FUROSEMIDE TABLETS BP Uncoated tablet Ref.[6867] Active ingredients: Furosemide

Hypotension and/or hypovolaemia (see also section 4.3)

These and any acid-base disturbances should be corrected before furosemide is started.

Symptomatic hypotension leading to dizziness, fainting or loss of consciousness can occur in patients treated with furosemide, 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 (see section 4.2)

Patients with hypoproteinaemia (such as that associated with the nephotic syndrome) require careful dose titration (reduced furosemide effect: increased risk of ototoxicity).

In moderate liver congestion dosage adjustment may be needed.

Caution required

Caution needed in the following circumstances:

• Impaired hepatic function (see sections 4.2 & 4.3 and below – monitoring required).
• Impaired renal function and hepato-renal syndrome (see section 4.3 and below – 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 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.
• Furosemide should be discontinued before a glucose tolerance test.

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 ACEinhibitors can result in marked falls in blood pressure. Furosemide should be stopped or the dose reduced before starting an ACE-inhibitor. There is a risk of a first-dose effect with post-synaptic alphablockers eg prazosin. Furosemide may interact with ACE inhibitors causing impaired renal function.

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

Anti-arrhythmics (including amiodarone, disopyramide, flecanaide and sotalol): risk of cardiac toxicity (because of furosemide-induced hypokalaemia). The effects of lidocaine, tocainide or mexiletine may be antagonised by furosemide.

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

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

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

Renin inhibitors: aliskiren reduces plasma concentrations of furosemide.

Nitrates: enhanced hypotensive effect.

Lithium: furosemide reduces lithium excretion with increased plasma lithium concentrations (risk of toxicity). Avoid concomitant administration unless plasma levels are monitored.

Chelating agents: sucralfate may decrease the gastro-intestinal absorption of furosemide – the 2 drugs should be taken at least 2 hours apart.

Lipid regulating drugs: bile acid sequestrants (e.g. colestyramine: colestipol) – reduced absorption of furosemide – administer 2 to 3 hours apart.

NSAIDs: increased risk of nephrotoxicity (especially if there is hypovolaemia). Indometacin and ketorolac may antagonise the effects of furosemide. In patients with dehydration or hypovolaemia, NSAIDs may cause acute renal insufficiency.

Salicylates: effects may be potentiated by furosemide.

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

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

Antidiabetics: hypoglycaemic effects antagonised by furosemide.

Insulin: requirements may be increased (see section 4.4).

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

Antihistamines: hypokalaemia with increased risk of cardiac toxicity.

Antifungals: increased risk of hypokalaemia with amphoterecin.

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

CNS stimulants (drugs used for ADHD): hypokalaemia increases the risk of ventricular arrhythmias.

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

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

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

Dopaminergics: enhanced hypotensive effect with levodopa.

Immunomodulators: enhanced hypotensive effect with aldesleukin.

Muscle relaxants: enhanced hypotensive effect with baclofen or tizanidine (see also Anaesthetic agents below – curare).

Oestrogens and progestogens: diuretic effect antagonized.

Prostaglandins: enhanced hypotensive effect with alprostadil.

Sympathomimetics: increased risk of hypokalaemia with high doses of beta2 sympathomimetics (such as bambuterol, femoterol, salbutamol, salmeterol and terbutaline).

Theophylline: enhanced hypotensive effect.

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

Anaesthetic agents: general anaesthetic agents may enhance the hypotensive effects of furosemide. The effects of curare may be enhanced by furosemide.

Alcohol: enhanced hypotensive effect.

Laxative abuse: increases the risk of potassium loss.

Liquorice: excess intake may increase the risk of hypokalaemia.

The teratogenic and embryotoxic potential of furosemide in humans is unknown. 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.

The drug should not be used in pregnant women unless the benefits to the patient outweigh the possible risk to the foetus which includes persistence of patent ductus arteriosus (section 4.8).

Furosemide may inhibit lactation or may pass into the breast milk, it should therefore be used with caution in nursing mothers.

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

Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); Frequency not known (cannot be estimated from the available data).

Blood and lymphatic system disorders

Uncommon: aplastic anaemia.

Rare: bone marrow depression (necessitates withdrawal of treatment), eosinophilia, leucopenia.

Very rare: haemolytic anaemia, agranulocytosis, thrombocytopenia.

Metabolism and nutritional disorders

Very common: dehydration, hyponatraemia, hypochloremic metabolic alkalosis, hypocalcaemia, hypomagnesemia (incidences of the last three are reduced by triamterene).

Common: hypovolaemia, hypochloraemia.

Uncommon: impaired glucose tolerance (by hypokalaemia) hyperuricaemia, gout, reduction of serum HDL-cholesterol, elevation of serum LDL-cholesterol, elevation of serum triglycerides, hyperglycaemia.

Very rare: tetany.

Frequency not known: aggravated pre-existing metabolic alkalosis (in decompensated cirrhosis of the liver), fluid and electrolyte disturbances, excretion of potassium increased*.

Psychiatric disorder

Rare: psychiatric disorder NOC.

Nervous system disorders

Rare: paraesthesia, confusion, headache.

Not known: dizziness, fainting and loss of consciousness (caused by symptomatic hypotension).

Eye disorders

Uncommon: visual disturbance, blurred vision, yellow vision.

Ear and labyrinth disorders

Uncommon: deafness (sometimes irreversible).

Rare: 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

Uncommon: orthostatic intolerance, cardiac arrhythmias, increased risk or persistence of patent ductus arteriosus in premature infants.

Vascular disorders

Very common: 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).

Rare: vasculitis, thrombosis, shock.

Gastrointestinal disorders

Uncommon: dry mouth, thirst, nausea, bowel motility disturbances, vomiting, diarrhoea, constipation.

Rare: acute pancreatitis (in long-term diuretic treatment, including furosemide).

Hepatobiliary disorders

Rare: pure intrahepatic cholestasis (jaundice), hepatic function abnormal.

Skin and subcutaneous tissue disorders

Rare: rash, pruritus, photosensitivity, toxic epidermal necrolysis.

Frequency not known: 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.

Musculoskeletal and connective tissue disorders

Uncommon: muscle cramps, muscle weakness.

Renal and urinary disorders

Very common: nephrocalcinosis in infants.

Uncommon: reduced diuresis, urinary incontinence, urinary obstruction (in patients with hyperplasia of the prostate, bladder inability to empty, urethral stricture unspecified).

Rare: acute renal failure.

Very rare: interstitial nephritis.

Congenital, familial and genetic disorders

Rare: patent ductus arteriosus.

General disorders and administration site conditions

Uncommon: fatigue.

Rare: malaise, fever, severe anaphylactoid or anaphylactic reactions (e.g. with shock).

Investigations

Common: creatinine increased, blood urea increased.

Rare: 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 medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme; website: www.mhra.gov.uk/yellowcard.

None known.