Ursodeoxycholic Acid

Usage

Ursodeoxycholic acid (UDCA) is prescribed for various hepatobiliary disorders. Its primary uses include:

• Dissolution of cholesterol gallstones: Specifically, small to medium-sized, radiolucent (X-ray negative) cholesterol stones in patients with a functioning gallbladder.
• Primary Biliary Cholangitis (PBC): UDCA is the first-line treatment for PBC, a chronic liver disease characterized by the destruction of small bile ducts within the liver.
• Hepatobiliary disorders associated with cystic fibrosis: In children aged 6 to 18 years.
• Other conditions: UDCA is sometimes used off-label for other cholestatic conditions, such as primary sclerosing cholangitis (PSC), and for the prevention of gallstones in patients undergoing rapid weight loss.

Pharmacological classification: Bile acid. Specifically, it is a hydrophilic bile acid.

Mechanism of Action: UDCA works by multiple mechanisms, primarily by decreasing the concentration of toxic bile acids (e.g., chenodeoxycholic acid) and stimulating hepatobiliary secretion. It also exhibits anti-inflammatory and immunomodulatory effects, protects cholangiocytes (bile duct cells), and potentially stabilizes hepatocyte membranes.

Alternate Names

• Ursodiol
• Actigall, Urso, Urso Forte (brand names)
• Other brand names may vary regionally.

How It Works

Pharmacodynamics: UDCA reduces the hepatic synthesis of cholesterol, increases cholesterol secretion into bile, and decreases intestinal absorption of cholesterol. It also exerts cytoprotective effects on hepatocytes and cholangiocytes.

Pharmacokinetics:

• Absorption: Absorption is mainly through passive diffusion in the small intestine, but can be enhanced by coadministration with food as it triggers bile release.
• Metabolism: UDCA undergoes enterohepatic circulation, meaning it is absorbed from the intestine, processed by the liver, secreted into bile, and then reabsorbed from the intestine.
• Elimination: UDCA is eliminated primarily in feces, with a small amount excreted in urine.

Mode of Action:

• Displaces toxic bile acids: UDCA reduces the proportion of hydrophobic, cytotoxic bile acids in the bile, thereby reducing their damaging effects on liver cells.
• Choleretic action: Stimulates bile flow.
• Anti-inflammatory and immunomodulatory effects: Inhibits the production of inflammatory cytokines.
• Membrane stabilization: May stabilize cell membranes, protecting hepatocytes and cholangiocytes from damage.

Dosage

Standard Dosage

Adults:

• Gallstone Dissolution: 8-12 mg/kg/day, usually given as a single nighttime dose or in divided doses. Treatment duration is typically up to 2 years.
• PBC: 13-15 mg/kg/day, divided into 2-4 doses taken with food. UDCA is generally considered a lifelong treatment for PBC.

Children:

• Cystic Fibrosis-Associated Hepatobiliary Disorders (6-18 years): 20 mg/kg/day, divided into 2-3 doses, may be increased up to 30 mg/kg/day if necessary.

Special Cases:

• Elderly Patients: Dosage adjustments may be necessary based on liver function.
• Patients with Renal Impairment: Generally, no dose adjustment is necessary, but caution should be exercised in severe renal impairment.
• Patients with Hepatic Dysfunction: Dosage adjustments may be needed depending on the severity of liver disease. Start at lower doses initially.
• Patients with Comorbid Conditions: Individualized dosing may be required.

Clinical Use Cases

UDCA does not have specific dosing recommendations for intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Its use in these settings is primarily for the management of underlying cholestatic liver disease.

Dosage Adjustments: Dosage may need to be adjusted based on individual patient factors such as renal or hepatic function, response to therapy, and tolerance.

Side Effects

Common Side Effects:

• Diarrhea
• Constipation
• Nausea
• Abdominal pain
• Itching

Rare but Serious Side Effects:

• Severe liver injury (rare)
• Allergic reactions

Long-Term Effects: Generally, UDCA is well-tolerated for long-term use.

Adverse Drug Reactions (ADR): Serious ADRs are rare but may include severe liver injury or allergic reactions.

Contraindications

• Non-functioning gallbladder
• Biliary obstruction
• Acute cholangitis
• Inflammatory bowel disease
• Hypersensitivity to UDCA

Drug Interactions

• Cholestyramine, colestipol, aluminum-containing antacids: These medications can decrease the absorption of UDCA.
• Estrogens, oral contraceptives: May increase biliary cholesterol saturation, potentially counteracting the gallstone-dissolving effects of UDCA.
• Ciclosporin: UDCA may increase ciclosporin absorption.

Pregnancy and Breastfeeding

• Pregnancy: UDCA is considered generally safe during pregnancy (Pregnancy Category B in the old FDA classification).
• Breastfeeding: UDCA is present in breast milk. While it is generally considered compatible with breastfeeding, the potential risks and benefits should be evaluated.

Drug Profile Summary

• Mechanism of Action: Decreases toxic bile acids, stimulates bile flow, anti-inflammatory, cytoprotective.
• Side Effects: Diarrhea, constipation, nausea, abdominal pain, pruritus.
• Contraindications: Non-functioning gallbladder, biliary obstruction, acute cholangitis, inflammatory bowel disease, hypersensitivity.
• Drug Interactions: Cholestyramine, colestipol, aluminum antacids, estrogens, ciclosporin.
• Pregnancy & Breastfeeding: Generally safe in pregnancy; compatible with breastfeeding, but caution advised.
• Dosage: Varies depending on indication and patient factors; see dosage section for details.
• Monitoring Parameters: Liver function tests (ALT, AST, ALP, bilirubin), bile acid levels (if needed).

Popular Combinations

UDCA is often used as monotherapy. For PBC patients who do not adequately respond to UDCA, obeticholic acid may be added.

Precautions

• General Precautions: Monitor liver function tests periodically.
• Specific Populations: Consider age-specific dosage adjustments for children and the elderly. Careful monitoring and potential dose reductions in patients with liver dysfunction.
• Lifestyle Considerations: No specific restrictions related to alcohol, smoking, or diet are typically necessary unless relevant to the underlying condition.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Ursodeoxycholic Acid?

A: The dosage varies depending on the condition being treated. For gallstone dissolution, it is 8-12 mg/kg/day. For PBC, it is 13-15 mg/kg/day. For cystic fibrosis-associated hepatobiliary disorders in children, it is 20-30 mg/kg/day.

Q2: How long does it take for UDCA to dissolve gallstones?

A: Gallstone dissolution with UDCA can take up to 2 years.

Q3: Is UDCA a lifelong treatment for PBC?

A: Yes, UDCA is generally recommended as a lifelong treatment for PBC.

Q4: What are the common side effects of UDCA?

A: Common side effects include diarrhea, constipation, nausea, abdominal pain, and itching.

Q5: Can UDCA be used during pregnancy?

A: UDCA is generally considered safe during pregnancy, but you should always consult with your doctor before starting or continuing any medication during pregnancy.

Q6: Does UDCA interact with any other medications?

A: Yes, UDCA can interact with certain medications, such as cholestyramine, colestipol, aluminum-containing antacids, estrogens, oral contraceptives, and ciclosporin.

Q7: How does UDCA work in PBC?

A: UDCA works in PBC by reducing the concentration of toxic bile acids, protecting liver cells, and exhibiting anti-inflammatory and immunomodulatory effects.

Q8: What should be monitored in patients taking UDCA?

A: Liver function tests should be monitored periodically.

Q9: Can UDCA prevent gallstones?

A: UDCA can be used to prevent gallstone formation in certain situations, such as in patients undergoing rapid weight loss.

Q10: Are there any contraindications to using UDCA?

A: Yes, contraindications to using UDCA include a non-functioning gallbladder, biliary obstruction, acute cholangitis, inflammatory bowel disease, and hypersensitivity to UDCA.