Furosemide: Uses and Composition

Name of Medicine

• Furosemide.

Qualitative and Quantitative Composition

• Each tablet contains 20 mg or 40 mg furosemide as the active ingredient.
• Contains lactose monohydrate.

Pharmaceutical Form

• 20 mg tablets are white to off-white, round, and debossed with 'F2' on one side.
• 40 mg tablets are white to off-white, round, debossed with 'F4' on one side with a breakline on the other side.

Therapeutic Indications

• Indicated for adults, infants, and children for treating oedema associated with congestive heart failure, cirrhosis, and renal disease, including nephrotic syndrome.
• Useful when a potent diuretic is needed.
• Parenteral therapy reserved for patients unable to take oral medication or in emergencies, switching to oral as soon as practical.
• Oral furosemide can treat hypertension in adults, alone or with other agents, but may not adequately control hypertension if thiazides alone are ineffective.

Dose and Method of Administration

• APO-Frusemide tablets are for oral use, preferably on an empty stomach.
• Dosage should be individualized.

Dosage for Oedema

• Therapy should be tailored to patient response for maximal effect at minimal dose.
• Adults: Initially 20-80 mg daily as a single dose, increased in 20-40 mg increments no sooner than 6-8 hours until desired effect, once or twice daily (e.g., 8 am and 2 pm).
• Doses can be carefully titrated up to 400 mg/day in severe cases, with administration on 2-4 consecutive days per week.
• Infants and children: Initially 2 mg/kg bodyweight as a single dose, increasing by 1-2 mg/kg no sooner than 6-8 hours, up to a maximum of 6 mg/kg.
• For maintenance, adjust to the minimum effective level.

Dosage for Hypertension

• Therapy should be individualized to patient response.
• Adults: Initially 80 mg daily, usually divided into 40 mg twice daily, adjusted according to response; additional antihypertensive agents may be added if needed.
• Monitor blood pressure when used with other antihypertensive drugs, especially initially; reduce other agents by at least 50% when adding furosemide.

Contraindications

• Known hypersensitivity to furosemide, sulfonamides, or inactive ingredients.
• Complete renal shutdown, impaired renal function, or anuria.
• Severe hypokalaemia, hyponatraemia, hypovolaemia, dehydration, or hypotension until corrected.
• Hepatic coma or precoma and conditions causing electrolyte depletion until corrected.
• Breastfeeding and pregnancy.
• Do not administer to newborns with jaundice or conditions inducing hyperbilirubinaemia.

Special Warnings and Precautions

• Contains lactose, avoid in galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption.
• Excessive diuresis may cause dehydration, reduced blood volume, circulatory collapse, vascular thrombosis and embolism in elderly patients.
• Excessive potassium loss with cardiac glycosides can cause digitalis toxicity.
• Monitor for tinnitus or hearing impairment, associated with rapid injection/infusion, renal impairment, hypoproteinaemia, or high doses.
• Caution with curare derivatives, discontinue furosemide one week before elective surgery.
• Consider risks and benefits when combining risperidone with furosemide or other potent diuretics.
• Avoid rigid sodium restriction.
• Use with care in impaired micturition (e.g., prostatic hypertrophy), ensure urinary outflow is secured.
• Monitor patients with gout, urinary outflow obstruction, hypotension, risk of blood pressure fall, diabetes, hepatorenal syndrome, or hypoproteinaemia.
• Electrolyte depletion may occur, monitor for hyponatraemia, hypochloraemic alkalosis, and hypokalaemia, especially with high doses and restricted salt intake; monitor serum electrolytes, creatinine, blood urea and CO2.
• Signs of imbalance include dry mouth, thirst, weakness, lethargy, drowsiness, muscle pains/cramps, hypotension, oliguria, arrhythmia, GI disturbances; correct these imbalances.
• High potassium diet recommended during long-term therapy, supplements may be needed, especially with high doses, digitalis glycosides, or potassium-depleting steroids; caution with infants/children.
• Periodic checks on urine and blood glucose in diabetics.
• May lower calcium levels, monitor periodically.
• Reversible elevations of blood urea may be seen, avoid dehydration, especially in renal insufficiency.
• Increases cholesterol and triglycerides short-term.
• Patients should be observed for blood dyscrasias, liver damage, or idiosyncratic reactions.
• Renal calcifications have occurred in premature infants treated intravenously, concurrent use of chlorothiazides may decrease hypercalciuria.
• Exacerbation or activation of systemic lupus erythematosus is possible.
• Asymptomatic hyperuricaemia can occur, and rarely, gout may be precipitated.

Use in Renal Impairment

• Reversible elevations of blood urea may be seen; avoid dehydration.

Use in Hepatic Impairment

• Initiate in hospital for patients with hepatic cirrhosis and ascites; strict observation needed due to potential fluid and electrolyte imbalances.

Use in the Elderly

• Exercise caution when using risperidone and furosemide concurrently due to increased mortality risk; avoid dehydration.

Paediatric Use

• Monitor renal function and perform ultrasonography due to potential development of nephrocalcinosis/nephrolithiasis in premature infants.
• May increase the risk of persistence of Botallo's duct in premature infants.

Interactions with Other Medicines

• Not Recommended: May increase ototoxic and nephrotoxic potential of certain antibiotics and other ototoxic drugs, especially in renal impairment.
• Not Recommended: Concomitant use with chloral hydrate is not recommended due to flushing, sweating attacks, and instability in blood pressure and heart rate.
• Precautions: Avoid concomitant use with ethacrynic acid or cisplatin due to ototoxicity risk; nephrotoxicity of cisplatin may be enhanced if furosemide is not given in low doses.
• Monitor Lithium Levels: Furosemide decreases excretion of lithium salts and may increase serum lithium levels, increasing the risk of lithium toxicity.
• Adjust Dosing Interval: Oral furosemide and sucralfate must be taken two hours apart.
• ACE Inhibitors: May lead to deterioration in renal function including renal failure, or may result in severe hypotension especially when an ACE inhibitor or angiotensin II receptor antagonist is given for the first time or for the first time in an increased dose.
• Combination Use: Exercise caution and weigh risks/benefits when treating a patient on risperidone with furosemide or other potent diuretics.
• High doses of furosemide may inhibit T4 binding to carrier proteins when administered with levothyroxine.
• Monitor thyroid hormones.

Take Into Account

• Digitalis preparations and drugs inducing QT interval prolongation syndrome may be potentiated by electrolyte changes.
• Potassium or magnesium deficiency increases the sensitivity of the myocardium to digitalis.
• Glucocorticoid administration during diuretic treatment should account for the potassium lowering effect.
• Carbenoxolone, corticosteroids, prolonged use of laxatives or ingestion of liquorice in large amounts may also predispose a patient to hypokalaemia.
• Patients receiving high doses of salicylates in conjunction with furosemide may experience salicylate toxicity at lower doses.
• Interactions between furosemide and neuromuscular blocking agents have been reported.
• The combination of furosemide and amphotericin may result in an excessive loss of potassium.
• Furosemide may decrease arterial responsiveness to noradrenaline (norepinephrine).
• Antihypertensive agents, diuretics or other drugs with blood pressure lowering potential are given concomitantly with furosemide, a more pronounced fall in blood pressure must be anticipated.
• Nonsteroidal anti-inflammatory drugs including acetylsalicylic acid may reduce the natriuretic and antihypertensive effects of furosemide.
• Salicylate toxicity may be increased by furosemide.
• Phenytoin, methotrexate, probenecid and other drugs which, like furosemide, undergo significant renal tubular secretion may reduce the effect of furosemide.
• IV furosemide was shown to increase the steady-state concentration of theophylline by 20% in a small number of asthmatic patients.
• The effects of curare type muscle relaxants or of theophylline may be increased.
• The effect of antidiabetics or of pressor amines may be attenuated by furosemide.
• Impairment of renal function may develop in patients receiving concurrent treatment with furosemide and high doses of certain cephalosporins.
• Concomitant use of ciclosporin A and furosemide is associated with increased risk of gouty arthritis.
• Patients who were at high risk for radiocontrast nephropathy treated with furosemide.
• Interactions with food. It is recommended that oral formulations of furosemide be taken on an empty stomach.

Fertility, Pregnancy and Lactation

• Must not be given during pregnancy unless there are compelling medical reasons.
• Treatment during pregnancy requires monitoring of foetal growth.
• Loop diuretics, like furosemide, are probably also associated with a risk of thrombocytopaenia.
• Furosemide passes into the breast milk and inhibits lactation.

Effects on Ability to Drive and Use Machines

• Some adverse effects may impair the patient's ability to concentrate and react.

Adverse Effects (Undesirable Effects)

• Furosemide dose should be reduced or therapy withdrawn.
• Metabolism and nutritional disorders may occur.
• Ear and labyrinth disorders may occur, like reversible hearing impairment and tinnitus.
• Skin and subcutaneous tissue disorders may occur.
• Blood and the lymphatic system disorders may occur like haemoconcentration.

Overdose

• The clinical picture in acute or chronic overdose depends primarily on the extent and consequences of electrolyte and fluid loss.
• Treatment of overdosage is supportive and consists of replacement of excessive fluid and electrolyte losses.

Pharmacodynamic Properties

• Furosemide is a potent diuretic.
• Furosemide has no significant pharmacological effects other than on renal function.

Pharmacokinetic Properties

• Furosemide is rapidly absorbed from the gastrointestinal tract.
• Furosemide is extensively bound to plasma proteins, mainly albumin.
• Furosemide glucuronide is the only, or at least the major, biotransformation product of furosemide in humans.