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  • Cholbam
    / Megapharm


    Active Ingredient
    Cholic Acid 50, 250 mg

    Status in Israel
    RX

    Presentation and Status in Health Basket

    Presentation Basket Yarpa Pharmasoft

    Capsules

    50mg x 90

    partial basket chart 62151

    Capsules

    250 mg x 90

    partial basket chart 62152

    Related information


    Dosage

    The recommended dosage for cholic acid in the treatment of inborn errors of primary bile acid synthesis is 10-15 mg/kg per day, either as a single daily dose or in divided doses, for both adult and paediatric patients. The dose should be subsequently titrated to the desired effect but should not exceed a maximum of 15mg/kg/day. Where the dose calculated is not a multiple of 50, the nearest dose below the maximum of 15mg/kg/day should be selected, provided that is sufficient to suppress urinary bile acids. If not, the next higher dose should be selected. The recommended dosage in patients with concomitant familial hypertriglyceridemia is 11 to 17 mg/kg once daily or in two divided doses and is adjusted based on clinical response. Monitor AST, ALT, GGT, alkaline phosphatase, bilirubin and INR every month for the first 3 months, every 3 months for the next 9 months, every 6 months during the next three years and annually thereafter. Administer the lowest dose that effectively maintains liver function. Discontinue CHOLBAM if liver function does not improve within 3 months of starting treatment, if complete biliary obstruction develops, or if there are persistent clinical or laboratory indicators of worsening liver function or cholestasis; continue to monitor liver function and consider restarting a lower dose when parameters return to baseline. During the initiation of therapy and dose adjustment, serum and urine bile acid levels should be monitored intensively using gas chromatography-mass spectrometry (GC-MS) or equivalent technology coupled to mass spectrometry. The concentrations of the abnormal bile acid metabolites synthesised subesquently should be determined. The lowest dose of cholic acid that effectively reduces the bile acid metabolites to as close to zero as possible should be chosen. Patients that have previously been treated with other bile acids or other cholic acid preparations should be closely monitored in the same manner during the initiation of treatment with Cholic acid FGK. The dose should be adjusted accordingly, as described above.
    Liver parameters should also be monitored. Concurrent elevation of serum gamma glutamyltransferase (Gamma GT), alanine aminotransferase (ALT) and/or serum bile acids above normal levels may indicate overdose. Transient elevations of transaminases at the initiation of cholic acid treatment have been observed and do not indicate the need for a dose reduction if Gamma GT is not elevated and if serum bile acid levels are falling or in the normal range. After the initiation period, serum and urine bile acids (using mass spectrometry technology) and liver parameters should be determined annually, at a minimum, and the dose adjusted accordingly. Additional or more frequent investigations should be undertaken to monitor therapy during periods of fast growth, concomitant disease and pregnancy.
    Special populations
    Patients with familial hypertriglyceridaemia: Patients with newly diagnosed or a family history of familial hypertriglyceridaemia are expected to poorly absorb cholic acid from the intestine. The cholic acid dose for patients with familial hypertriglyceridaemia will have to be established and adjusted as necessary, an elevated dose may be required in order to suppress urinary bile acids.
    Paediatric population: The safety and efficacy of cholic acid in neonates less than one month of age has not been established. No data are available.
    Elderly patients (older than 65 years): The safety and efficacy of cholic acid in elderly patients has not been established. No data available.
    Renal impairment: No data are available for patients with renal impairment. However, these patients should be carefully monitored and the dose of cholic acid titrated individually
    Hepatic impairment: The majority of patients with inborn errors of bile acid metabolism presented with some degree of hepatic impairment at the time of diagnosis; in most patients, the hepatic impairment improved or resolved with treatment. The dose of cholic acid should be adjusted individually. No data regarding cholic acid treatment are available in patients with inborn errors of bile acid metabolism with hepatic impairment unrelated to their primary disease. In the absence of clinical experience in such patients population, no recommendations on dosage adjustment can be made. Patients with hepatic impairment unrelated to their primary disease who are treated with cholic acid are monitored closely.
    Method of administration: It is recommended that cholic acid is taken with food at approximately the same time each day, in the morning and/or evening. The capsules should be swallowed whole with water. For infants and children who cannot swallow capsules, the capsules may be opened and the content added to infant formula or juice.
    See prescribing information for full details.


    Indications

    Treatment of  infants, children, adolescents aged 1 month to 18 years and adults of inborn errors in primary bile acid synthesis due to Sterol 27-hydroxylase (presenting as cerebrotendinous xanthomatosis, CTX) deficiency, 2- (or α-) methylacyl-coa racemase (AMACR) deficiency, Cholesterol 7α -hydroxylase (CYP7A1) deficiency, 3β-hydroxy-5-C27-steroid oxidoreductase deficiency (also known as 3β-hydroxy-5-C27-steroid dehydrogenase/isomerase or 3β-HSD or HSD3β7.


    Contra-Indications

    Hypersensitivity to the active substance or to any of the excipients. Concomitant use with phenobarbital.


    Special Precautions

    Treatment with cholic acid should be stopped if in case of abnormal hepatocellular function, as measured by prothrombin time, hepatocellular function does not improve within 3 months of the initiation of cholic acid treatment. A concomitant decrease of urine total bile acids should be observed. Treatment should be stopped earlier if there are clear indicators of severe hepatic failure.
    Familial hypertriglyceridemia: Patients with newly diagnosed, or a family history of, familial hypertriglyceridaemia may have poor absorption of cholic acid from the intestine. The cholic acid dose for patients with familial triglyceridaemia will have to be established and adjusted as necessary.
    See prescribing information for full details.


    Side Effects

    Mild peripheral neuropathy, diarrhoea, mild nausea, mild reflux, moderate diarrhea, Reflux esophagitis.
    See prescribing information for full details.


    Drug interactions

    No interaction studies with cholic acid and concomitantly administered medicinal products or food have been carried out. Phenobarbital has been shown to increase the pool size and turnover of cholic acid and therefore has an antagonistic effect to the desired action of cholic acid in patients. Therefore use of phenobarbital in patients treated with cholic acid is contraindicated.
    Drug interactions with cholic acid mainly relate to medicinal products capable of interrupting the enterohepatic circulation of bile acids, such as the sequestering agents cholestyramine, colestipol, or colesevalem. Aluminium-based antacids have been shown to adsorb bile acids in vitro and may be expected to reduce the levels of cholic acid in the same manner as the bile acid sequestering agents. Should the use of a preparation containing one of these substances be necessary, it must be taken at least 5 hours before or after cholic acid.
    Ciclosporin alters the pharmacokinetics of cholic acid by inhibition of the hepatic uptake and hepatobiliary secretion of bile acids, as well as via its pharmacodynamics by inhibiting cholesterol 7α-hydroxylase. Co-administration should be avoided. If administration of ciclosporin is considered necessary, serum and urinary bile acid levels should be closely monitored and the cholic acid dose adjusted accordingly. Oestrogens, oral contraceptives, and clofibrate (and perhaps other lipid-lowering substances) increase hepatic cholesterol secretion, and encourage cholesterol gallstone formation and hence may counteract the effectiveness of cholic acid. Any medicinal products implicated in drug-induced cholestasis through inhibition of transporters could reduce the effectiveness of cholic acid treatment on co-administration. In these cases, serum/bile levels of cholic acid should be closely monitored and the dose adjusted accordingly.
    The effect of food on the bioavailability of cholic acid has not been studied. There is a theoretical possibility that administration of food may increase cholic acid bioavailability and improve tolerability. It is recommended that cholic acid is taken with food.
    See prescribing information for full details.


    Pregnancy and Lactation

    Pregnancy: There are limited safety data from the use of cholic acid in pregnant women.
    LactationThere is insufficient information on the excretion of cholic acid and its metabolites in human milk.
    See prescribing information for full details.


    Overdose

    Episodes of symptomatic overdose (or excessive dosing regimen) have been reported, including accidental overdose. Clinical features were limited to pruritus and diarrhoea. Laboratory tests showed elevation of serum gamma glutamyltransferase (Gamma GT) transaminases and serum bile acid concentrations. Reduction of the dose led to resolution of the clinical signs and correction of abnormal laboratory parameters. In the event of overdose the patient should be monitored and treated symptomatically.


    Important notes

    Storage: Do not store above 25°C. Store in original package in order to protect from light.


    Manufacturer
    Pantheon Pharmaceuticals Inc. USA
    Licence holder
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