Mannitol

Registered South African indications:

• Prophylaxis against acute renal failure
• Differential diagnosis of acute oliguria
• Reduction of cerebrospinal pressure
• Reduction of intra-ocular fluid pressure

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Pre-existing plasma hyperosmolarity
• Severe dehydration
• Established anuria
• Severe heart failure
• Severe pulmonary congestion or pulmonary oedema
• Active intracranial bleeding (except during craniotomy)
• Disturbance of the blood-brain barrier
• Failure to respond to test dosing
• Progressive renal damage or dysfunction after institution of mannitol therapy, including increasing oliguria and azotemia

Cautions

• Pregnancy
• Breastfeeding
• Renal impairment
• Elderly
• High doses
• Preexisting compromised blood-brain barrier
• Disturbances of electrolyte and acid/base balance secondary to mannitol administration
• Administration of nephrotoxic medicinal products
• High infusion rate
• Children (≤16 years)
• Women (in particular, premenopausal women)
• Post-operatively
• Psychogenic polydipsia
• Hypoxaemia
• Underlying central nervous system disease
• Exposure of mannitol to low temperatures
• Risk of air embolism
  - Plastic containers in series connections
  - Pressurizing intravenous solutions in flexible plastic containers to increase flow rates
  - Vented intravenous administration sets with vent in the open position used with flexible plastic containers

Forms avail. in SA and covered in this monograph: inj, sol

Acute renal failure

• IV: 50-200g in 24hrs as an infusion; Max: 50g/dose

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Rate of administration adjusted to maintain urine flow of at least 30-50ml/hr

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Emergency situations in acute renal failure

• IV: 200mg/kg infused over 5mins; Max: 200g/24hrs

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After 5mins, readjust infusion rate to maintain urine flow of at least 30-50ml/hr

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Oliguria or renal impairment 
- Promotion of diuresis in the prevention and/or treatment of the oliguric phase of acute renal failure before irreversible oliguric renal failure becomes established

• IV: Test dose: 200mg/kg infused over 3-5mins; Repeat if adequate response not attained

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If adequate response to the second test dose is not attained, discontinue treatment and reassess patient since established renal failure may be present

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Adequate response to test dose if at least 30-50ml/hr of urine is excreted for 2-3hrs

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Reduction of intracranial pressure, cerebral volume and intraocular pressure
- 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

• IV: 1.5-2g/kg infused over 30-60mins

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When used preoperatively, administer dose 1-1.5hrs before surgery for maximum effect

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Promotion of elimination of renally excreted toxic substances in poisoning

• IV: Loading dose: 25g; Adjust to maintain urinary output of at least 100ml/hr; Positive fluid balance of 1-2 litres should be aimed for

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See additional prescribing points for general administration considerations 

Paed. forms avail. in SA and covered in this monograph: inj

Oliguria or renal impairment 
- Promotion of diuresis in the prevention and/or treatment of the oliguric phase of acute renal failure before irreversible oliguric renal failure becomes established

• IV: Test dose: 200mg/kg infused over 3-5mins; Repeat if up to two more times after 4-8hrs if needed; Treatment dose: 0.5-1.5g/kg

Reduction of intracranial pressure, cerebral volume and intraocular pressure
- 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

• IV: 1.5-2g/kg infused over 30-60mins

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See additional prescribing points for general administration considerations

Pregnancy 

• Caution
• 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

Breastfeeding 

• Caution
• There is no information on the excretion of mannitol in breast milk. Mannitol should not be used during breastfeeding unless clearly needed

Renal Impairment

• Caution; no dose adjustment recommended
  A test dose should be employed in severe renal impairment and therapy with mannitol should only be continued if an adequate urine flow is achieved

Hepatic Impairment

• No dose adjustment recommended

Elderly

• Caution; no dose adjustment recommended
  Dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or drug therapy

Porphyria Information

• Not porphyrinogenic (NP)

Drugs in Sport

• Prohibited - At all times

Central Nervous System Disorders

• Headache
• Dizziness
• Rebound intracranial pressure increase
• CNS toxicity
  - Convulsions
  - Coma
  - Confusion
  - Lethargy
• Asthenia

Cardiovascular Disorders

• Cardiac arrhythmia
• Congestive heart failure
• Palpitations
• Hypotension
• Hypertension

Respiratory Disorders

• Pulmonary oedema
• Rhinitis

Gastrointestinal Disorders

• Dry mouth
• Thirst
• Nausea and vomiting

Genitourinary Disorders

• Excessive diuresis
• Osmotic nephrosis
• Urinary retention
• Acute renal failure
• Azotemia
• Anuria
• Haematuria
• Oliguria
• Polyuria

Endocrine and Metabolic Disorders

• Fluid and electrolyte imbalance
  - Hypovolaemia
  - Peripheral oedema
  - Hyponatraemia
  - Hyponatraemia
  - Hyperkalaemia
  - Hypokalaemia  
• Dehydration
• Oedema
• Metabolic acidosis

Musculoskeletal Disorders

• Cramps

Skin and Subcutaneous Tissue Disorders

• Skin necrosis
• Urticaria
• Infusion site reactions
  - Infusion thrombophlebitis
  - Infusion site inflammation
  - Infusion site pain
  - Infusion site rash
  - Infusion site erythema
  - Infusion site pruritis
• Compartment syndrome (associated with extravasation and swelling at the injection site)

Immune, Blood and Lymphatic Disorders 

• Allergic reaction
• Anaphylactic reaction
  - Hypotension
  - Hypertension
  - Fever
  - Chills
  - Sweating
  - Cough
  - Musculoskeletal stiffness
  - Myalgia
  - Urticaria
  - Rash
  - Generalized pain
  - Discomfort
  - Nausea and vomiting
  - Headache
  - Anaphylactic shock
  - Cardiac arrest
  - Death
• Fever
• Chills

Sensory Disorders

• Blurred vision

• Other diuretics
• Medicinal products that are renally absorbed
• Lithium
• Cyclosporine
• Aminoglycoside
• Nephrotoxic agents
• Neurotoxic agents
• Digoxin
• QT-prolonging agents
• Neuromuscular blockers
• Tubocurarine
• Oral anticoagulants
• Blood products

Other interactions

• Laboratory test interferences (see additional prescribing points)

• Renal function
• Acid base balance
• Serum osmolarity
• Electrolytes

Additional observations

• Daily fluid in and out
• Infusion site

Administration considerations

• The solution is for intravenous administration through a sterile and non-pyrogenic equipment
• The osmolarity of the solution should be considered. Hyperosmolar mannitol solutions may cause vein damage
• This hypertonic solution should be administered via a large peripheral or, preferably, a central vein. Rapid infusion in peripheral veins may be harmful
• Use an administration set which includes a final in-line filter, because of the potential for mannitol crystals to form, and use an aseptic technique. The equipment should be primed with the solution in order to prevent air entering the system
• Do not remove the unit from the overwrap until ready for use. The inner bag maintains the sterility of the product
• Use only if the solution is clear without visible particles or discoloration and the seal is intact. Confirm the integrity of the bag. Use only if the container is undamaged. Administer immediately following insertion of the infusion set
• Mannitol solutions may crystallize when exposed to low temperatures. At higher concentrations, the solutions have a greater tendency to crystallize. Inspect for crystals prior to administration. If crystals are visible, re-dissolve by warming the solution up to 37°C, followed by gentle agitation. Solutions should not be heated in water or in a microwave oven due to the potential for product contamination or damage. Only dry heat (for example, a warming cabinet) should be used. Allow the solution to cool to room or body temperature before re-inspection for crystals and use

Laboratory test interferences

• Mannitol can cause false low results in some tests systems for inorganic phosphorus blood concentrations
• Mannitol produces false positive results in tests for blood ethylene glycol concentrations in which mannitol is initially oxidized to an aldehyde

Mannitol, a carbohydrate, is confined to the extracellular compartment. It has an osmotic effect which causes fluid to pass from the intracellular to the extracellular compartment. Mannitol is freely filterable at the kidney glomerulus and less than 10% is reabsorbed back from the kidney tubule. In the kidney tubules, mannitol exerts an osmotic effect which diminishes water reabsorption from the glomerular filtrate and produces diuresis. Mannitol thereby promotes urine flow in oliguria/anuria or in situations where the patient is at risk of onset of acute renal failure. Mannitol also increases electrolyte excretion, especially sodium, potassium and chloride. Excretion of renally excreted substances such as salicylates and barbiturates is also increased. Mannitol does not penetrate the intact blood-brain barrier under usual circumstances. Confined to the plasma, mannitol exerts an osmotic pressure, causing fluid to leave the brain tissue, and brain volume and intracranial pressure to be reduced. Mannitol does not penetrate the eye. Mannitol reduces the intraocular pressure due to its osmotic effect.

Solution (per 1000ml) 50g

• Sabax Osmitrol 5% Vial 500MI (Adcock Ingram) originator
• Mannitol Fresenius 5% Irrigation Solution (Fresenius Kabi)

Solution (per 100ml) 200g

• Sabax Osmitrol 20% Viaf 500MI (Adcock Ingram) originator

Injection (per 500ml) 100g

• Intramed Mannitol 20% M/V (Bodene)
• Mannitol Fresenius 20% (Fresenius Kabi)

Injection (per 50ml) 12.5g

• Intramed Mannitol 25% M/V (Bodene)
• Mannitol Fresenius 25% (Fresenius Kabi)