Medication Summary

Many pharmacological agents have been used in the treatment of intrahepatic cholestasis of pregnancy (ICP). These include phenobarbital (100 mg qd), hydroxyzine (25-50 mg qd), glutathione precursor S-adenosyl methionine (SAME) (800 mg qd IV or 1600 mg qd orally), cholestyramine (8-16 g/d) and dexamethasone (12 mg 4 times daily for 7 days followed by a tapering dose). All these agents showed some limited clinical benefit (eg, phenobarbital relieved pruritus in 50% of patients but showed no reduction of liver enzymes or bile salts) but also had significant adverse effects.^[60]Vitamin K deficiency was observed with the use of cholestyramine in high doses.^{[49, 61, 62, 63, 64, 65, 66]}Dexamethasone demonstrated limited benefits in cases of ICP with significant side effects.^{[65, 67]}

Ursodeoxycholic acid (UDCA) improves clinical symptoms and liver parameters in a number of cholestatic liver disorders.^{[66, 68, 69, 70]}The mechanism of UDCA is unknown. One putative action of UDCA is that the drug inserts a key translocator or transporter protein, improving bile salt export from the liver and theoretically reducing the risk to the fetus.^[71]

UDCA remains the drug of choice for the treatment of ICP. UDCA at a daily dose ranging from 600-2000 mg was effective at reducing pruritus, decreasing the total serum bile acid levels, ALT values, and bilirubin levels and allowing delivery closer to term (37.8 ± 0.9 wk vs 33.8 ± 7.1 wk).^{[72, 73]}UDCA also improved the cholic acid/chenodeoxycholic acid ratio seen in ICP.^{[74, 75, 76]}UDCA has no significant maternal adverse effects. An infant follow-up study of 26 children over a 12-year period showed no long-term sequelae.^[77]Based on a meta-analysis, UDCA is effective in reducing pruritus and improving liver test results in patients with ICP, and may also improve fetal outcomes.^[78]

Antihistamines are commonly administered in conjunction with UDCA to alleviate pruritus symptoms. Diphenhydramine or Hydroxyzine can help treat the insomnia that typically accompanies severe pruritus.

Follow-up

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Author

Fidelma B Rigby, MD Associate Professor, Department of Obstetrics and Gynecology, Section of Maternal-Fetal Medicine, Virginia Commonwealth University Medical Center

Fidelma B Rigby, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, Society for Maternal-Fetal Medicine

Disclosure: Nothing to disclose.

Coauthor(s)

Stacey Ehrenberg-Buchner, MD Fellow in Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Michigan Health System

Stacey Ehrenberg-Buchner, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Medical Association, Society for Maternal-Fetal Medicine

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

Ronald M Ramus, MD Professor of Obstetrics and Gynecology, Director, Division of Maternal-Fetal Medicine, Virginia Commonwealth University School of Medicine

Ronald M Ramus, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Institute of Ultrasound in Medicine, Medical Society of Virginia, Society for Maternal-Fetal Medicine

Disclosure: Nothing to disclose.

Additional Contributors

Suzanne R Trupin, MD, FACOG Clinical Professor, Department of Obstetrics and Gynecology, University of Illinois College of Medicine at Urbana-Champaign; CEO and Owner, Women's Health Practice; CEO and Owner, Hada Cosmetic Medicine and Midwest Surgical Center

Suzanne R Trupin, MD, FACOG is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Institute of Ultrasound in Medicine, International Society for Clinical Densitometry, AAGL, North American Menopause Society, American Medical Association, Association of Reproductive Health Professionals

Disclosure: Nothing to disclose.

Acknowledgements

George A VanBuren, MD Assistant Professor, Department of Reproductive Biology, Case Western Reserve University School of Medicine

George A VanBuren, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists

Disclosure: Nothing to disclose.