Mannitol (mannitol)

The dosage, concentration of solution, and rate of administration of mannitol vary with the condition being treated and the patient's fluid requirements, urinary output, and response to the drug.

Mannitol is administered by IV infusion. To measure glomerular filtration rate (GFR), one manufacturer recommends that 100 mL of a 20% solution (20 g) of mannitol be diluted with 180 mL of 0.9% sodium chloride injection, and the resulting 280 mL of solution infused at a rate of 20 mL/minute. Another source suggests that 200 mg/kg, in a 15-25% solution, be administered in 3-5 minutes.

Mannitol clearance is determined by simultaneously measuring plasma mannitol concentrations and the quantity of mannitol excreted in urine in a given time and calculating the ratio of the amount of mannitol excreted to the plasma mannitol concentration. Catheterization is performed to facilitate complete urine collection. Mannitol clearance, and therefore GFR, is calculated using the formula:

where U is the average concentration of mannitol in the urine in mg/dL, V is the average volume of urine collected per minute in mL, and P is the average concentration of mannitol in plasma in mg/dL. Normal values for mannitol clearance (and consequently GFR), corrected to a standard 1.73 m2 of body surface area, average 125 mL for men and 116 mL for women.

Mannitol injections are administered by IV infusion. An administration set with a filter should be used for infusion of injections containing 20% or more, since mannitol crystals may be present. For transurethral prostatic resection, mannitol irrigation solutions are instilled into the bladder via an indwelling urethral catheter.

Because mannitol increases urinary excretion of lithium, patients being treated with lithium should be observed for possible impairment of response to that drug if they receive mannitol.

There are no contraindication interactions for this drug.

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Diuretics/Sodium Phosphate Bowel Cleanser

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Bowel cleansing with sodium phosphate causes dehydration, decreased intravascular volume and hyperphosphatemia, which increases phosphate levels in the renal tubules. Abnormally high levels of calcium and phosphate in the renal tubules may precipitate out, resulting in renal injury.(1)

CLINICAL EFFECTS: Use of sodium phosphate for bowel cleansing in patients maintained on diuretics may increase the risk of acute phosphate nephropathy, which is an acute kidney injury associated with deposits of calcium phosphate crystal in the renal tubules that may result in permanent renal function impairment. Acute phosphate nephropathy presents as acute kidney injury with minimal proteinuria and a bland urine sediment.(2) Use of oral sodium phosphate products at laxative doses has not been associated with acute kidney injury.(3)

PREDISPOSING FACTORS: Patients who may be at an increased risk of acute phosphate nephropathy include those who are over age 55; are hypovolemic or have decreased intravascular volume; have baseline kidney disease, bowel obstruction, or active colitis; and who are using medications that affect renal perfusion or function (such as diuretics, angiotensin converting enzyme (ACE) inhibitors, angiotension receptor blockers (ARBs) and possibly nonsteroidal anti-inflammatory drugs (NSAIDs).(2)

PATIENT MANAGEMENT: If possible, use an alternative agent for bowel cleansing.(1) Use sodium phosphate products with caution in patients taking medications that affect kidney function or perfusion, such as diuretics. Obtain baseline and post-procedure labs (electrolytes, calcium, phosphate, BUN, creatinine, and [in smaller, frail individuals] glomerular filtration rate). Instruct patients to drink sufficient quantities of clear fluids before, during, and after bowel cleansing and to avoid other laxatives that contain sodium phosphate. Consider hospitalization and intravenous hydration during bowel cleansing to support frail patients who may be unable to drink an appropriate volume of fluid or who may be without assistance at home.(2) Use of an electrolyte solution for rehydration may decrease the risk of acute phosphate nephropathy.(4,5)

DISCUSSION: Since May 2006, the FDA has received 20 reports of acute phosphate nephropathy associated with the use of Osmo Prep. Concomitant medications included ACE inhibitors or ARBs (11), diuretics (6), and NSAIDs (4).(2) In a retrospective review of colonoscopy patients, simultaneous use of ACE inhibitors or ARBs significantly increased the risk of acute kidney injury from oral sodium phosphate. Diuretic use was also a risk factor.(6) In a case series study of 21 cases of acute phosphate nephropathy in patients who had used oral sodium phosphate, 14 patients received an ACE inhibitor or ARB, 4 used a diuretic, and 3 used an NSAID.(7) Cases have also been reported with rectal products.(8)

Moderate Interaction: Assess the risk to the patient and take action as needed.

Diuretics/Zoledronic Acid

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Concurrent use of zoledronic acid and a diuretic may have adverse effects on the renal system.(1,2)

CLINICAL EFFECTS: Concurrent use of zoledronic acid and a diuretic may result in renal dysfunction. Deterioration in renal function, acute renal failure requiring dialysis, and death have been reported.(1)

PREDISPOSING FACTORS: The interaction may be more likely in elderly patients, patients who are taking other drugs that impact renal function, patients with pre-existing renal compromise, and patients who are dehydrated.(1)

PATIENT MANAGEMENT: Patients should be adequately hydrated with 500 ml (2 glasses of water) before and after zoledronic acid administration.(1) Creatinine clearance should be monitored before and after therapy and zoledronic acid should not be administered in patients with a creatinine clearance less than 35 ml/min.(1,3)

DISCUSSION: Zoledronic acid has been associated with renal dysfunction, including deterioration in renal function, acute renal failure requiring dialysis, and death. Risk factors include advanced age, concomitant nephrotoxic agents, and dehydration.(1) The FDA has received 16 reports of fatal acute renal failure and 9 reports of renal injury requiring dialysis following the administration of Reclast (zoledronic acid).(3)

Selected Diuretics/Tobramycin Inhalation

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: The combination may have additive or synergistic risks for ototoxicity and/or nephrotoxicity.(1,2)

CLINICAL EFFECTS: Concurrent use may result in an increased risk of aminoglycoside toxicity.(1)

PREDISPOSING FACTORS: Severe renal impairment, sepsis, or concomitant use of additional ototoxic or nephrotoxic agents may further increase the risk for toxicity. Patients carrying certain variants in the MT-RNR1 gene (m.1555A>G, m.1095T>C, and m.1494C>T) are at greatly increased risk of developing ototoxicity. An additional risk factor includes patients with a maternal relative known to have a clinically relevant MT-RNR1 variant. The risk of ototoxicity can occur at standard recommended doses of aminoglycosides.(3)

PATIENT MANAGEMENT: Instruct patients to contact their provider for new onset or worsening tinnitus. Tinnitus may be a sentinel symptom of ototoxicity. In clinical trials of tobramycin inhalation 8 patients (3%) receiving tobramycin reported tinnitus while no patients in the placebo group reported this symptom.(1) For renally impaired patients receiving long term tobramycin inhalation therapy, consider measurement of serum tobramycin to assure low systemic levels. The manufacturer of tobramycin for inhalation states that the product should not be administered concurrently with ethacrynic acid, furosemide, intravenous mannitol, or urea.(1)

DISCUSSION: Although systemic absorption of inhaled tobramycin is limited, the manufacturer states that because these diuretics may enhance the risk for aminoglycoside toxicity, they should not be administered concurrently with inhaled tobramycin.(1)

There is no enhanced messaging for this drug.

• Anuria
• Capillary fragility
• Pulmonary congestion
• Severe chronic heart failure
• Severe dehydration

• Hypernatremia
• Intracranial bleeding
• Kidney disease with reduction in glomerular filtration rate (GFr)

• Hyperkalemia
• Hyponatremia
• Hypovolemia

There is no enhanced messaging for this drug.

Less Frequent

• Urticaria

Rare or Very Rare

• Acute renal failure
• Allergic dermatitis
• Anaphylaxis
• Anuria
• Azotemia
• Cardiac arrest
• Chest pain
• Chills
• Chronic heart failure
• Coma
• Dysuria
• Fever
• Hematuria
• Hyperkalemia
• Hypernatremia
• Hypertension
• Hypervolemia
• Hypokalemia
• Hyponatremia
• Hypotension
• Hypovolemia
• Kidney disease with reduction in glomerular filtration rate (GFr)
• Metabolic acidosis
• Muscle rigidity
• Pulmonary congestion
• Pulmonary edema
• Seizure disorder
• Tachycardia
• Urinary retention
• Venous thrombosis

More Frequent

• Headache disorder
• Nausea
• Polydipsia
• Polyuria
• Vomiting
• Xerostomia

Less Frequent

• Blurred vision
• Dizziness
• Skin rash

Rare or Very Rare

• Acute cognitive impairment
• Back pain
• Cough
• Dehydration
• Dyspnea
• Edema
• General weakness
• Hyperhidrosis
• Injection site sequelae
• Lethargy
• Malaise
• Myalgia
• Oliguria
• Pain
• Palpitations
• Peripheral edema
• Phlebitis after infusion
• Pruritus of skin
• Rhinitis

No enhanced messaging available.

No enhanced messaging available.

Animal reproduction studies have not been performed with mannitol. It is also not known whether mannitol can caused fetal harm when administered to pregnant women. Mannitol should be used during pregnancy only when clearly needed.

Animal reproduction studies have not been performed with mannitol. It is also not known whether mannitol can cause fetal harm when administered to pregnant women. Mannitol should be used during pregnancy only when clearly needed.

No enhanced messaging available.

No enhanced messaging available.