Anktiva

Posology Induction therapy ANKTIVA is recommended at a dose of 400 micrograms; administered intravesically as a mixture with BCG recommended at a dose of 50 mL once a week for 6 weeks. 4. concerning the re-consideration of cystectomy in patients with residual disease).

1 for pharmacodynamic properties. Maintenance therapy After BCG and ANKTIVA induction therapy, for patients with lack of disease or low-grade Ta, continued treatment is recommended at a dose of 400 micrograms administered intravesically with BCG once a week for 3 consecutive weeks at months 4, 7, 10, 13 and 19 (for a total of 15 doses).

Presence of a low-grade Ta will require a transurethral resection of bladder tumour (TURBT) procedure prior to instillation. Treatment may be delayed by up to 28 days after TURBT procedure if required. For patients with an ongoing complete response as defined by negative results for cystoscopy 3 [with TURBT/biopsies as applicable] and urine cytology at month 25 and later, maintenance instillations with ANKTIVA and BCG may be administered once a week for 3 consecutive weeks at months 25, 31, and 37 for a maximum of 9 additional instillations.

Assessment of tumour status should be performed every 3 months for up to 24 months. Assessment for ongoing response beyond month 24 is per local community standards. The recommended duration of treatment is until disease persistence after the last induction cycle (initial, or if administered, second induction) disease recurrence or progression (new CIS and/or any T1 disease or greater), unacceptable toxicity, or a maximum treatment duration of 37 months.

Special populations Elderly No dose adjustments are necessary in the elderly population. Hepatic and/or renal impairment No dose adjustments are necessary in patients with hepatic and/or renal impairment. Paediatric population There is no relevant use of ANKTIVA in the paediatric population in children aged 0 to less than 18 years in the indication BCG-unresponsive NMIBC CIS with or without papillary tumours.

Method of administration For intravesical use. Do not shake. 6. ANKTIVA is administered intravesically with BCG into the bladder via a catheter. Connect a catheter to the suspension container directly or using a 50-mL syringe connected to an appropriate size needle/connecter, withdraw the 50 mL ANKTIVA with BCG mixture and attach to a urinary catheter.

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.

Traceability In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded. 4 For intravesical use only. ANKTIVA should NOT be administered by subcutaneous or intravenous or intramuscular use.

Severe systemic BCG-infections/reactions The possibility of severe systemic BCG-infections with the necessity of anti-tuberculosis therapy should be considered before initiating the BCG-therapy. See Summary of product Characteristics for the specific BCG being used.

Risk of progression to muscle invasive and metastatic bladder cancer with delayed cystectomy Delaying cystectomy in patients with BCG-unresponsive NMIBC with CIS, with or without papillary tumours, treated with ANKTIVA therapy in combination with BCG could lead to development of muscle invasive or metastatic bladder cancer.

6%), progressed to muscle-invasive (T2 or greater) bladder cancer, including 2 cases occuring during the treatment period. 1 weeks). Four out of these 7 subjects without CR received a second induction (re-induction). Four patients had progression determined at the time of cystectomy.

The median time between determination of persistent or recurrent CIS and progression to muscle-invasive disease was 224 days (range: 0-854). 5 months of follow up, 5% of participants developed metastatic disease by 24 months (none at 12 months).

Progression to muscle invasive or metastatic disease occurred in five of seventy (5/70) patients who were not re-inducted, and in five of thirty (5/30) patients that received a second induction course (re-induction). 5). 7, not reached).

). The risk of developing muscle-invasive or metastatic bladder cancer increases the longer cystectomy is delayed in the presence of persisting CIS. e. essentially ‘potassium-free’. This medicinal product contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially ‘sodium-free’.

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