Kayfanda

Treatment must be initiated and supervised by physicians experienced in the management of ALGS. Posology The recommended dose of odevixibat is 120 mcg/kg administered orally once daily in the morning. Odevixibat can be taken with or without food.

Table 1 shows the strength and number of capsules that should be administered daily based on body weight to approximate a 120 mcg/kg/day dose, with a maximum daily dose of 7 200 mcg per day. 5 7 200 12 or 6 Capsule strength/number in bold is recommended based on predicted ease of administration.

If necessary, any of the four capsule strengths can be combined as needed to achieve the nominal dose. 4)) occur in the absence of other causes. Once tolerability issues stabilise, the dose should be increased to 120 mcg/kg/day. Table 2 shows the strength and number of capsules that should be administered daily based on body weight to approximate a 40 mcg/kg/day dose.

5 2 400 12 or 6 4 Capsule strength/number in bold is recommended based on predicted ease of administration. If necessary, any of the four capsule strengths can be combined as needed to achieve the nominal dose. Alternative treatment should be considered in patients for whom no treatment benefit can be established following 6 months of continuous daily treatment with odevixibat.

Missed doses If a dose of odevixibat is missed, the patient should take the forgotten dose as soon as possible without exceeding one dose per day. Renal impairment No dose adjustment is required for patients with mild renal impairment.

There are no available clinical data for the use of odevixibat in patients with moderate or severe renal impairment or end-stage renal disease (ESRD) requiring haemodialysis. 2). 2). Odevixibat has not been sufficiently studied in patients with severe hepatic impairment (Child-Pugh C).

Due to minimal absorption, no dose adjustment is required. 4). Paediatric population The safety and the efficacy of odevixibat in children aged less than 6 months have not been established. No data are available. Method of administration KAYFANDA is for oral use.

2). The larger 200 mcg and 600 mcg capsules are intended to be opened and sprinkled on food or in a liquid but may be swallowed whole. The smaller 400 mcg and 1 200 mcg capsules are intended to be swallowed whole but may be opened and sprinkled on food or in a liquid.

5%). 8%). Tabulated list of adverse reactions Table 3 lists adverse reactions identified in patients with ALGS. Adverse reactions are ranked according to system organ class and frequency grouping. Frequencies are defined using the following convention: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1 000 to < 1/100), rare (≥ 1/10 000 to < 1/1 000), very rare (< 1/10 000) and not known (cannot be estimated from the available data).

8 Table 3: Frequency of adverse reactions reported in patients with ALGS MedDRA system organ class Frequency Adverse reaction Gastrointestinal disorders Very common diarrhoea abdominal paina* Common vomiting* Hepatobiliary disorders Common hepatomegaly, alanine aminotransferase increased*, aspartate aminotransferase increased*, gamma-glutamyl transferase increased*, blood bilirubin increased* Metabolism and nutrition site disorders Very common vitamin D deficiency* Common vitamin E deficiency* a Includes abdominal pain upper *See section ‘Description of selected adverse reactions‘.

Description of selected adverse reactions Gastrointestinal adverse reactions The most frequently reported adverse drug reaction was diarrhoea, mostly mild to moderate in severity and non-serious. 4). Other gastrointestinal adverse reactions were reports of abdominal pain and vomiting, mild to moderate in severity and in most cases of limited duration.

Hepatobiliary disorders The most common hepatic adverse reactions were increases in blood bilirubin, ALT, AST and GGT. Most of these excursions were mild in severity and non-serious, and increases were not indicative of drug-induced liver injury.

4). 4). Reductions in vitamin levels were observed during long-term treatment with odevixibat; the majority of these patients responded to appropriate vitamin supplementation. Overall, few patients had fat-soluble vitamin deficiencies that were refractory to supplementation.

Enterohepatic circulation The mechanism of action of odevixibat requires that the enterohepatic circulation of bile acids and bile salt transport into biliary canaliculi is preserved. Conditions, medications, or surgical procedures that impair either gastrointestinal motility, or enterohepatic circulation of bile acids, including bile salt transport to biliary canaliculi have the potential to reduce the efficacy of odevixibat.

Diarrhoea Diarrhoea has been reported as a common adverse reaction when taking odevixibat. Diarrhoea may lead to dehydration. 8). Treatment interruption or discontinuation may be required for persistent diarrhoea. 8). Liver function tests should be monitored prior to start and during treatment with odevixibat.

For patients with liver function test elevations and severe hepatic impairment (Child-Pugh C), more frequent monitoring is to be considered. 6 Fat-soluble vitamin absorption Assessment of fat-soluble vitamin (FSV) levels (Vitamins A, D, E) and international normalised ratio (INR) are recommended for all patients prior to initiating odevixibat, with monitoring per standard clinical practice.

If FSV deficiency is diagnosed, supplemental therapy should be prescribed.

1.