Furosemide 40 Biotech 40 mg Capsules

Treatment of oedema of cardiac, hepatic or renal origin. In the management of refractory oedema, it may be used in conjunction with other types of diuretics, particularly the potassium-sparing medicines.

In most cases 40 mg daily will suffice. If no response is obtained, this dose may be increased after 6 hours to 80 mg and - if necessary - after another 6 hours to 120 mg. Daily doses of more than 120 mg should preferably be distributed over 2 - 3 individual doses. After mobilising the oedema, maintenance therapy is continued i.e., 20 to 40 mg daily. Children generally receive daily oral doses of 1 mg/kg body weight. If necessary, this dose may be increased step by step to a maximum of 3 mg/kg body weight per day. A dose of 120 mg per day should not be exceeded with children.

Method of administration

For oral administration.

Patients who exhibit hypersensitivity to furosemide, sulphonamides, or to any of the excipients as listed in section 6.1. Furosemide 40 Biotech is contraindicated if increasing azotaemia and oliguria occurs during treatment of severe progressive renal disease, anuria, hypokalaemia, hyponatraemia, hypovolaemia with or without hypotension, dehydration - in these cases the medicine should be discontinued. Drug induced renal failure and renal failure associated with hepatic coma. In hepatic coma and in states of electrolyte depletion, therapy with Furosemide 40 Biotech should not be instituted until the basic condition is corrected or improved. Furosemide 40 Biotech should not be given to lactating women (see section 4.6).

Hypotension and/or hypovolaemia (see also section 4.3) These and any acid-base disturbances should be corrected before Furosemide 40 Biotech is started. Symptomatic hypotension leading to dizziness, fainting or loss of consciousness can occur in patients treated with Furosemide 40 Biotech, particularly in the elderly, patients on other medications which can cause hypotension and patients with other medical conditions that are risks for hypotension.

Dose titration/adjustment

• Patients with hypoproteinaemia (such as that associated with the nephrotic syndrome) require careful dose titration (reduced furosemide effect: increased risk of ototoxicity).
• In moderate liver congestion dosage adjustment may be needed

Caution required:

• impaired hepatic function
• impaired renal function and hepato-renal syndrome (see section 4.3 and below u2013 monitoring required)
• diabetes mellitus (latent diabetes may become overt: insulin requirements in established diabetes may increase)
• elderly patients
• difficulty with micturition/potential obstruction in the urinary tract including prostatic hypertrophy (increased risk of acute retention)
• gout (increased risk of hyperuricaemia)
• patients at risk of pronounced falls in blood pressure

Clinical monitoring requirements (see also section 4.8): Regular monitoring for

• blood dyscrasias. If these occur, stop Furosemide 40 Biotech immediately
• liver damage
• idiosyncratic reactions

In premature infants there is a risk of development of nephrocalcinosis/ nephrolithiasis. Renal function must be monitored, and renal ultrasonography performed.

Laboratory monitoring requirements:

• frequent BUN in first few months of treatment, periodically thereafter
• serum electrolytes with replacement as appropriate

Other alterations in lab values

• Serum creatinine and urea levels tend to rise during treatment
• Serum cholesterol and triglycerides may rise but usually return to normal within 6 months of starting Furosemide 40 Biotech
• Furosemide 40 Biotech should be discontinued before a glucose tolerance test

Not to be used in the first trimester of pregnancy. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Antihypertensives - enhanced hypotensive effect possible with all types. Concurrent use with ACE inhibitors can result in marked falls in blood pressure. Furosemide 40 Biotech should be stopped or the dose reduced before starting an ACE-inhibitor. There is a risk of a first-dose effect with post-synaptic alpha blockers e.g., prazosin. Furosemide 40 Biotech may interact with ACE inhibitors causing impaired renal function.

Antipsychotics u2013 furosemide-induced hypokalaemia increases the risk of cardiac toxicity. Avoid concurrent use with pimozide. Increased risk of ventricular dysrhythmias with amisulpride or sertindole. Enhanced hypotensive effect with phenothiazines.

Anti-dysrhythmics (including amiodarone, disopyramide, flecainide and sotalol) - risk of cardiac toxicity (because of furosemide-induced hypokalaemia). The effects of lidocaine, tocainide or mexiletine may be antagonised by Furosemide 40 Biotech.

Medicines associated with QT prolongation u2013 cardiac toxicity may be increased by furosemide-induced hypokalaemia and/or hypomagnesaemia.

Cardiac glycosides u2013 hypokalaemia and electrolyte disturbances (including magnesium) increase the risk of cardiac toxicity.

Vasodilators u2013 enhanced hypotensive effect with moxisylyte (thymoxamine) or hydralazine.

Renin inhibitors u2013 aliskiren reduces plasma concentrations of Furosemide 40 Biotech.

Nitrates u2013 enhanced hypotensive effect.

Lithium u2013 Furosemide 40 Biotech reduces lithium excretion with increased plasma lithium concentrations (risk of toxicity). Avoid concomitant administration unless plasma levels are monitored.

Chelating medicines u2013 sucralfate may decrease the gastro-intestinal absorption of Furosemide 40 Biotech u2013 the 2 medicines should be taken at least 2 hours apart.

Lipid regulating medicines u2013 Bile acid sequestrants (e.g., colestyramine: colestipol) u2013 reduced absorption of furosemide u2013 administer 2 to 3 hours apart.

NSAIDs u2013 increased risk of nephrotoxicity (especially if there is hypovolaemia). Indomethacin and ketorolac may antagonise the effects of Furosemide 40 Biotech. In patients with dehydration or hypovolaemia, NSAIDs may cause acute renal insufficiency.

Salicylates u2013 effects may be potentiated by Furosemide 40 Biotech.

Antibiotics u2013 increased risk of ototoxicity with aminoglycosides, polymixins or vancomycin. Increased risk of nephrotoxicity with aminoglycosides or cefaloridine. Furosemide 40 Biotech can decrease vancomycin serum levels after cardiac surgery.

Antidepressants u2013 enhanced hypotensive effect with MAOIs. Increased risk of postural hypotension with TCAs (tricyclic antidepressants). Possible increased risk of hypokalaemia with reboxetine.

Antidiabetics u2013 hypoglycaemic effects antagonised by Furosemide 40 Biotech. Insulin - requirements may be increased (see section 4.4).

Antiepileptics u2013 increased risk of hyponatraemia with carbamazepine. Diuretic effect reduced by phenytoin.

Antihistamines u2013 hypokalaemia with increased risk of cardiac toxicity.

Antifungals u2013 increased risk of hypokalaemia with amphotericin.

Anxiolytics and hypnotics u2013 enhanced hypotensive effect. Chloral or triclorfos may displace thyroid hormone from binding site.

CNS stimulants (medicines used for ADHD) u2013 hypokalaemia increases the risk of ventricular dysrhythmias.

Corticosteroids u2013 diuretic effect antagonised (sodium retention) and increased risk of hypokalaemia.

Cytotoxics u2013 increased risk of nephrotoxicity and ototoxicity with platinum compounds.

Other diuretics u2013 profound diuresis possible when furosemide given with metolazone. Increased risk of hypokalaemia with thiazides.

Dopaminergics u2013 enhanced hypotensive effect with levodopa.

Immunomodulators u2013 enhanced hypotensive effect with aldesleukin.

Muscle relaxants u2013 enhanced hypotensive effect with baclofen or tizanidine (see also Anaesthetic medicines below u2013 curare).

Oestrogens and progestogens u2013 diuretic effect antagonized.

Prostaglandins u2013 enhanced hypotensive effect with alprostadil.

Sympathomimetics u2013 increased risk of hypokalaemia with high doses of beta 2 sympathomimetics (such as bambuterol, formoterol, salbutamol, salmeterol and terbutaline).

Theophylline u2013 enhanced hypotensive effect.

Probenecid u2013 reduced renal clearance of furosemide and decreased diuretic effect.

Anaesthetic medicines u2013 general anaesthetic medicines may enhance the hypotensive effects of furosemide. The effects of curare may be enhanced by Furosemide 40 Biotech.

Alcohol u2013 enhanced hypotensive effect.

Laxative abuse - increases the risk of potassium loss.

Liquorice - excess intake may increase the risk of hypokalaemia.

Pregnancy There is little evidence of safety of high-dose furosemide in human pregnancy, although the results of animal work, in general, show no hazardous effects.

Breastfeeding Furosemide 40 Biotech may inhibit lactation or may pass into the breast milk, it should therefore not be used during lactation (see section 4.3).

Patients should be warned that reduced mental alertness may impair ability to drive or operate dangerous machinery.

MedDRA System Organ Class Description

Blood and lymphatic system disorders Less frequent aplastic anaemia, bone marrow depression (necessitates withdrawal of treatment), eosinophilia, leukopenia, haemolytic anaemia, agranulocytosis, thrombocytopenia

Metabolism and nutrition disorders Frequent dehydration, hyponatraemia, hypochloraemia metabolic alkalosis, hypocalcaemia, hypomagnesemia (incidences of the last three are reduced by triamterene), hypovolaemia, hypochloraemia

Less Frequent impaired glucose tolerance (by hypokalaemia) hyperuricaemia, gout, reduction of serum HDL-cholesterol, elevation of serum LDL-cholesterol, elevation of serum triglycerides, hyperglycaemia, tetany

Frequency unknown aggravated pre-existing metabolic alkalosis (in decompensated cirrhosis of the liver), fluid and electrolyte disturbances, excretion of potassium increased*

Psychiatric disorder Less frequent psychiatric disorder NOC

Nervous system disorders Less frequent paraesthesia, confusion, headache

Frequency unknown dizziness, fainting and loss of consciousness (caused by symptomatic hypotension)

Eye disorders Less frequent visual disturbance, blurred vision, yellow vision

Ear and labyrinth disorders Less frequent deafness (sometimes irreversible), tinnitus and reversible or irreversible loss of hearing (although usually transitory, particularly in patients with renal failure, hypoproteinaemia (e.g., in nephritic syndrome)

Cardiac disorders Less frequent orthostatic intolerance, cardiac dysrhythmias, increased risk or persistence of patent ductus arteriosus in premature infants

Vascular disorders Frequent hypotension, (which, if pronounced may cause signs and symptoms such as impairment of concentration and reactions, light-headedness, sensations of pressure in the head, headache, drowsiness, weakness, disorders of vision, dry mouth, orthostatic intolerance)

Less frequent vasculitis, thrombosis, shock

Gastro-intestinal disorders Less frequent dry mouth, thirst, nausea, bowel motility disturbances, vomiting, diarrhoea, constipation, acute pancreatitis (in long-term diuretic treatment, including furosemide)

Hepato-biliary disorders Less frequent pure intrahepatic cholestasis (jaundice), hepatic function abnormal

Skin and sub-cutaneous tissue disorders Less frequent rash, pruritus, photosensitivity, toxic epidermal necrolysis

Frequency unknown urticaria, erythema multiforme, purpura, exfoliative dermatitis, itching, allergic reactions, such as skin rashes, various forms of dermatitis including urticaria, bullous lesions, acute generalised exanthematous pustulosis (AGEP). When these occur treatment should be withdrawn, Stevens-Johnson syndrome

Musculo-skeletal and connective tissue disorders Less frequent muscle cramps, muscle weakness

Renal and urinary disorders Frequent nephrocalcinosis in infants

Less frequent reduced diuresis, urinary incontinence, urinary obstruction (in patients with hyperplasia of the prostate, bladder inability to empty, urethral stricture unspecified), acute renal failure, interstitial nephritis

Congenital, familial and genetic disorders Less frequent patent ductus arteriosus

Investigations Frequent creatinine increased; blood urea increased

Less frequent transaminases increased, blood

*Potassium deficiency manifests itself in neuromuscular symptoms (muscular weakness, paralysis), intestinal symptoms (vomiting, constipation, meterorism), renal symptoms (polyuria) or cardiac symptoms. Severe potassium depletion can result in paralytic ileus or confusion, which can result in coma.

Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/ risk balance of the medicine. Healthcare providers are asked to report any suspected adverse reactions to SAHPRA via the u201c6.04 Adverse Drug Reactions Reporting Formu201d, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8.

Fluid and electrolyte depletion is the most serious danger of overdosage. Treatment should therefore be aimed at electrolyte and fluid replacement. The medicine should be discontinued, and electrolyte and water replacement instituted immediately; adjustment should be on the basis of careful monitoring.