Mannitol

Mannitol is an antihypertensive agent belonging to Osmosis Diuretics.

Mannitol is an Osmotic diuretic used to remove excess water and toxins from the body in patients with kidney disease. It is also used in the treatment of cerebral edema and intraocular pressure.

Approximately 7% of ingested mannitol is absorbed during gastrointestinal perfusion in uremic patients. Mannitol administered intravenously has a volume of distribution of 34.3 L. Mannitol is metabolized only slightly, if at all, to glycogen in the liver.

Mannitol is primarily excreted unchanged in the urine. Intravenous administration of mannitol yields a total clearance of 5.1 L/hr and renal clearance of 4.4 L/hr.

Mannitol shows common side effects Headache, nausea, diarrhea, vomiting, dry mouth, thirst, dehydration, blurred vision, runny nose, arm pain, chills, dizziness, low blood pressure (hypotension), hives, irregular heartbeat, and electrolyte imbalance, etc.

Mannitol is available in the form of an Injectable solution

Mannitol is available in India, US, Japan, England, China, Austria, Canada, Europe and Italy.

Mannitol belonging to the Osmotic Diuretics acts as an antihypertensive agent.

Produces osmotic diuresis by increasing the osmotic pressure of glomerular filtrate, which inhibits tubular reabsorption of water and electrolytes and increases urinary output. The mechanism of action in the 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 excreting water in the urine.

The onset of action of Mannitol is for Diuresis: 1 to 3 hours; Reduction in intracranial pressure: ~15 to 30 minutes.

The Duration of Action for Mannitol in the body for Reduction in intracranial pressure: 1.5 to 6 hours.

The Tmax was not clinically established.

Mannitol is available in the form of an Injectable solution.

Mannitol Injectable solutions by Intravenous as single or several doses.

Mannitol is a diuretic used to force urine production in people with acute (sudden) kidney failure. Mannitol injection is also used to reduce swelling and pressure inside the eye or around the brain.

Mannitol is an antihypertensive agent belonging to Osmosis Diuretics. Mannitol is an osmotic diuretic used to remove excess water and toxins from the body in patients with kidney disease. It is also used in the treatment of cerebral edema and intraocular pressure. Frequent monitoring of electrolytes levels is necessary during treatment with this medicine.

Mannitol is approved for use in the following clinical indications

• The reduction of intracranial pressure and treatment of cerebral edema by reducing brain mass.
• The reduction of elevated intraocular pressure when the pressure cannot be lowered by other means.
• Promoting the urinary excretion of toxic substances.

• Intracranial pressure, cerebral edema, reduction (off-label dosing):

IV: 0.25 to 1 g/kg/dose; may repeat every 6 to 8 hours as needed. Some suggest maintaining serum osmolality <320 mOsm/kg.

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.

• 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 Intraocular pressure >35 mm Hg; may administer every 8 hours in patients with extremely high pressure.

• Kidney transplant, intraoperative volume optimization (off label): Note: Concentrated mannitol (ie, 20%) is preferred to optimize intravascular volume status.

IV: 12.5 to 25 g at kidney revascularization doses up to 50 g have been studied. Some experts utilize 1 g/kg (maximum dose: 75 g); however, many centers utilize fixed dosing.

Mannitol is available in various strength as 5%, 10%, 15%, 20% and 25%.

Mannitol is available in the form of an Injectable solution.

Mannitol is contraindicated in patients with:

• Well-established anuria due to severe renal disease.
• Severe pulmonary congestion or frank pulmonary edema.
• Active intracranial bleeding except during craniotomy.
• Severe dehydration.
• Progressive heart failure or pulmonary congestion after institution of mannitol therapy.
• Do not administer to patients with a known hypersensitivity to mannitol.

● 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 the dose to avoid dehydration.

● Hypersensitivity: Serious hypersensitivity reactions (eg, anaphylaxis), including fatalities, have been reported. Discontinue mannitol immediately if a 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.

● 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 are 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; the 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.

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when mannitol is administered to a nursing woman

Pregnancy category C

Animal reproduction studies have not been conducted with mannitol injection. It is also not known whether mannitol injection can cause fetal harm when given to a pregnant woman or can affect reproduction. Mannitol injection should be given to a pregnant woman only if clearly needed.

Common Adverse effects

• Cardiac failure, chest pain, edema, hypertension, localized phlebitis, palpitations, peripheral edema, tachycardia, thrombophlebitis, Chills, coma, confusion, dizziness, headache, increased intracranial pressure (rebound), lethargy, malaise, pain, seizure, Diaphoresis, localized erythema, localized rash, pruritus, skin necrosis, skin rash, urticaria, Dehydration, fluid and electrolyte disturbance, hyperkalemia, hypernatremia, hypervolemia, hypokalemia, hyponatremia, hypovolemia, increased thirst, metabolic acidosis, metabolic alkalosis, Nausea, vomiting, xerostomia, Anuria, azotemia, diuresis, hematuria, oliguria, osmotic nephrosis, urinary retention, Hemoconcentration, Local inflammation, local pain, local pruritus, Arm and/or wrist pain, asthenia, muscle rigidity, myalgia, Blurred vision, Polyuria, Cough, pulmonary congestion, pulmonary edema, rhinitis, Fever.

Rare Adverse effects

• Acute renal failure, anaphylaxis, central nervous system toxicity, dyspnea, hypersensitivity reaction, hypotension.

• Amikacin Liposome

May enhance the nephrotoxic effect of Mannitol (Systemic).

● Aminoglycosides

Mannitol may enhance the nephrotoxic effect of Aminoglycosides.

● 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 osmotic diuretics.

● Desmopressin

Hyponatremia-Associated Agents may enhance the hyponatremic effect of Desmopressin.

● Diacerein

May enhance the therapeutic effect of Diuretics. Specifically, the risk for dehydration or hypokalemia may be increased.

● Opioid Agonists

May enhance the adverse/toxic effect of Diuretics. Opioid Agonists may diminish the therapeutic effect of Diuretics.

● 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.

● Tobramycin

Mannitol may enhance the nephrotoxic effect of Tobramycin (Oral Inhalation).

The common side effects of Mannitol include the following

Common

• Headache, nausea, diarrhea, vomiting, dry mouth, thirst, dehydration, blurred vision, runny nose, arm pain, chills, dizziness, low blood pressure (hypotension), hives, irregular heartbeat, and electrolyte imbalance.

Rare

• Fever, infection at the injection site, blot clot in a deep vein, thrombosis, leakage of intravenously infused medication, and fluid overload in the blood (hypervolemia).

• Pregnancy

Pregnancy Category C

Animal reproduction studies have not been conducted with Mannitol Injection. It is also not known whether mannitol can cause fetal harm when given to a pregnant woman or can affect reproduction. Mannitol Injection should be given to a pregnant woman only if clearly needed.

• Nursing mothers

It is not known whether Mannitol is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when mannitol is administered to a nursing woman.

• Pediatric use

Safety and effectiveness in children below the age of 12 have not been established.

Dosage requirements for patients 12 years of age and under have not been established.

• Geriatric use

Clinical studies of Mannitol Injection did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

• Too rapid infusion of large amounts of mannitol will cause a shift of intracellular water into the extracellular compartment resulting in cellular dehydration and overexpansion of the intravascular space with hyponatremia, congestive heart failure, and pulmonary edema.
• Repeated doses should not be given to patients with persistent oliguria as this can produce a hyperosmolar state and precipitate congestive heart failure and pulmonary edema due to volume overload. Dosage must be carefully monitored and adjusted in accordance with the clinical situation to avoid the consequences of overdosage.

Pharmacodynamic

Chemically, mannitol is an alcohol and a sugar, or a polyol; it is similar to xylitol or sorbitol. However, mannitol has a tendency to lose a hydrogen ion in aqueous solutions, which causes the solution to become acidic. For this reason, it is not uncommon to add a substance to adjust its pH, such as sodium bicarbonate. Mannitol is commonly used to increase urine production (diuretic). It is also used to treat or prevent medical conditions that are caused by an increase in body fluids/water (e.g., cerebral edema, glaucoma, kidney failure). Mannitol is frequently given along with other diuretics (e.g., furosemide, chlorothiazide) and/or IV fluid replacement. Inhaled mannitol has the possibility to cause bronchospasm and hemoptysis; the occurrence of either should lead to discontinuation of inhaled mannitol.

Pharmacokinetics

• Absorption

Approximately 7% of ingested mannitol is absorbed during gastrointestinal perfusion in uremic patients. Inhalation of 635 mg of mannitol powder yields a plasma C_max of 13.71 μg/mL in 1.5 hours (T_max) and a mean systemic AUC of 73.15 μg*h/mL.

• Distribution
  

Mannitol administered intravenously has a volume of distribution of 34.3 L.

• Metabolism and Excretion
  

Mannitol is metabolized only slightly, if at all, to glycogen in the liver.

Mannitol is primarily excreted unchanged in the urine. Following oral inhalation of 635 mg of mannitol in healthy volunteers, 55% of the total dose was recovered unchanged in the urine; following oral or intravenous administration of 500 mg, the corresponding values were 54 and 87%, respectively. Mannitol has an elimination half-life of 4.7 hours following oral administration; the mean terminal elimination half-life is similar regardless of administration route (oral, inhalation, and intravenous. Intravenous administration of mannitol yields a total clearance of 5.1 L/hr and renal clearance of 4.4 L/hr.

• https://www.uptodate.com/contents/mannitol-systemic-drug-information?search=mannitol&source=panel_search_result&selectedTitle=1~145&usage_type=panel&showDrugLabel=true&display_rank=1#F28662122

• https://www.rxlist.com/consumer_mannitol_osmitrol/drugs-condition.htm
• https://reference.medscape.com/drug/osmitrol-mannitol-343061#0
• https://www.syrianclinic.com/med/en/ProfDrugs/Mannitolpd.html#forms-cost
• https://go.drugbank.com/drugs/DB00742
• https://www.drugs.com/dosage/mannitol.html
• https://www.practo.com/medicine-info/mannitol-174-api