Version May 2024
Bladder cancer, high-risk, BCG-unresponsive non–muscle invasive: Note: Premedication with an anticholinergic is recommended prior to each nadofaragene firadenovec instillation to minimize irritative voiding symptoms (Ref). Individuals who are immunosuppressed or immune-deficient should not prepare, administer, or come into contact with nadofaragene firadenovec.
Intravesicular: 75 mL (at a concentration of 3 × 1011 viral particles [vp]/mL) instilled once every 3 months into the bladder via a urinary catheter for up to 12 months (total of 4 doses) or until disease progression or unacceptable toxicity; may continue beyond 12 months in patients without evidence of high-grade recurrence. If patient does not have a complete response to treatment after 3 months or if carcinoma in situ recurs, consider cystectomy (Ref). Refer to protocol for further information.
There are no dosage adjustments provided in the manufacturer's labeling.
There are no dosage adjustments provided in the manufacturer's labeling.
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.
>10%:
Endocrine & metabolic: Decreased serum phosphate (16%), increased serum glucose (38%), increased serum triglycerides (30%)
Genitourinary: Bladder spasm (20%), dysuria (16%), hematuria (17%), urinary urgency (19%)
Hematologic & oncologic: Decreased hemoglobin (16%; grades 3/4: <1%)
Local: Application-site discharge (33%)
Nervous system: Chills (16%), fatigue (24%)
Renal: Increased serum creatinine (17%)
Miscellaneous: Fever (15%)
1% to 10%:
Cardiovascular: Acute coronary syndrome (1%), atrial fibrillation (1%), coronary artery disease (1%), syncope (1%)
Endocrine & metabolic: Dehydration (1%), hypoglycemia (1%)
<1%:
Cardiovascular: Heart failure, pericarditis
Gastrointestinal: Choledocholithiasis
Infection: Sepsis
Nervous system: Brain edema
Frequency not defined: Genitourinary: Bladder neoplasm (benign)
Prior hypersensitivity reactions to interferon alfa or any component of the formulation.
Disease-related concerns:
• Risk of muscle-invasive or metastatic bladder cancer: Delaying cystectomy in patients with BCG-unresponsive carcinoma in situ (CIS) may lead to the development of muscle-invasive or metastatic bladder cancer. The risk of developing more advanced or metastatic disease increases the longer cystectomy is delayed (in the presence of persisting CIS). Of the patients with CIS who received nadofaragene firadenovec and later underwent subsequent radical cystectomy, 14% had muscle-invasive (T2 or greater) disease at cystectomy. The median time from persistence or recurrence of CIS to cystectomy was 235 days (range: 38 to 582 days). Consider cystectomy if complete response to nadofaragene firadenovec does not occur after 3 months or if CIS recurs
Dosage form specific issues:
• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.
Other warnings/precautions:
• Risk of disseminated adenovirus infection: Low levels of replication-competent adenovirus may be present in nadofaragene firadenovec. Immunocompromised patients (including those receiving immunosuppressive therapy) may be at risk for disseminated adenovirus infection.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Suspension, Intravesical [preservative free]:
Adstiladrin: Nadofaragene Firadenov-vncg 300 billion vp/mL (1 ea) [contains polysorbate 80]
Yes
Intravesicular: Nadofaragene firadenovec is for intravesicular (bladder instillation) administration only; do not administer IV, orally, or topically. Individuals who are immunosuppressed or immune-deficient should not prepare, administer, or come into contact with nadofaragene firadenovec. Bring to room temperature prior to administration. Premedication with an anticholinergic is recommended prior to each instillation to minimize irritative voiding symptoms (Ref). Refer to manufacturer's labeling for further information.
Insert a straight, or intermittent, urinary catheter with a proximal funnel opening that will accommodate the Luer lock adapter; use catheters made of vinyl/PVC (uncoated or coated with hydrogel), red rubber latex, or silicone only to instill nadofaragene firadenovec. Do not use catheters coated or embedded with silver or antibiotics. Use the catheter to completely empty the patient's bladder. Do not remove the catheter.
Attach the Luer lock end of the same catheter adaptor to the syringe containing nadofaragene firadenovec and insert the tapered end of the catheter adaptor into the funnel opening of the catheter. Slowly instill 75 mL of nadofaragene firadenovec into the bladder through the catheter; ensure that the complete volume is instilled.
Retain nadofaragene firadenovec in the bladder for 1 hour. Patient should reposition approximately every 15 minutes from left to right, back, and abdomen to maximize bladder surface exposure. If the patient experiences bladder cramping or premature voiding during the dwell time, repositioning may be adjusted or discontinued.
Evacuate nadofaragene from the bladder as part of routine bladder emptying, or the patient may void and completely empty the bladder after 1 hour has elapsed. For 2 days following administration, disinfect voided urine for 15 minutes with an equal volume of virucidal agent before flushing the toilet.
Bladder cancer, high-risk, BCG-unresponsive non–muscle invasive: Treatment of high-risk Bacillus Calmette-Guérin (BCG)-unresponsive non–muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors in adults.
Nadofaragene firadenovec may be confused with etranacogene dezaparvovec, onasemnogene abeparvovec, voretigene neparvovec.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Corticosteroids (Systemic): May enhance the adverse/toxic effect of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid combination
Immunosuppressants (Cytotoxic Chemotherapy): May enhance the adverse/toxic effect of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid combination
Immunosuppressants (Miscellaneous Oncologic Agents): May enhance the adverse/toxic effect of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid combination
Immunosuppressants (Therapeutic Immunosuppressant Agents): May enhance the adverse/toxic effect of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid combination
Methotrexate: May enhance the adverse/toxic effect of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid combination
Verify pregnancy status prior to treatment initiation in patients who could become pregnant.
Patients who could become pregnant should use effective contraception during therapy and for 6 months after the last dose of nadofaragene firadenovec. Patients with partners who could become pregnant should also use effective contraception during therapy and for 3 months after the last nadofaragene firadenovec dose.
Animal reproduction studies have not been conducted with nadofaragene firadenovec.
It is not known if nadofaragene firadenovec is present in breast milk.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.
Verify pregnancy status prior to therapy initiation (in patients who could become pregnant). Monitor for development of muscle-invasive or metastatic bladder cancer. Monitor for disseminated adenovirus infection.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Nadofaragene firadenovec is a nonreplicating adenoviral vector-based gene therapy. It consists of rAd-IFNα, a nonreplicating recombinant adenovirus (serotype 5) vector-based gene therapy that transports a copy of interferon alfa-2b gene to urothelial cells, and Syn3, a polyamide surfactant that augments the viral transduction of the urothelium (Boorjian 2021). Intravesicular administration produces cell transduction and transient local expression of the IFNα2b protein, which is believed to have antitumor effects.
Onset: In a phase 2 study, all patients had quantifiable concentrations of IFNα2b protein in the urine at day 2 after nadofaragene firadenovec administration; measurable concentration of urine IFNα2b protein was detected up to day 12 post dose.
Duration: In clinical studies where nadofaragene firadenovec 3 × 1011 viral particles [vp]/mL was administered, 1 patient had detectable levels of vector DNA at day 14 (phase 1 study) and most patients had detectable levels of vector DNA at day 12 (phase 2 study).
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