Prescribing Information and Adverse Events Reporting

LIVTENCITY▼(maribavir) 200 mg film coated tablets

PRESCRIBING INFORMATION FOR GREAT BRITAIN (ENGLAND, SCOTLAND, WALES)

Refer to the Summary of Product Characteristics (SmPC) before prescribing.

Presentation: Each tablet contains 200 mg maribavir

Indication: Treatment of cytomegalovirus (CMV) infection and/or disease that are refractory (with or without resistance) to one or more prior therapies, including ganciclovir, valganciclovir, cidofovir or foscarnet in adult patients who have undergone a haematopoietic stem cell transplant (HSCT) or solid organ transplant (SOT). LIVTENCITY is indicated in adults.

Dosage and administration: Treatment with LIVTENCITY should be initiated by a physician experienced in the management of patients who have undergone solid organ transplant or haematopoietic stem cell transplant. Posology: Recommended dose is 400 mg (two 200 mg tablets) twice daily resulting in a daily dose of 800 mg for 8 weeks. Treatment duration may need to be individualised based on the clinical characteristics of each patient. Elderly patients:No dose adjustment is required for patients over 65 years. Paediatric population: The safety and efficacy in patients below 18 years of age have not been established. No data are available. Method of administration: Intended for oral use only and can be taken with or without food. The film coated tablet can be taken as a whole tablet, a crushed tablet, or a crushed tablet through a nasogastric or orogastric tube.

Contraindications: Hypersensitivity to the active substance or to any of the excipients. Co administration with ganciclovir or valganciclovir.

Warnings and precautions: Virologic failure during treatment and relapse post-treatment: Can occur during and after treatment with LIVTENCITY. Virologic relapse during the post-treatment period usually occurred within 4-8 weeks after treatment discontinuation. Some maribavir pUL97 resistance-associated substitutions confer cross-resistance to ganciclovir and valganciclovir. CMV DNA levels should be monitored and resistance mutations should be investigated in patients who do not respond to treatment. Treatment should be discontinued if maribavir resistance mutations are detected. CMV disease with CNS involvement: LIVTENCITY was not studied in patients with CMV CNS infection. Based on nonclinical data, CNS penetration of maribavir is expected to be low compared to plasma levels. Therefore, LIVTENCITY is not expected to be effective in treating CMV CNS infections (e.g. meningo encephalitis). Use with immunosuppressants: LIVTENCITY has the potential to increase the concentrations of immunosuppressants that are cytochrome P450 (CYP)3A/P-gp substrates with narrow therapeutic margins (including tacrolimus, cyclosporine, sirolimus and everolimus). The plasma levels of these immunosuppressants must be frequently monitored throughout treatment, especially following initiation and after discontinuation of LIVTENCITY, and doses should be adjusted, as needed. Risk of adverse reactions or reduced therapeutic effect due to medicinal product interactions: The concomitant use of LIVTENCITY and certain medicinal products may result in known or potentially significant medicinal product interactions, some of which may lead to possible clinically significant adverse reactions from greater exposure of concomitant medicinal products. May also lead to reduced therapeutic effect of LIVTENCITY. Sodium content: LIVTENCITY contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium free’.

Interactions: Effect of other medicinal products on maribavir: Maribavir is primarily metabolised by CYP3A, and medicinal products that induce or inhibit CYP3A are expected to affect the clearance of maribavir. Co-administration of maribavir and medicinal products that are inhibitors of CYP3A may result in increased plasma concentrations of maribavir. However, no dose adjustment is needed when maribavir is co administered with CYP3A inhibitors. Concomitant administration of strong or moderate CYP3A inducers, is expected to significantly decrease maribavir plasma concentrations, which may result in decrease in efficacy. Therefore, alternative medicinal products with no CYP3A induction potential should be considered. Co-administration of maribavir with strong cytochrome P450 3A (CYP3A) inducers is not recommended. If co-administration of maribavir with other strong or moderate CYP3A inducers cannot be avoided, the maribavir dose should be increased to 1200 mg twice daily. Effect of maribavir on other medicinal products: Co-administration of maribavir with valganciclovir and ganciclovir is contraindicated. LIVTENCITY may antagonise the antiviral effect of ganciclovir and valganciclovir by inhibiting human CMV UL97 serine/threonine kinase, which is required for activation/phosphorylation of ganciclovir and valganciclovir. General information: If dose adjustments of concomitant medicinal products are made due to treatment with maribavir, doses should be readjusted after treatment with maribavir is completed. Please refer to SmPC for further information and guidance.

Fertility, pregnancy and lactation: Pregnancy: There are no data of maribavir use in pregnant women. Studies in animals have shown reproductive toxicity. LIVTENCITY is not recommended during pregnancy and in women of childbearing potential not using contraception. Maribavir is not expected to affect the plasma concentrations of systemically acting oral contraceptive steroids. Breast feeding: It is unknown whether maribavir or its metabolites are excreted in human milk. A risk to the suckling child cannot be excluded. Breast feeding should be discontinued during treatment with LIVTENCITY. Fertility: Studies were not conducted in humans with LIVTENCITY.

Undesirable effects: Very common (≥1/10): Taste disturbance, Diarrhoea, Nausea, Vomiting and Fatigue. Common (≥1/100 to <1/10): Headache, Abdominal pain upper, Decreased appetite, Immunosuppressant drug level increased and Weight decreased. Refer to the SmPC for details on full side effect profile and interactions. UK basic NHS price: £206.25 per tablet. Legal Classification: POM. Marketing authorisation (MA) number: PLGB 16189/0127. Business responsible for sale and supply: Takeda UK Limited, 1 Kingdom Street, London, W2 6BD, United Kingdom.

PI approval code: pi-02176

Date of preparation: November 2022

▼This medicinal product is subject to additional monitoring. Adverse events should be reported. Reporting forms and information can be found at: www.mhra.gov.uk/yellowcard Adverse events should also be reported to Takeda at: AE.GBR-IRL@takeda.com.

LIVTENCITY▼(maribavir) 200 mg film coated tablets

PRESCRIBING INFORMATION FOR NORTHERN IRELAND

Refer to the Summary of Product Characteristics (SmPC) before prescribing.

Presentation: Each tablet contains 200 mg maribavir

Indication: Treatment of cytomegalovirus (CMV) infection and/or disease that are refractory (with or without resistance) to one or more prior therapies, including ganciclovir, valganciclovir, cidofovir or foscarnet in adult patients who have undergone a haematopoietic stem cell transplant (HSCT) or solid organ transplant (SOT). LIVTENCITY is indicated in adults.

Dosage and administration: Treatment with LIVTENCITY should be initiated by a physician experienced in the management of patients who have undergone solid organ transplant or haematopoietic stem cell transplant. Posology: Recommended dose is 400 mg (two 200 mg tablets) twice daily resulting in a daily dose of 800 mg for 8 weeks. Treatment duration may need to be individualised based on the clinical characteristics of each patient. Elderly patients:No dose adjustment is required for patients over 65 years. Paediatric population: The safety and efficacy in patients below 18 years of age have not been established. No data are available. Method of administration: Intended for oral use only and can be taken with or without food. The film coated tablet can be taken as a whole tablet, a crushed tablet, or a crushed tablet through a nasogastric or orogastric tube.

Contraindications: Hypersensitivity to the active substance or to any of the excipients. Co administration with ganciclovir or valganciclovir.

Warnings and precautions: Virologic failure during treatment and relapse post-treatment: Can occur during and after treatment with LIVTENCITY. Virologic relapse during the post-treatment period usually occurred within 4-8 weeks after treatment discontinuation. Some maribavir pUL97 resistance-associated substitutions confer cross-resistance to ganciclovir and valganciclovir. CMV DNA levels should be monitored and resistance mutations should be investigated in patients who do not respond to treatment. Treatment should be discontinued if maribavir resistance mutations are detected. CMV disease with CNS involvement: LIVTENCITY was not studied in patients with CMV CNS infection. Based on nonclinical data, CNS penetration of maribavir is expected to be low compared to plasma levels. Therefore, LIVTENCITY is not expected to be effective in treating CMV CNS infections (e.g. meningo encephalitis). Use with immunosuppressants: LIVTENCITY has the potential to increase the concentrations of immunosuppressants that are cytochrome P450 (CYP)3A/P-gp substrates with narrow therapeutic margins (including tacrolimus, cyclosporine, sirolimus and everolimus). The plasma levels of these immunosuppressants must be frequently monitored throughout treatment, especially following initiation and after discontinuation of LIVTENCITY, and doses should be adjusted, as needed. Risk of adverse reactions or reduced therapeutic effect due to medicinal product interactions: The concomitant use of LIVTENCITY and certain medicinal products may result in known or potentially significant medicinal product interactions, some of which may lead to possible clinically significant adverse reactions from greater exposure of concomitant medicinal products. May also lead to reduced therapeutic effect of LIVTENCITY. Sodium content: LIVTENCITY contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium free’.

Interactions: Effect of other medicinal products on maribavir: Maribavir is primarily metabolised by CYP3A, and medicinal products that induce or inhibit CYP3A are expected to affect the clearance of maribavir. Co-administration of maribavir and medicinal products that are inhibitors of CYP3A may result in increased plasma concentrations of maribavir. However, no dose adjustment is needed when maribavir is co administered with CYP3A inhibitors. Concomitant administration of strong or moderate CYP3A inducers, is expected to significantly decrease maribavir plasma concentrations, which may result in decrease in efficacy. Therefore, alternative medicinal products with no CYP3A induction potential should be considered. Co-administration of maribavir with strong cytochrome P450 3A (CYP3A) inducers is not recommended. If co-administration of maribavir with other strong or moderate CYP3A inducers cannot be avoided, the maribavir dose should be increased to 1200 mg twice daily. Effect of maribavir on other medicinal products: Co-administration of maribavir with valganciclovir and ganciclovir is contraindicated. LIVTENCITY may antagonise the antiviral effect of ganciclovir and valganciclovir by inhibiting human CMV UL97 serine/threonine kinase, which is required for activation/phosphorylation of ganciclovir and valganciclovir. General information: If dose adjustments of concomitant medicinal products are made due to treatment with maribavir, doses should be readjusted after treatment with maribavir is completed. Please refer to SmPC for further information and guidance.

Fertility, pregnancy and lactation: Pregnancy: There are no data of maribavir use in pregnant women. Studies in animals have shown reproductive toxicity. LIVTENCITY is not recommended during pregnancy and in women of childbearing potential not using contraception. Maribavir is not expected to affect the plasma concentrations of systemically acting oral contraceptive steroids. Breast feeding: It is unknown whether maribavir or its metabolites are excreted in human milk. A risk to the suckling child cannot be excluded. Breast feeding should be discontinued during treatment with LIVTENCITY. Fertility: Studies were not conducted in humans with LIVTENCITY.

Undesirable effects: Very common (≥1/10): Taste disturbance, Diarrhoea, Nausea, Vomiting and Fatigue. Common (≥1/100 to <1/10): Headache, Abdominal pain upper, Decreased appetite, Immunosuppressant drug level increased and Weight decreased. Refer to the SmPC for details on full side effect profile and interactions. UK basic NHS price: £206.25 per tablet. Legal Classification: POM. Marketing authorisation (MA) number(s): EU/1/22/1672/001, EU/1/22/1672/002.

Business responsible for sale and supply: Takeda UK Limited, 1 Kingdom Street, London, W2 6BD, United Kingdom.

PI approval code: pi-02238

Date of preparation: November 2022

Adverse events should be reported. Reporting forms and information can be found at: www.mhra.gov.uk/yellowcard Adverse events should also be reported to Takeda at: AE.GBR-IRL@takeda.com.