032 were: dysuria (35%), haematuria (35%), pollakiuria (32%), urinary tract infection (24%), micturition urgency (22%), fatigue (20%), chills (13%), musculoskeletal pain (11%), and pyrexia (10%). Adverse drug reaction frequencies presented may not be fully attributable to the drug alone but may contain contributions from the underlying disease or from other drugs used in a combination.
More than one patient experienced the following grade > 3 adverse reactions: urinary tract infection (4 patients, 2%), bacteraemia (2 patients, 1%), sepsis (2 patients, 1%), haematuria (5 patients, 3%), musculoskeletal pain (2 patients, 1%), and myalgia (2 patients, 1%).
More than one patient experienced the following serious adverse reactions: urinary tract infection (3 patients, 2%), bacteraemia (2 patients, 1%), haematuria (5 patients, 3%). Tabulated list of adverse reactions Table 1 lists adverse reactions in a clinical study (n=180) where ANKTIVA in combination with BCG was administered to subjects (aged 46 to 93 years).
Adverse reaction frequency was determined according to the following criteria: 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).
Adverse drug reactions are listed by MedDRA System Organ Class (SOC) and by frequency. 6 Table 1: Adverse reactions with ANKTIVA in combination with BCG System organ class Frequency category Adverse reaction Infections and infestations Very common Urinary tract infection Common Cystitis, Bacteriuriaa, Bacteraemia, Sepsis Blood and lymphatic system disorders Common Anaemiab, Leukocytosis, Lymphadenopathy Metabolism and nutrition disorders Common Decreased appetite, Dehydration Nervous system disorders Common Dizziness, Headache Respiratory, thoracic and mediastinal disorders Common Dyspnoea Gastrointestinal disorders Common Diarrhoea, Nausea, Abdominal painc, Constipation, Vomiting Skin and subcutaneous tissue disorders Common Night sweats, Pruritus, Rash Musculoskeletal and connective tissue disorders Very common Musculoskeletal paind Common Myalgiae, Arthralgia, Muscular weakness Uncommon Arthritis Renal and urinary disorders Very Common Haematuriaf, Dysuria, Pollakiuria, Micturition urgency Common Bladder spasm, Cystitis noninfective, Nocturia, Urinary incontinence, Urinary tract paing, Urinary retention, Bladder painh, Urge incontinence, Lower urinary tract symptoms, Urinary hesitation, Urine flow decreased, Leukocyturiai Uncommon Urine abnormality, Polyuria, Glomerular filtration rate decreased, Blood urea increased Reproductive system and breast disorders Common Genital painj, Prostatitis, Benign prostatic hyperplasia Uncommon Penile discharge 7 General disorders and administration site conditions Very common Fatigue, Chills, Pyrexia Common Influenza like illness, Chest pain Uncommon Installation site pain Investigations Common Blood creatinine increased, Cancer cells urine present a includes bacteriuria, asymptomatic bacteriuria and bacterial test positive b includes anaemia and anaemia macrocytic c includes abdominal pain, abdominal pain lower and suprapubic pain d includes musculoskeletal pain, back pain, flank pain and pain in extremity e includes myalgia and pain f includes haematuria, cystitis haemorrhagic and blood urine present g includes urinary tract pain and urinary tract discomfort h includes bladder pain, bladder discomfort and bladder irritation i includes leukocyturia and white blood cells in urine j includes penile pain, penile burning sensation, vulvovaginal burning sensation Immune-related adverse events Given the immune-activating mechanism of nogapendekin alfa inabakicept, immune-related toxicities cannot be excluded, although systemic exposure following intravesical administration is below the limit of quantitation.
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.