Individual generic drug information

febuxostat

Reference monograph

Part of registered formulation

FEBUXOSTAT

Reference record: Febuxostat
Source: BNF 80 (2020–2021)
Printed source pages: 1206, 1207, 1208
Age groups indexed: 1

Individual active ingredientSource records are displayed separately

Some source sections could not be separated reliably in the extraction. Review the printed source pages when a field is missing or incomplete.

Overview

Extracted information for Febuxostat only.

Indications And Dose

Treatment of chronic hyperuricaemia in gout ▶BY MOUTH ▶Adult: Initially 80 mg once daily, if after 2–4 weeks of initial dose, serum uric acid greater than 6 mg/100 mL then increase dose; increased if necessary to 120 mg once daily Prophylaxis and treatment of acute hyperuricaemia with initial chemotherapy for haematologic malignancies ▶BY MOUTH ▶Adult: 120 mg once daily, to be started 2 days before start of cytotoxic therapy and continued for 7–9 days, according to chemotherapy duration

Source page 1206

Contra Indications

Not a treatment for acute gout but continue if attack develops when already receiving febuxostat, and treat attack separately

Source page 1206

Cautions

Congestive heart failure. ischaemic heart disease. major cardiovascular disease. thyroid disorders. transplant recipients CAUTIONS, FURTHER INFORMATION Administer prophylactic NSAID (not aspirin or salicylates) or colchicine for at least 6 months after starting febuxostat to avoid precipitating an acute attack.

Source page 1206

Pre Treatment Screening

Monitor liver function tests before treatment as indicated.

Source page 1207

National Funding Access Decisions

NICE decisions ▶Febuxostat for the management of hyperuricaemia in patients with gout (December 2008) NICE TA164 Febuxostat (Adenuric ®) is recommended as an option for the management of chronic hyperuricaemia in gout only for patients who are intolerant of allopurinol or for whom allopurinol is contra-indicated. For the purposes of this guidance, intolerance of allopurinol is deﬁned as adverse effects that are sufﬁciently severe to warrant discontinuation, or to prevent full dose escalation for optimal effectiveness. www.nice.org.uk/guidance/ta164 Scottish Medicines Consortium (SMC) decisions SMC No. 637/10 The Scottish Medicines Consortium has advised (September 2010) that febuxostat (Adenuric ®) is accepted for restricted use within NHS Scotland for the treatment of chronic hyperuricaemia when treatment with allopurinol is inadequate, not tolerated or contra-indicated. SMC No. 1153/16 The Scottish Medicines Consortium has advised (June 2016) that febuxostat (Adenuric ®) is accepted for restricted use within NHS Scotland for the prevention and treatment of hyperuricaemia in patients undergoing chemotherapy for haematological malignancies at intermediate to high risk of tumour lysis syndrome, only when allopurinol is not tolerated or contra-indicated.

Source page 1207

Safety

Extracted information for Febuxostat only.

Important Safety Information

MHRA/CHM ADVICE: SERIOUS HYPERSENSITIVITY REACTIONS (JUNE 2012) There have been rare but serious reports of hypersensitivity reactions, including Stevens-Johnson syndrome and acute anaphylactic shock with febuxostat. Patients should be advised of the signs and symptoms of severe hypersensitivity; febuxostat must be stopped immediately if these occur (early withdrawal is associated with a better prognosis), and must not be restarted in patients who have ever developed a hypersensitivity reaction to febuxostat. Most cases occur during the ﬁrst month of treatment; a prior history of hypersensitivity to allopurinol and/or renal disease may indicate potential hypersensitivity to febuxostat. MHRA/CHM ADVICE: FEBUXOSTAT (ADENURIC ®): INCREASED RISK OF CARDIOVASCULAR DEATH AND ALL-CAUSE MORTALITY IN CLINICAL TRIAL IN PATIENTS WITH A HISTORY OF MAJOR CARDIOVASCULAR DISEASE (JULY 2019) Results from the clinical study (CARES) in patients with gout and a history of major cardiovascular disease showed an increased risk of cardiovascular-related death and all-cause mortality associated with febuxostat compared with allopurinol. Healthcare professionals are advised to avoid treatment with febuxostat in patients with pre-existing major cardiovascular disease (e.g. myocardial infarction, stroke, or unstable angina), unless no other therapy options are appropriate; clinical guidelines for gout recommend treatment with febuxostat only when allopurinol is not tolerated or is contra-indicated.

Source page 1206

Interactions

→Appendix 1: febuxostat

Source page 1206

Side Effects

▶Common or very common Diarrhoea. gout aggravated. headache. hepatic disorders. nausea. oedema. skin reactions ▶Uncommon Altered smell sensation. appetite abnormal. arrhythmias. arthritis. bundle branch block. chest discomfort. cholelithiasis. constipation. cough. diabetes mellitus. dizziness. drowsiness. dry mouth. dyspnoea. fatigue. gastrointestinal discomfort. gastrointestinal disorders. haemorrhage. hemiparesis. hyperlipidaemia. hypertension. increased risk of infection. insomnia. joint disorders. muscle complaints. muscle weakness. musculoskeletal pain. nephrolithiasis. palpitations. proteinuria. renal failure. sensation abnormal. sexual dysfunction. taste altered. urinary disorders. vasodilation . vomiting. weight changes ▶Rare or very rare Agranulocytosis. alopecia. angioedema. hyperhidrosis. hypersensitivity. musculoskeletal stiffness . nephritis tubulointerstitial. nervousness. oral ulceration . pancreatitis. pancytopenia. rhabdomyolysis. severe cutaneous adverse reactions (SCARs). sudden cardiac death. thirst. thrombocytopenia. tinnitus. vision blurred

Source pages 1206, 1207

Pregnancy

Manufacturer advises avoid—limited information available.

Source page 1207

Breast Feeding

Manufacturer advises avoid—present in milk in animal studies.

Source page 1207

Hepatic Impairment

Manufacturer advises caution. Dose adjustments Manufacturer advises max. 80 mg daily in mild impairment; no dose information available in moderate to severe impairment.

Source page 1207

Renal Impairment

Use with caution if eGFR less than 30 mL/minute/1.73 m2—no information available.

Source page 1207

Monitoring Requirements

Monitor liver function tests periodically during treatment as indicated.

Source page 1207

Dose and formulations

Extracted information for Febuxostat only.

Medicinal Forms

There can be variation in the licensing of different medicines containing the same drug. Tablet ▶Febuxostat (Non-proprietary) Febuxostat 80 mg Febuxostat 80mg tablets | 28 tablet P £24.36 DT = £5.64 Febuxostat 120 mg Febuxostat 120mg tablets | 28 tablet P £24.36 DT = £24.36 ▶Adenuric (A. Menarini Farmaceutica Internazionale SRL) Febuxostat 80 mg Adenuric 80mg tablets | 28 tablet P £24.36 DT = £5.64 Febuxostat 120 mg Adenuric 120mg tablets | 28 tablet P £24.36 DT = £24.36 Neuromuscular disorders Neuromuscular disorders Drugs that enhance neuromuscular transmission Anticholinesterases are used as ﬁrst-line treatment in ocular myasthenia gravis and as an adjunct to immunosuppressant therapy for generalised myasthenia gravis. Corticosteroids are used when anticholinesterases do not control symptoms completely. A second-line immunosuppressant such as azathioprine p. 881 is frequently used to reduce the dose of corticosteroid. Plasmapheresis or infusion of intravenous immunoglobulin [unlicensed indication] may induce temporary remission in severe relapses, particularly where bulbar or respiratory function is compromised or before thymectomy. Anticholinesterases Anticholinesterase drugs enhance neuromuscular transmission in voluntary and involuntary muscle in myasthenia gravis. Excessive dosage of these drugs can impair neuromuscular transmission and precipitate cholinergic crises by causing a depolarising block. This may be difﬁcult to distinguish from a worsening myasthenic state. Musculoskeletal system Muscarinic side-effects of anticholinesterases include increased sweating, increased salivary and gastric secretions, increased gastro-intestinal and uterine motility, and bradycardia. These parasympathomimetic effects are antagonised by atropine sulfate p. 1404. Neostigmine p. 1188 produces a therapeutic effect for up to 4 hours. Its pronounced muscarinic action is a disadvantage, and simultaneous administration of an antimuscarinic drug such as atropine sulfate or propantheline bromide p. 93 may be required to prevent colic, excessive salivation, or diarrhoea. In severe disease neostigmine can be given every 2 hours. The maximum that most patients can tolerate is 180 mg daily. Pyridostigmine bromide p. 1188 is less powerful and slower in action than neostigmine but it has a longer duration of action. It is preferable to neostigmine because of its smoother action and the need for less frequent dosage. It is particularly preferred in patients whose muscles are weak on waking. It has a comparatively mild gastrointestinal effect but an antimuscarinic drug may still be required. Neostigmine is also used to reverse the actions of the non- depolarising neuromuscular blocking drugs. Immunosuppressant therapy Corticosteroids are established as treatment for myasthenia gravis; although they are commonly given on alternate days there is little evidence of beneﬁt over daily administration. Corticosteroid treatment is usually initiated under in-patient supervision and all patients should receive osteoporosis prophylaxis. In generalised myasthenia gravis prednisolone p. 716 is given. About 10% of patients experience a transient but very serious worsening of symptoms in the ﬁrst 2–3 weeks, especially if the corticosteroid is started at a high dose. Smaller doses of corticosteroid are usually required in ocular myasthenia. Once clinical remission has occurred (usually after 2–6 months), the dose of prednisolone should be reduced slowly to the minimum effective dose. In generalised myasthenia gravis azathioprine is usually started at the same time as the corticosteroid and it allows a lower maintenance dose of the corticosteroid to be used. Ciclosporin p. 883, methotrexate p. 963, or mycophenolate mofetil p. 891 can be used in patients unresponsive or intolerant to other treatments [unlicensed indications]. Acetylcholine-release enhancers Amifampridine p. 1188 is licensed for the symptomatic treatment of Lambert-Eaton myasthenic syndrome (LEMS), a rare disorder of neuromuscular transmission. Fampridine p. 895 is licensed for the improvement of walking in patients with Multiple sclerosis p. 893 who have a walking disability. Skeletal muscle relaxants The drugs described are used for the relief of chronic muscle spasm or spasticity associated with Multiple sclerosis p. 893 or other neurological damage; they are not indicated for spasm associated with minor injuries. Baclofen, diazepam, and tizanidine act principally on the central nervous system. Dantrolene has a peripheral site of action; cannabis extract has both a central and a peripheral action. Skeletal muscle relaxants differ in action from the muscle relaxants used in anaesthesia, which block transmission at the neuromuscular junction. The underlying cause of spasticity should be treated and any aggravating factors (e.g. pressure sores, infection) remedied. Skeletal muscle relaxants are effective in most forms of spasticity except the rare alpha variety. The major disadvantage of treatment with these drugs is that reduction in muscle tone can cause a loss of splinting action of the spastic leg and trunk muscles and sometimes lead to an increase in disability. Baclofen p. 1190 inhibits transmission at spinal level and Musculoskeletal system also depresses the central nervous system. The dose should be increased slowly to avoid the major side-effects of sedation and muscular hypotonia (other adverse events are uncommon). Dantrolene sodium p. 1417 acts directly on skeletal muscle and produces fewer central adverse effects making it a drug of choice. The dose should be increased slowly. Diazepam p. 360 can also be used. Sedation and occasionally extensor hypotonus are disadvantages. Other benzodiazepines also have muscle-relaxant properties. Muscle-relaxant doses of benzodiazepines are similar to anxiolytic doses. Tizanidine p. 1192 is an alpha2-adrenoceptor agonist indicated for spasticity associated with Multiple sclerosis p. 893 or spinal cord injury. g Cannabis extract p. 1190 can be trialled as an adjunct treatment for moderate to severe spasticity in multiple sclerosis if other pharmacological treatments are not effective. Treatment must be initiated and supervised by a specialist. For further information see Multiple sclerosis p. 893. h Other muscle relaxants The clinical efﬁcacy of methocarbamol p. 1191 and meprobamate p. 363 as muscle relaxants is not well established, although they have been included in compound analgesic preparations. NEUROPROTECTIVE DRUGS

Source pages 1207, 1208

Dose text by age group

Filter the extracted dose blocks for this individual drug.

Adults

First line only; read the complete Indications and dose section above.

Initially 80 mg once daily, if after 2–4 weeks of

This is a first-line fragment. Read the full Indications and Dose section above.

Candidate age grouping · source page 1206

Adults

First line only; read the complete Indications and dose section above.

120 mg once daily, to be started 2 days before

This is a first-line fragment. Read the full Indications and Dose section above.

Candidate age grouping · source page 1206

Age labels are extracted from the printed dose headings and require clinical review. Confirm current local guidance, dose, route, formulation, contraindications and interactions before prescribing.

Individual generic drug information

febuxostat

Reference monograph

Part of registered formulation

FEBUXOSTAT

Reference record: Febuxostat
Source: BNF 80 (2020–2021)
Printed source pages: 1206, 1207, 1208
Age groups indexed: 1

Individual active ingredientSource records are displayed separately

Some source sections could not be separated reliably in the extraction. Review the printed source pages when a field is missing or incomplete.

Overview

Extracted information for Febuxostat only.

Indications And Dose

Source page 1206

Contra Indications

Not a treatment for acute gout but continue if attack develops when already receiving febuxostat, and treat attack separately

Source page 1206

Cautions

Source page 1206

Pre Treatment Screening

Monitor liver function tests before treatment as indicated.

Source page 1207

National Funding Access Decisions

Source page 1207

Safety

Extracted information for Febuxostat only.

Important Safety Information

Source page 1206

Interactions

→Appendix 1: febuxostat

Source page 1206

Side Effects

Source pages 1206, 1207

Pregnancy

Manufacturer advises avoid—limited information available.

Source page 1207

Breast Feeding

Manufacturer advises avoid—present in milk in animal studies.

Source page 1207

Hepatic Impairment

Manufacturer advises caution. Dose adjustments Manufacturer advises max. 80 mg daily in mild impairment; no dose information available in moderate to severe impairment.

Source page 1207

Renal Impairment

Use with caution if eGFR less than 30 mL/minute/1.73 m2—no information available.

Source page 1207

Monitoring Requirements

Monitor liver function tests periodically during treatment as indicated.

Source page 1207

Dose and formulations

Extracted information for Febuxostat only.

Medicinal Forms

Source pages 1207, 1208

Dose text by age group

Filter the extracted dose blocks for this individual drug.

Adults

First line only; read the complete Indications and dose section above.

Initially 80 mg once daily, if after 2–4 weeks of

This is a first-line fragment. Read the full Indications and Dose section above.

Candidate age grouping · source page 1206

Adults

First line only; read the complete Indications and dose section above.

120 mg once daily, to be started 2 days before

This is a first-line fragment. Read the full Indications and Dose section above.

Candidate age grouping · source page 1206

Age labels are extracted from the printed dose headings and require clinical review. Confirm current local guidance, dose, route, formulation, contraindications and interactions before prescribing.