Obeticholic acid (Ocaliva) is a derivative of human bile acid, chenodeoxycholic acid. It has got 100 times more affinity than chenodeoxycholic acid for the farnesoid x receptors that are responsible for bile acid homeostasis.

Indications of Obeticholic acid (Ocaliva):

• Primary biliary cholangitis:

  • It is used for the management of primary biliary cholangitis either as a single agent or in combination with ursodeoxycholic acid to achieve the desired response [Ref].

Obeticholic acid (Ocaliva) dose in Adults

Dose for the treatment of primary biliary cholangitis:

• Noncirrhotic or compensated Child-Pugh class A:

  • The maximum dose is 10 mg/day.
  • The initial dosage is 5 mg per mouth once a day, increasing to 10 mg once daily if total bilirubin/alkaline phosphatase levels do not decrease after 3 months of treatment.
  • Before increasing the dosage, recalculate the Child-Pugh classification.

• Child-Pugh classes B or C, or people who have experienced a previous decompensation episode (such as gastric variceal haemorrhage, fresh or increasing jaundice, or spontaneous bacterial peritonitis):

  • Initial: 5 mg per oral once every week, titrated to 5 mg b.i.d weekly alkaline phosphatase/ total bilirubin is not reduced despite 3 months of therapy.
  • Depending on reaction and tolerance, the dose may be raised to 10 mg twice weekly (at least 3 days apart).
  • 10 mg twice weekly is the maximum dosage (at least 3 days apart).

Note: Based on expert opinion, use in patients with decompensated liver disease (Child-Pugh B or C) is not recommended.

Obeticholic acid (Ocaliva) use in children:

Obeticholic acid's effectiveness and safety in youngsters are unknown.

Pregnancy Risk Category: C

• Studies on animal reproduction did not show any adverse outcomes.

Use of obseticholic acid during breastfeeding:

• The secretionObeticholic acid in breast milk is not known.
• According to the manufacturer breastfeeding during therapy is a decision that depends on the risks to the infant and the benefits to the mother.

Obeticholic acid (Ocaliva) Dose adjustment in renal disease:

There are no dosage adjustments provided in the manufacturer′s labeling.

Obeticholic acid (Ocaliva) Dose adjustment in liver disease:

• Hepatic impairment before treatment:

  • Refer to adult dosing.

• Hepatotoxicity during treatment:

  • Lab or clinical proof of deteriorating liver function:

    • Treatment should be withheld and liver function monitoring should be done.
    • Treatment can be restarted with dose adjustment for Child-Pugh classification once the liver function returns to baseline.

  • Significant liver-related adverse reactions: 

    • Treatment should be stopped.

• Complete biliary obstruction:

  • Permanently discontinue treatment.

Common Side Effects of Obeticholic acid (Ocaliva):

• Central Nervous System:

  • Fatigue

• Dermatologic:

  • Pruritus

• Endocrine & Metabolic:

  • Decreased HDL Cholesterol

• Gastrointestinal:

  • Abdominal Pain

Uncommon Side Effects of Obeticholic acid (Ocaliva):

• Cardiovascular:

  • Peripheral Edema
  • Palpitations

• Central Nervous System:

  • Dizziness

• Dermatologic:

  • Skin Rash
  • Eczema

• Endocrine & Metabolic:

  • Thyroid Dysfunction

• Gastrointestinal:

  • Constipation

• Neuromuscular & Skeletal:

  • Arthralgia

• Respiratory:

  • Oropharyngeal Pain

• Miscellaneous:

  • Fever

Frequency of side effects not defined:

• Gastrointestinal:

  • Cholangitis (worsening)

Contraindication to Obeticholic acid (Ocaliva):

These include:

• Complete biliary obstruction
• Hypersensitivity to any component of the formulation or obeticholic Acid.

Warnings and precautions

• Hepatic effects

  • Jaundice, worsening symptoms, and primary biliary Cholangitis flare can all be caused by drug therapy.
  • Therefore, it is important to monitor LFTs closely and not treat any liver function that may have been compromised.

• The Lipid Effects

  • Lipid monitoring is required since it may result in a drop in the amount of HDL cholesterol (HDL-C).

• Pruritus

  • It is necessary to reduce dose or add bile acid resins and antihistamines when there is severe pruritus, or excessive or strong itching.

Obeticholic acid: Drug Interaction

Monitoring parameters:

• Signs of hepatic reactions
• Signs of pruritus
• LFTs, including alkaline phosphatase and bilirubin
• Lipid profile
• Progressive signs of primary biliary cholangitis

How to administer Obeticholic acid (Ocaliva)?

It can be ingested with or without meals. If you have extreme pruritus, you should take obeticholic acid 4 hours before or after taking a bile acid-binding resin.

Mechanism of action of Obeticholic acid (Ocaliva):

• Obeticholic acid can be used as a farnesoid-X receptor agonist. FXR activation inhibits the de novo synthesis from the cholesterol of bile acid.
• This results in an increase in the transport of bile acids through the liver cells, which limits the size of the circulating pool of bile acids and promotes choleretic.

Protein binding:

• >99%

Metabolism

• Obeticholic acids are transformed by the liver into active metabolites (glyco and tauroobeticholic acids), which are subsequently converted back to obeticholic acids by intestinal microorganisms and either absorbed or eliminated. The pharmacologic activity of 3 glucuronide is minimal.

The time to reach peak plasma concentration:

• Obeticholic acid: 1.5 hours
• glyco- and tauro-obeticholic acid: 10 hours

Excretion:

• Occurs in feces :87%
• urine <3%

Obeticholic acid Brand Names (International):

• Ocaliva

Obeticholic acid Brand Names in Pakistan:

No Brands Available in Pakistan.