Chenodeoxycholic acid (chenodiol) for Gallstones!

Chenodeoxycholic acid (chenodiol) is a natural human bile that constitutes about one-third of the bile. It suppresses the synthesis of cholesterol and cholic acid and prevents the cholesterol from being excreted into the bile. Thus, it results in the dissolution of cholesterol gallstones and is used for the treatment of radiolucent cholesterol gallstones as an alternative to surgery. It is also used as an off-label treatment in patients with Cerebrotendinous xanthomatosis (CTX). 

Chenodeoxycholic acid dose in adults:

  • As monotherapy for Gallstone dissolution:

    • 250 mg two times a day for the first two weeks.
    • The dose may be increased by 250 mg daily every week thereafter until the maximum tolerated dose or the recommended dose is achieved.
    • The usual maintenance dose is 13 - 16 mg/kg/day in two divided doses.

  • Off-label dose in combination therapy of Gallstone dissolution:

    • 5 - 7.5 mg/kg/day once a day at bedtime in combination with Urso (ursodeoxycholic acid), with or without adjuvant lithotripsy.

  • Off-label use of Chenodeoxycholic acid in the treatment of Cerebrotendinous xanthomatosis :

    • 750 mg/day in three divided doses for at least one year.

Chenodeoxycholic acid dose in children:

  • Dose in Cerebrotendinous xanthomatosis::

  • Infants, Children, and Adolescents:
    • 10 to 15 mg/kg/day in one to three divided doses to a maximum daily dose of 750 mg/day.

  • Gallstone dissolution: 

  • Children older than 12 years and Adolescents:
    • 15 mg/kg/day in three divided doses daily with meals
    • It is not a first-line of therapy because of frequent adverse effects and low efficacy.

  • Inborn errors of bile acid biosynthesis and steroid dehydrogenase or reductase deficiencies

  • Infants, Children, and Adolescents:
    • 5 - 10 mg/kg/day divided into one or two divided doses daily.

Pregnancy Risk Factor X

  • It is not recommended for pregnant women or women who are pregnant.

Use of chenodeoxycholic acids during breastfeeding

  • You should use it with caution, as the excretion into breast milk of the drug is unknown.
  • It is important to weigh the risks and the benefits for the mother as well as the potential exposure for the child.

Chenodeoxycholic acid dose in Renal Disease:

The manufacturer has not recommended any dose adjustment in patients with kidney disease.

Chenodeoxycholic acid in Liver disease:

  • Patients with Preexisting hepatic impairment:

    • Avoid its use in patients with preexisting hepatocyte dysfunction or bile ductal pathology.

  • Hepatotoxicity during treatment:

    • Aminotransferase level of 1.5 - 3 times the upper limits of normal that persists for more than 3 to 6 months:
      • Withhold the treatment temporarily.
      • Therapy may be resumed when the liver enzymes return to the baseline.
    • Liver enzymes more than 3 times the upper limits of normal:
      • Therapy should be immediately discontinued.

Common Side Effects Of Chenodeoxycholic acid include:

  • Endocrine & metabolic:
    • Increased LDL cholesterol
    • Increased serum total cholesterol
  • Gastrointestinal:
    • Diarrhea
    • Biliary colic
    • Abdominal cramps
    • Abdominal pain
    • Anorexia
    • Constipation
    • Dyspepsia
    • Flatulence
    • Heartburn
    • Nausea
    • Vomiting
  • Hematologic & oncologic:
    • Leukopenia
  • Hepatic:
    • Increased serum transaminases

Contraindications to Chenodeoxycholic acid include:

  • Patients with liver dysfunction and bile ductal abnormalities such as intrahepatic cholesterol, primary biliary obstruction, and sclerosing Cholangitis should be avoided
  • Radio-opaque stone patients
  • Use in gallstones that have complications
  • Use in patients with cholangitis, gallstone pancreatitis, biliary obstruction, biliary-gastrointestinal fistula, or unremitting acute cholecystitis.
  • Do not use it in pregnant women, or in women who are likely to get pregnant.

Warnings and Precautions

  • Diarrhoea:
    • About half of patients may experience diarrhoea. It may be severe enough that it is necessary to temporarily discontinue therapy, reduce the dosage, or add anti-diarrheal medications.
  • Hepatotoxicity:
    • Hepatotoxicity should be checked in patients. Patients who have hepatocyte dysfunction or pre-existing ductal abnormalities should not use it.
    • Stopping therapy should be initiated if the elevations of aminotransferase are 3 or more times greater than the normal upper limit.
    • Very rare cases of active hepatitis that have been histologically confirmed have been reported.
    • Patients with transaminase levels greater than 1 to 3 times the normal limit should temporarily be withheld.
  • Colon cancer:
    • There is little evidence to support the association of chenodiol with an increase in colon cancer incidence.

Chenodeoxycholic acid (chenodiol): Drug Interaction

Note: Drug Interaction Categories:

  • Risk Factor C: Monitor When Using Combination
  • Risk Factor D: Consider Treatment Modification
  • Risk Factor X: Avoid Concomitant Use    

Risk Factor C (Monitor therapy).

Estrogen Derivatives It may reduce the therapeutic effects of Chenodiol. When using chenodiol in combination with estrogen derivatives, be sure to monitor the clinical response.
Fibric Acid Derivatives The therapeutic effects of Chenodiol may be diminished. When using chenodiol in combination with fibric acid derivatives, be sure to monitor the clinical response.
Vitamin K antagonists (eg warfarin) Vitamin K Antagonists may have an anticoagulant effect that Chenodiol might enhance.

Risk Factor D (Regard therapy modification)

 
Aluminum Hydroxide The serum concentration of Chenodiol may be decreased. Management: To prevent adsorption into the gastrointestinal tract, chenodiol should be administered 2 hours or 6 hours before aluminum-containing anticid products.
Bile Acid Sequestrants The serum concentration of Chenodiol may be decreased. Management: Chenodiol may be administered 5 hours after the administration of bile acids sequestrants to reduce chenodiol's adsorption into the gastrointestinal tract. Patients receiving bile acids sequestrants should be monitored for decreased therapeutic effects of Chenodiol.

Monitor:

  • Serum aminotransferase levels monthly for the first 3 months, then 3 monthly thereafter during therapy
  • Serum cholesterol levels 6 monthly
  • Oral cholecystography and/or ultrasonograms should be monitored at 6 to 9-month intervals for response to therapy
  • Dissolutions of stones should be confirmed 1 to 3 months after the initiation of therapy.

How to administer Chenodeoxycholic acid?

It is to be taken orally with or without regard to meals.

Mechanism of action of Chenodeoxycholic acid:

  • It is a naturally occurring human liver acid and normally makes up about one-third of the total bile acids pool.
  • It inhibits the production of cholesterol and cholic acids and the secretion of cholesterol into the liver.
  • This causes the dissolution of cholesterol gallstones.

It happens quickly and almost immediately absorbed in the proximal small intestines. It is Metabolized In the liver as it is converted to taurine or glycine conjugates, and is secreted into the bile. It is subject to extensive testing. First-pass liver clearance is then metabolized in the enterohepatic circulation. It is further metabolized by colonic bacteria to lithocholic. It has a Half-life It is excreted in the faeces primarily as lithocholic Acid. 

Chenodeoxycholic acid International brands:

  • Aylehning
  • Chebil
  • Chendol
  • Cheno
  • Chenofalk
  • Chenossil
  • Quenobilan
  • Theramatic

Chenodeoxycholic acid Brands in Pakistan:

No brands available in Pakistan