to 20 (Erstad 2016; García-Morales 2004).
Intraocular pressure (IOP), reduction: IV: 1.5 to 2 g/kg administered over 30 to 60 minutes 1 to 1.5 hours prior to surgery
IOP (traumatic hyphema), reduction: 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 (Crouch 1999)
Kidney transplant:
Donor: 12.5 g (with adequate hydration) prior to nephrectomy; may repeat (Morris 2008)
Recipient: 50 g before kidney revascularization (Sprung 2000; Tiggeler 1984; van Valenberg 1987; Weimar 1983)
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 renal impairment. Use caution in patients with underlying renal disease. May be used to reduce the incidence of acute tubular necrosis when administered prior to revascularization during kidney transplantation.
No dosage adjustment necessary.
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); 20% (250 mL, 500 mL)
Generic: 20% (250 mL [DSC], 500 mL); 25% (50 mL)
Solution, Intravenous [preservative free]:
Generic: 20% (250 mL, 500 mL); 25% (50 mL [DSC])
Solution, Irrigation:
Resectisol: 5% (2000 mL [DSC])
Yes
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: Do not administer IM or SubQ. In-line filter set (≤5 micron) should always be used for mannitol infusion with concentrations ≥20% (WHO 2011); maximum concentration for administration: 25%. 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 with blood; crenation and agglutination of red blood cells may occur. Infusion rate is dependent upon indication:
Acute renal failure: Administer over 2 to 6 hours.
Cerebral edema or increased intracranial pressure: Administer over 20 to 30 minutes.
Test dose (for oliguria): Administer over 3 to 5 minutes.
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 dry cold compresses (Hurst 2004); elevate extremity.
IV: Concentration and rate of administration depends on indication/severity or may be adjusted to urine flow. For cerebral edema or elevated intracranial pressure, administer over 30 to 60 minutes. Inspect for crystals prior to administration. If crystals are present, redissolve by warming solution. Do not place mannitol 25% injection in polyvinyl chloride (PVC) bags; a white flocculent precipitate may form from contact with PVC surfaces. Use filter-type administration set (≤5 micron) for infusion solutions containing mannitol ≥20% (WHO 2011). Do not administer with blood. Crenation and agglutination of red blood cells may occur if administered with whole blood.
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 and disconnect (leave needle/cannula in place); gently aspirate extravasated solution (do NOT flush the line); initiate hyaluronidase antidote; remove needle/cannula; apply dry cold compresses (Hurst 2004; Reynolds 2014); elevate extremity.
Hyaluronidase: Intradermal or SubQ: Inject a total of 1 to 1.7 mL (15 units/mL) as five separate 0.2 to 0.3 mL injections (using a tuberculin syringe) into area of extravasation at the leading edge in a clockwise manner (Reynolds 2014) or SubQ: Administer multiple 0.5 to 1 mL injections of a 15 units/mL solution around the periphery of the extravasation (Kumar 2003).
Irrigation: Administer using only the appropriate transurethral urologic instrumentation.
Injection: Store at controlled room temperature; do not freeze. Crystallization of solution may occur at low temperatures; do not use solutions that contain crystals. To dissolve crystals in plastic containers, heat solution up to 60°C to 70°C (140°F to 158°F) (recommended temperature may vary; refer to manufacturer’s labeling), with agitation; do not immerse in water or microwave (may contaminate or damage product); allow solution to return to room or body temperature before use. To dissolve crystals in vials/bottles, warm vial in hot water at 80°C (176°F) and periodically shake vigorously or vial may be autoclaved at 121°C (250°F) for 20 minutes at 15 psi. Allow solution to return to room or body temperature before use.
Irrigation: Store at room temperature of 25°C (77°F); excursions permitted up to 40°C. Avoid excessive heat; do not warm above 150°F (66°C). Do not freeze.
Injection: Reduction of increased intracranial pressure associated with cerebral edema; reduction of increased intraocular pressure; promoting urinary excretion of toxic substances; genitourinary irrigant in transurethral prostatic resection or other transurethral surgical procedures
Note: Although FDA-labeled indications, the use of mannitol for the prevention of acute renal failure and/or promotion of diuresis is not routinely recommended (Kellum 2008).
Osmitrol may be confused with esmolol
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 renal dysfunction especially with high doses; use caution in patients taking other nephrotoxic agents, with sepsis or preexisting renal disease. To minimize adverse renal effects, adjust to keep serum osmolality <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; reassess dose and use of mannitol if cerebral perfusion pressure decreased.
• CNS effects: CNS toxicity (eg, coma, confusion, lethargy) may occur; risk may be increased in patients with impaired renal function or with concomitant use of neurotoxic drugs. Discontinue mannitol if CNS toxicity develops.
• Renal impairment: Use with caution. In patients with severe impairment, do not use until adequacy of renal function and urine flow is established; use 1 to 2 test doses to assess renal response.
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.
None known.
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
Opioid Agonists: May enhance the adverse/toxic effect of Diuretics. Opioid Agonists may diminish the therapeutic effect of Diuretics. 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. Management: Consider avoiding this combination by temporarily suspending treatment with diuretics, or seeking alternatives to oral sodium phosphate bowel preparation. If the combination cannot be avoided, hydrate adequately and monitor fluid and renal status. Risk D: Consider therapy modification
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).
Renal function, daily fluid I & O, serum electrolytes, serum and urine osmolality; for treatment of elevated intracranial pressure, maintain serum osmolality <300 to 320 mOsm/kg
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 2016]).
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; 6 to 36 hours in renal failure
Excretion: Urine (~80% as unchanged drug)
Approximate osmolarity: Mannitol 20%: 1100 mOsm/L; mannitol 25%: 1375 mOsm/L
Solution (Mannitol Intravenous)
20% (per mL): $0.05 - $0.07
25% (per mL): $0.05 - $0.12
Solution (Osmitrol Intravenous)
10% (per mL): $0.11
15% (per mL): $0.13
20% (per mL): $0.22
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.
