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Logo INTRAMED MANNITOL 20% m/v INFUSION

SCHEDULING STATUS:
S1

PROPRIETARY NAME
(and dosage form):

INTRAMED MANNITOL 20% m/v INFUSION

COMPOSITION:
Each 500 mL contains 100g of
Mannitol

PHARMACOLOGICAL CLASSIFICATION:
A18.1 Diuretics

PHARMACOLOGICAL ACTION:
Mannitol is an osmotic diuretic. It is freely filterable at the glomerulus, undergoes limited reabsorption by the renal tubule and is pharmacologically inert by conventional criteria. These three characteristics permit the administration of this agent in sufficiently large quantities to contribute significantly to the osmolality of the plasma, the glomerular filtrate and the tubular fluid. The action within the kidney depends primarily, upon the concentration of osmotically active particles in solution. In addition, most osmotic diuretics are selected because of their resistance to metabolic alteration. However, a sugar such as glucose will act in a similar manner it its concentration becomes excessively high in the plasma and, as a consequence, also in the tubular fluid.

When there is a significant increase in the amount of any osmotically active solute in the voided urine, this is usually accompanied by an increase m urine volume. In general, there are three separate ways by which the rate of solute excretion may be augmented; the inhibition of electrolyte reabsorption by specific drugs, an increase in the filtered load of electrolytes that are poorly or incompletely reabsorbed, and an increase in the filtered load of the nonelectrolyte osmotic agents

It is important to appreciate the circumstances under which the osmotic diuretics may play a unique role in either maintaining or increasing urine volume. When the rate of glomerular filtration is acutely reduced, either experimentally in the laboratory or clinically as a result of hypovolaemic shock, dehydration or trauma, the solutes of the glomerular filtrate undergo more complete reabsorption so that there is a disproportionately large fall in the rate of urine flow and solute excretion.

As indicated previously, the administration of a normal solute, such as sodium chloride, may restore renal excretory function, but only if there is improvement in renal haemodynamics. II the rate of glomerular titration remains severely reduced, sodium chloride administration fails to augment urine flow because of the virtually complete tubular reabsorption of this normal electrolyte. Under the same conditions the diuretics that normally act by inhibiting tubular transport may also be ineffective because the extent to which they reduce tubular reabsorptive capacity is not of sufficient magnitude to compensate for the greatly diminished filtered load.

However, under the same conditions, that is, when the renal circulation is acutely compromised, the osmotic diuretics retain their efficacy. Even though the filtration is reduced, mannitol is still filtered at the glomerulus. The tubular impermeability to mannitol is not altered by acute renal ischemia of short duration. Hence the amount of mannitol that is filtered is also excreted in the voided urine. Unreabsorbed solute limits the back diffusion of water. As a consequence, urine volume can be maintained even in the presence of decreased glomerular function. As a first approximation urine volume is proportional to the rate of solute excretion, which under these circumstances may be composed largely of the agent administered as the osmotic diuretic.

An additional action of the osmotic diuretics is to increase the rate of electrolyte excretion, particularly sodium, chloride and potassium. However, this occurs only with large doses. The action on electrolyte reabsorption is related to the isosmotic characteristics of the proximal tubule. Mannitol undergoes very little reabsorption, and for many practical purposes the tubule may be considered to be impermeable to it. Osmotic diuretics must be administered parenterally in order to achieve effective plasma concentrations.

INDICATIONS:
Osmotic diuretics may be used for several purposes that are distinct and separate, but all of which depend on the same fundamental characteristics. Their uses include prophylaxis against acute renal failure, differential diagnosis of acute oliguria, and reduction of cerebrospinal and intra-ocular fluid pressures. Mannitol is extensively employed. Perhaps one of the clearest and most important indications is the prophylaxis of acute renal failure. It is used for this purpose in conditions as diverse as cardiovascular operations, severe traumatic injury, operations in the presence of severe jaundice, and management of haemolytic transfusion reactions. Mannitol exerts an osmotic effect within the tubular fluid, inhibits water reabsorption and maintains the rate of urine flow within reasonably normal limits. In this way it protects the kidney against damage. In the presence of hypotension mannitol is more effective than saline solution in maintaining glomerular filtration.

If given in sufficiently large amounts, mannitol increases extracellular osmolarity, which in turn may decrease cellular swelling and improve renal blood flow.

For the evaluation of acute oliguria:– With a partial reduction in glomerular function, such as might occur from excessive loss of body fluids, urine flow may be increased toward normal by the administration of an osmotic diuretic, and this response may serve as a guide for the additional administration of parenteral fluids. However, if either glomerular or tubular function is too severely compromised mannitol will not increase urine flow. This may help orient the further management of the patient with acute anuria.

Mannitol is also used for the reduction of the pressure and volume of the intraocular and cerebrospinal fluids. By elevating the osmolality of the plasma, one is able to enhance, the diffusion of water from those fluids back into the plasma and the extra cellular space.

CONTRA-INDICATIONS:
Renal disease of sufficient severity to produce anuria and marked pulmonary congestion. Mannitol should not be given to patients with pulmonary congestion or oedema, intracranial bleeding, congestive heart failure, to dehydrated patients, or to patients with renal failure unless a test dose has produced a diuretic response.

WARNINGS:
This is a hyperosmolar solution. This solution may not be mixed with other products.

DOSAGE AND DIRECTIONS FOR USE:
Warm before use to dissolve crystals. Do not use unless solution is clear. Use filter type administration set.

The adult dose for promotion of diuretics ranges from 50 to 200 g over a 24 hour period of infusion; the rate is generally adjusted to maintain a urinary output of at least 30 to 50 mL per hour. It should be preceded by a test dose in patients with marked oliguria or questionable adequacy of renal function. The recommended test dose is 200 mg/kg (approximately 75 mL Intramed Mannitol 20% m/v infusion OR 60 mL Intramed Mannitol 25% m/v injection for an adult patient), infused over 3 to 5 minutes; if the first or a second test dose fails to promote a urinary flow greater than 30 mL per hour for 2 to 3 hours, the patient's status should be re-evaluated prior to continuation of therapy. When used for the prevention of acute renal failure during various types of surgery or for the treatment of oliguria, the total dose is 50 to 100 g of mannitol for an adult patient. The dose for the reduction of intracranial pressure and brain mass prior to neurosurgery, or for the reduction of intraocular tension during an acute attack of congestive glaucoma or for ophthalmic surgery, is 1,5 to 2 g/kg given as a 20% solution over a period of 30 to 60 minutes.

SIDE EFFECTS AND SPECIAL PRECAUTIONS:
The infusion of mannitol should be terminated if the patient develops signs of progressive renal dysfunction, heart failure or pulmonary congestion. Acute water toxicity may follow the intravenous administration of mannitol if renal flow is inadequate. Hyperosmotic solutions of mannitol should be administered slowly by intravenous injection and should not be mixed with blood in the transfusion apparatus. Patients should be closely observed for signs of electrolyte and fluid imbalance.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
See under side-effects and special precautions.

IDENTIFICATION:
Sterile non-pyrogenic solution of Mannitol in Water for Injections.

PRESENTATION:
500 mL in flexible bags.

STORAGE INSTRUCTIONS:
Store below 25°C

REGISTRATION NUMBER:
L/18.1/228

NAME AND BUSINESS ADDRESS OF APPLICANT:
INTRAMED (PTY) LTD
6 Gibaud Road
Port Elizabeth 6001

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
January 1979 12-214/8-94
  KOHLER C&P P E

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