Recommended Dose of Ursofalk for Intrahepatic Cholestasis of Pregnancy
The recommended starting dose of ursodeoxycholic acid (UDCA/Ursofalk) for intrahepatic cholestasis of pregnancy is 10-15 mg/kg/day, divided into 2-3 daily doses, which can be titrated up to a maximum of 21 mg/kg/day if pruritus persists. 1
Standard Dosing Regimen
Initial dosing should be 10-15 mg/kg/day divided into 2-3 doses daily. 1 For a 25-year-old pregnant woman, typical practical regimens include:
The dose should be calculated based on the patient's body weight and can be started at the lower end (10 mg/kg/day) and slowly increased to 15-20 mg/kg/day as tolerated. 1, 2
Dose Titration Strategy
If pruritus is not adequately relieved within 1-2 weeks, the dose can be titrated upward to a maximum of 21 mg/kg/day. 1 Biochemical improvement (reduction in bile acids and liver enzymes) is typically observed within 3-4 weeks of treatment. 1
The 2023 EASL guidelines suggest that if standard therapy does not provide adequate relief after several days, the dose may be increased up to 25 mg/kg/day on an individual basis. 1
Expected Clinical Response
UDCA improves maternal pruritus in 67-80% of patients and reduces serum bile acids and liver aminotransferases. 1, 3 Patients should expect:
- Reduction in pruritus within 1-2 weeks 1
- Biochemical improvement within 3-4 weeks 1
- Approximately 79-90% of patients respond to treatment 4, 3
Important Dosing Considerations
Drug Interactions and Timing
UDCA must be separated from bile acid sequestrants (cholestyramine or colestipol) by at least 4 hours to maintain efficacy. 1, 2 If cholestyramine is added for refractory pruritus, ensure proper timing separation. 1
Safety Profile
UDCA is FDA pregnancy category B and is considered safe throughout pregnancy and breastfeeding. 2 The drug is generally well tolerated, though mild nausea and dizziness occur in up to 25% of patients. 1
Non-Responders
Approximately 10-11% of patients do not respond to UDCA treatment. 4, 3 For these patients, consider:
- Rifampicin 300-600 mg daily as second-line therapy 1, 2
- Cholestyramine 4-8 g/day or colestipol 5-10 g/day (given at least 4 hours after UDCA) 1, 2
Critical Evidence Nuance
While UDCA effectively improves maternal symptoms, its impact on perinatal outcomes remains controversial. The 2019 PITCHES trial (n=605), the largest randomized controlled trial to date, found no significant reduction in the composite outcome of perinatal death, preterm delivery, or NICU admission (adjusted risk ratio 0.85,95% CI 0.62-1.15). 5 However, this trial was conducted in the context of modern obstetric management with fetal surveillance and planned early delivery.
Despite this, multiple guidelines continue to recommend UDCA as first-line therapy based on its proven efficacy for maternal symptom relief and its excellent safety profile. 1 The Society for Maternal-Fetal Medicine provides a GRADE 1A recommendation for UDCA as first-line treatment for maternal symptoms. 1
Monitoring Requirements
Serum bile acids should be monitored at least weekly starting at 32 weeks gestation to guide delivery timing. 6 Vitamin K status should be assessed if the patient is also taking anion exchange resins or rifampicin, as these can exacerbate vitamin K deficiency. 1, 2
Common Pitfalls to Avoid
- Do not use doses below 10 mg/kg/day initially, as this may be subtherapeutic, though some evidence suggests even lower doses (4-6 mg/kg/day) may provide benefit in select patients. 4
- Do not co-administer UDCA with cholestyramine without proper time separation (minimum 4 hours apart). 1, 2
- Do not discontinue UDCA based solely on the PITCHES trial results, as symptom relief alone justifies its use, and meta-analyses suggest potential perinatal benefits. 1
- Do not delay treatment while awaiting bile acid results if clinical suspicion is high and pruritus is significant. 1