Furosemide (fyoor OH se mide)

U.S. Brand Names Lasix®

Index Terms Frusemide

Generic Available Yes

Pharmacologic Category Diuretic, Loop

Medication Safety Issues

Sound-alike/look-alike issues:

Furosemide may be confused with famotidine, finasteride, fluconazole, FLUoxetine, fosinopril, loperamide, torsemide

Lasix® may be confused with Esidrix®, Lanoxin®, Lidex®, Lomotil®, Lovenox®, Luvox®, Luxiq®

 

International issues:

Urex® [Australia] may be confused with Eurax® which is a brand name for crotamiton in the U.S.

Urex® [Australia]: Brand name for methenamine in the U.S.

Pregnancy Risk Factor C

Lactation Enters breast milk/use caution

Use Management of edema associated with heart failure and hepatic or renal disease; acute pulmonary edema; treatment of hypertension (alone or in combination with other antihypertensives)

Mechanism of Action/Effect Inhibits reabsorption of sodium and chloride in the ascending loop of Henle and distal renal tubule, interfering with the chloride-binding cotransport system, thus causing increased excretion of water, sodium, chloride, magnesium, and calcium

Contraindications Hypersensitivity to furosemide or any component of the formulation; anuria

Warnings/Precautions [U.S. Boxed Warning]: If given in excessive amounts, furosemide, similar to other loop diuretics, can lead to profound diuresis, resulting in fluid and electrolyte depletion; close medical supervision and dose evaluation are required. Watch for and correct electrolyte disturbances; adjust dose to avoid dehydration. When electrolyte depletion is present, therapy should not be initiated unless serum electrolytes, especially potassium, are normalized. In cirrhosis, avoid electrolyte and acid/base imbalances that might lead to hepatic encephalopathy.; correct electrolyte and acid/base imbalances prior to initiation when hepatic coma is present. Coadministration of antihypertensives may increase the risk of hypotension.

 

Monitor fluid status and renal function in an attempt to prevent oliguria, azotemia, and reversible increases in BUN and creatinine; close medical supervision of aggressive diuresis is required. Rapid I.V. administration, renal impairment, excessive doses, and concurrent use of other ototoxins is associated with ototoxicity. Asymptomatic hyperuricemia has been reported with use; rarely, gout may precipitate. Photosensitization may occur.

 

Use with caution in patients with prediabetes or diabetes mellitus; may see a change in glucose control. Use with caution in patients with systemic lupus erythematosus (SLE); may cause SLE exacerbation or activation. Chemical similarities are present among sulfonamides, sulfonylureas, carbonic anhydrase inhibitors, thiazides, and loop diuretics (except ethacrynic acid). A risk of cross-reaction exists in patients with allergy to any of these compounds; avoid use when previous reaction has been severe. Discontinue if signs of hypersensitivity are noted.

Drug Interactions

Avoid Concomitant Use:

Avoid concomitant use of Furosemide with any of the following: Ethacrynic Acid

Decreased Effect:

Furosemide may decrease the levels/effects of: Lithium; Neuromuscular-Blocking Agents

The levels/effects of Furosemide may be decreased by: Aliskiren; Bile Acid Sequestrants; Herbs (Hypertensive Properties); Methylphenidate; Nonsteroidal Anti-Inflammatory Agents; Phenytoin; Salicylates; Yohimbine

Increased Effect/Toxicity:

Furosemide may increase the levels/effects of: ACE Inhibitors; Allopurinol; Amifostine; Aminoglycosides; Antihypertensives; Dofetilide; Ethacrynic Acid; Lithium; Neuromuscular-Blocking Agents; RiTUXimab; Salicylates

The levels/effects of Furosemide may be increased by: Corticosteroids (Orally Inhaled); Corticosteroids (Systemic); Diazoxide; Herbs (Hypotensive Properties); Prostacyclin Analogues

Nutritional/Ethanol Interactions

Food: Furosemide serum levels may be decreased if taken with food.

Herb/Nutraceutical: Avoid bayberry, blue cohosh, cayenne, ephedra, ginger, ginseng (American), kola, licorice (may worsen hypertension). Avoid black cohosh, California poppy, coleus, golden seal, hawthorn, mistletoe, periwinkle, quinine, shepherd's purse (may increase antihypertensive effect).

Adverse Reactions Frequency not defined.

Cardiovascular: Acute hypotension, chronic aortitis, necrotizing angiitis, orthostatic hypotension, vasculitis

Central nervous system: Dizziness, fever, headache, hepatic encephalopathy, lightheadedness, restlessness, vertigo

Dermatologic: Bullous pemphigoid, cutaneous vasculitis, erythema multiforme, exfoliative dermatitis, photosensitivity, pruritus, purpura, rash, urticaria

Endocrine & metabolic: Glucose tolerance test altered, gout, hyperglycemia, hyperuricemia, hypocalcemia, hypochloremia, hypokalemia, hypomagnesemia, hyponatremia, metabolic alkalosis

Gastrointestinal: Anorexia, constipation, cramping, diarrhea, nausea, oral and gastric irritation, pancreatitis, vomiting

Genitourinary: Urinary bladder spasm, urinary frequency

Hematological: Agranulocytosis (rare), anemia, aplastic anemia (rare), hemolytic anemia, leukopenia, thrombocytopenia

Hepatic: Intrahepatic cholestatic jaundice, ischemic hepatitis

Local: Injection site pain (following I.M. injection), thrombophlebitis

Neuromuscular & skeletal: Muscle spasm, paresthesia, weakness

Ocular: Blurred vision, xanthopsia

Otic: Hearing impairment (reversible or permanent with rapid I.V. or I.M. administration), tinnitus

Renal: Allergic interstitial nephritis, fall in glomerular filtration rate and renal blood flow (due to overdiuresis), glycosuria, transient rise in BUN

Miscellaneous: Anaphylaxis (rare), exacerbate or activate systemic lupus erythematosus

Pharmacodynamics/Kinetics

Onset of Action: Diuresis: Oral, S.L.: 30-60 minutes; I.M.: 30 minutes; I.V.: ~5 minutes

Symptomatic improvement with acute pulmonary edema: Within 15-20 minutes; occurs prior to diuretic effect

Peak effect: Oral: 1-2 hours

Duration of Action: Oral, S.L.: 6-8 hours; I.V.: 2 hours

Bioavailability: Oral tablet: 47-64%; Oral solution: 60%; S.L. administration of tablet: ~60%; results of a small comparative study (n=11) showed bioavailability of SL administration of tablet was ~12% higher than oral administration of tablet (Haegeli, 2007).

Protein Binding: 91% to 99%; primarily to albumin

Half-Life Elimination: Normal renal function: 0.5-2 hours; End-stage renal disease: 9 hours

Metabolism: Minimally hepatic

Excretion: Urine (Oral: 50%, I.V.: 80%) within 24 hours; feces (as unchanged drug); nonrenal clearance prolonged with renal impairment

Available Dosage Forms

Injection, solution: 10 mg/mL (2 mL, 4 mL, 10 mL)

Injection, solution [preservative free]: 10 mg/mL (2 mL, 4 mL, 10 mL)

Solution, oral: 10 mg/mL, 40 mg/5 mL

Tablet: 20 mg, 40 mg, 80 mg

Lasix®: 20 mg

Lasix®: 40 mg, 80 mg [scored]

Dosing

Adults:

Edema, heart failure:

Oral: Initial: 20-80 mg/dose; if response not adequate, may repeat the same dose or increase dose in increments of 20-40 mg/dose at intervals of 6-8 hours; usual maintenance dose interval is once or twice daily; may be titrated up to 600 mg/day with severe edematous states. Note: May also be given on 2-4 consecutive days every week.

I.M., I.V.: Initial: 20-40 mg/dose; if response not adequate, may repeat the same dose or increase dose in increments of 20 mg/dose and administer 1-2 hours after previous dose (maximum dose: 200 mg/dose). Individually determined dose should then be given once or twice daily although some patients may initially require dosing as frequent as every 6 hours. Note: ACC/AHA 2009 guidelines for heart failure recommend a maximum single dose of 160-200 mg.

Continuous I.V. infusion (Howard, 2001; Hunt, 2009): Initial: I.V. bolus dose 20-40 mg over 1-2 minutes, followed by continuous I.V. infusion doses of 10-40 mg/hour. If urine output is <1 mL/kg/hour, double as necessary to a maximum of 80-160 mg/hour. The risk associated with higher infusion rates (80-160 mg/hour) must be weighed against alternative strategies. Note: ACC/AHA 2009 guidelines for heart failure recommend 40 mg I.V. load, then 10-40 mg/hour infusion.

Acute pulmonary edema: I.V.: 40 mg over 1-2 minutes. If response not adequate within 1 hour, may increase dose to 80 mg. Note: ACC/AHA 2009 guidelines for heart failure recommend a maximum single dose of 160-200 mg.

Hypertension, resistant (Chobanian, 2003; JNC 7): Oral: 20-80 mg/day in 2 divided doses

Refractory heart failure: Oral, I.V.: Doses up to 8 g/day have been used.

Elderly: Oral, I.M., I.V.: Initial: 20 mg/day; increase slowly to desired response.

Pediatrics:

Edema, heart failure: Infants and Children:

Oral: Initial: 2 mg/kg/dose increased in increments of 1-2 mg/kg/dose with each succeeding dose at intervals of 6-8 hours until a satisfactory response is achieved; maximum dose: 6 mg/kg/dose

I.M., I.V.: Initial: 1 mg/kg/dose; if response not adequate, may increase dose in increments of 1 mg/kg/dose and administer not sooner than 2 hours after previous dose, until a satisfactory response is achieved; may administer maintenance dose at intervals of every 6-12 hours; maximum dose: 6 mg/kg/dose

Hypertension, resistant (unlabeled; AAP, 2004): Children 1-17 years: Oral: Initial: 0.5-2 mg/kg/dose once or twice daily; maximum dose: 6 mg/kg/dose

Renal Impairment:

Acute renal failure: Doses up to 1-3 g/day may be necessary to initiate desired response; avoid use in oliguric states.

Not removed by hemo- or peritoneal dialysis; supplemental dose is not necessary.

Hepatic Impairment: Diminished natriuretic effect with increased sensitivity to hypokalemia and volume depletion in cirrhosis. Monitor effects, particularly with high doses.

Administration

Oral: Administer on an empty stomach (Bard, 2004). May be administered with food or milk if GI distress occurs; however, this may reduce diuretic efficacy.

I.V.: I.V. injections should be given slowly. In adults, undiluted direct I.V. injections may be administered at a rate of 20-40 mg per minute; maximum rate of administration for short-term intermittent infusion is 4 mg/minute; exceeding this rate increases the risk of ototoxicity. In children, a maximum rate of 0.5 mg/kg/minute has been recommended.

Other: When I.V. or oral administration is not possible, the sublingual route may be used. Place 1 tablet under tongue for at least 5 minutes to allow for maximal absorption. Patients should be advised not to swallow during disintegration time (Haegeli, 2007).

Stability

Reconstitution: I.V. infusion solution mixed in NS or D5W solution is stable for 24 hours at room temperature. May also be diluted for infusion to 1-2 mg/mL (maximum: 10 mg/mL).

Compatibility: Stable in D5LR, D5NS, D5W, D10W, D20W, mannitol 20%, LR, NS.

Y-site administration: Incompatible with amsacrine, azithromycin, chlorpromazine, ciprofloxacin, diltiazem, droperidol, esmolol, fenoldopam, filgrastim, fluconazole, gemcitabine, gentamicin, hydralazine, idarubicin, labetalol, levofloxacin, metoclopramide, midazolam, milrinone, nesiritide, nicardipine, ondansetron, phenylephrine, quinidine gluconate, vasopressin, vecuronium, vinblastine, vincristine, vinorelbine.

Compatibility in syringe: Incompatible with caffeine citrate, dimenhydrinate, doxapram, doxorubicin, droperidol, metoclopramide, milrinone, pantoprazole, vinblastine, vincristine.

Compatibility when admixed: Incompatible with buprenorphine, chlorpromazine, diazepam, dobutamine, erythromycin lactobionate, isoproterenol, meperidine, metoclopramide, prochlorperazine edisylate, promethazine.

Storage:

Injection: Store at room temperature of 15°C to 30°C (59°F to 86°F). Protect from light. Exposure to light may cause discoloration; do not use furosemide solutions if they have a yellow color. Furosemide solutions are unstable in acidic media, but very stable in basic media. Refrigeration may result in precipitation or crystallization; however, resolubilization at room temperature or warming may be performed without affecting the drug's stability.

Tablet: Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 89°F). Protect from light.

Monitoring and Teaching Issues

Laboratory Monitoring: Serum electrolytes, renal function

Physical Assessment: Assess for allergy to sulfonylurea before beginning therapy. Assess potential for interactions with other pharmacological agents or herbal products patient may be taking (especially anything that may impact fluid balance, electrolyte balance, or increase potential for ototoxicity or hypotension). For intravenous use, see Administration specifics. Assess results of laboratory tests (electrolytes), therapeutic effectiveness, and adverse response on a regular basis during therapy (eg, dehydration, electrolyte imbalance, postural hypotension). Caution patients with diabetes about closely monitoring glucose levels (glucose tolerance may be decreased). Teach patient appropriate use, possible side effects/appropriate interventions, and adverse symptoms to report.

Patient Education: Do not take any new medication during therapy unless approved by prescriber. Take as directed with food or milk (to reduce GI distress) early in the day (daily), or if twice daily, take last dose in late afternoon in order to avoid sleep disturbance and achieve maximum therapeutic effect. Keep medication in original container, away from light; do not use discolored medication. Follow dietary advice of prescriber; include bananas or orange juice or other potassium-rich foods in daily diet. Do not take potassium supplements without advice of prescriber. If you have diabetes, monitor glucose levels closely (this medication may alter glucose tolerance requiring an adjustment in the dose of hypoglycemic agent). Weigh yourself each day, at the same time, in the same clothes when beginning therapy and weekly on longterm therapy. Report unusual or unanticipated weight gain or loss. May cause dizziness, blurred vision, or drowsiness (use caution when driving or engaging in tasks that require alertness until response to drug is known); postural hypotension (use caution when rising from lying or sitting position or when climbing stairs); or sensitivity to sunlight (use sunblock or wear protective clothing and sunglasses). Report signs of edema (eg, weight gains; swollen ankles, feet, or hands), trembling, numbness or fatigue, cramping or muscle weakness, palpitations, unresolved nausea or vomiting, or change in hearing. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. Consult prescriber if breast-feeding.

Dietary Considerations: May cause potassium loss; potassium supplement or dietary changes may be required.

Geriatric Considerations: Loop diuretics are potent diuretics; excess amounts can lead to profound diuresis with fluid and electrolyte loss; close medical supervision and dose evaluation is required, particularly in the elderly. Severe loss of sodium and/or increase in BUN can cause confusion. For any change in mental status in patients on furosemide, monitor electrolytes and renal function.

Breast-Feeding Issues: Crosses into breast milk; may suppress lactation. AAP has NO RECOMMENDATION.

Pregnancy Issues: Animal studies have demonstrated maternal death, fetal toxicity, and fetal loss. There are no adequate and well-controlled studies in pregnant women. Crosses the placenta. Increased fetal urine production, electrolyte disturbances reported. Generally, use of diuretics during pregnancy is avoided due to risk of decreased placental perfusion.

Related Information

Compatibility of Drugs

Heart Failure (Systolic)