Hay recursos disponibles en español. Explorar los recursos aquí »
For US HCPs Only
Prescribing Information
  Indication
Important Safety Information
Visit Patient Website
Patient Info + Instructions for Use: English  |  Español
Request an Account Manager
PRESENTATIONS OF CHOLESTATIC PRURITUS

Identifying Patients With Cholestatic Pruritus in PFIC

Impact of Cholestatic Pruritus

Cholestatic Pruritus Is More Than Just Scratching

Cholestatic pruritus, which has been correlated with elevated serum bile acids (sBA), is a consequence of ongoing cholestasis.1

  • Other consequences may include jaundice or growth deficiencies1

Cholestatic pruritus affects up to 76% to 100% of patients with progressive familial intrahepatic cholestasis (PFIC). It has been identified as the most debilitating symptom.1,2

Cholestatic Pruritus Can Be Hard to Identify and Assess

Cholestatic pruritus can present in conventional ways, like scratching of the skin, or in unconventional ways, including sleep disruptions and irritability. Even more, many patients and caregivers minimize and/or normalize the severity of their cholestatic pruritus.3,4

Unsure if your patients are experiencing cholestatic pruritus?

Here are some questions to ask:

  • Do you notice scratching when undistracted?
  • Have you noticed any changes in mood or irritability?
  • Has there been an issue with falling or staying asleep?
  • Does feeling itchy impact daily life (eg, unable to focus in school, can’t participate in activities)?
  • Has there been frequent scratching or biting of the skin? Has it caused damage to the skin?
  • Are there certain times of the day or certain times of the year when symptoms seem to be worse?

As a result of cholestatic pruritus, approximately 60% of caregivers report that their child suffers from sleep disturbances, including needing help falling asleep, needing soothing, and sleeping alongside a caregiver.5

The impacts of the itch can also frequently lead to3,6-9:

Skin damage
Irritability
Negative impact on social activities
Cognitive impact
Physical discomfort
Impaired school performance
Decreased physical function
Burning, tingling, or prickling sensation

Do you see patients like this in your practice?

Find out if LIVMARLI can help

Assess the Itch!

Track Their Score, Measure Treatment Success

The Itch Reported Outcome (ItchRO) scale—a helpful tool for identifying patients and tracking progress

What is ItchRO?

ItchRO is an assessment tool that can help measure itch-related symptoms in patients suffering from cholestatic pruritus. The scale determines symptom severity using a 0 to 4 scale, where 0 is none and 4 is very severe. ItchRO takes itch-related symptoms into consideration, including patients’ skin damage, sleep, and irritability.3,10

0
Not itchy at all
1
A little bit itchy
2
Somewhat itchy
3
Very itchy
4
Extremely itchy
How can ItchRO scores help you measure treatment success?
  • Tracking changes in ItchRO scores over time can be an effective way to determine whether a patient’s symptoms are getting better or worse. The goal is to reduce ItchRO scores as much as possible
  • In the MARCH-PFIC study for patients with PFIC, a change in ItchRO score of 1.0 or more was considered to be clinically meaningful11
What could a ≥1-point Itch Reported Outcome (Observer) (ItchRO[Obs]) reduction mean for patients?3,10,11
  • Less rubbing or scratching when undistracted
  • Fewer sleep problems
  • Less moody and/or irritable

Improvements in Cholestatic Pruritus

Meaningful improvements in cholestatic pruritus were seen as early as 2 weeks and sustained through 2 years.1,11,12

See the Efficacy Data

A Primer for
Your Patients

Share this downloadable resource with your patients who are considering or receiving LIVMARLI treatment.

Download the Patient Brochure

Mirum Access Plus assists both you and your patients at every turn, helping you navigate the payer approval process—and beyond—with ease.

Learn More About
Mirum Access Plus

References: 1. Kamath BM, Stein P, Houwen RHJ, Verkade HJ. Potential of ileal bile acid transporter inhibition as a therapeutic target in Alagille syndrome and progressive familial intrahepatic cholestasis. Liver Int. 2020;40(8):1812-1822. doi:10.1111/liv.1455 2. Baker A, Kerkar N, Todorova L, Kamath BM, Houwen RHJ. Systematic review of progressive familial intrahepatic cholestasis. Clin Res Hepatol Gastroenterol. 2019;43(1)20-36. doi:10.1016/j.clinre.2018.07.010 3. Kamath BM, Abetz-Webb L, Kennedy C, et al. Development of a novel tool to assess the impact of itching in pediatric cholestasis. Patient. 2018;11(1):69-82. doi:10.1007/s40271-017-0266-4 4. Data on file. REF-01342. Mirum Pharmaceuticals, Inc. 5. Gwaltney C, Ivanescu C, Karlsson L, Warholic N, Kjems L, Horn P. Validation of the PRUCISION instruments in pediatric patients with progressive familial intrahepatic cholestasis. Adv Ther. 2022;39(11):5105-5125. doi:10.1007/s12325-022-02262-7 6. Srivastava A. Progressive familial intrahepatic cholestasis. J Clin Exp Hepatol. 2014;4(1):25-36. doi:10.1016/j.jceh.2013.10.005 7. Cohran VC, Heubi JE. Treatment of pediatric cholestatic liver disease. Curr Treat Options Gastroenterol. 2003;6(5):403-415. doi:10.1007/s11938-003-0043-4 8. de Azevedo RA, Takamatsu FY, Kondo M, et al. Pruritus in cholestasis. Rev Soc Bras Clin Med. 2017;15(1):61-67. 9. Talcott JB, Beath SV, Patel T, Griffiths G, Kelly DA. Long-term effects of cholestatic liver disease in childhood on neuropsychological outcomes and neurochemistry. J Pediatr Gastroenterol Nutr. 2019;69(2):145-151. doi:10.1097/MPG.0000000000002380 10. Kamath BM, Spino C, McLain R, et al. Unraveling the relationship between itching, scratch scales, and biomarkers in children with Alagille syndrome. Hepatol Commun. 2020;4(7):1012-1018. doi:10.1002/hep4.1522 11. Miethke AG, Moukarzel A, Porta G, et al. Maralixibat in progressive familial intrahepatic cholestasis (MARCH-PFIC): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Gastroenterol Hepatol. 2024;9(7):620-631. doi:10.1016/s2468-1253(24)00080-3 12. Miethke A, Moukarzel A, Porta G, et al. Long-term maintenance of response and improved liver health with maralixibat in patients with progressive familial intrahepatic cholestasis (PFIC): 2-year data from the MARCH-ON study. Presented at: American Association for the Study of Liver Diseases (AASLD) The Liver Meeting: November 10-14, 2023; Boston, MA.

INDICATION

LIVMARLI is indicated for the treatment of cholestatic pruritus in patients 12 months of age and older with progressive familial intrahepatic cholestasis (PFIC).

Limitations of Use: LIVMARLI is not recommended in a subgroup of PFIC type 2 patients with specific ABCB11 variants resulting in nonfunctional or complete absence of bile salt export pump (BSEP) protein.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

LIVMARLI is contraindicated in patients with prior or active hepatic decompensation events (eg, variceal hemorrhage, ascites, or hepatic encephalopathy).

WARNINGS AND PRECAUTIONS

Hepatotoxicity: LIVMARLI treatment is associated with a potential for drug-induced liver injury (DILI).

In the PFIC trial, treatment-emergent hepatic decompensation events and elevations of liver tests or worsening of liver tests occurred. Two patients experienced DILI attributable to LIVMARLI. Two additional patients experienced DILI in the open-label extension portion of the trial. Of these 4 patients, 1 patient required liver transplant and another patient died.

Obtain baseline liver tests and monitor during treatment. Liver-related adverse reactions and physical signs of hepatic decompensation should also be monitored. Dose reduction or treatment interruption may be considered if abnormalities occur in the absence of other causes. Permanently discontinue LIVMARLI if a patient experiences the following: persistent or recurrent liver test abnormalities, clinical hepatitis upon rechallenge, or a hepatic decompensation event.

Gastrointestinal (GI) Adverse Reactions: Diarrhea and abdominal pain were reported as the most common adverse reactions. Monitor for dehydration and treat promptly. Consider reducing the dosage or interrupting LIVMARLI dosing if a patient experiences persistent diarrhea or diarrhea with bloody stool, vomiting, dehydration requiring treatment, or fever.

Fat-Soluble Vitamin (FSV) Deficiency: Patients can have FSV deficiency (vitamins A, D, E, and K) at baseline, and LIVMARLI may adversely affect absorption of FSVs. Treatment-emergent bone fracture events have been observed more frequently with patients treated with LIVMARLI compared with patients treated with placebo. If bone fractures or bleeding occur, consider interrupting LIVMARLI and supplement with FSVs. LIVMARLI can be restarted once FSV deficiency is corrected and maintained at corrected levels.

Risk of Propylene Glycol Toxicity (Pediatric Patients Less Than 5 Years of Age): Total daily intake of propylene glycol should be considered for managing the risk of propylene glycol toxicity. Monitor patients for signs of propylene glycol toxicity. Discontinue LIVMARLI if toxicity is suspected.

ADVERSE REACTIONS

The most common adverse reactions are diarrhea, FSV deficiency, abdominal pain, liver test abnormalities, hematochezia, and bone fractures.

DRUG INTERACTIONS

Administer bile acid binding resins at least 4 hours before or 4 hours after administration of LIVMARLI.
A decrease in the absorption of OATP2B1 substrates (eg, statins) due to OATP2B1 inhibition by LIVMARLI in the GI tract cannot be ruled out. Consider monitoring the drug effects of OATP2B1 substrates as needed.

DOSING INFORMATION

LIVMARLI should be taken twice daily 30 minutes before a meal. The provided oral dosing dispenser must be used to accurately measure the dose. Any remaining LIVMARLI should be discarded 100 days after first opening the bottle.

Collapse icon

References: 1. Kamath BM, Stein P, Houwen RHJ, Verkade HJ. Potential of ileal bile acid transporter inhibition as a therapeutic target in Alagille syndrome and progressive familial intrahepatic cholestasis. Liver Int. 2020;40(8):1812-1822. doi:10.1111/liv.1455 2. Baker A, Kerkar N, Todorova L, Kamath BM, Houwen RHJ. Systematic review of progressive familial intrahepatic cholestasis. Clin Res Hepatol Gastroenterol. 2019;43(1)20-36. doi:10.1016/j.clinre.2018.07.010 3. Kamath BM, Abetz-Webb L, Kennedy C, et al. Development of a novel tool to assess the impact of itching in pediatric cholestasis. Patient. 2018;11(1):69-82. doi:10.1007/s40271-017-0266-4 4. Data on file. REF-01342. Mirum Pharmaceuticals, Inc. 5. Gwaltney C, Ivanescu C, Karlsson L, Warholic N, Kjems L, Horn P. Validation of the PRUCISION instruments in pediatric patients with progressive familial intrahepatic cholestasis. Adv Ther. 2022;39(11):5105-5125. doi:10.1007/s12325-022-02262-7 6. Srivastava A. Progressive familial intrahepatic cholestasis. J Clin Exp Hepatol. 2014;4(1):25-36. doi:10.1016/j.jceh.2013.10.005 7. Cohran VC, Heubi JE. Treatment of pediatric cholestatic liver disease. Curr Treat Options Gastroenterol. 2003;6(5):403-415. doi:10.1007/s11938-003-0043-4 8. de Azevedo RA, Takamatsu FY, Kondo M, et al. Pruritus in cholestasis. Rev Soc Bras Clin Med. 2017;15(1):61-67. 9. Talcott JB, Beath SV, Patel T, Griffiths G, Kelly DA. Long-term effects of cholestatic liver disease in childhood on neuropsychological outcomes and neurochemistry. J Pediatr Gastroenterol Nutr. 2019;69(2):145-151. doi:10.1097/MPG.0000000000002380 10. Kamath BM, Spino C, McLain R, et al. Unraveling the relationship between itching, scratch scales, and biomarkers in children with Alagille syndrome. Hepatol Commun. 2020;4(7):1012-1018. doi:10.1002/hep4.1522 11. Miethke AG, Moukarzel A, Porta G, et al. Maralixibat in progressive familial intrahepatic cholestasis (MARCH-PFIC): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Gastroenterol Hepatol. 2024;9(7):620-631. doi:10.1016/s2468-1253(24)00080-3 12. Miethke A, Moukarzel A, Porta G, et al. Long-term maintenance of response and improved liver health with maralixibat in patients with progressive familial intrahepatic cholestasis (PFIC): 2-year data from the MARCH-ON study. Presented at: American Association for the Study of Liver Diseases (AASLD) The Liver Meeting: November 10-14, 2023; Boston, MA.

INDICATION

LIVMARLI is indicated for the treatment of cholestatic pruritus in patients 12 months of age and older with progressive familial intrahepatic cholestasis (PFIC).

Limitations of Use: LIVMARLI is not recommended in a subgroup of PFIC type 2 patients with specific ABCB11 variants resulting in nonfunctional or complete absence of bile salt export pump (BSEP) protein.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

LIVMARLI is contraindicated in patients with prior or active hepatic decompensation events (eg, variceal hemorrhage, ascites, or hepatic encephalopathy).

WARNINGS AND PRECAUTIONS

Hepatotoxicity: LIVMARLI treatment is associated with a potential for drug-induced liver injury (DILI).

In the PFIC trial, treatment-emergent hepatic decompensation events and elevations of liver tests or worsening of liver tests occurred. Two patients experienced DILI attributable to LIVMARLI. Two additional patients experienced DILI in the open-label extension portion of the trial. Of these 4 patients, 1 patient required liver transplant and another patient died.

Obtain baseline liver tests and monitor during treatment. Liver-related adverse reactions and physical signs of hepatic decompensation should also be monitored. Dose reduction or treatment interruption may be considered if abnormalities occur in the absence of other causes. Permanently discontinue LIVMARLI if a patient experiences the following: persistent or recurrent liver test abnormalities, clinical hepatitis upon rechallenge, or a hepatic decompensation event.

Gastrointestinal (GI) Adverse Reactions: Diarrhea and abdominal pain were reported as the most common adverse reactions. Monitor for dehydration and treat promptly. Consider reducing the dosage or interrupting LIVMARLI dosing if a patient experiences persistent diarrhea or diarrhea with bloody stool, vomiting, dehydration requiring treatment, or fever.

Fat-Soluble Vitamin (FSV) Deficiency: Patients can have FSV deficiency (vitamins A, D, E, and K) at baseline, and LIVMARLI may adversely affect absorption of FSVs. Treatment-emergent bone fracture events have been observed more frequently with patients treated with LIVMARLI compared with patients treated with placebo. If bone fractures or bleeding occur, consider interrupting LIVMARLI and supplement with FSVs. LIVMARLI can be restarted once FSV deficiency is corrected and maintained at corrected levels.

Risk of Propylene Glycol Toxicity (Pediatric Patients Less Than 5 Years of Age): Total daily intake of propylene glycol should be considered for managing the risk of propylene glycol toxicity. Monitor patients for signs of propylene glycol toxicity. Discontinue LIVMARLI if toxicity is suspected.

ADVERSE REACTIONS

The most common adverse reactions are diarrhea, FSV deficiency, abdominal pain, liver test abnormalities, hematochezia, and bone fractures.

DRUG INTERACTIONS

Administer bile acid binding resins at least 4 hours before or 4 hours after administration of LIVMARLI.
A decrease in the absorption of OATP2B1 substrates (eg, statins) due to OATP2B1 inhibition by LIVMARLI in the GI tract cannot be ruled out. Consider monitoring the drug effects of OATP2B1 substrates as needed.

DOSING INFORMATION

LIVMARLI should be taken twice daily 30 minutes before a meal. The provided oral dosing dispenser must be used to accurately measure the dose. Any remaining LIVMARLI should be discarded 100 days after first opening the bottle.