MANNITOL Solution for infusion Ref.[8194] Active ingredients: Mannitol

Posology

The choice of the specific mannitol concentration, dosage and rate of administration depends on the age, weight and clinical condition of the patient and concomitant therapy.

Adults and adolescents

Acute renal failure

The general dose range for adults is 50 to 200 g mannitol (330 to 1320 ml) in a 24-hour period, with a dosage limit of 50 g mannitol (330 ml) on any one occasion. In most instances adequate response will be achieved at a dosage of 50 to 100 g mannitol/day (330 to 660 ml). The rate of administration is usually adjusted to maintain a urine flow of at least 30-50 ml per hour.

Only in emergency situations, the maximum infusion rate can be as high as 200 mg/kg infused over 5 minutes (see also test dose). After 5 minutes, the infusion rate should be readjusted to maintain a urine flow of at least 30-50 ml per hour, with a maximum dose of 200 g/24h.

Use in patients with oliguria or renal impairment

Patients with marked oliguria or suspected inadequate renal function should first receive a test dose of approximately 200 mg mannitol/kg bw (body weight) (1.3 ml/kg) infused over a period of 3 to 5 minutes. For example in an adult patient with a body weight of 70 kg: approximately 100 ml of a 15% solution. The response to the test dose is considered adequate if at least 30-50 ml/hour of urine is excreted for 2-3 hours. If an adequate response is not attained, a further test dose may be given. If an adequate response to the second test dose is not attained, treatment with mannitol should be discontinued and the patient reassessed as established renal failure may be present.

Reduction of intracranial pressure, cerebral volume and intraocular pressure

The usual dose is 1.5 to 2 g/kg bw (10 to 13 ml/kg bw), infused over 30 to 60 minutes. When used preoperatively, the dose should be administered 1 to 1.5 hours before surgery to obtain the maximum effect.

Promotion of elimination of renally excreted toxic substances in poisoning

In forced diuresis the dose of mannitol should be adjusted to maintain urinary output of at least 100 ml/hour. Positive fluid balance of 1-2 litres should be aimed for. An initial loading dose of approximately 25 g (165 ml) may be given.

Paediatric population

In renal insufficiency, the test dose should be 200 mg mannitol/kg bw (1.3 ml/kg bw) over 3-5 minutes. The treatment dose ranges from 0.5 to 1.5 g/kg bw (3 ml to 10 ml/kg bw). This dose may be repeated once or twice, after an interval of 4 to 8 hours, if necessary.

For increased intracranial and intraocular pressure, the dose may be given over 30 to 60 minutes as for adults.

Elderly population

As for adults, the dosage depends on the weight, clinical and biological condition of the patient and concomitant therapy. The general dose range is the same as for adults 50 to 200 g mannitol in a 24 hour period (330 to 1320 ml in a day ), with a dosage limit of 50 g mannitol (330 ml) on any one occasion. Since incipient renal insufficiency may be present, caution should be used when reviewing patient’s status prior to dose selection.

Method of administration

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. Please see also sections 4.4 and 6.6.

For information on incompatibilities and preparation of the product and additives, please see sections 6.2 and 6.6.

Signs and symptoms of overdose with mannitol may include acute renal failure, electrolyte imbalance, hypervoalaemia, CNS toxicity. Prolonged administration or rapid infusion of large volumes of hyperosmotic solutions may results in circulatory overload and acidosis. Headache, nausea and shivering without temperature change may represent initial signs/symptoms. Confusion, lethargy, convulsions, stupor and coma may follow.

In case of suspected overdose, treatment with mannitol should be stopped immediately.

Management is symptomatic and supportive, with monitoring of fluid and electrolyte balance.

Mannitol is dialyzable. Haemodialysis may be helpful.

Unopened:

100 and 250 ml containers: 2 years.

500 ml containers: 3 years.

After opening, with or without additives:

From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user.

Do not refrigerate or freeze.

The bags, known as Viaflo, are composed of polyolefin/polyamide co-extruded plastic (PL 2442) and contain Mannitol solution. The bags are overwrapped with a protective plastic pouch composed of polyamide/polypropylene which serves only to provide physical protection to the bag.

The bag size is either 100, 250 or 500 ml.

Outer carton contents:

50 bags of 100 ml
30 bags of 250 ml
20 bags of 500 ml

Not all pack sizes may be marketed.

Use administration sets with a final in-line filter because of the potential for mannitol crystals to form. For instructions on precautions to be taken before administration, in case of crystallization of the medicinal product, see section 4.2.

Additives may be introduced before infusion or during infusion through the re-sealable medication port.

Thorough and careful aseptic mixing of any additive is mandatory. Solutions containing additives should be used immediately and not stored.

Before adding a medicinal product,verify it is soluble in water at the pH of mannitol solution.

Chemical and Physical stability of any additive at the pH of Mannitol solution (4.5 to 7.0) in the Viaflo container should be established prior to use.

Discard after single use.

Discard any unused portion.

Do not reconnect partially used bags.

Opening

• Remove the Viaflo container from the overpouch just before use.
• Check for minute leaks by squeezing inner bag firmly. If leaks are found, discard solution, as sterility may be impaired.
• Check solution for limpidity and absence of foreign matter. If solution is not clear or contains foreign matter, discard the solution.

Preparation for administration

Use sterile material for preparation and administration.

• Suspend container from eyelet support.
• Remove plastic protector from outlet port at bottom of container:
  • grip the small wing on the neck of the port with one hand
  • grip the large wing on the cap with the other hand and twist
  • the cap will pop off.
• Use an aseptic method to set up the infusion.
• Attach administration set. Refer to directions accompanying set for connection, priming of the set and administration of the solution.

Techniques for injection of additive medications

Warning: Additives may be incompatible. Check additive compatibility with both the solution and container prior to use.

To add medication before administration

• Disinfect medication site.
• Using syringe with 19 to 22 gauge needle, puncture resealable medication port and inject.
• Mix solution and medication thoroughly. For high-density medication such as potassium chloride, tap the ports gently while ports are upright and mix.

Caution: Do not store bags containing added medications.

To add medication during administration

• Close clamp on the set
• Disinfect medication site.
• Using syringe with 19 to 22 gauge needle, puncture resealable medication port and inject.
• Remove container from IV pole and/or turn to an upright position.
• Evacuate both ports by tapping gently while the container is in an upright position.
• Mix solution and medication thoroughly.
• Return container to in use position, re-open the clamp and continue administration.