Livtencity Adverse Reactions

Clinical trial experience: The safety of LIVTENCITY was evaluated in Study 303 in which 352 patients were randomised and treated with LIVTENCITY (N=234) or Investigator Assigned Treatment (IAT) consisting of monotherapy or dual therapy with ganciclovir, valganciclovir, foscarnet, or cidofovir (N=117) for an 8-week treatment phase following a diagnosis of resistant/refractory CMV. Adverse events were collected during the treatment phase and follow up phase through Study Week 20. The mean exposures (SD) for LIVTENCITY were 48.6 (13.82) days. LIVTENCITY treated patients received treatment a maximum of 60 days. The most common adverse events occurring in more than 10% of subjects in the LIVTENCITY, ganciclovir/valganciclovir or foscarnet are outlined in Table 8. (See Table 8.)

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The most commonly reported adverse reactions occurring in at least 10% of subjects in the LIVTENCITY group were: taste disturbance (46%), nausea (21%), diarrhoea (19%), vomiting (14%), and fatigue (12%). The most commonly reported serious adverse reactions were diarrhoea (2%), and nausea, weight decreased, fatigue, immunosuppressant drug level increased, and vomiting occurring at <1%.
Treatment-emergent serious adverse events (SAEs) considered related to study-assigned treatment occurred less frequently in the LIVTENCITY group than in the IAT group (5.1% and 14.7% respectively). No patients in the LIVTENCITY group experienced serious, drug-related neutropenia or febrile neutropenia. In contrast in patients treated with ganciclovir/valganciclovir, 4% of patients had serious related neutropenia and 7% had serious related febrile neutropenia. In addition, 1% of patients in the LIVTENCITY group and 11% in the foscarnet group experienced serious related renal disorders (acute kidney injury and renal impairment).
The following convention is used for the classification of the frequency of an adverse drug reaction (ADR) and is based on the Council for International Organizations of Medical Sciences (CIOMS) guidelines: 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). (See Table 9.)

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Description of selected adverse reactions: Taste Disturbance: Taste disturbance (comprising the reported preferred terms ageusia, dysgeusia, hypogeusia, and taste disorder) occurred in 46% of patients treated with LIVTENCITY. These events rarely led to discontinuation of LIVTENCITY (0.9%) and resolved either while patients remained on therapy (37%) or within a median of 7 days (Kaplan-Meier estimate, 95% CI: 4-8 days) after treatment discontinuation.
Immunosuppressant Drug Level Increase: Immunosuppressant drug level increase was reported as an adverse event in 9% of patients treated with LIVTENCITY. LIVTENCITY has the potential to increase the drug concentrations of immunosuppressant drugs that are CYP3A/ P-gp substrates with narrow therapeutic ranges (including tacrolimus, cyclosporin, sirolimus and everolimus). Frequently monitor immunosuppressant drug levels throughout treatment with LIVTENCITY, especially following initiation and after discontinuation of LIVTENCITY and adjust the dose, as needed (see Precautions, Interactions and Pharmacology: Pharmacokinetics under Actions).
Reporting suspected adverse effects: Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product.