On-Treatment Hepatic Flares and Thrombocytopenia  

• On-Treatment Hepatic Flares 

During treatment with HIBSAGO, increases in ALT ≥3 x ULN to 69 x ULN were observed in clinical trials [see Adverse Reactions (6.1)]. Most ALT increases occurred in the first 12 weeks of treatment (typically between Weeks 5 to 10), started to resolve within 2 weeks, and were not associated with any clinical signs or symptoms of liver dysfunction. The ALT increases were temporally associated with a preceding or concurrent decline in HBsAg suggesting host immune response. Two percent of participants receiving HIBSAGO had ALT increases ≥20 x ULN that resolved when treatment was interrupted or permanently discontinued. There have been isolated cases of ALT increases associated with an increase in total bilirubin up to 4 x ULN that resolved when treatment was permanently discontinued. 

ALT and total bilirubin must be measured prior to initiation of treatment. Do not initiate HIBSAGO in patients with evidence of acute hepatic impairment or cirrhosis [see Contraindications (4)]. During and after HIBSAGO treatment, follow the recommended monitoring for ALT and total bilirubin and the treatment recommendations as specified in Table 1 [see Dosage and Administration (2.4)]. In all patients, the minimum recommended on-treatment monitoring of ALT and total bilirubin is weekly through Week 12 and every other week from Weeks 12 through 24, but more frequent monitoring may be necessary. In addition, HIBSAGO dose reduction or temporary or permanent discontinuation of HIBSAGO may be necessary based on the results of liver laboratory testing. In all patients with abnormal values at the time of HIBSAGO discontinuation, obtain ALT and total bilirubin values at 4, 12, and 24 weeks post-treatment to assess recovery of ALT values to within the normal range, as appropriate [see Dosage and Administration (2.4)]. 

• Thrombocytopenia  

HIBSAGO may cause reductions in platelet count at any time during treatment that may result in sudden and unpredictable thrombocytopenia that can be life-threatening. In the HIBSAGO clinical trials, two participants reported serious adverse reactions of thrombocytopenia <50 × 10⁹/L, including one participant with immune thrombocytopenia [see Adverse Reactions (6.1)]. In addition, a gradual, dose-dependent decline in platelet count was observed in most patients that continued to worsen while on HIBSAGO. 

Platelet Monitoring and Dosing 

Platelet count must be measured prior to initiation of treatment. Do not initiate HIBSAGO in patients with a platelet count below 100 x 109/L [see Contraindications (4)]. In patients with platelet count below the normal range but ≥100 x 109/L, rule out cirrhosis before initiating HIBSAGO [see Contraindications (4)]. 

During and after HIBSAGO treatment, follow recommended monitoring and treatment recommendations for platelet count as specified in Table 2 [see Dosage and Administration (2.4)]. In all patients, the minimum recommended on-treatment monitoring of platelet counts is weekly through Week 24, but more frequent monitoring may be necessary. In addition, HIBSAGO treatment interruption or permanent discontinuation may be necessary based on the results of platelet testing. If platelet count falls below 50 x 109/L, permanently discontinue treatment with HIBSAGO and consider corticosteroid treatment in consultation with an expert. In all patients with abnormal values at the time of HIBSAGO discontinuation, obtain repeat platelet counts 4 and 12 weeks post-treatment to assess for platelet count recovery, as appropriate. 

Symptoms of Thrombocytopenia 

Symptoms of thrombocytopenia can include unusual or prolonged bleeding (e.g., petechiae, easy bruising, hematoma, subconjunctival bleeding, gingival bleeding, epistaxis, hemoptysis, irregular or heavier than normal menstrual bleeding, hematemesis, hematuria, hematochezia, melena), neck stiffness, or atypical severe headache. Instruct patients to report to their healthcare provider immediately if they experience any symptoms of thrombocytopenia. If a patient develops signs or symptoms of thrombocytopenia, treatment with HIBSAGO must be paused and a platelet count obtained as soon as possible [see Dosage and Administration (2.4)]. 

Additional Considerations 

Consider the risks and benefits of treatment with HIBSAGO when treating patients who may be particularly susceptible to platelet count decreases, e.g., elderly patients, or patients with bleeding diathesis/coagulopathy, history of major bleeding events or patients taking antiplatelets, anticoagulants, or drugs that lower platelet count [see Drug Interactions (7.1)].