Osmitrol

Side effects of Mannitol are:

• pulmonary congestion,
• fluid and electrolyte imbalance,
• dry mouth,
• thirst,
• headache,
• blurred vision,
• dizziness,
• nausea, and
• chest pain.

Mannitol intravenous injections are available in following strengths and sizes: 5% and 10% in 1000 ml containers; 15% in 500 ml containers, 20% in 250 ml and 500 ml containers; and 25% in 50 ml flip-top vials.

Store mannitol injections at room temperature between 20 C to 25 C (68 F to 77 F).

Mannitol is injected into a vein through an IV. A healthcare provider will give you this injection.

Mannitol must be given slowly through an IV infusion, and you may receive the medication around the clock.

To be sure mannitol is helping your condition and not causing harmful effects, your blood will need to be tested often. This will help your doctor determine how long to treat you with mannitol. Your heart function will also need to be tested.

General

• Dosage, concentration of solution, and rate of administration vary with the condition being treated and the patient’s fluid requirements, urinary output, and response to the drug.a

• Do not administer drug until adequacy of patient’s renal function and urine flow have been established.a

• Replace fluids, plasma, blood, and electrolytes prior to initiating therapy in patients with shock with oliguria and rising BUN.a

Administration

Administer mannitol injection IV.a b Administer sorbitol-mannitol irrigation solution by transurethral instillation.d

IV Administration

For drug compatibility information, see Compatibility under Stability.

Administer by IV infusion using an administration set with a filter.a b

When used in surgical procedures to prevent oliguric acute renal failure, administration may be initiated before or immediately following surgery and may be continued postoperatively.a

When used preoperatively to reduce IOP, administer 1–1.5 hours prior to surgery in order to achieve maximum reduction of pressure before surgery.a b

Administer a test dose to patients with marked oliguria or suspected inadequate renal function to establish renal response before therapy is initiated.a b

A response is considered adequate if at least 30–50 mL of urine per hour is excreted over the next 2–3 hours.a b

If an adequate response is not attained, a second test dose may be given.a b

If a satisfactory response is not obtained after the second test dose, reevaluate patient, and mannitol should not be used.a b

Test dose in adults and children >12 years of age: Infuse over a period of 3–5 minutes to produce urine flow of ≥30–50 mL/hour.a b

Treatment of oliguria in adults: Infuse over 90 minutes to several hours.a

Cerebral or ocular edema in children >12 years of age: Usually, infuse over 30–60 minutes.a

Reduction of intracranial or IOP in adults: Usually, infuse over 30–60 minutes.a

Edema and ascites† in adults and children >12 years of age: Has been infused over 2–6 hours.a

Transurethral Irrigation

Sorbitol-mannitol irrigation solution is for urologic irrigation only; do not use for injection.d

Administer only by transurethral instillation using appropriate and disposable urologic instrumentation.d

Placing the flexible irrigation container >60 cm above the operating table may increase intravascular absorption of irrigation solution.d

Dosage

Pediatric Patients

Children >12 years of age: 0.2 g/kg or 6 g/m2 as a single dose.a

Children >12 years of age: 2 g/kg or 60 g/m2.a

Children >12 years of age: 2 g/kg or 60 g/m2 administered as a 15 or 20% solution.a

Children >12 years of age: 2 g/kg or 60 g/m2 administered as a 5 or 10% solution as needed.a

Children >12 years of age: 2 g/kg or 60 g/m2 administered as a 15 or 20% solution.a

Adults

20–100 g administered in a 24-hour period.b

Approximately 0.2 g/kg or 12.5 g infused IV as a 15 or 20% solution (usually 100 or 75 mL of a 15 or 20% solution, respectively).a b

50–100 g as a 5, 10, or 15% solution.a b Generally, a concentrated solution is administered initially followed by a 5 or 10% solution.a

100 g infused IV as a 15 or 20% solution.a b

12.5 g administered immediately before and after each dose of amphotericin B.a

Usually, 0.25 g/kg administered not more frequently than every 6–8 hours will achieve a maximum reduction of intracranial pressure.b Alternatively, 1.5–2 g/kg infused IV as a 15, 20, or 25% solution.a

A satisfactory reduction in intracranial pressure can be achieved with an osmotic gradient between blood and CSF of approximately 10 mOsmol.b

Usually, 1.5–2 g/kg infused IV as a 15, 20, or 25% solution.a b

Some clinicians have recommended as little as 1 g or as much as 3.2 g/kg infused IV as a 15, 20, or 25% solution.a

In general, maintain a urinary output of >100 mL/hour, but preferably 500 mL/hour, and a positive fluid balance of 1–2 L.a

Initially, 25 g, followed by infusion of a solution at a rate that will maintain a urinary output of ≥100 mL/hour.a

In barbiturate poisoning, initially 0.5 g/kg, followed by administration of a 5 or 10% solution at a rate to maintain the desired urine output.a

Alternatively, administer 1 L of a 10% solution during the first hour.a Measure urine volume and pH and calculate cumulative fluid balance at the end of the first hour and subsequent 2-hour periods.a If positive fluid balance is 1–2 L, administer 1 L of a 10% solution over the next 2 hours.a If positive fluid balance is <1 L, replace mannitol with 1 L of (1/6) M sodium lactate over the next 2 hours (if urine pH <7) or 1 L of 0.9% sodium chloride over 2 hours (if urine pH >7).a If the positive fluid balance is >2 L, administer 10% mannitol at the slowest possible rate.a IV administration of furosemide recommended if the positive fluid balance >2.5 L.a

Administer a sufficient volume of sorbitol-mannitol irrigation solution; volume determined at the discretion of clinician.d

50 g/m2 has been given in 24 hours.a

1 g/kg.102

100 g infused IV as a 10–20% solution.a

Special Populations

Geriatric Patients

Select dosage with caution, starting at the low end of the dosing range, because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.a b

Absorption

Bioavailability

Has been thought not to be absorbed when administered orally; however, about 17% of an oral dose was excreted unchanged in urine.a

Absorbed into systemic circulation following transurethral instillation as sorbitol-mannitol irrigation solution.d

Onset

Following IV administration, diuresis generally occurs within 1–3 hours, lowering of elevated CSF pressure occurs within 15 minutes, and lowering of elevated intraocular pressure occurs within 30–60 minutes.a

Duration

Lowering of elevated CSF pressure and elevated IOP persists for 3–8 and 4–6 hours, respectively, after infusion is stopped.a

Distribution

Extent

Following IV administration, mannitol remains confined to the extracellular compartment; does not cross the blood-brain barrier unless very high concentrations are present in the plasma or the patient has acidosis; and does not penetrate the eye.a

Elimination

Metabolism

Slightly metabolized to glycogen in the liver.a b

Elimination Route

Freely filtered by the glomeruli, with <10% tubular reabsorption; not secreted by tubular cells.a

Excreted principally in urine as unchanged drug.a

Half-life

100 minutes.a

Special Populations

Decreased clearance in patients with renal disease in which glomerular function is impaired.a

Decreased clearance in patients with conditions that impair small vessel circulation (e.g., CHF, cirrhosis with ascitic accumulation, shock, dehydration).a

• Induces diuresis mainly by elevating the osmotic pressure of the glomerular filtrate, which hinders the tubular reabsorption of water and solutes and increases the excretion of sodium.a b

• Increased renal blood flow resulting from dilation of vascular segments between the renal artery and glomeruli, lowered renal vascular resistance, and reduced blood viscosity also may contribute to the diuretic effect.a

  Increases excretion of potassium, chloride, calcium, phosphorus, lithium, magnesium, urea, and uric acid.a

• Increases extracellular fluid volume, plasma volume, and circulation time and dilutes extracellular stores of sodium by causing water to be drawn from cells to extracellular fluid and from erythrocytes to plasma.a Fluid shifts result in reduction of cerebral edema (by reduction in brain mass) and lowering of CSF pressure.a b Reduction of elevated IOP associated with withdrawal of fluids from anterior chamber of the eye.a b

• Prevents or reverses acute functional renal failure by reversing the acute reductions in renal blood flow, glomerular filtration rate, urine flow, and sodium excretion that may occur after trauma.a

• Protects kidneys from nephrotoxins by preventing toxins from becoming concentrated in the tubular fluid.a

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about Osmitrol, please talk with your doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about Osmitrol. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using Osmitrol.

Review Date: October 4, 2017

Osmitrol Injection (Mannitol Injection, USP) is a sterile, nonpyrogenic solution of Mannitol, USP in a single dose container for intravenous administration. It contains no antimicrobial agents. Mannitol** is a six carbon sugar alcohol prepared commercially by the reduction of dextrose. Although virtually inert metabolically in humans, it occurs naturally in fruits and vegetables. Mannitol is an obligatory osmotic diuretic. The pH is adjusted with sodium hydroxide or hydrochloric acid. Composition, osmolarity, and pH are shown in Table 1

The VIAFLEX plastic container is fabricated from a specially formulated polyvinyl chloride (PL 146 Plastic). The amount of water that can permeate from inside the container into the overwrap is insufficient to affect the solution significantly. Solutions in contact with the plastic container can leach out certain of its chemical components in very small amounts within the expiration period, e.g., di-2-ethylhexyl phthalate (DEHP), up to 5 parts per million. However, the safety of the plastic has been confirmed in tests in animals according to USP biological tests for plastic containers as well as by tissue culture toxicity studies.

Osmitrol Injection (Mannitol Injection, USP) is indicated for:

The promotion of diuresis, in the prevention and/or treatment of the oliguric phase of acute renal failure before irreversible renal failure becomes established;

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, and

Promoting the urinary excretion of toxic substances.

Applies to mannitol: inhalation capsule

Along with its needed effects, mannitol (the active ingredient contained in Osmitrol) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur while taking mannitol:

• Chest discomfort
• cough
• difficult or labored breathing
• dry heaves
• runny nose
• shortness of breath
• sore throat
• tightness in the chest
• troubled breathing
• vomiting
• wheezing

• Gagging

Some side effects of mannitol may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Headache

• Dizziness
• nausea
• sore throat