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Mannitol (Systemic)


General


Pronunciation

(MAN i tole)


Brand Names: U.S.

  • Osmitrol
  • Resectisol

Indications


Use: Labeled Indications

Injection: Reduction of increased intracranial pressure associated with cerebral edema; reduction of increased intraocular pressure; promoting urinary excretion of toxic substances

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).

Genitourinary irrigation solution: Irrigation in transurethral prostatic resection or other transurethral surgical procedures


Contraindications


Injection: Hypersensitivity to mannitol or any component of 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

Genitourinary irrigation solution: Anuria


Dosing and Administration


Dosing: Adult

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 (Bratton 2007; Kochanek 2012); maintain serum osmolality <300 to 320 mOsm/kg (Kochanek 2012; Rabinstein 2006)

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.


Dosing: Geriatric

Refer to adult dosing. Consider initiation at lower end of dosing range.


Dosing: Pediatric

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 (Bratton 2007; 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 administered over 45 minutes twice daily for IOP >35 mm Hg; may administer every 8 hours in patients with extremely high pressure (Crouch 1999)


Dosing: Renal Impairment

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.


Dosing: Hepatic Impairment

No dosage adjustment necessary.


Administration

IV: Concentration and rate of administration depends on indication/severity, or may be adjusted to urine flow. For cerebral edema or elevated ICP, administer over 30 to 60 minutes. Inspect for crystals prior to administration. If crystals are present, redissolve by warming solution. Use filter-type administration set for infusion solutions containing mannitol ≥20%. 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.

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); elevate extremity.

Hyaluronidase: 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.


Storage

Injection: Should be stored at room temperature of 15 ‚ °C to 30 ‚ °C (59 ‚ °F to 86 ‚ °F); do not freeze. In concentrations ≥15%, 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.

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.


Dosage Forms/Strengths


Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous:

Osmitrol: 5% (1000 mL); 10% (500 mL); 15% (500 mL); 20% (250 mL, 500 mL)

Generic: 5% (1000 mL); 10% (1000 mL); 15% (500 mL); 20% (250 mL, 500 mL); 25% (50 mL)

Solution, Intravenous [preservative free]:

Generic: 25% (50 mL)

Solution, Irrigation:

Resectisol: 5% (2000 mL)


Compatibility

Stable in D5W, D5NS, LR, NS, R.

Y-site administration: Incompatible with cefepime, doxorubicin liposome, filgrastim, pantoprazole.


Drug Interactions

Aminoglycosides: Mannitol (Systemic) may enhance the nephrotoxic effect of Aminoglycosides. Avoid combination

Analgesics (Opioid): May enhance the adverse/toxic effect of Diuretics. Analgesics (Opioid) may diminish the therapeutic effect of Diuretics. 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. Consider therapy modification

Tobramycin (Oral Inhalation): Mannitol (Systemic) may enhance the nephrotoxic effect of Tobramycin (Oral Inhalation). Avoid combination


Monitoring Parameters

Renal function, daily fluid I & O, serum electrolytes, serum and urine osmolality; for treatment of elevated intracranial pressure, maintain serum osmolality in the range of 300 to 320 mOsm/kg (serum osmolality >320 mOsm/kg may increase the risk of acute renal tubular damage).


Adverse Reactions


Injection: Frequency not defined:

Cardiovascular: Chest pain, CHF, circulatory overload, hyper-/hypotension, peripheral edema, tachycardia

Central nervous system: Chills, convulsions, dizziness, fever, headache

Dermatologic: Bullous eruption, 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 (adult dose >200 g/day; serum osmolality >320 mOsm/L)

Respiratory: Pulmonary edema, rhinitis

Miscellaneous: Allergic reactions


Warnings/Precautions


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.

- 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 preexisting 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 ensure adequate.

Other warnings/precautions:

- Adequate renal function: Should not be administered until adequacy of renal function and urine flow is established; use 1 to 2 test doses to assess renal response.


Pregnancy Risk Factor

C


Pregnancy Considerations

Reproduction studies have not been conducted.


Actions


Pharmacology

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 controversial. However, it is thought that mannitol reduces ICP by reducing blood viscosity which transiently increases cerebral blood flow and oxygen transport. 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; Bratton, 2007; Miller, 2010).


Distribution

34.3 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


Excretion

Urine (~55% to 87% as unchanged drug)


Onset of Action

Diuresis: 1 to 3 hours; Reduction in intracranial pressure: ~15 to 30 minutes


Duration of Action

Reduction in intracranial pressure: 3 to 6 hours


Half-Life Elimination

0.25 to 1.7 hours; 6 to 36 hours in renal failure


Patient and Family Education


Patient Education

- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

- Patient may experience rhinorrhea, nausea, or xerostomia. Have patient report immediately to prescriber dyspnea, severe dizziness, syncope, considerable headache, angina, tachycardia, signs of fluid and electrolyte imbalance, vision changes, significant edema, chills, or injection site pain or irritation (HCAHPS).

- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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