MANNITOL INFUSION BP 20%W/V (For IV Infusion only)
OSMOL INFUSION
COMPOSITION
Each ml contains:
Mannitol BP 20 gm
Water for Injections BP q.s.
DESCRIPTION
A clear, colorless to almost colorless solution.
PHARMACODYNAMIC
Pharmacotherapeutic group: “solutions producing osmotic diuresis.”
ATC code: B05BC01.
Mannitol solution for infusion 20% belongs to the osmotically active diuretics.
Mannitol, a virtually non-metabolizable carbohydrate, is rapidly eliminated by the renal
glomerulus and is not reabsorbed by the renal tubules, entraining water and sodium. The
distribution of mannitol is confined to the extracellular fluid volume.
PHARMACOKINETICS
When administered intravenously, mannitol is eliminated largely unmetabolized through the
glomeruli. Only 10% is reabsorbed back from the kidney tubule. The elimination half-life in
adults is approximately 2 hours, longer where renal failure is present. 80% of an intravenous
dose is excreted unchanged within 3 hours.
THERAPEUTIC INDICATION
Mannitol 20% w/v is indicated for use as an osmotic diuretic in the following situations:
Promotion of diuresis in the prevention and/or treatment of the oliguric phase of acute
renal failure before irreversible oliguric renal failure becomes established.
Reduction of intracranial pressure and cerebral oedema, when the blood-barrier is intact.
Reduction of elevated intraocular pressure when it cannot be lowered by other means.
Promotion of elimination of renally excreted toxic substances in poisoning.
DOSAGE AND ADMINISTRATION
Mannitol solution for infusion 20% should be administered only by intravenous infusion. The
total dosage, concentration, and rate of administration should be governed by the nature and
severity of the condition being treated, fluid requirement, and urinary output. The usual adult
dosage ranges from 20 to 100 g in a 24-hour period, but in most instances an adequate
response will be achieved at a dosage of approximately 50 to 100 g in a 24-hour period. The
rate of administration is usually adjusted to maintain a urine flow of at least 30 to 50
mL/hour. This outline of administration and dosage are only a general guide to therapy.
Parenteral drug products should be inspected visually for particulate matter and discoloration
prior to administration whenever solution and container permit. Use of a final filter is
recommended during administration of all parenteral solutions, where possible.
Test Dose:
A test dose of mannitol should be given prior to instituting Mannitol solution for infusion
20% therapy for patients with marked oliguria, or those believed to have inadequate renal
function. Such a test dose may be approximately 0.2 g/kg body weight (about 75 mL of a
20% solution or 100 mL of a 15% solution) infused in a period of three to five minutes to
produce a urine flow of at least 30 to 50 mL/hour. If urine flow does not increase, a second
test dose may be given; if there is an inadequate response, the patient should be reevaluated.
Prevention of Acute Renal Failure (Oliguria):
When used during cardiovascular and other types of surgery, 50 to 100 g of mannitol as a 5,
10, or 15% solution may be given. The concentration will depend upon the fluid requirements
of the patient.
Treatment of Oliguria:
The usual dose for treatment of oliguria is 100 g administered as a 15 or 20% solution.
Reduction of Intraocular Pressure:
A dose of 1.5 to 2.0 g/kg as a 20% solution (7.5 to 10 mL/kg) or as a 15% solution (10 to 13
mL/kg) may be given over a period as short as 30 minutes in order to obtain a prompt and
maximal effect. When used preoperatively the dose should be given one to one and one-half
hours before surgery to achieve maximal reduction of intraocular pressure before operation.
Reduction of Intracranial Pressure:
Usually, a maximum reduction in intracranial pressure in adults can be achieved with a dose
of 0.25 g/kg given not more frequently than every six to eight hours. An osmotic gradient
between the blood and cerebrospinal fluid of approximately 10 mOsmol will yield a
satisfactory reduction in intracranial pressure.
Adjunctive Therapy for Intoxications:
As an agent to promote diuresis in intoxications, 5%, 10%, 15% or 20% mannitol is
indicated.
The concentration will depend upon the fluid requirement and urinary output of the patient.
Measurement of glomerular filtration rate by creatinine clearance may be useful for
determination of dosage.
OVERDOSE
In case of suspected overdose, treatment with mannitol should be stopped immediately.
Prolonged administration or rapid infusion of large volumes of hyperosmotic solutions may
result in circulatory overload and acidosis. Headache, nausea and shivering without
temperature change may represent initial signs/symptoms. Confusion, lethargy, convulsions,
unconsciousness and coma may follow.
Treatment: The infusion is stopped immediately and supportive measures are applied to
correct water and electrolyte disorders. Haemodialysis helps to eliminate mannitol and reduce
the increased osmotic pressure of the serum.
CONTRAINDICATION
Mannitol solution for infusion 20% is contra-indicated in patients presenting with:
Hypersensitivity to mannitol
Severe pulmonary congestion or pulmonary oedema
Irreversible anuria
Recent intracranial bleeding, except during craniotomy
Heart failure
Loss of water and electrolytes
Chronic kidney disease
WARNING AND PRECAUTIONS
Caution in administration in renal failure and pregnancy. Prior to administration, careful
assessment of the condition of the cardiovascular system is required, followed by continuous
monitoring of diuresis and serum electrolytes.
Administration should not be repeated to patients who remain anuric following
administration of a test dose.
Patients with pre-existing renal disease, or those receiving potentially nephrotoxic drugs, are
at increased risk of renal failure following administration of mannitol. Serum osmolal gap
and renal function should be closely monitored and necessary action initiated, should signs of
worsening renal function appear.
In patients with shock and renal dysfunction, mannitol should not be administered until
volume (fluid; blood) and electrolytes have been replaced.
Patients receiving mannitol should be monitored for any deterioration in renal, cardiac or
pulmonary function and treatment discontinued in the case of adverse events.
The cardiovascular status of the patient should be carefully evaluated before rapidly
administering mannitol, since sudden expansion of the extracellular fluid may cause sudden
congestive heart failure.
Shift of sodium-free intracellular fluid into the extracellular compartment following mannitol
infusion may lower serum sodium concentration and aggravate pre-existing hyponatraemia.
Sodium may be lost in the urine. Mannitol may obscure and intensify inadequate hydration
and hypovolaemia.
Urinary output, fluid balance, central venous pressure and electrolyte balance (in particular
serum sodium and potassium levels) should be carefully monitored.
Accumulation of mannitol may result if urine output continues to decline during
administration and this may intensify existing or latent congestive heart failure.
Precautions during administration
Avoid extravasation (risk of local necrosis).
Mannitol in the 20% solution may crystallize.
To dissolve crystals, the bottle is heated in hot water and shaken vigorously.
The solution should be infused at body temperature.
It is recommended to use a haemofilter when infusing 20% mannitol solution to prevent
potential infusion of mannitol microcrystals.
PREGNANCY AND LACTATION
There are no relevant published data from the use of mannitol in pregnant women.
There are no relevant published data from animal studies with respect to mannitol effect on
pregnancy and/or embryo/foetal development and/or parturition and/or postnatal
development.
Mannitol should not be used during pregnancy unless clearly needed. There is no information
on excretion of mannitol in breast milk. Mannitol should not be used during lactation unless
clearly needed.
DRUG INTERACTION
Concurrent use of other diuretics may potentiate the effects of mannitol and dose adjustments
may be required.
Mannitol increases the elimination of medicinal products excreted through urine (e.g. lithium
and methotrexate) and, therefore, concomitant use of mannitol may impair the response to
these medicinal products.
Patients receiving concomitant cyclosporine should be closely monitored for signs of
nephrotoxicity.
Other potential interactions are with aminoglycosides (potentiation of their ototoxic effects
by
mannitol), depolarizing neuromuscular blocking drugs (enhancement of their effects by
mannitol), oral anticoagulants (mannitol may reduce their effects by increasing the
concentration of clotting factors secondary to dehydration) and digitalis (if hypokalaemia
follows mannitol treatment, there is a risk of digitalis toxicity), although there is limited
evidence of such interactions occurring in humans.
It should not be administered concomitantly with blood.
If it is essential that blood be given simultaneously, at least 20 milliequivalents of sodium
chloride should be added to each liter of mannitol solution to avoid pseudo agglutination.
ADVERSE EFFECTS
Adverse reactions are classified as follows: very common (≥1/10), common (≥1/100 to
<1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000)
and not known (cannot be estimated from the available data).
Frequency System Organ Class Adverse Reactions
Uncommon
Metabolism and
nutrition disorder
Fluid and electrolyte
disorders
Vascular Disorder Hypotension
Thrombophlebitis
Rare Immune system
disorder
Allergic reaction*
Anaphylactic shock*
Metabolism and
nutrition disorders
Dehydration
Oedema
Nervous system
disorders
Headache
Convulsions
Dizziness
Rebound intracranial
pressure increase
Eye disorder Blurred vision
Cardiac disorders Cardiac arrhythmia
Vascular Disorder Hypertension
Pulmonary oedema
Gastrointestinal
Disorder
Dry mouth
Thirst
Nausea
Vomiting
Skin and subcutaneous
tissue disorder
Skin necrosis
Urticaria
Musculoskeletal and
connective tissue
disorder
Cramps
Renal and urinary
disorders
Excessive diuresis
Osmotic nephrosis
Urinary retention
General Disorder and
administration site
condition
Chest pain (angina-like chest
pain)
Fever
Very Rare
Cardiac Disorders Congestive heart failure
Renal and urinary
disorders Acute renal failure
Not Known
Nervous system
disorder
Convulsion
Painful arm
Cardiac Disorders
Pulmonary congestion
Metabolic acidosis
Tachycardia
Respiratory, thoracic
and mediastinal
disorders
Rhinitis
Gastrointestinal
disorder Diarrhoea
Musculoskeletal and
connective tissue
disorders
Chills
General disorders and
administration site
conditions
Infusion site
thrombosis/phlebitis
*It can be manifested with skin, gastrointestinal, and severe
circulatory (hypotension) and respiratory manifestation (e.g. dyspnea).
Other hypersensitivity/infusion reaction include hypertension, pyrexia,
chills, sweating, cough, shivering and myalgia, urticaria/rash, pruritus,
generalized pain, discomfort, nausea, vomiting and headache.
PRESENTATION
OSMOL Infusions are supplied in 100 ml Flint, Type II USP, Molded infusion vials.
STORAGE AND OTHER INFORMATION
Mannitol Infusion should be stored at a temperature of 20°C to 30°C. Exposure to lower
temperatures may cause the deposition of crystals, which should be dissolved by warming
before use.
Caution: Not to be used if container is found leaking or solution is hazy or contain any
visible solid particles.
Keep this medicine out of the sight and reach of
