Furosemide

Pronunciation: (fyu-ROH-se-mide)

Class: Loop diuretic

Trade Names:
Lasix
- Tablets 20 mg
- Tablets 40 mg
- Tablets 80 mg
- Oral solution 8 mg/mL
- Oral solution 10 mg/mL
- Injection 10 mg/mL
Apo-Furosemide (Canada)
Furosemide Special (Canada)
Lasix Special (Canada)
Pharmacology
Inhibits reabsorption of sodium and chloride in proximal and distal tubules and loop of Henle.

Pharmacokinetics

Absorption

Mean bioavailability is 64% with the tablet and 60% with the oral solution.

Distribution

Protein binding is 91% to 99% (albumin).

Metabolism

The major metabolite is furosemide glucuronide.

Elimination

The t 1/ 2 is about 2 h; furosemide is excreted in urine.

Onset

PO 1 h, IV 5 min.
Peak

PO 1 to 2 h, IV 30 min.
Duration

PO 6 to 8 h, IV 2 h.
Indications and Usage

Adjunctive therapy in acute pulmonary edema, edema associated with CHF, hepatic cirrhosis, and renal disease ( IV only); hypertension ( PO only)
.
Contraindications

Hypersensitivity to any component of the product; anuria.

Dosage and Administration

Acute Pulmonary Edema

Adults

IV 40 mg (over 1 to 2 min). If response not satisfactory within 1 h, increase to 80 mg.

Infants and Children

IV/IM Usual initial dose: 1 mg/kg. If response not satisfactory, may increase by 1 mg/kg not sooner than 2 h after previous dose. Max dose: 6 mg/kg. Premature infant's max dose: 1 mg/kg/day.
Edema

Adults

PO Usual initial dose: 20 to 80 mg/day as a single dose may repeat 6 to 8 h later if needed; may titrate up to 600 mg/day. Maintenance: Give determined single dose once or twice daily (8 AM and 2 PM). IV/IM 20 to 40 mg over 1 to 2 min. Repeat 2 h later if needed.
Children


PO Usual initial dose: 2 mg/kg as a single dose. May increase by 1 or 2 mg/kg 6 to 8 h later if needed. Max dose: 6 mg/kg.
Hypertension

Adults

PO 40 mg twice daily.

General Advice

* Tablets and oral solution
* Administer without regard to meals. Administer with food if GI upset occurs.
* Do not use tablets that are discolored.
* Measure and administer prescribed dose of oral solution using supplied dosing cup, calibrated dosing syringe, or calibrated dosing spoon.

* Injection
* For IM or IV administration only. Not for intradermal, subcutaneous, or intra-arterial administration.
* Administer IV injection of usual doses (eg, 20 to 80 mg) over 1 to 2 min.
* For high-dose IV therapy, dilute prescribed dose of furosemide in sodium chloride 0.9% injection, Ringers lactate injection, or dextrose 5% injection (after adjusting pH to more than 5.5) and administer at controlled infusion rate not more than 4 mg/min.
* Furosemide injection precipitates at pH values less than 7. Ensure that pH of prepared infusion solution is in neutral to weakly alkaline range. Do not administer furosemide through infusion line containing acidic solution or acidic drugs.
* Do not administer if particulate matter, cloudiness, or discoloration is noted.

Storage/Stability

Store tablets, oral solution, and injection at controlled room temperature (59° to 86°F). Protect from light. Protect tablets from moisture. Protect injection from freezing.

Drug Interactions


Furosemide (frusemide) has the following interaction information:

Chloral administration of parenteral furosemide (frusemide) with chloral may displace thyroid hormone from binding sites
Metolazone profound diuresis possible when furosemide (frusemide) given with metolazone
Phenytoin effects of furosemide (frusemide) antagonised by phenytoin
Triclofos administration of parenteral furosemide (frusemide) with triclofos may displace thyroid hormone from binding sites
Furosemide (frusemide) belongs to Diuretics, Loop and will have the following interactions:

Acetazolamide increased risk of hypokalaemia when loop diuretics given with acetazolamide
Aminoglycosides increased risk of otoxicity when loop diuretics given with aminoglycosides
Amiodarone hypokalaemia caused by loop diuretics increases cardiac toxicity with amiodarone Amiodarone has a long half-life; there is a potential for drug interactions to occur for several weeks (or even months) after treatment with it has been stopped
Amphotericin increased risk of hypokalaemia when loop diuretics given with amphotericin Close monitoring required with concomitant administration of nephrotoxic drugs or cytotoxics
Antidiabetics loop diuretics antagonise hypoglycaemic effect of antidiabetics
Cardiac Glycosides hypokalaemia caused by loop diuretics increases cardiac toxicity with cardiac glycosides
Corticosteroids increased risk of hypokalaemia when loop diuretics given with corticosteroids Interactions do not generally apply to corticosteroids used for topical action (including inhalation) unless specified
Disopyramide hypokalaemia caused by loop diuretics increases cardiac toxicity with disopyramide
Diuretics, Thiazide and related increased risk of hypokalaemia when loop diuretics given with thiazides and related diuretics
Flecainide hypokalaemia caused by loop diuretics increases cardiac toxicity with flecainide
Lidocaine (lignocaine) hypokalaemia caused by loop diuretics antagonises action of lidocaine (lignocaine) Interactions less likely when lidocaine used topically
Lithium loop diuretics reduce excretion of lithium (increased plasma concentration and risk of toxicity)—loop diuretics safer than thiazides
Mexiletine hypokalaemia caused by loop diuretics antagonises action of mexiletine
Polymyxins increased risk of otoxicity when loop diuretics given with polymyxins
Reboxetine possible increased risk of hypokalaemia when loop diuretics given with reboxetine
Sotalol hypokalaemia caused by loop diuretics increases risk of ventricular arrhythmias with sotalol
Sympathomimetics, Beta2 increased risk of hypokalaemia when loop diuretics given with high doses of beta2 sympathomimetics —for CSM advice (hypokalaemia) see section 3.1.1.1
Theophylline increased risk of hypokalaemia when loop diuretics given with theophylline
Vancomycin increased risk of otoxicity when loop diuretics given with vancomycin
Furosemide (frusemide) belongs to Diuretics and will have the following interactions:

ACE Inhibitors enhanced hypotensive effect when diuretics given with ACE inhibitors
Adrenergic Neurone Blockers enhanced hypotensive effect when diuretics given with adrenergic neurone blockers
Alcohol enhanced hypotensive effect when diuretics given with alcohol
Aldesleukin enhanced hypotensive effect when diuretics given with aldesleukin
Alpha-blockers enhanced hypotensive effect when diuretics given with alpha-blockers , also increased risk of first-dose hypotension with post-synaptic alpha-blockers such as prazosin
Alprostadil enhanced hypotensive effect when diuretics given with alprostadil
Amisulpride hypokalaemia caused by diuretics increases risk of ventricular arrhythmias with amisulpride
Anaesthetics, General enhanced hypotensive effect when diuretics given with general anaesthetics See also Surgery and Long-term Medication, section 15.1
Angiotensin-II Receptor Antagonists enhanced hypotensive effect when diuretics given with angiotensin-II receptor antagonists
Antidepressants, Tricyclic increased risk of postural hypotension when diuretics given with tricyclics
Anxiolytics and Hypnotics enhanced hypotensive effect when diuretics given with anxiolytics and hypnotics
Atomoxetine hypokalaemia caused by diuretics increases risk of ventricular arrhythmias with atomoxetine
Baclofen enhanced hypotensive effect when diuretics given with baclofen
Beta-blockers enhanced hypotensive effect when diuretics given with beta-blockers Since systemic absorption may follow topical application of beta-blockers to the eye the possibility of interactions, in particular, with drugs such as verapamil should be borne in mind
Calcium-channel Blockers enhanced hypotensive effect when diuretics given with calcium-channel blockers Dihydropyridine calcium-channel blockers include amlodipine, felodipine, isradipine, lacidipine, lercanidipine, nicardipine, nifedipine, nimodipine, and nisoldipine
Carbamazepine increased risk of hyponatraemia when diuretics given with carbamazepine
Clonidine enhanced hypotensive effect when diuretics given with clonidine
Corticosteroids diuretic effect of diuretics antagonised by corticosteroids Interactions do not generally apply to corticosteroids used for topical action (including inhalation) unless specified
Diazoxide enhanced hypotensive effect when diuretics given with diazoxide
Hydralazine enhanced hypotensive effect when diuretics given with hydralazine
Indometacin effects of diuretics antagonised by indometacin
Ketorolac effects of diuretics antagonised by ketorolac
Levodopa enhanced hypotensive effect when diuretics given with levodopa
Lymecycline avoidance of diuretics advised by manufacturer of lymecycline
MAOIs enhanced hypotensive effect when diuretics given with MAOIs For interactions of reversible MAO-A inhibitors (RIMAs) see Moclobemide, and for interactions of MAO-B inhibitors see Rasagiline and Selegiline; the antibacterial Linezolid is a reversible, non-selective MAO inhibitor
Methyldopa enhanced hypotensive effect when diuretics given with methyldopa
Minoxidil enhanced hypotensive effect when diuretics given with minoxidil
Moxisylyte (thymoxamine) enhanced hypotensive effect when diuretics given with moxisylyte
Moxonidine enhanced hypotensive effect when diuretics given with moxonidine
Nitrates enhanced hypotensive effect when diuretics given with nitrates
NSAIDs diuretics increase risk of nephrotoxicity of NSAIDs , also antagonism of diuretic effect See also Aspirin. Interactions do not generally apply to topical NSAIDs
Oestrogens diuretic effect of diuretics antagonised by oestrogens Interactions of combined oral contraceptives may also apply to combined contraceptive patches; in case of hormone replacement therapy low dose unlikely to induce interactions
Phenothiazines enhanced hypotensive effect when diuretics given with phenothiazines
Pimozide hypokalaemia caused by diuretics increases risk of ventricular arrhythmias with pimozide (avoid concomitant use)
Platinum Compounds increased risk of nephrotoxicity and ototoxicity when diuretics given with platinum compounds
Sertindole hypokalaemia caused by diuretics increases risk of ventricular arrhythmias with sertindole
Sodium Nitroprusside enhanced hypotensive effect when diuretics given with sodium nitroprusside
Tizanidine enhanced hypotensive effect when diuretics given with tizanidine




Adverse Reactions

Cardiovascular

Chronic aortitis; orthostatic hypotension; thrombophlebitis.
CNS

Dizziness; fever; headache; paresthesia; restlessness; vertigo.
Dermatologic

Erythema multiforme; exfoliative dermatitis; local irritation and pain with parenteral use; necrotizing angiitis; photosensitivity; pruritus; purpura; rash; systemic vasculitis; urticaria.
EENT

Blurred vision; hearing impairment; tinnitus; xanthopsia (yellow vision).
GI

Anorexia; constipation; cramping; diarrhea; nausea; oral and gastric irritation; pancreatitis; vomiting.
Genitourinary

Glycosuria; interstitial nephritis; urinary bladder spasm.
Hematologic

Anemia, hemolytic anemia, leukopenia, thrombocytopenia; aplastic anemia, agranulocytosis (rare).
Hepatic

Jaundice.
Metabolic

Hyperglycemia; hyperuricemia; hypokalemia; metabolic alkalosis.
Miscellaneous

Muscle spasm; weakness.
Precautions
Monitor

Monitor for possible occurrence of blood dyscrasia and liver damage. Monitor urine and blood glucose in diabetes. Frequently monitor serum electrolytes, magnesium, calcium, CO 2 , uric acid, and renal function early in therapy and periodically thereafter during active diuresis. Assess patients for signs or symptoms of fluid or electrolyte imbalance.

Pregnancy

Category C .
Lactation

Excreted in breast milk.
Children

May increase incidence of patent ductus arteriosus in premature infants with respiratory distress syndrome, especially in first few weeks of life.
Hypersensitivity

Patients with known sulfonamide sensitivity may show allergic reactions to furosemide.
Renal Function

Discontinue if increasing azotemia and oliguria occur during treatment of severe progressive renal disease.
Photosensitivity

May occur.
Dehydration

Excessive diuresis may cause dehydration and decreased blood volume with circulatory collapse and possible vascular thrombosis and embolism, especially in elderly cardiac patients.
Diarrhea

Furosemide solution vehicle contains sorbitol and may induce diarrhea, especially in children.
Glucose intolerance

May increase blood glucose; precipitation of diabetes mellitus has been reported rarely.
Hepatic cirrhosis

Sudden alterations of electrolyte balance may precipitate hepatic and coma; monitor carefully.
Hyperuricemia/gout

Asymptomatic hyperuricemia can occur; gout may rarely be precipitated.
Ototoxicity (deafness, tinnitus, vertigo)

Associated with rapid injection, severe renal impairment, very large doses, or concurrent use of other ototoxic drugs. Usually reversible within 1 to 24 h, but may be permanent in some patients. Infusion rates not exceeding 4 mg/min may reduce risk.
Systemic lupus erythematosus

May be exacerbated or activated.

Overdosage

Symptoms

Dehydration, electrolyte imbalance, hypochloremic alkalosis, hypokalemia, hypotension, reduction of blood volume.

Patient Information

* Injection
* Advise patient or caregiver that injection is used when a rapid onset of diuresis is needed, when GI absorption is impaired, or when taking oral medications is not practical, and that conversion to oral therapy will be made as soon as possible.

* Tablets and oral solution
* Advise patient to take prescribed dose without regard to meals but to take with food if stomach upset occurs.
* Advise patient or caregiver using oral solution to measure and administer prescribed dose using supplied dosing cup, calibrated dosing syringe, or calibrated dosing spoon.
* Advise patient that medication will increase urination and not to take before bedtime or before activities in which increased urination would be a problem. Instruct patient that if dose is delayed to take the dose later in the day to prevent interference with activities. Caution patient not to skip doses.
* Caution patient not to change the dose or stop taking unless advised by health care provider.
* Ensure patient understands how to implement fluid and salt restriction if prescribed as part of therapeutic regimen.
* Instruct patient to lie or sit down if they experience dizziness or lightheadedness when standing.
* Caution patient that inadequate fluid intake, excessive perspiration, diarrhea, or vomiting can lead to excessive fall in BP resulting in lightheadedness or fainting.
* Instruct diabetic patient to monitor blood glucose more frequently when drug is started or dose is changed and to inform health care provider of significant changes in readings.
* Caution patient to avoid unnecessary exposure to UV light (sunlight, tanning booths) and to use sunscreen and wear protective clothing when exposed to UV light until tolerance is determined.
* Advise women to notify health care provider if pregnant, planning to become pregnant, or breastfeeding.
* Instruct patient to inform health care provider if any of the following occur: muscle pain, weakness, or cramps; persistent nausea or vomiting; diarrhea; excessive thirst; unexplained tiredness; drowsiness; dizziness or feeling of the room spinning; ringing in the ears or decreased hearing; confusion or changes in thinking; increased heart rate; unexplained joint pain; abnormal skin sensations.