MULPLEO

Posology The recommended dose is 3 mg lusutrombopag once daily for 7 days. The procedure should be performed from day 9 after the start of lusutrombopag treatment. Platelet count should be measured prior to the procedure. Missed dose If a dose is missed it should be taken as soon as possible.

A double dose should not be taken to make up for a missed dose. Duration of treatment Mulpleo should not be taken for more than 7 days. 2). 2). 1). No dosage adjustment is expected for these patients. 2). No dosage adjustment is necessary for patients with mild (Child-Pugh class A) to moderate (Child-Pugh class B) hepatic impairment.

Paediatric population The safety and efficacy of lusutrombopag in children and adolescents (< 18 years of age) have not been established. No data are available. Method of administration Mulpleo is for oral use. The film-coated tablet is to be taken once daily with liquid, swallowed whole and should not be chewed, divided, or crushed.

It can be taken with or without food.

2%, 2/171 patients in the lusutrombopag group; 0%, 0/170 patients in the placebo group). Tabulated list of adverse reactions Adverse reactions with 3 mg of lusutrombopag once daily for up to 7 days in randomised, double-blind, placebo-controlled trials in thrombocytopenic patients with chronic liver disease undergoing an invasive procedure (M0626, M0631 and M0634; N=171) are listed in Table 1 by MedDRA System Organ Class.

6%, 1/171) in the lusutrombopag group only. In the phase 2b study one patient had portal vein thrombosis reported as a treatment-emergent adverse event (TEAE) in the lusutrombopag 2 mg and 4 mg groups. 4). Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

Thrombotic/thromboembolic complications Patients with chronic liver disease have a risk of portal vein thrombosis and mesenteric vein thrombosis. The risk may be increased due to an invasive procedure. Thromboembolic and thrombotic complications are known to occur with thrombopoetin (TPO) receptor agonists based upon mechanism of action associated with increases in platelets.

Caution should be exercised with respect to thromboembolic events after invasive procedures as well as post-treatment regardless of platelet counts. In patients with thrombosis or thromboembolism, with a history of thrombosis or thromboembolism, with absence of hepatopetal blood flow in the main trunk of the portal vein, or patients with congenital coagulopathy the risk for thrombosis or thromboembolism may increase.

These patients should be clinically monitored when treated with lusutrombopag. 1). 2). Due to the unstable nature of these patients, they should be supported in line with clinical practice by close monitoring for early signs of worsening or new onset hepatic encephalopathy, ascites, and thrombotic or bleeding tendency, through monitoring of liver function tests, tests used for assessing clotting status and through imaging of portal vasculature as needed.

In addition, although no dose adjustment is required in these subjects, platelet count should be measured at least once approximately 5 days after the first dose and as necessary thereafter. Appropriate measures such as discontinuation of lusutrombopag should be taken, if the platelet count reaches ≥50,000/μL as a result of a 20,000/μL increase from baseline.

Use in patients with chronic liver disease undergoing invasive procedures Lusutrombopag should be used when risk for bleeding is considered to be high according to clinical laboratory test values such as platelet counts and of the coagulation-fibrinolysis system, clinical symptoms and type of invasive procedure.

1.