Ursodeoxycholic acid oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of ursodeoxycholic acid.
Drugs List
Therapeutic Indications
Uses
Dissolution of radiolucent cholesterol gallstones in functional gallbladder
Gall reflux gastritis
Hepatobiliary disorder associated with cystic fibrosis in children
Treatment of primary biliary cirrhosis
Unlicensed Uses
Cholestasis - congenital
Cholestasis associated with total parenteral nutrition
Primary sclerosing cholangitis
Dosage
Adults
Dissolution of Gallstones
Normal total daily dose is 8mg/kg to 12mg/kg as a single night time dose or in two divided doses after meals with the second dose always taken after the evening meal. If doses are divided unequally, the largest dose should be given in the evening to counteract the rise in biliary cholesterol which occurs in the early morning.
The lowest effective dose has been found to be 4mg/kg and up to 15mg/kg may be necessary in obese patients.
Measurement of the lithogenic index on bile-rich duodenal drainage fluid after 4 to 6 weeks of therapy may be useful for determining the minimum effective dose.
Duration of treatment
Dissolution may take 6 months to 2 years depending on gallstone size and composition and treatment should be continued for a further 3 to 4 months after radiological disappearance of the gallstones or until two successive cholecystograms (and/or ultrasounds) four to twelve weeks apart confirm gallstone removal.
If treatment is temporarily withheld for 3 to 4 weeks bile returns to a state of supersaturation and the time to achieve litholysis will be extended.
Follow up cholecystograms or ultrasound investigation may be useful at 6 monthly intervals to determine efficacy.
The likelihood of recurrence following successful treatment has been estimated as up to 50% at 5 years.
Primary biliary cirrhosis
10mg/kg to 16mg/kg daily for the first 3 months taken in 3 divided doses. With improvement of liver values the daily dose may be taken once daily in the evening. The greatest part of divided doses should be given towards the evening (e.g. if four capsules a day are given these would be split one in the morning, one at midday and two in the evening).
Duration of treatment
May be continued indefinitely.
In rare cases the clinical symptoms may worsen at the beginning of treatment e.g. itching. In such cases, therapy should first be continued with a reduced daily dose, and the dose then gradually increased until the dose regimen indicated is reached again.
Treatment of gall reflux gastritis
250mg once daily in the evening before bed for 10 to 14 days.
Children
Dissolution of Gallstones
Children aged 12 to 18 years and over 47kg
(See Dosage; Adult)
Primary biliary cirrhosis
Children aged 12 to 18 years and over 47kg
(See Dosage; Adult)
Treatment of gall reflux gastritis
Children aged 12 to 18 years and over 47kg
250mg once daily in the evening before bed for 10 to 14 days.
Hepatobiliary disorder in children with cystic fibrosis
Children aged 6 to 18 years
20mg/kg daily taken in two to three divided doses. Maximum dose 30mg/kg daily if necessary.
Children aged 1 month to 6 years (unlicensed)
20mg/kg daily taken in two to three divided doses. Maximum dose 30mg/kg daily if necessary.
Cholestasis (unlicensed)
Children aged 1 month to 2 years
5mg/kg three times a day, adjust dose and frequency according to response. Maximum dose 10mg/kg three times a day.
Cholestasis associated with total parenteral nutrition (unlicensed)
Children aged 1 month to 18 years
10mg/kg three times a day.
Primary sclerosing cholangitis (unlicensed)
Children aged 1 month to 18 years
5mg/kg to 10mg/kg two to three times a day, adjusted according to response. Maximum dose 15mg/kg three times a day.
Neonates
Cholestasis (unlicensed)
5mg/kg three times a day, adjust dose and frequency according to response. Maximum dose 10mg/kg three times a day.
Cholestasis associated with total parenteral nutrition (unlicensed)
10mg/kg three times a day.
Contraindications
Acute cholecystitis
Cholestasis
Duodenal ulcer
Enterocolitis
First trimester of pregnancy
Gastric ulcer
Impaired contractility of gallbladder
Inflammatory bowel disease
Radio-opaque gallstones
Significant ileal resection
Precautions and Warnings
Children under 6 years
Females of childbearing potential
Breastfeeding
Chronic hepatic disorder
Galactosaemia
Glucose-galactose malabsorption syndrome
Lactose intolerance
Second trimester of pregnancy
Third trimester of pregnancy
Some formulations contain more than 1mmol (23mg) sodium per dose
Long term prophylaxis may be required to prevent recurrence
Not all available brands/formulations are licensed for use in children
Not all presentations are licensed for all indications
Some formulations contain lactose
Some products may contain soya or soya derivative
Exclude pregnancy prior to initiation of treatment
Monitor hepatic function every 4 weeks for 3 months, then every 3 months
Radiological monitoring required
Discontinue therapy if marked diarrhoea occurs
Pregnancy confirmed: Advise patient to discontinue and consult doctor
Reduced dietary cholesterol advisable
Female: Ensure adequate contraception during treatment
Non-hormonal or low dose oestrogen contraception is advised during treatment. When taken for gallstone dissolution, non-hormonal methods of contraception may be preferable as hormonal contraceptives may increase biliary lithiasis.
In very rare cases when ursodeoxycholic acid has been used for the treatment of advanced stage of primary biliary cirrhosis, decompensation of hepatic cirrhosis has been observed, which partially regressed after the treatment was discontinued.
Pregnancy and Lactation
Pregnancy
Ursodeoxycholic acid is contraindicated in first trimester of pregnancy and should be used with caution in the second and third trimester of pregnancy.
Pregnancy should be excluded before treatment. Patients are advised to discontinue treatment and seek medical advice if they become pregnant. Schaefer states that after exposure during the first trimester, a follow up sonogram may be offered to verify normal fetal development (Schaefer 2015).
Ursodeoxycholic acid has been used to manage intrahepatic cholestasis of pregnancy, with administration occurring in the late second and third trimester without apparent adverse effects. Administration may improve foetal outcomes when taken in the second and third trimesters.
The results of studies in pregnant animals however have proved conflicting. Some studies have shown no evidence of impaired fertility or foetal harm while others have revealed embryotoxicity at high doses.
Blood levels of ursodeoxycholic acid remain low following absorption due to continuous hepatic uptake. Combined with tight binding to albumin, this probably indicates that placental passage to the foetus does not occur (Briggs 2015).
Lactation
Ursodeoxycholic acid should be used with caution in breastfeeding.
Only small amounts appear in the mother's systemic circulation and this is tightly bound to albumin so only limited amounts are available to enter breast milk. Authorities vary in whether they consider that ursodeoxycholic acid is suitable for use whilst breastfeeding, and whether suitability varies with indication. No adverse effects on breastfed infants were seen in the small number of cases reported of use during breastfeeding.
Side Effects
Decompensation of hepatic cirrhosis
Diarrhoea
Formation of calcified layer to gallstones
Gamma glutamyl transferase (GGT) increased
Increase in alkaline phosphatase
Nausea
Pasty stools
Pruritus
Serum bilirubin increased
Upper abdominal pain
Urticaria
Vomiting
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: April 2019
Reference Sources
Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 3rd edition (2015) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.
Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.
Summary of Product Characteristics: Cholurso 250mg film-coated tablets. Laboratoires Mayoly Spindler. Revised August 2018
Summary of Product Characteristics: Cholurso 500mg film-coated tablets. Laboratoires Mayoly Spindler. Revised August 2018
Summary of Product Characteristics: Destolit 150mg tablets. Norgine Ltd. Revised October 2018
Summary of Product Characteristics: Urdox (Ursodeoxycholic Acid) 300mg Film-Coated Tablets. Wockhardt UK Ltd. Revised February 2018
Summary of Product Characteristics: Ursofalk 250mg Hard Capsules. Dr. Falk Pharma UK Ltd. Revised November 2014
Summary of Product Characteristics: Ursofalk 250mg/5ml Suspension. Dr. Falk Pharma UK Ltd. Revised November 2014
Summary of Product Characteristics: Ursofalk 500mg film-coated tablets. Dr. Falk Pharma UK Ltd. Revised November 2014
Summary of Product Characteristics: Ursonorm 250mg capsules, hard. PRO.MED.CS Praha a.s. Revised July 2018
Summary of Product Characteristics: Ursonorm 500mg film-coated tablets. PRO.MED.CS Praha a.s. Revised June 2018
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 4 April 2019
US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Ursodiol (USAN for Ursodeoxycholic acid) Last revised: 3 December 2018
Last accessed: 4 April 2019
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