SLOS Disrupts the Cholesterol Biosynthesis Pathway1

SLOS results from an autosomal recessive mutation on the 7-dehydrocholesterol reductase (DHCR7) gene1-3 Deficient activity of DHCR7 impairs the last step in cholesterol biosynthesis4

  • Cholesterol levels are low1,5
  • Toxic cholesterol precursors 7-DHC (7-dehydrocholesterol) and 8-DHC (8-dehydrocholesterol) build up4,5
  • Bile acids are impacted because cholesterol is needed for bile acid synthesis1,6
  • Low cholesterol levels and high concentrations of 7-DHC and 8-DHC are seen in patients with SLOS1,5,7,8
  • Low cholesterol levels result in low levels of bile acids2

How may CHOLBAM help in patients with SLOS?9,10

CHOLBAM may help:

  • INCREASE IN HEIGHT AND WEIGHT
    • Body weight increased by 10% or stable at greater than the 50th percentile
  • INCREASE IN CHOLESTEROL ABSORPTION AND CHOLESTEROL LEVELS
  • LOWER LIVER ENZYMES
    • ALT or AST values reduced to less than 50 U/L, or baseline levels reduced by 80%;
    • Total bilirubin values reduced to less than or equal to 1 mg/dL

ALT, alanine aminotransferase; AST, aspartate aminotransferase.

How is CHOLBAM® administered?

CHOLBAM® should be taken with food. For infants and children who cannot swallow capsules, CHOLBAM® capsules can be opened and mixed with either infant formula or breast milk (for younger children), or soft food such as mashed potatoes or apple puree (for older children and adults) in order to mask any unpleasant taste.1

CHOLBAM®—Approved and available since 201510

  • In clinical trials, the most common adverse reaction (~2%) reported was diarrhea

Most common adverse reactions in trials 1 and 2

Adverse reactionsTrial 1Trial 2aOverall (%)
Diarrhea12a3 (2%)
Reflux esophagitis101 (1%)
Malaise101 (1%)
Jaundice101 (1%)
Skin lesion101 (1%)
Nausea01a1 (1%)
Abdominal pain01a1 (1%)
Intestinal polyp01a1 (1%)
Urinary tract infection01a1 (1%)
Peripheral neuropathy011 (1%)

aAdverse reactions that occurred in new patients.

For more information about CHOLBAM for patients with SLOS and to learn about available support programs, contact your Travere Clinical Account Manager.

Download the enrollment form to get started today.

REFERENCES:  1. Porter FD. Smith-Lemli-Opitz syndrome: pathogenesis, diagnosis and management. Eur J Hum Genet. 2008;16(5):535-541. doi: 10.1038/ejhg.2008.10 2. Tint GS, Irons M, Elias ER, et al. Defective cholesterol biosynthesis associated with the Smith-Lemli-Opitz syndrome. N Engl J Med. 1994;330(2):107-113. doi: 10.1056/NEJM199401133300205 3. Jezela-Stanek A, Siejka A, Kowalska EM, Hosiawa V, Krajewska-Walasek M. GC-MS as a tool for reliable non-invasive prenatal diagnosis of Smith-Lemli-Opitz syndrome but essential also for other cholesterolopathies verification. Ginekol Pol. 2020;91(5):287-293. doi: 10.5603/GP.2020.0049 4. DeBarber AE, Eroglu Y, Merkens LS, Pappu AS, Steiner RD. Smith-Lemli-Opitz syndrome. Expert Rev Mol Med. 2011;13:e24. doi: 10.1017/S146239941100189X 5. Griffiths WJ, Abdel-Khalik J, Crick PJ, et al. Sterols and oxysterols in plasma from Smith-Lemli-Opitz syndrome patients. J Steroid Biochem Mol Biol. 2017;169:77-87. doi: 10.1016/j.jsbmb.2016.03.018 6. Staels B, Fonseca VA. Bile acids and metabolic regulation: mechanisms and clinical responses to bile acid sequestration. Diabetes Care. 2009;32 Suppl 2(Suppl 2):S237-S245. doi: 10.2337/dc09-S355 7. Ballout, RA. Smith-Lemli-Opitz Syndrome (SLOS). In: Rezae, N, ed. Genetic Syndromes. Springer, Cham. 2021. https://doi. org/10.1007/978-3-319-66816-1_501-1 8. Kelley RI, Hennekam RC. The Smith-Lemli-Opitz syndrome. J Med Genet. 2000;37(5):321-135. doi: 10.1136/jmg.37.5.321 9. Woollett LA, Buckley DD, Yao L, et al. Cholic acid supplementation enhances cholesterol absorption in humans. Gastroenterology. 2004;126(3):724-731. doi: 10.1053/j.gastro.2003.11.058 10. CHOLBAM. Prescribing information. Travere Therapeutics, Inc.

ENROLLMENT FORM

INDICATION

CHOLBAM® (cholic acid) is a bile acid indicated for
  • Treatment of bile acid synthesis disorders due to single enzyme defects.
  • Adjunctive treatment of peroxisomal disorders, including Zellweger spectrum disorders, in patients who exhibit manifestations of liver disease, steatorrhea, or complications from decreased fat-soluble vitamin absorption.

LIMITATIONS OF USE

The safety and effectiveness of CHOLBAM on extrahepatic manifestations of bile acid synthesis disorders due to single enzyme defects or peroxisomal disorders, including Zellweger spectrum disorders, have not been established.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS – Exacerbation of liver impairment

  • Monitor liver function and discontinue CHOLBAM in patients who develop worsening of liver function while on treatment.
  • Concurrent elevations of serum gamma glutamyltransferase (GGT) and alanine aminotransferase (ALT) may indicate CHOLBAM overdose.
  • Discontinue treatment with CHOLBAM at any time if there are clinical or laboratory indicators of worsening liver function or cholestasis.

ADVERSE REACTIONS

  • The most common adverse reactions (≥1%) are diarrhea, reflux esophagitis, malaise, jaundice, skin lesion, nausea, abdominal pain, intestinal polyp, urinary tract infection, and peripheral neuropathy.

DRUG INTERACTIONS

  • Inhibitors of Bile Acid Transporters: Avoid concomitant use of inhibitors of the bile salt efflux pump (BSEP) such as cyclosporine. Concomitant medications that inhibit canalicular membrane bile acid transporters such as the BSEP may exacerbate accumulation of conjugated bile salts in the liver and result in clinical symptoms. If concomitant use is deemed necessary, monitoring of serum transaminases and bilirubin is recommended.
  • Bile Acid Binding Resins: Bile acid binding resins such as cholestyramine, colestipol, or colesevelam adsorb and reduce bile acid absorption and may reduce the efficacy of CHOLBAM. Take CHOLBAM at least 1 hour before or 4 to 6 hours (or at as great an interval as possible) after a bile acid binding resin.
  • Aluminum-Based Antacids: Aluminum-based antacids have been shown to adsorb bile acids in vitro and can reduce the bioavailability of CHOLBAM. Take CHOLBAM at least 1 hour before or 4 to 6 hours (or at as great an interval as possible) after an aluminum-based antacid.

PREGNANCY

No studies in pregnant women or animal reproduction studies have been conducted with CHOLBAM.

LACTATION

Endogenous cholic acid is present in human milk. Clinical lactation studies have not been conducted to assess the presence of CHOLBAM in human milk, the effects of CHOLBAM on the breastfed infant, or the effects of CHOLBAM on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for CHOLBAM and any potential adverse effects on the breastfed infant from CHOLBAM or from the underlying maternal condition.

GERIATRIC USE

It is not known if elderly patients respond differently from younger patients.

HEPATIC IMPAIRMENT

  • Discontinue treatment with CHOLBAM if liver function does not improve within 3 months of the start of treatment.
  • Discontinue treatment with CHOLBAM at any time if there are clinical or laboratory indicators of worsening liver function or cholestasis. Continue to monitor laboratory parameters of liver function and consider restarting at a lower dose when the parameters return to baseline.

OVERDOSAGE

Concurrent elevations of serum GGT and serum ALT may indicate CHOLBAM overdose. In the event of overdose, the patient should be monitored and treated symptomatically. Continue to monitor laboratory parameters of liver function and consider restarting at a lower dose when the parameters return to baseline.
Please see accompanying full Prescribing Information for additional Important Safety Information.
SEE MORE

INDICATION

CHOLBAM® (cholic acid) is a bile acid indicated for
  • Treatment of bile acid synthesis disorders due to single enzyme defects.
  • Adjunctive treatment of peroxisomal disorders, including Zellweger spectrum disorders, in patients who exhibit manifestations of liver disease, steatorrhea, or complications from decreased fat-soluble vitamin absorption.

LIMITATIONS OF USE

The safety and effectiveness of CHOLBAM on extrahepatic manifestations of bile acid synthesis disorders due to single enzyme defects or peroxisomal disorders, including Zellweger spectrum disorders, have not been established.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS – Exacerbation of liver impairment

  • Monitor liver function and discontinue CHOLBAM in patients who develop worsening of liver function while on treatment.
  • Concurrent elevations of serum gamma glutamyltransferase (GGT) and alanine aminotransferase (ALT) may indicate CHOLBAM overdose.
  • Discontinue treatment with CHOLBAM at any time if there are clinical or laboratory indicators of worsening liver function or cholestasis.

ADVERSE REACTIONS

  • The most common adverse reactions (≥1%) are diarrhea, reflux esophagitis, malaise, jaundice, skin lesion, nausea, abdominal pain, intestinal polyp, urinary tract infection, and peripheral neuropathy.

DRUG INTERACTIONS

  • Inhibitors of Bile Acid Transporters: Avoid concomitant use of inhibitors of the bile salt efflux pump (BSEP) such as cyclosporine. Concomitant medications that inhibit canalicular membrane bile acid transporters such as the BSEP may exacerbate accumulation of conjugated bile salts in the liver and result in clinical symptoms. If concomitant use is deemed necessary, monitoring of serum transaminases and bilirubin is recommended.
  • Bile Acid Binding Resins: Bile acid binding resins such as cholestyramine, colestipol, or colesevelam adsorb and reduce bile acid absorption and may reduce the efficacy of CHOLBAM. Take CHOLBAM at least 1 hour before or 4 to 6 hours (or at as great an interval as possible) after a bile acid binding resin.
  • Aluminum-Based Antacids: Aluminum-based antacids have been shown to adsorb bile acids in vitro and can reduce the bioavailability of CHOLBAM. Take CHOLBAM at least 1 hour before or 4 to 6 hours (or at as great an interval as possible) after an aluminum-based antacid.

PREGNANCY

No studies in pregnant women or animal reproduction studies have been conducted with CHOLBAM.

LACTATION

Endogenous cholic acid is present in human milk. Clinical lactation studies have not been conducted to assess the presence of CHOLBAM in human milk, the effects of CHOLBAM on the breastfed infant, or the effects of CHOLBAM on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for CHOLBAM and any potential adverse effects on the breastfed infant from CHOLBAM or from the underlying maternal condition.

GERIATRIC USE

It is not known if elderly patients respond differently from younger patients.

HEPATIC IMPAIRMENT

  • Discontinue treatment with CHOLBAM if liver function does not improve within 3 months of the start of treatment.
  • Discontinue treatment with CHOLBAM at any time if there are clinical or laboratory indicators of worsening liver function or cholestasis. Continue to monitor laboratory parameters of liver function and consider restarting at a lower dose when the parameters return to baseline.

OVERDOSAGE

Concurrent elevations of serum GGT and serum ALT may indicate CHOLBAM overdose. In the event of overdose, the patient should be monitored and treated symptomatically. Continue to monitor laboratory parameters of liver function and consider restarting at a lower dose when the parameters return to baseline.
Please see accompanying full Prescribing Information for additional Important Safety Information.