Intrahepatic Cholestasis of Pregnancy Medication

Updated: Jan 14, 2019
  • Author: Fidelma B Rigby, MD; Chief Editor: Ronald M Ramus, MD  more...
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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.