Bylvay

Treatment must be initiated and supervised by physicians experienced in the management of PFIC. Posology The recommended dose of odevixibat is 40 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 40 mcg/kg/day dose. 5 12 or 6 Capsule strength/number in bold is recommended based on predicted ease of administration.

Dose escalation Improvement in pruritus and reduction of serum bile acid levels may occur gradually in some patients after initiating odevixibat therapy. ). Table 2 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 12 or 6 Capsule strength/number in bold is recommended based on predicted ease of administration. Alternative treatment should be considered in patients for whom no treatment benefit can be established following 6 months of continuous daily treatment with odevixibat.

4 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. 2). However, due to the negligible renal excretion, no dose adjustment is required for patients with mild or moderate renal impairment.

2). Odevixibat has not been sufficiently studied in patients with severe hepatic impairment (Child Pugh C). 4). Paediatric population The safety and efficacy of odevixibat in children aged less than 6 months have not been established.

No data are available. Method of administration Bylvay 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.

If the capsule is to be swallowed whole, the patient should be instructed to take it with a glass of water in the morning. Administration in soft foods For capsules to be opened and sprinkled on soft food, the patient should be instructed to: • place a small quantity (30 mL/2 tablespoons) of soft food (yoghurt, apple sauce, oatmeal porridge, banana puree, carrot puree, chocolate-flavoured pudding or rice pudding) in a bowl.

6%). 6%), and decreases in Vitamin D (11%) and E levels (5%). Tabulated list of adverse reactions The table lists adverse reactions identified in clinical trials in patients with PFIC aged between 4 months to 25 years of age (median 3 years 7 months).

Adverse reactions are ranked according to system organ class, 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).

Table 3:

Frequency of adverse reactions in PFIC patients MedDRA system organ class Frequency Adverse drug reaction Gastrointestinal disorders Very common diarrhoeaa, vomiting abdominal painb Hepatobiliary disorders Very common blood bilirubin increased, ALT increased Common hepatomegaly, AST increased Metabolism and nutrition site disorders Very common vitamin D deficiency Common vitamin E deficiency a Based on the combined frequency of diarrhoea, diarrhoea haemorrhagic and faeces soft b Includes abdominal pain upper and abdominal pain lower ALT = alanine aminotransferase AST = aspartate aminotransferase Description of selected adverse reactions Gastrointestinal adverse reactions In clinical trials, diarrhoea was the most common gastrointestinal adverse drug reaction.

Adverse reactions of diarrhoea, diarrhoea haemorrhagic and soft faeces were of short duration with most events ≤ 5 days in duration. Most cases of diarrhoea were mild to moderate in intensity and non-serious. 4). Other commonly reported gastrointestinal disorders were vomiting and abdominal pain (including upper and lower abdominal pain), all non-serious, mild to moderate and in general not requiring dose adaption.

8 Hepatobiliary disorders The most common hepatic adverse reactions were increases in blood bilirubin, AST and ALT. The majority of these were mild to moderate in severity. Treatment interruption due to increases in liver function tests were noted in patients with PFIC treated with odevixibat.

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, medicinal products 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.

g. e. patients with BSEP3 subtype of PFIC2) will not respond to odevixibat. There are limited clinical data with odevixibat in PFIC subtypes other than 1 and 2. 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. Liver monitoring Elevations in liver enzymes and bilirubin levels have been observed in patients treated with odevixibat.

Assessment of liver function tests is recommended for all patients prior to initiating odevixibat, with monitoring per standard clinical practice. For patients with liver function test elevations and severe hepatic impairment (Child-Pugh C), more frequent monitoring is to be considered.

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. 6

1.