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Unconjugated Hyperbilirubinemia Medication

  • Author: Hisham Nazer, MB, BCh, FRCP, , DTM&H; Chief Editor: BS Anand, MD  more...
 
Updated: May 02, 2016
 

Medication Summary

In Crigler-Najjar syndrome type 2, patients with symptomatic jaundice are occasionally treated to improve their quality of life.

In patients with Crigler-Najjar syndrome type 1, phenobarbital, ursodeoxycholic acid, calcium (infusions), metalloporphyrins, cholestyramine, chlorpromazine, and clofibrate (no longer on the US market), as well as alkalinization of urine, have all been considered as potential therapies. Problems associated with the use of cholestyramine include taste and concern about bile salt depletion and fat malabsorption. The exact roles and adverse effects of many of these drugs are not yet defined.

Metalloporphyrins have been used as a synthetic analogue of heme to inhibit the heme oxygenase enzyme, the rate-limiting step in heme catabolism to bilirubin. Tin mesoporphyrin (SnMp) is the drug of choice (DOC) for clinical use because of its increased potency, stability, and photophysical properties.

For Gilbert syndrome, no medical therapy is needed. As with Crigler-Najjar syndrome type 2, phenobarbital has been shown to decrease bilirubin production.

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Anticonvulsants

Class Summary

These drugs induce hepatic-enzyme metabolism, decreasing serum bilirubin levels. They are used to avoid potentially devastating neurologic sequelae in Crigler-Najjar syndrome type 1 and for the management of neurologic symptoms in Crigler-Najjar syndrome type 2.

Phenobarbital

 

Phenobarbital increases the conjugation and excretion of bilirubin. It reduces serum bilirubin levels by at least 25%.

The drug functions by means of phenobarbital-responsive enhancer module that stimulates the gene for UGT 1A1 to induce production of bilirubin-conjugating enzyme. It does not, however, directly act on the UGT enzyme, as previously thought.

Phenobarbital is used to treat Crigler-Najjar syndrome type 2 and as an adjunct to phototherapy in some cases of Crigler-Najjar syndrome type 1. In addition, it has been shown to be effective in the treatment and prevention of neonatal hyperbilirubinemia.

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Lipid-Lowering Agents

Class Summary

Agents in this class reduce serum bilirubin levels. They have been used for their effects in lowering bilirubin levels in newborns.

Fenofibrate (TriCor, Triglide, Antara)

 

Fenofibrate lowers serum triglycerides and very low-density lipoprotein (VLDL) levels. However, in addition to its hypolipidemic action, it also has the ability to induce bilirubin conjugation.

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Calcium Salts

Class Summary

These agents bind bilirubin in the gut, enhancing bilirubin’s fecal excretion.

Calcium phosphate (Posture)

 

Calcium phosphate may reduce plasma bilirubin concentration in Crigler-Najjar syndrome type 1 and may be a useful adjunct to phototherapy in reducing serum bilirubin levels.

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Gallstone-Solubilizing Agents

Class Summary

Ursodeoxycholic acid (or ursodiol) partially replaces the circulating pool of endogenous bile acids. Because it is highly hydrophilic, it replaces toxic detergent bile acids (eg, chenodeoxycholic acid, lithocholic acid). This effect may enhance the biliary excretion of the toxic bile acids and may protect cells against liver-cell toxicity induced by detergent bile acids.

Ursodeoxycholic acid (Actigall, Urso)

 

This agent decreases liver enzymes (by decreasing liver-cell toxicity) and is therefore recommended in chronic liver disease. Routine administration in Crigler-Najjar syndrome has not been universally adopted.

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Antipsychotics, Phenothiazine

Class Summary

These drugs are used in therapy for acute intermittent porphyria, psychotic disorders, nausea, and vomiting.

Chlorpromazine

 

This agent is usually employed to treat acute intermittent porphyria, psychotic disorders, nausea, and vomiting. It is recommended as an adjunct to phototherapy in the treatment of Crigler-Najjar syndrome type 1.

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Contributor Information and Disclosures
Author

Hisham Nazer, MB, BCh, FRCP, , DTM&H Professor of Pediatrics, Consultant in Pediatric Gastroenterology, Hepatology and Clinical Nutrition, University of Jordan Faculty of Medicine, Jordan

Hisham Nazer, MB, BCh, FRCP, , DTM&H is a member of the following medical societies: American Association for Physician Leadership, Royal College of Paediatrics and Child Health, Royal College of Surgeons in Ireland, Royal Society of Tropical Medicine and Hygiene, Royal College of Physicians and Surgeons of the United Kingdom

Disclosure: Nothing to disclose.

Coauthor(s)

Praveen K Roy, MD, AGAF Chief of Gastroenterology, Presbyterian Hospital; Medical Director of Endoscopy, Presbyterian Medical Group; Adjunct Associate Research Scientist, Lovelace Respiratory Research Institute

Praveen K Roy, MD, AGAF is a member of the following medical societies: American Gastroenterological Association, American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

BS Anand, MD Professor, Department of Internal Medicine, Division of Gastroenterology, Baylor College of Medicine

BS Anand, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Additional Contributors

Ann Ouyang, MBBS Professor, Department of Internal Medicine, Pennsylvania State University College of Medicine; Attending Physician, Division of Gastroenterology and Hepatology, Milton S Hershey Medical Center

Disclosure: Nothing to disclose.

Julian Katz, MD Clinical Professor of Medicine, Drexel University College of Medicine

Julian Katz, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Geriatrics Society, American Medical Association, American Society for Gastrointestinal Endoscopy, American Society of Law, Medicine & Ethics, American Trauma Society, Association of American Medical Colleges, Physicians for Social Responsibility

Disclosure: Nothing to disclose.

Acknowledgements

BS Anand, MD Professor, Department of Internal Medicine, Division of Gastroenterology, Baylor College of Medicine

BS Anand, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American Gastroenterological Association, and American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Showkat Bashir, MD Assistant Professor, Department of Medicine, Division of Gastroenterology, George Washington University, Washington, DC

Showkat Bashir, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, and American Medical Association

Disclosure: Nothing to disclose.

David Eric Bernstein, MD Director of Hepatology, North Shore University Hospital; Professor of Clinical Medicine, Albert Einstein College of Medicine

David Eric Bernstein, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, and American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Manoop S Bhutani, MD Professor, Co-Director, Center for Endoscopic Research, Training and Innovation (CERTAIN), Director, Center for Endoscopic Ultrasound, Department of Medicine, Division of Gastroenterology, University of Texas Medical Branch; Director, Endoscopic Research and Development, The University of Texas MD Anderson Cancer Center

Manoop S Bhutani, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Institute of Ultrasound in Medicine, and American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Jack Bragg, DO Associate Professor, Department of Clinical Medicine, University of Missouri School of Medicine

Jack Bragg, DO is a member of the following medical societies: American College of Osteopathic Internists and American Osteopathic Association

Disclosure: Nothing to disclose.

Annie T Chemmanur, MD Attending Physician, Metrowest Medical Center and University of Massachusetts Memorial Hospital, Marlborough Campus

Annie T Chemmanur, MD is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine, American Gastroenterological Association, American Medical Association, and Massachusetts Medical Society

Disclosure: Nothing to disclose.

Carmen Cuffari, MD Associate Professor, Department of Pediatrics, Division of Gastroenterology/Nutrition, Johns Hopkins University School of Medicine

Carmen Cuffari, MD is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition, and Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

Gautam Dehadrai, MD Department Chair, Section Chief, Department of Interventional Radiology, Norman Regional Hospital

Gautam Dehadrai, MD is a member of the following medical societies: American College of Radiology, Medical Council of India, and Radiological Society of North America

Disclosure: Nothing to disclose.

Jayant Deodhar, MD Associate Professor in Pediatrics, BJ Medical College, India; Honorary Consultant, Departments of Pediatrics and Neonatology, King Edward Memorial Hospital, India

Disclosure: Nothing to disclose.

Shirley Donelson, MD Program Director, Assistant Professor, Department of Internal Medicine, Division of Digestive Diseases, University of Mississippi Medical School

Shirley Donelson, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Medical Association, and Mississippi State Medical Association

Disclosure: Nothing to disclose.

Sandeep Mukherjee, MB, BCh, MPH, FRCPC Associate Professor, Department of Internal Medicine, Section of Gastroenterology and Hepatology, University of Nebraska Medical Center; Consulting Staff, Section of Gastroenterology and Hepatology, Veteran Affairs Medical Center

Disclosure: Merck Honoraria Speaking and teaching; Ikaria Pharmaceuticals Honoraria Board membership

Dena Nazer, MD Medical Director, Child Protection Center, Children's Hospital of Michigan; Assistant Professor, Wayne State University

Dena Nazer, MD is a member of the following medical societies: Ambulatory Pediatric Association, American Academy of Pediatrics, American Professional Society on the Abuse of Children, and Helfer Society

Disclosure: Nothing to disclose.

Mohamed Othman, MD Resident Physician, Department of Internal Medicine, University of New Mexico School of Medicine

Disclosure: Nothing to disclose.

Nuri Ozden, MD Assistant Professor, Department of Internal Medicine, Meharry Medical College

Nuri Ozden, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, and American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Tushar Patel, MB, ChB Professor of Medicine, Ohio State University Medical Center

Tushar Patel, MB, ChB is a member of the following medical societies: American Association for the Study of Liver Diseases and American Gastroenterological Association

Disclosure: Nothing to disclose.

David A Piccoli, MD Chief of Pediatric Gastroenterology, Hepatology and Nutrition, The Children's Hospital of Philadelphia; Professor, University of Pennsylvania School of Medicine

David A Piccoli, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American Gastroenterological Association, and North American Society for Pediatric Gastroenterology and Nutrition

Disclosure: Nothing to disclose.

Alessio Pigazzi, MD PhD, Head, Minimally Invasive Surgery Program, Division of Surgery, Department of General Oncologic Surgery, City of Hope National Medical Center

Disclosure: Nothing to disclose.

Praveen K Roy, MD, AGAF Gastroenterologist, Ochsner Clinic Foundation; Adjunct Associate Research Scientist, Lovelace Respiratory Research Institute; Editor-in-Chief, The Internet Journal of Gasteroenterology; Editorial Board, Signal Transduction Insights; Editorial Board, The Internet Journal of Epidemiology; Editorial Board, Gastrointestinal Endoscopy Review Letter

Praveen K Roy, MD, AGAF is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, and American Society of Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Jeanette G Smith, MD Fellow, Department of Gastroenterology-Hepatology, University of Connecticut School of Medicine

Jeanette G Smith, MD is a member of the following medical societies: American College of Physicians, American Gastroenterological Association, and American Public Health Association

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

George Y Wu, MD, PhD Professor, Department of Medicine, Director, Hepatology Section, Herman Lopata Chair in Hepatitis Research, University of Connecticut School of Medicine

George Y Wu, MD, PhD is a member of the following medical societies: American Association for the Study of Liver Diseases, American Gastroenterological Association, American Medical Association, American Society for Clinical Investigation, and Association of American Physicians

Disclosure: Springer Consulting fee Consulting; Gilead Consulting fee Review panel membership; Vertex Honoraria Speaking and teaching; Bristol-Myers Squibb Honoraria Speaking and teaching; Springer Royalty Review panel membership; Merck Honoraria Speaking and teaching

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Production of bilirubin.
Enterohepatic circulation of bilirubin.
Conjugation of bilirubin.
 
 
 
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