Biliary disorders

▶Aurobeverine MR(Milpharm Ltd)

Mebeverine hydrochloride 200 mgAurobeverine MR200mg capsules|60capsule^P £6.92DT = £8.29

▶Colofac MR(Mylan)

Mebeverine hydrochloride 200 mgColofac MR200mg capsules| 60capsule^P£6.92DT = £8.29

Tablet

▶Mebeverine hydrochloride (Non-proprietary)

Mebeverine hydrochloride 135 mgMebeverine135mg tablets| 100tablet^P £20.00DT = £4.30

▶Colofac(Mylan)

Mebeverine hydrochloride 135 mgColofac135mg tablets| 100tablet^P £9.02DT = £4.30

Colofac IBS135mg tablets|15tablet^p £2.83

7 Liver disorders and related

conditions

within the liver, subsequently evolving tofibrosis and cirrhosis.

Treatment

gUrsodeoxycholic acid p.89is recommended for the management of primary biliary cholangitis, including those with asymptomatic disease. It slows disease progression, but the effect on overall survival is uncertain. Liver

transplantation can be considered in patients with advanced primary biliary cholangitis.h

BILE ACIDS

Chenodeoxycholic acid

05-Apr-2018 lINDICATIONS AND DOSE

Cerebrotendinous xanthomatosis (specialist use only)

▶BY MOUTH

▶Adult:Initially750mg daily in3divided doses, increased if necessary up to1000mg daily in divided doses

lCONTRA-INDICATIONSNon-functioning gall bladder

.

radio-opaque stones

lINTERACTIONS→Appendix1: chenodeoxycholic acid lSIDE-EFFECTSConstipation

lPREGNANCYManufacturer advises avoid—fetotoxicity reported inanimalstudies.

lHEPATIC IMPAIRMENTManufacturer advises monitor—no information available.

lRENAL IMPAIRMENT Manufacturer advises monitor—no information available.

lMONITORING REQUIREMENTSManufacturer advises to monitor serum cholestanol levels and/or urine bile alcohols every3months during the initiation of therapy and dose adjustment, and then at least annually; liver function should also be monitored during initiation of therapy and then at least annually; additional or more frequent investigations may need to be undertaken to monitor therapy during periods of fast growth or concomitant disease.

lDIRECTIONS FOR ADMINISTRATIONFor administrationby mouthin patients who are unable to swallow capsules and/or need to take a dose below250mg, manufacturer advises to add capsule contents to sodium bicarbonate solution8^.4^%—for further information, consult product literature.

lMEDICINAL FORMSThere can be variation in the licensing of different medicines containing the same drug.

Capsule

▶Chenodeoxycholic acid (non-proprietary)^A

Chenodeoxycholic acid 250 mgChenodeoxycholic acid250mg capsules|100capsule^P£14,000.00

Cholic acid

12-Jul-2018

lDRUG ACTIONCholic acid is the predominant primary bile acid in humans, which can be used to provide a source of bile acid in patients with inborn deficiencies in bile acid synthesis.

lINDICATIONS AND DOSE

Inborn errors of primary bile acid synthesis (initiated by a specialist)

▶BY MOUTH

▶Adult:Usual dose5–15mg/kg daily; increased in steps of50mg daily in divided doses if required, dose to be given with food at the same time each day; Usual maximum500^mg/24^hours

lINTERACTIONS→Appendix1: cholic acid

lSIDE-EFFECTSCholelithiasis (long term use)

.

diarrhoea

.

pruritus

SIDE-EFFECTS, FURTHER INFORMATIONPatients presenting with pruritus and/or persistent diarrhoea should be investigated for potential overdose by a serum and/or urine bile acid assay.

lPREGNANCYLimited data available—not known to be harmful, manufacturer advises continue treatment.

MonitoringManufacturer advises monitor patient parameters more frequently in pregnancy.

lBREAST FEEDINGPresent in milk but not known to be harmful.

lHEPATIC IMPAIRMENTManufacturer advises caution and stop treatment if there are signs of severe hepatic failure— limited information available (no experience with impairment from causes not related to inborn errors of primary bile acid synthesis).

Dose adjustmentsManufacturer advises adjust dose as the degree of impairment improves during treatment.

lMONITORING REQUIREMENTSManufacturer advises monitor serum and/or urine bile-acid concentrations every 3months for thefirst year, then every6months for three years, then annually; monitor liver function tests at the same or greater frequency.

lDIRECTIONS FOR ADMINISTRATIONManufacturer advises capsules may be opened and the content added to infant formula, juice, fruit compote, or yoghurt for

administration.

lPATIENT AND CARER ADVICECounselling advised on administration.

lMEDICINAL FORMSThere can be variation in the licensing of different medicines containing the same drug.

Capsule

CAUTIONARY AND ADVISORY LABELS25

▶Orphacol(Laboratoires CTRS)^A

Cholic acid 50 mgOrphacol50mg capsules|30capsule^P

£1,860.00

Cholic acid 250 mgOrphacol250mg capsules|30capsule^P

£6,630.00

Obeticholic acid

15-May-2018 lDRUG ACTIONObeticholic acid is a selective farnesoid X

receptor agonist, which decreases circulating bile acid.

lINDICATIONS AND DOSE

Primary biliary cholangitis in combination with ursodeoxycholic acid when response to ursodeoxycholic acid has been inadequate, or as monotherapy in patients intolerant of ursodeoxycholic acid

▶BY MOUTH

▶Adult:Initially5mg once daily for6months, then increased to10mg once daily if necessary and if tolerated, for dose adjustments due to severe pruritus, consult product literature

IMPORTANT SAFETY INFORMATION

MHRA/CHM ADVICE: OBETICHOLIC ACID (OCALIVA^®): RISK OF SERIOUS LIVER INJURY IN PATIENTS WITH PRE-EXISTING MODERATE OR SEVERE HEPATIC IMPAIRMENT; REMINDER TO ADJUST DOSING ACCORDING TO LIVER FUNCTION MONITORING (APRIL 2018)

The MHRA is aware of reports of serious liver injuries and deaths in patients with primary biliary cholangitis with pre-existing moderate or severe liver impairment who were not adequately dose-adjusted. Follow dose reduction and monitoring advice in these patients to

88 Liver disorders and related conditions

BNF78

Gastro-intestinalsystem

1

reduce the risk of serious liver injury; for further information, seeHepatic impairmentandMonitoring.

lCONTRA-INDICATIONSComplete biliary obstruction lINTERACTIONS→Appendix1: obeticholic acid lSIDE-EFFECTS

▶Common or very commonArthralgia

.

constipation

.

dizziness

.

fatigue

.

fever

.

gastrointestinal discomfort

.

oropharyngeal pain

.

palpitations

.

peripheral oedema

.

skin reactions

▶Frequency not knownHepatic failure lPREGNANCY

Dose adjustmentsNo evidence of harm but manufacturer advises avoid.

lBREAST FEEDINGNot known to be harmful but manufacturer advises avoid.

lHEPATIC IMPAIRMENTManufacturer advises caution in moderate to severe impairment or decompensated cirrhosis (risk of increased exposure).

Dose adjustmentsManufacturer advises initial dose reduction to5mg once weekly in moderate to severe impairment or decompensated cirrhosis; titrate dose according to alkaline phosphatase and/or total bilirubin level—consult product literature.

lMONITORING REQUIREMENTSManufacturer advises assess hepatic status before treatment initiation and then monitor for progression of primary biliary cholangitis with laboratory and clinical assessment to evaluate the need for dose reduction; patients at an increased risk of hepatic decompensation, including those with laboratory evidence of worsening liver function and/or progression to cirrhosis, should be monitored more closely.

lNATIONAL FUNDING/ACCESS DECISIONS NICE decisions

▶Obeticholic acid for treating primary biliary cholangitis (April 2017^{)NICE TA443}

Obeticholic acid (Ocaliva^®) is recommended as an option for treating primary biliary cholangitis, in combination with ursodeoxycholic acid when response to ursodeoxycholic acid is inadequate, or as monotherapy when ursodeoxycholic acid is not tolerated and only if the manufacturer provides obeticholic acid with the discount agreed in the patient access scheme. Response to obeticholic acid should be assessed after12^{months and} treatment continued only if there is evidence of clinical benefit.

www.nice.org.uk/guidance/ta443

Scottish Medicines Consortium (SMC) decisions TheScottish Medicines Consortiumhas advised (June2017⁾ that obeticholic acid (Ocaliva^®) is accepted for use within NHS Scotland for the treatment of primary biliary cholangitis in combination with ursodeoxycholic acid when response to ursodeoxycholic acid is inadequate, or as monotherapy when ursodeoxycholic acid is not tolerated.

This advice is contingent upon the continuing availability of the patient access scheme in NHS Scotland or a list price that is equivalent or lower.

lMEDICINAL FORMSThere can be variation in the licensing of different medicines containing the same drug.

Tablet

▶Ocaliva(Intercept Pharma UK & Ireland Ltd)^A Obeticholic acid 5 mgOcaliva5mg tablets|30tablet^P

£2,384.04(Hospital only)

Obeticholic acid 10 mgOcaliva10mg tablets|30tablet^P

£2,384.04(Hospital only)

Ursodeoxycholic acid

lINDICATIONS AND DOSE Dissolution of gallstones

▶BY MOUTH

▶Adult:8–12mg/kg once daily, dose to be taken at bedtime, alternatively8–12mg/kg daily in2^divided doses for up to2years; treatment is continued for 3–4months after stones dissolve

Primary biliary cirrhosis

▶BY MOUTH

▶Adult:12–16mg/kg daily in3divided doses for 3months, then12–16mg/kg once daily, dose to be taken at bedtime

lCONTRA-INDICATIONSAcute inflammation of the gall bladder

.

frequent episodes of biliary colic

.

inflammatory diseases and other conditions of the colon, liver or small intestine which interfere with enterohepatic circulation of bile salts

.

non-functioning gall bladder

.

radio-opaque stones

lCAUTIONSLiver disease

lINTERACTIONS→Appendix1: ursodeoxycholic acid lSIDE-EFFECTS

▶Common or very commonDiarrhoea

.

pale faeces

▶Rare or very rareCholelithiasis calcification

.

skin reactions

▶Frequency not knownNausea

.

vomiting

lPREGNANCYNo evidence of harm but manufacturer advises avoid.

lBREAST FEEDINGNot known to be harmful but manufacturer advises avoid.

lHEPATIC IMPAIRMENTAvoid in chronic liver disease (but used in primary biliary cirrhosis).

lMONITORING REQUIREMENTSIn primary biliary cirrhosis, monitor liver function every4^{weeks for}3months, then every3^months.

lPATIENT AND CARER ADVICEPatients should be given dietary advice (including avoidance of excessive cholesterol and calories).

lMEDICINAL FORMSThere can be variation in the licensing of different medicines containing the same drug. Forms available from special-order manufacturers include: oral suspension, oral solution

Oral suspension

CAUTIONARY AND ADVISORY LABELS21

▶Ursofalk(Dr. Falk Pharma UK Ltd)

Ursodeoxycholic acid 50 mg per 1 mlUrsofalk250mg/5ml oral suspension sugar-free|250ml^P £26.98DT = £26.98 Tablet

CAUTIONARY AND ADVISORY LABELS21

▶Ursodeoxycholic acid (Non-proprietary)

Ursodeoxycholic acid 150 mgUrsodeoxycholic acid150mg tablets

|60tablet^P£19.02DT = £19.02

Ursodeoxycholic acid 300 mgUrsodeoxycholic acid300mg tablets

|60tablet^P£47.63–£62.52DT = £55.08

▶Cholurso(HFA Healthcare Products Ltd)

Ursodeoxycholic acid 250 mgCholurso250mg tablets| 60tablet^P£15.25DT = £15.25

Ursodeoxycholic acid 500 mgCholurso500mg tablets| 60tablet^P£45.00

▶Destolit(Norgine Pharmaceuticals Ltd)

Ursodeoxycholic acid 150 mgDestolit150mg tablets| 60tablet^P£18.39DT = £19.02

▶Ursofalk(Dr. Falk Pharma UK Ltd)

Ursodeoxycholic acid 500 mgUrsofalk500mg tablets| 100tablet^P£80.00DT = £80.00

▶Ursonorm(PRO.MED.CS Praha a.s.)

Ursodeoxycholic acid 500 mgUrsonorm500mg tablets| 60tablet^P£45.00|100tablet^P £49.00DT = £80.00

BNF78

Biliary disorders 89

Gastro-intestinalsystem

1

Capsule

CAUTIONARY AND ADVISORY LABELS21

▶Ursodeoxycholic acid (Non-proprietary)

Ursodeoxycholic acid 250 mgUrsodeoxycholic acid250mg capsules

|60capsule^P£29.00DT = £16.16|100capsule^P £25.47

▶Ursofalk(Dr. Falk Pharma UK Ltd)

Ursodeoxycholic acid 250 mgUrsofalk250mg capsules| 60capsule^P£30.17DT = £16.16|100capsule^P £31.88

▶Ursonorm(PRO.MED.CS Praha a.s.)

Ursodeoxycholic acid 250 mgUrsonorm250mg capsules| 60capsule^P£29.00DT = £16.16

COUGH AND COLD PREPARATIONS

›

^TERPENES

Borneol with camphene, cineole, menthol, menthone and pinene

lINDICATIONS AND DOSE Biliary disorders

▶BY MOUTH

▶Adult:1–2^capsules3times a day, to be taken before food

lLESS SUITABLE FOR PRESCRIBINGRowachol^®is less suitable for prescribing.

lMEDICINAL FORMSThere can be variation in the licensing of different medicines containing the same drug.

Gastro-resistant capsule CAUTIONARY AND ADVISORY LABELS22

▶Rowachol(Meadow Laboratories Ltd)

Cineole 2 mg, Borneol 5 mg, Camphene 5 mg, Menthone 6 mg, Pinene 17 mg, Menthol 32 mgRowachol gastro-resistant capsules| 50capsule^P£7.35

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