Ctexli (chenodiol)
Gallstone Solubilizing Agents Oral Tablet
Last reviewed · Source: First Databank (FDB) drug data
Overview
Chenodiol (chenodeoxycholic acid) is a naturally occurring human bile acid.
Chenodal(R)
At therapeutic doses, chenodiol suppresses hepatic synthesis of both cholesterol and cholic acid, gradually replacing the latter and its metabolite, deoxycholic acid, in an expanded bile acid pool. These actions contribute to biliary cholesterol desaturation and gradual dissolution of radiolucent cholesterol gallstones in the presence of a gallbladder visualized by oral cholecystography. Chenodiol has no effect on radiopaque (calcified) gallstones or on radiolucent bile pigment stones.
Ctexli(TM)
Endogenous chenodiol (chenodeoxycholic acid) is a primary bile acid, synthesized from cholesterol in the liver. In cerebrotendinous xanthomatosis (CTX), the major bile acid synthesis pathways are disrupted due to partial or total deficiency in sterol 27-hydroxylase encoded by the CYP27A1 gene.
Ctexli(TM) may act to replace deficient levels of the endogenous bile acid chenodeoxycholic acid in patients with CTX. Increased chenodiol levels in the enterohepatic bile acid pool restore the activation of farnesoid X receptor (FXR) and downregulate CYP7A1 leading to suppression and reduction of atypical bile acids and bile alcohols including cholestanol and 23S-pentol.
In the trial of patients treated for CTX, plasma cholestanol and urine 23S-pentol concentrations were elevated. Treatment resulted in reductions of plasma cholestanol and urine 23S-pentol concentrations in the 8-week run-in, open label treatment period. Continued treatment for 4 weeks in the double-blind treatment period resulted in the maintenance of low levels of urine 23S-pentol and additional reductions of plasma cholestanol.
Chenodiol is well absorbed from the small intestine and taken up by the liver where it is converted to its taurine and glycine conjugates and secreted into the bile along with other endogenous bile acids in the enterohepatic circulation. Due to first-pass hepatic clearance, the body pool of chenodiol resides mainly in the enterohepatic circulation. The plasma protein binding of chenodiol is approximately 98%.
Chenodiol that escapes to the colon is converted by bacterial action to lithocholic acid. Humans have the capacity to form sulfate conjugates of lithocholic acid. About 80% of the lithocholate is excreted in the feces and the remainder is absorbed and converted in the liver to its poorly absorbed sulfolithocholyl conjugates.
Conjugated chenodiol is either reabsorbed in the terminal ileum, deconjugated before excretion, or decomposed by bacteria to lithocholic acid.
In patients with CTX, the median time to reach maximum concentration of Ctexli(TM) following oral administration was 3 (0.5 to 8) hours.
USES: Chenodiol is used to dissolve certain types of gallstones (non-calcified). Chenodiol is a bile acid. Chenodiol may be tried before surgery in patients that are at high risk of complications from gallstone surgery.
If the gallstones do not dissolve, emergency surgery may still be needed.
Generic name: chenodiol
Pronunciation: (KEE-noe-DYE-ol)
Drug class: Gallstone Solubilizing Agents
Therapeutic class: Gastrointestinal Therapy Agents
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Ctexli
Indications
The following indications are listed for Ctexli:
- Cerebrotendinous Xanthomatosis
Also known as: Cholestanolosis, Sterol 27 Hydroxylase Deficiency, Van Bogaert-Scherer-Epstein Syndrome.
Dosing
In patients with gallstones, if diarrhea occurs during dosage titration or later during treatment, temporarily adjust dosage until symptoms abate, after which the previous dosage usually is tolerated.
In patients with gallstones, if aminotransferase levels are elevated >3 times the upper limit of normal (ULN), discontinue chenodiol treatment.
In patients with cerebrotendinous xanthomatosis, if liver transaminase (ALT, AST) levels are elevated >3 times the ULN or total bilirubin level is >2 times ULN, interrupt treatment until the levels have returned to baseline values. Monitor liver transaminase and total bilirubin levels yearly and as clinically indicated.
No dosing information is available for this tab.
| Drug label | Dosing type | Instructions |
|---|---|---|
| Ctexli 250 Mg Tablet | Maintenance | Take 2 tablets (500 mg) by oral route 2 times per day in the morning and evening. |
No dosing information is available for this tab.
Drug interactions
Chenodiol and its glyco- and tauro-conjugates are not expected to inhibit cytochrome P450 (CYP) isoenzymes 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, or 3A4, or induce CYP 1A2 or 2B6 at the recommended dose of chenodiol of 250 mg three times daily. Chenodiol and its tauro-conjugate may upregulate CYP3A4 mRNA. The clinical significance of this in vitro upregulation is unknown.
The glyco- and tauro-conjugates of chenodiol are high affinity substrates for bile salt export pump (BSEP), and studies suggest that chenodiol may inhibit organic anion transporting polypeptide (OATP)1B1 and 1B3 at the in vitro recommended dose of 250 mg three times daily (clinical significance unknown). Chenodiol and its glyco- and tauro-conjugates are not predicted to inhibit P-glycoprotein, breast cancer resistance protein (BCRP), OATP2B1, organic anion transporter (OAT)1, OAT3, organic cation transporter (OCT)1, OCT2, multidrug and toxin compound extrusion (MATE)1, or MATE2-K.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
Moderate Interaction: Assess the risk to the patient and take action as needed.
Chenodiol/Aluminum-Based Antacids; Bile Acid Sequestrants
SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.
MECHANISM OF ACTION: Aluminum-based antacids, cholestyramine, or colestipol may bind to chenodiol, which may decrease gastrointestinal absorption and impair enterohepatic recirculation of chenodiol.(1,2)
CLINICAL EFFECTS: Simultaneous administration of an aluminum-based antacid, cholestyramine, or colestipol may result in decreased absorption and effectiveness of chenodiol.(1,2)
PREDISPOSING FACTORS: None determined.
PATIENT MANAGEMENT: If concomitant therapy with aluminum-based antacids or colestipol is necessary, administer chenodiol at least 2 hours before or after the antacid or colestipol. If concomitant therapy with cholestyramine is necessary, administer chenodiol at least 1 hour before or 4-6 hours after cholestyramine.(2)
DISCUSSION: Aluminum-based antacids have been shown to adsorb bile acids in vitro. Bile acid sequestrants reduce bile acid absorption.(1)
Contraindications
Chenodal(R)
*Women who are or may become pregnant.
*Presence of known hepatocyte dysfunction or bile duct abnormalities (e.g., intrahepatic cholestasis, primary biliary cirrhosis, sclerosing cholangitis).
*Gallbladder confirmed as nonvisualizing after 2 consecutive single doses of dye, radiopaque stone, gallstone complications, or compelling reasons for gallbladder surgery (e.g., unremitting acute cholecystitis, cholangitis, biliary obstruction, gallstone pancreatitis, biliary-GI fistula).
Ctexli(TM)
*None.
- Cholestasis
- Disease of liver
- Primary biliary cholangitis
There are no severe contraindications for this drug.
- Diarrhea
- Hypercholesterolemia
Adverse reactions
Chenodal(R): Serum aminotransferase elevations, diarrhea (usually mild, translucent, well tolerated), increased serum total cholesterol and low-density lipoprotein (LDL)-cholesterol, and decreased leukocyte count (not below 3000/mm3) have been reported.
Ctexli(TM): The most common adverse reactions (incidence >14%) are diarrhea, headache, abdominal pain, constipation, hypertension, muscular weakness, and upper respiratory infection.
More Frequent
- Abnormal hepatic function tests
Rare or Very Rare
- Neutropenic disorder
More Frequent
- Diarrhea
- Dyspepsia
Less Frequent
- Abdominal pain with cramps
- Anorexia
- Constipation
- Cough
- Fecal urgency
- Flatulence
- Nausea
- Vomiting
Rare or Very Rare
- Hypercholesterolemia
Precautions
No enhanced messaging available.
Safety and efficacy of chenodiol in pediatric patients have not been established.
Chenodal(R) may cause fetal harm when administered during pregnancy based on animal studies. Serious hepatic, renal, and adrenal lesions occurred in fetuses of female Rhesus monkeys given 60 to 90 mg/kg per day (4 to 6 times the maximum recommended human dose, MRHD) from day 21 to day 45 of pregnancy. Hepatic lesions also occurred in neonatal baboons whose mothers had received 18 to 38 mg/kg, all during pregnancy.
Fetal malformations were not observed. Neither fetal liver damage nor fetal abnormalities occurred in reproduction studies in rats and hamsters.
Chenodal(R) is contraindicated in women who are or may become pregnant. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, inform the patient of the potential hazard to the fetus.
Ctexli(TM) (used for cerebrotendinous xanthomatosis) does not have a contraindication for use in pregnancy. According to the manufacturer, the safety findings in animal studies have not been observed with human use.
It is not known whether chenodiol is distributed into human or animal milk or its effect on the breast-fed infant or on milk production. Use the drug with caution in nursing women, taking into consideration the mother's clinical need for the drug and potential adverse effects on the breast-fed infant from the medication or the underlying maternal condition.
The manufacturer provides no specific dosage recommendations for geriatric patients.
Evaluation of Ctexli(TM) in patients with cerebrotendinous xanthomatosis did not include patients >=65 years of age.
ICD codes
| Code | Type | Description |
|---|---|---|
| Cerebrotendinous xanthomatosis | ||
| E75.5 | ICD10CM | Other lipid storage disorders |
ICD code information from First Databank (FDB).
Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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