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| Product NDC Code | 55566-1050 | ||||
|---|---|---|---|---|---|
| Drug Name | Adstiladrin |
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| Type | Brand | ||||
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| Route | INTRAVESICAL | ||||
| Dosage Form | SUSPENSION | ||||
| RxCUI drug identifier | 2644440, 2644445 |
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| Application Number | BLA125700 | ||||
| Labeler Name | Ferring Pharmaceuticals | ||||
| Packages |
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Adverse reactions
Information about undesirable effects, reasonably associated with use of the drug, that may occur as part of the pharmacological action of the drug or may be unpredictable in its occurrence. Adverse reactions include those that occur with the drug, and if applicable, with drugs in the same pharmacologically active and chemically related class. There is considerable variation in the listing of adverse reactions. They may be categorized by organ system, by severity of reaction, by frequency, by toxicological mechanism, or by a combination of these.6 ADVERSE REACTIONS The most common (>10%) adverse reactions, including laboratory abnormalities (>15%), were glucose increased, instillation site discharge, triglycerides increased, fatigue, bladder spasm, micturition (urination urgency), creatinine increased, hematuria (blood in urine), phosphate decreased, chills, pyrexia (fever), and dysuria (painful urination). ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Ferring Pharmaceuticals at 1-888-337-7464 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of ADSTILADRIN was evaluated in Study CS-003, a multicenter, single-arm, open-label study in 157 U.S. patients [ see Clinical Studies ( 14 ) ] with high-risk BCG‑unresponsive NMIBC, 107 of whom had BCG-unresponsive carcinoma in situ (CIS) with or without papillary tumors. Patients received 75 mL (3 x 10 11 vp/mL) ADSTILADRIN administered intravesically once every 3 months for up to 12 months [ see Clinical Studies ( 14 ) ]. All patients with an absence of high-risk recurrence or progression were offered continued treatment every 3 months beyond 12 months. The median number of instillations of ADSTILADRIN was 2 (range 1 to 5). Serious adverse reactions occurred in 11% of patients who received ADSTILADRIN. Serious adverse reactions occurring in >1% of patients included coronary artery disease and hematuria (blood in urine). Permanent discontinuation of ADSTILADRIN due to an adverse reaction occurred in 3 (1.9%) patients. Adverse reactions that resulted in permanent discontinuation of ADSTILADRIN included bladder spasm instillation site discharge, and benign neoplasm of the bladder. Dosage interruptions of ADSTILADRIN due to an adverse reaction occurred in 54 (34%) patients. Adverse reactions in >10% of patients that required dosage interruption included instillation site discharge, bladder spasm, and micturition urgency. The most common (>10%) adverse reactions, including laboratory abnormalities (>15%), were glucose increased, instillation site discharge, triglycerides increased, fatigue, bladder spasm, micturition (urination) urgency, creatinine increased, hematuria (blood in urine), phosphate decreased, chills, dysuria, and pyrexia (fever). Tables 1 and 2 summarize adverse reactions and laboratory abnormalities, respectively, in patients on ADSTILADRIN in CS-003. Clinically relevant adverse reaction in <10% of patients who received ADSTILADRIN include syncope (fainting) (1.3%). Table 1: Adverse Reactions (>10%) in Patients with NMIBC in CS-003 Adverse Reaction ADSTILADRIN n=157 Graded per NCI CTCAE v4.03; there were no Grade 3 or 4 reactions. Grades 1 or 2 (%) General disorders and administration site conditions Instillation site discharge 33 Fatigue 24 Chills 16 Pyrexia 15 Renal and urinary disorders Bladder spasm 20 Micturition urgency 19 Hematuria 17 Dysuria 16 Clinically relevant adverse reactions in <10% of patients who received ADSTILADRIN included coronary artery disease (1.3%), acute coronary syndrome (1.3%), atrial fibrillation (1.3%), dehydration (1.3%), hypoglycemia (low blood sugar) (1.3%), syncope (fainting) (1.3%), heart failure (0.6%), pericarditis, (0.6%), brain edema (swelling) (0.6%), bile duct stone (0.6%), and sepsis (0.6%). Table 2 summarizes the laboratory abnormalities in CS-003. Table 2: Selected Laboratory Abnormalities (>15.0%) That Worsened from Baseline in Patients with NMIBC in CS-003 Laboratory Abnormality ADSTILADRIN The denominator used to calculate the rate varied from 148 to 156 based on the number of patients with a baseline value and at least one post-treatment value. All Grades (%) ADSTILADRIN* Grade 3 or 4 (%) Chemistry Glucose increased 38 6 Triglycerides increased 30 1.9 Creatinine increased 17 0 Phosphate decreased 16 1.4 Hematology Hemoglobin decreased 16 0.6
| Instillation site discharge | 33 |
| Fatigue | 24 |
| Chills | 16 |
| Pyrexia | 15 |
| Bladder spasm | 20 |
| Micturition urgency | 19 |
| Hematuria | 17 |
| Dysuria | 16 |
| Glucose increased | 38 | 6 |
| Triglycerides increased | 30 | 1.9 |
| Creatinine increased | 17 | 0 |
| Phosphate decreased | 16 | 1.4 |
| Hemoglobin decreased | 16 | 0.6 |
Clinical pharmacology
Information about the clinical pharmacology and actions of the drug in humans.12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action ADSTILADRIN is a non-replicating adenoviral vector-based gene therapy designed to deliver a copy of a gene encoding a human interferon-alfa 2b (IFNα2b) to the bladder urothelium. Intravesical instillation of ADSTILADRIN results in cell transduction and transient local expression of the IFNα2b protein that is anticipated to have anti-tumor effects. 12.2 Pharmacodynamics A Phase 1 first-in-human study was performed to determine the safety, tolerability, and maximum tolerated dose (MTD) of ADSTILADRIN in 17 patients with BCG-unresponsive NMIBC. Five dose levels (3 x 10 9 vp/mL, 1 x 10 10 vp/mL, 3 x 10 10 vp/mL, 1 x 10 11 vp/mL, and 3 x 10 11 vp/mL; all in a dose volume of 75 mL) of ADSTILADRIN were tested and quantifiable concentrations of the pharmacodynamic marker IFNα2b protein were detected in the urine of all patients, with the exception of two patients at the lowest dose level. Measurable concentrations of urine IFNα2b protein up to Day 10 post-dose suggested expression of IFNα2b in the bladder. In a Phase 2 study, all patients had quantifiable concentrations of IFNα2b protein in the urine at Day 2 after dosing with ADSTILADRIN at two different dose levels (1 x 10 11 vp/mL and 3 x 10 11 vp/mL). Measurable concentrations of urine IFNα2b protein was detected up to Day 12 post-dose. This was more common in patients at the high dose level. Generally, higher IFNα2b concentrations and exposure were observed with increasing doses of ADSTILADRIN. 12.3 Pharmacokinetics Nonclinical data Human IFN protein in urine, and vector-specific DNA in blood and tissue samples, were detectable following ADSTILADRIN dosing in monkeys, with higher levels at higher doses. All monkeys had vector-specific DNA in the bladder tissue at necropsy on Days 8 and 98 (i.e., seven days after the first and second dose, respectively). Vector-specific DNA was also detected in a limited number of monkeys in the liver, kidney and gonad. At Day 148, only one animal showed vector-specific DNA in one tissue (kidney). Clinical data ADSTILADRIN biodistribution and shedding were investigated in two clinical studies. Only a single patient receiving a second dose in one study (Phase 2 study) at dose level of 3 x 10 11 vp/mL (2.25 x 10 13 vp) had measurable vector DNA in blood; no other patients in either study had measurable vector DNA at one hour post-dosing in blood. In urine, measurable vector DNA was detected in both studies. Generally, a higher frequency of detection of urine samples positive for vector-derived DNA, and persistence of vector-derived DNA, correlated with increasing dose level. At the dose level of 3 x 10 11 vp/mL (2.25 x 10 13 vp), one patient (out of 4 enrolled) had detectable levels of vector DNA at Day 14 in the Phase 1 study and 16 subjects (out of 19 at visit) had detectable levels of vector DNA at Day 12 in the Phase 2 study.
Mechanism of action
Information about the established mechanism(s) of the drugÕs action in humans at various levels (for example receptor, membrane, tissue, organ, whole body). If the mechanism of action is not known, this field contains a statement about the lack of information.12.1 Mechanism of Action ADSTILADRIN is a non-replicating adenoviral vector-based gene therapy designed to deliver a copy of a gene encoding a human interferon-alfa 2b (IFNα2b) to the bladder urothelium. Intravesical instillation of ADSTILADRIN results in cell transduction and transient local expression of the IFNα2b protein that is anticipated to have anti-tumor effects.
Pharmacodynamics
Information about any biochemical or physiologic pharmacologic effects of the drug or active metabolites related to the drugÕs clinical effect in preventing, diagnosing, mitigating, curing, or treating disease, or those related to adverse effects or toxicity.12.2 Pharmacodynamics A Phase 1 first-in-human study was performed to determine the safety, tolerability, and maximum tolerated dose (MTD) of ADSTILADRIN in 17 patients with BCG-unresponsive NMIBC. Five dose levels (3 x 10 9 vp/mL, 1 x 10 10 vp/mL, 3 x 10 10 vp/mL, 1 x 10 11 vp/mL, and 3 x 10 11 vp/mL; all in a dose volume of 75 mL) of ADSTILADRIN were tested and quantifiable concentrations of the pharmacodynamic marker IFNα2b protein were detected in the urine of all patients, with the exception of two patients at the lowest dose level. Measurable concentrations of urine IFNα2b protein up to Day 10 post-dose suggested expression of IFNα2b in the bladder. In a Phase 2 study, all patients had quantifiable concentrations of IFNα2b protein in the urine at Day 2 after dosing with ADSTILADRIN at two different dose levels (1 x 10 11 vp/mL and 3 x 10 11 vp/mL). Measurable concentrations of urine IFNα2b protein was detected up to Day 12 post-dose. This was more common in patients at the high dose level. Generally, higher IFNα2b concentrations and exposure were observed with increasing doses of ADSTILADRIN.
Pharmacokinetics
Information about the clinically significant pharmacokinetics of a drug or active metabolites, for instance pertinent absorption, distribution, metabolism, and excretion parameters.12.3 Pharmacokinetics Nonclinical data Human IFN protein in urine, and vector-specific DNA in blood and tissue samples, were detectable following ADSTILADRIN dosing in monkeys, with higher levels at higher doses. All monkeys had vector-specific DNA in the bladder tissue at necropsy on Days 8 and 98 (i.e., seven days after the first and second dose, respectively). Vector-specific DNA was also detected in a limited number of monkeys in the liver, kidney and gonad. At Day 148, only one animal showed vector-specific DNA in one tissue (kidney). Clinical data ADSTILADRIN biodistribution and shedding were investigated in two clinical studies. Only a single patient receiving a second dose in one study (Phase 2 study) at dose level of 3 x 10 11 vp/mL (2.25 x 10 13 vp) had measurable vector DNA in blood; no other patients in either study had measurable vector DNA at one hour post-dosing in blood. In urine, measurable vector DNA was detected in both studies. Generally, a higher frequency of detection of urine samples positive for vector-derived DNA, and persistence of vector-derived DNA, correlated with increasing dose level. At the dose level of 3 x 10 11 vp/mL (2.25 x 10 13 vp), one patient (out of 4 enrolled) had detectable levels of vector DNA at Day 14 in the Phase 1 study and 16 subjects (out of 19 at visit) had detectable levels of vector DNA at Day 12 in the Phase 2 study.
Contraindications
Information about situations in which the drug product is contraindicated or should not be used because the risk of use clearly outweighs any possible benefit, including the type and nature of reactions that have been reported.4 CONTRAINDICATIONS ADSTILADRIN is contraindicated in patients with prior hypersensitivity reactions to interferon alfa or to any component of the product [ see Description ( 11 ) ]. ADSTILADRIN is contraindicated in patients with hypersensitivity to interferon alfa or any component of the product. ( 4 )
Description
General information about the drug product, including the proprietary and established name of the drug, the type of dosage form and route of administration to which the label applies, qualitative and quantitative ingredient information, the pharmacologic or therapeutic class of the drug, and the chemical name and structural formula of the drug.11 DESCRIPTION ADSTILADRIN (nadofaragene firadenovec-vncg) is a non-replicating adenoviral vector-based gene therapy for intravesical instillation. It is a recombinant adenovirus serotype 5 vector containing a transgene encoding the human interferon alfa-2b (IFNα2b). ADSTILADRIN has a nominal concentration of 3 x 10 11 vp/mL. A single-use vial of ADSTILADRIN contains an extractable volume of 20 mL and the following excipients: [N-(3-cholamidopropyl)-N-(3-lactobionamidopropyl)]-cholamide (Syn3) (0.95 mg/mL), citric acid monohydrate (0.01 mg/mL), glycerol (84 mg/mL), hydroxypropyl-beta-cyclodextrin (7.9 mg/mL), magnesium chloride hexahydrate (0.34 mg/mL), polysorbate 80 (Tween 80) (0.48 mg/mL), sodium dihydrogen phosphate dihydrate (1.4 mg/mL), sucrose (17 mg/mL), tri-sodium citrate dihydrate (0.04 mg/mL), tromethamine (1.4 mg/mL) and Water for Injection (q.s. 1 mL). ADSTILADRIN is a sterile, clear to opalescent suspension, and contains no preservative.
Dosage and administration
Information about the drug product’s dosage and administration recommendations, including starting dose, dose range, titration regimens, and any other clinically sigificant information that affects dosing recommendations.2 DOSAGE AND ADMINISTRATION Important Administration Instructions ADSTILADRIN is for intravesical instillation only. ADSTILADRIN is not for intravenous use, topical use, or oral administration. Premedication with an anticholinergic is recommended before each instillation of ADSTILADRIN. ( 2.1 ) Administer ADSTILADRIN by intravesical instillation only. ( 2.1 ) ADSTILADRIN is not for intravenous use, topical use, or oral administration. The dose is 75 mL of ADSTILADRIN at a concentration of 3 x 10 11 viral particles (vp)/mL, instilled once every three (3) months. ( 2.1 ) Allow ADSTILADRIN to be left in the bladder for 1 hour following instillation 2.1 Dose The recommended dose of ADSTILADRIN is 75 mL at a concentration of 3 x 10 11 viral particles (vp)/mL instilled once every three (3) months into the bladder via a urinary catheter [ see Dosage and Administration ( 2.2 ) ]. Premedication with an anti-cholinergic is recommended before each instillation of ADSTILADRIN. 2.2 Preparation and Handling ADSTILADRIN is a non-replicating adenoviral vector-based gene therapy. Follow universal biosafety precautions for handling. Individuals who are immunosuppressed or immune-deficient, should not prepare, administer, or come into contact with ADSTILADRIN [ see Warnings and Precautions ( 5 ) ]. ADSTILADRIN is provided as a sterile frozen suspension. Thaw four (4) vials of ADSTILADRIN at room temperature (20°C to 25°C [68°F to 77 ° F]) until ADSTILADRIN is liquid. Do not expose the vials to higher temperatures. Protect from light. ADSTILADRIN must be brought to room temperature (20°C to 25°C [68°F to 77°F]) prior to use. The time for thawing and bringing ADSTILADRIN to room temperature is approximately 8-10 h when thawing in the cardboard nest and approximately 3-5 h when thawing the vials outside the cardboard nest. DO NOT Refreeze. Once the vial thawing procedure is initiated, the vials may be stored for up to 24 hours at room temperature or refrigerated at 2°C to 8°C (36°F to 46°F). Visually inspect all 4 vials for visible particles and discoloration. The suspension is clear to slightly opalescent and may contain opalescent flecks. Do not use if visible particles or discoloration are observed. Mix gently. Do not shake. Items required for instillation: • Four (4) thawed vials of ADSTILADRIN • Four (4) vented vial adaptors suitable for a standard 20 mLvial • Two (2) standard 50 or 60 mL polypropylene Luer lock syringes or one (1) Luer lock syringe equal to or greater than 75 mL (max 100 mL) • Two (2) Luer lock adaptors - One (1) straight, or intermittent, urethral catheter with a proximal funnel opening that will accommodate the Luer lock adapter. - Use only catheters made of vinyl/PVC (uncoated or coated with hydrogel), red rubber latex or silicone to instill ADSTILADRIN. Do not use catheters coated or embedded with silver or antibiotics. 1. Using aseptic technique, remove the cap from an ADSTILADRIN vial and attach a vented vial adapter according to manufacturer's instructions. 2. Connect the syringe to the vial adaptor and withdraw the contents of the vial into the syringe. Repeat steps 1-2 for the remaining three (3) vials until 75 mL has been withdrawn into one (1) or two (2) syringes. The volumes in the syringes do not have to be equal. 3. Discard any remaining volume according to universal precautions. Use ADSTILADRIN within 1 hour of drawing into syringe. Treat any ADSTILADRIN spills with a virucidal agent (such as sodium hypochlorite with 0.5% active chlorine or 6% hydrogen peroxide solution) for 15 minutes. Disposable materials that have come into contact with ADSTILADRIN should be placed in biohazard containers for destruction. Non-disposable equipment may be decontaminated according to the facility's standard operating procedures. [ see Patient Counseling Information ( 17 ) ]. 2.3 Bladder instillation of ADSTILADRIN Premedication with an anticholinergic before each instillation of ADSTILADRIN is recommended. ADSTILADRIN must be brought to room temperature before administration. Use ADSTILADRIN within 24 hours after taking it out from the freezer. Before administering ADSTILADRIN to the patient, insert one straight, or intermittent, urinary catheter with a proximal funnel opening that will accommodate the Luer lock adapter. Use only catheters made of vinyl/PVC (uncoated or coated with hydrogel), red rubber latex or silicone to instill ADSTILADRIN. Do not use catheters coated or embedded with silver or antibiotics. Use the catheter to completely empty the patient's bladder before instillation of ADSTILADRIN. Do not remove the catheter. Attach the Luer lock end of the same catheter adaptor to the syringe containing ADSTILADRIN and insert the tapered end of the catheter adaptor into the funnel opening of the catheter. Slowly instill 75 mL of ADSTILADRIN into the bladder through the catheter, ensuring that the complete volume is administered. After the instillation, ADSTILADRIN should be retained in the bladder for 1 hour. During the 1 hour dwell time, the patient should reposition approximately every 15 minutes from left to right, back and abdomen to maximize bladder surface exposure. If, during the dwell time, the patient exhibits bladder cramping or premature voiding, repositioning of the patient may be adjusted or discontinued. Evacuate ADSTILADRIN from the bladder as part of routine emptying of the bladder, or the patient may void and completely empty the bladder after 1 hour has elapsed. Voided urine should be disinfected for 15 minutes with an equal volume of virucidal agent before flushing of the toilet. [ see Patient Counseling Information ( 17 ) ].
Dosage forms and strengths
Information about all available dosage forms and strengths for the drug product to which the labeling applies. This field may contain descriptions of product appearance.3 DOSAGE FORMS AND STRENGTHS ADSTILADRIN is a sterile, clear to opalescent suspension for intravesical instillation, supplied as single-use vials. ADSTILADRIN is provided in a carton containing four (4) vials. All vials have a nominal concentration of 3 × 10 11 viral particles (vp)/mL. Each vial of ADSTILADRIN contains an extractable volume of not less than 20 mL. ADSTILADRIN is a suspension for intravesical instillation, supplied as single-use vials. ( 3 ) ADSTILADRIN is provided in a carton containing four (4) vials. All vials have a nominal concentration of 3 × 10 11 viral particles (vp)/mL. Each vial of ADSTILADRIN contains an extractable volume of not less than 20 mL. ( 3 )
Indications and usage
A statement of each of the drug products indications for use, such as for the treatment, prevention, mitigation, cure, or diagnosis of a disease or condition, or of a manifestation of a recognized disease or condition, or for the relief of symptoms associated with a recognized disease or condition. This field may also describe any relevant limitations of use.1 INDICATIONS AND USAGE ADSTILADRIN ® is indicated for the treatment of adult patients with high-risk Bacillus Calmette-Guérin (BCG)-unresponsive non-Muscle Invasive Bladder Cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors. ADSTILADRIN is a non-replicating adenoviral vector-based gene therapy indicated for the treatment of adult patients with high-risk Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors. ( 1 )
Spl product data elements
Usually a list of ingredients in a drug product.ADSTILADRIN nadofaragene firadenovec-vncg NADOFARAGENE FIRADENOVEC NADOFARAGENE FIRADENOVEC (N-(3-CHOLAMIDOPROPYL)-N-(3-LACTOBIONAMIDOPROPYL))CHOLAMIDE CITRIC ACID MONOHYDRATE TRISODIUM CITRATE DIHYDRATE POLYSORBATE 80 HYDROXYPROPYL BETADEX SODIUM PHOSPHATE, MONOBASIC, DIHYDRATE TROMETHAMINE SUCROSE MAGNESIUM CHLORIDE GLYCERIN WATER
Animal pharmacology and or toxicology
Information from studies of the drug in animals, if the data were not relevant to nor included in other parts of the labeling. Most labels do not contain this field.13.2 Animal Toxicology and/or Pharmacology In cynomolgus monkeys, two repeat intravesical administrations of ADSTILADRIN of either 2.5 x 10 11 or 1.25 x 10 13 viral particles (1 x 10 11 or 5x10 11 viral particles/mL, 90 days apart) were associated with inflammation, urothelial hyperplasia, cytoplasmic vacuolation, and focal/multifocal ulceration in the urinary bladder and irritation in the ureter and urethra at necropsy 7 days after the first and second doses. Near complete resolution of these findings was observed following the 57-day recovery period after the second administration, with minimal fibrosis in the lamina propria of the bladder in a limited number of monkeys. Both dose level groups developed antibodies to the adenovirus and human interferon protein.
Carcinogenesis and mutagenesis and impairment of fertility
Information about carcinogenic, mutagenic, or fertility impairment potential revealed by studies in animals. Information from human data about such potential is part of the warnings field.13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility No animal studies have been conducted to evaluate the effects of ADSTILADRIN on carcinogenesis, mutagenesis, or impairment of fertility.
Nonclinical toxicology
Information about toxicology in non-human subjects.13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility No animal studies have been conducted to evaluate the effects of ADSTILADRIN on carcinogenesis, mutagenesis, or impairment of fertility. 13.2 Animal Toxicology and/or Pharmacology In cynomolgus monkeys, two repeat intravesical administrations of ADSTILADRIN of either 2.5 x 10 11 or 1.25 x 10 13 viral particles (1 x 10 11 or 5x10 11 viral particles/mL, 90 days apart) were associated with inflammation, urothelial hyperplasia, cytoplasmic vacuolation, and focal/multifocal ulceration in the urinary bladder and irritation in the ureter and urethra at necropsy 7 days after the first and second doses. Near complete resolution of these findings was observed following the 57-day recovery period after the second administration, with minimal fibrosis in the lamina propria of the bladder in a limited number of monkeys. Both dose level groups developed antibodies to the adenovirus and human interferon protein.
Package label principal display panel
The content of the principal display panel of the product package, usually including the product’s name, dosage forms, and other key information about the drug product.PRINCIPAL DISPLAY PANEL - Outer Carton NDC 55566-1050-1 Rx Only nadofaragene firadenovec-vncg ADSTILADRIN 75 mL Intravesical Suspension Each carton contains 4 x 20 mL vials Each vial contains 3 x 10 11 viral particles/mL No U.S. standard of potency For Intravesical Instillation Only Sterile suspension Preservative free Discard unused portion U.S. Licence No. 2222 Manufactured for Ferring Pharmaceuticals A/S, 2770 Kastrup, Denmark by FinVector Oy, Kuopio, Finland Principal Display Panel - Outer Carton
ADSTILADRIN: Information for patients
Information necessary for patients to use the drug safely and effectively, such as precautions concerning driving or the concomitant use of other substances that may have harmful additive effects.17 PATIENT COUNSELING INFORMATION Risk of Metastatic Bladder Cancer with Delayed Cystectomy Inform patients that delaying cystectomy in patients with BCG-unresponsive CIS could lead to development of muscle-invasive or metastatic bladder cancer. Discuss the risk of muscle-invasive or metastatic bladder cancer and that the risk increases the longer cystectomy is delayed in the presence of persisting CIS [ see Warnings and Precautions ( 5.1 ) ] . Risk of Disseminated Adenovirus Infection Inform patients and their caregivers that treatment or contact with ADSTILADRIN in those who are immunocompromised, including those receiving immunosuppressive therapy, may increase the risk for disseminated adenovirus infection [ see Warnings and Precautions ( 5.2 ) ] . Shedding of ADSTILADRIN Inform patients and their caregivers that transient and low‑level shedding of ADSTILADRIN may occur in urine. Instruct patients and their caregivers that for 2 days following treatment, voided urine should be disinfected for 15 minutes with an equal volume of bleach before flushing [ see Dosage and Administration ( 2.2 ) ] . Manufactured for: Ferring Pharmaceuticals 2770 Kastrup, Denmark by: FinVector Oy. Kuopio, Finland U.S. License No. 2222 ADSTILADRIN ® is a trademark of Ferring Pharmaceuticals BV. ADS-PI-001
Spl patient package insert
Information necessary for patients to use the drug safely and effectively.PATIENT INFORMATION ADSTILADRIN ® (add-STILL-a-drin) (nadofaragene firadenovec-vncg) Suspension for Intravesical Use Read this Patient Information before you have each ADSTILADRIN treatment. This information is not comprehensive and there may be new information. How to get more information: Talk to your health care provider Call 1-888-337-7464 What is the most important information I should know about ADSTILADRIN? Individuals who are immunosuppressed or immune-deficient should not prepare, administer, receive or come into contact with ADSTILADRIN. What is ADSTILADRIN used for? ADSTILADRIN is a prescription medicine for the treatment of a certain type of bladder cancer. What is ADSTILADRIN? ADSTILADRIN is a therapy that contains a copy of the gene for human interferon alfa-2b. When administered into the bladder, the treatment delivers this gene, which is non-replicating, to cells in your bladder wall. Interferon alfa-2b has anti-tumor effects. The purpose of this gene therapy is to increase the level and length of time your bladder wall is exposed to interferon alfa-2b protein. You should not receive ADSTILADRIN if: You have a sensitivity to interferon alfa or any of its components. What should I tell my healthcare provider? Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. What are the possible side effects of ADSTILADRIN? The most common side effects of ADSTILADRIN include: Urinary discharge Fatigue Bladder spasm Urgency to urinate Blood in your urine These common side effects (above) are not all the possible side effects of ADSTILADRIN. For more information, ask your healthcare provider. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. You may also report side effects to Ferring Pharmaceuticals at 1-888-337-7464. How is ADSTILADRIN used? Once every 3 months your healthcare provider will administer 75 mL (about 2 and a half ounces) of ADSTILADRIN into your bladder through a urinary catheter and leave it there for 1 hour. During this time your healthcare provider may move you about every 15 minutes. What other information should I know about using ADSTILADRIN? Take these steps to prepare your toilet bowl after each treatment: Add about half a cup of bleach to the toilet bowl before you urinate After urinating, wait 15 minutes before flushing the toilet Repeat these steps every time you urinate for the first 2 days after treatment. For more information, call 1-888-337-7464 or talk with your health care provider. This Patient Information has been approved by the U.S. Food and Drug Administration. Issued: Dec. 2022 Rx Only Manufactured for: Ferring Pharmaceuticals 2770 Kastrup, Denmark By: FinVector Oy. Kuopio, Finland. ADSTILADRIN ® is a trademark of Ferring BV.
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Clinical studies
This field may contain references to clinical studies in place of detailed discussion in other sections of the labeling.14 CLINICAL STUDIES The efficacy of ADSTILADRIN was evaluated in CS-003 ( NCT02773849 ), an open-label, multicenter, single-arm trial in 103 adults with BCG-unresponsive, high-risk, non-muscle invasive bladder cancer with carcinoma in situ (CIS) with or without papillary tumors following transurethral resection, of whom 98 were considered evaluable for response. BCG-unresponsive high-risk NMIBC was defined as persistent disease following adequate BCG therapy, disease recurrence after an initial tumor-free state following adequate BCG therapy, or T1 disease following a single induction course of BCG. Adequate BCG was defined as the administration of at least five of six doses of an initial induction course plus either of: at least two of three doses of maintenance therapy or at least two of six doses of a second induction course. Prior to treatment, all patients had undergone transurethral resection of bladder tumor (TURBT) to remove all resectable disease (Ta and T1 components). Residual CIS (Tis components) not amenable to complete resection was allowed. The trial excluded patients with extra-vesical (i.e., urethra, ureter, or renal pelvis), muscle invasive (T2-T4), or metastatic urothelial carcinoma. Patients received ADSTILADRIN 75 mL intravesical instillation (3 x 10 11 vp) once every three months for up to 12 months (four doses) or until unacceptable toxicity or recurrent high-grade (HG) NMIBC. Patients without evidence of HG recurrence were allowed to continue ADSTILADRIN treatment every three months. The major efficacy outcome measures were complete response (CR) at any time (as defined by negative results for cystoscopy [with TURBT/biopsies as applicable] and urine cytology) and duration of response. Low-grade (Ta) papillary disease was not considered a recurrence for the purposes of evaluating CR. CR was assessed at 3, 6, 9, and 12 months by cystoscopy and cytology. Random bladder biopsy of five sites was conducted in patients remaining in CR at Month 12. Assessment of durability of CR subsequent to these evaluations was performed per local standards of care. The evaluable CIS study population characteristics were median age of 70 (range 44-89) with 32% >75 years of age; 88% male, 92% White. Tumor pattern at study entry was CIS with T1 (5%), CIS with high-grade Ta (19%), and CIS (76%). The median number of instillations of prior BCG was 12 (range 8 to 18). Efficacy results are summarized in Table 3. Table 3: Efficacy Results in Study CS-003 Efficacy Outcome Measure ADSTILADRIN (n=98) Complete Response Rate, % (95% CI) 51% (41%, 61%) Duration of Response Based on patients (n=50) that achieved a complete response; reflects period from the time complete response was achieved. Median in months (range) 9.7 (3, 52+) % with duration ≥ 12 months 46%
| 51% (41%, 61%) | |
| Median in months (range) | 9.7 (3, 52+) |
| % with duration ≥ 12 months | 46% |
Geriatric use
Information about any limitations on any geriatric indications, needs for specific monitoring, hazards associated with use of the drug in the geriatric population.8.5 Geriatric Use Clinical studies of ADSTILADRIN in BCG-unresponsive high-risk NMIBC with CIS did not include sufficient numbers of patients younger than 65 years of age to determine whether safety and effectiveness differ from older patients.
Pediatric use
Information about any limitations on any pediatric indications, needs for specific monitoring, hazards associated with use of the drug in any subsets of the pediatric population (such as neonates, infants, children, or adolescents), differences between pediatric and adult responses to the drug, and other information related to the safe and effective pediatric use of the drug.8.4 Pediatric Use Safety and effectiveness of ADSTILADRIN in pediatric patients have not been established.
Pregnancy
Information about effects the drug may have on pregnant women or on a fetus. This field may be ommitted if the drug is not absorbed systemically and the drug is not known to have a potential for indirect harm to the fetus. It may contain information about the established pregnancy category classification for the drug. (That information is nominally listed in the teratogenic_effects field, but may be listed here instead.)8.1 Pregnancy Risk Summary Adequate and well-controlled studies with ADSTILADRIN have not been conducted in pregnant women. Animal reproductive and developmental toxicity studies have not been conducted with ADSTILADRIN. Advise pregnant women of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
Use in specific populations
Information about use of the drug by patients in specific populations, including pregnant women and nursing mothers, pediatric patients, and geriatric patients.8 USE IN SPECIFIC POPULATIONS Immunocompromise/immunodeficiency: Avoid in patients with immunocompromise or immunodeficiency. ( 8 ) 8.1 Pregnancy Risk Summary Adequate and well-controlled studies with ADSTILADRIN have not been conducted in pregnant women. Animal reproductive and developmental toxicity studies have not been conducted with ADSTILADRIN. Advise pregnant women of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. 8.2 Lactation Risk Summary There is no information regarding the presence of ADSTILADRIN in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for ADSTILADRIN and any potential adverse effects on the breastfed infant from ADSTILADRIN or from the underlying maternal condition. 8.3 Females and Males of Reproductive Potential No nonclinical or clinical studies were performed to evaluate the effect of ADSTILADRIN on fertility. Pregnancy Testing Verify pregnancy status in females of reproductive potential prior to initiating ADSTILADRIN. Contraception Females Advise females of reproductive potential to use effective contraception during treatment with ADSTILADRIN and for 6 months following the last dose. Males Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ADSTILADRIN and for 3 months following the last dose. 8.4 Pediatric Use Safety and effectiveness of ADSTILADRIN in pediatric patients have not been established. 8.5 Geriatric Use Clinical studies of ADSTILADRIN in BCG-unresponsive high-risk NMIBC with CIS did not include sufficient numbers of patients younger than 65 years of age to determine whether safety and effectiveness differ from older patients. 8.6 Gender-specific Use In clinical studies with ADSTILADRIN, no overall differences in safety or efficacy were observed between females and males.
How supplied
Information about the available dosage forms to which the labeling applies, and for which the manufacturer or distributor is responsible. This field ordinarily includes the strength of the dosage form (in metric units), the units in which the dosage form is available for prescribing, appropriate information to facilitate identification of the dosage forms (such as shape, color, coating, scoring, and National Drug Code), and special handling and storage condition information.16 HOW SUPPLIED/STORAGE AND HANDLING ADSTILADRIN is shipped frozen at ≤ -60°C (≤ -76°F) in an insulated shipping box that will maintain the required temperature for a minimum of 72 hours after being sealed. Each carton (NDC 55566-1050-1) contains a removable cardboard nest of four (4) clear glass vials of ADSTILADRIN. Each vial (NDC 55566-1050-0) contains a sterile frozen suspension with an extractable volume of 20 mL and is sealed with a bromobutyl rubber stopper and a tamper-evident aluminum crimp. Upon receipt, cartons of ADSTILADRIN can be stored as indicated below: In a freezer ≤ -60°C (≤ -76°F) until expiry date printed on the carton. In a freezer between -25°C to -15°C (-13°F to 5°F) up to 3 months, without exceeding the original expiry date printed on the vial and outer carton. When stored in freezer, the date of placement in freezer should be noted. In addition, the date for when the carton should be discarded if not used, must be written on the outer carton. These dates should be three months apart but should not past the original expiry date. This discard date supersedes the original expiry date. The vials may be stored for up to 24 hours at room temperature or refrigerated once it is taken out of the freezer. When thawed, ADSTILADRIN is a clear to opalescent suspension, with nominal concentration of 3 × 10 11 viral particles (vp)/mL. • Protect the vials from light. [ see Dosage and Administration ( 2.2 ) ]. • DO NOT REFREEZE • ADSTILADRIN is a non-replicating adenoviral vector-based gene therapy. Follow universal biosafety precautions for handling [ see Dosage and Administration ( 2.2 ) ]. • Dispose of unused product and disposable materials that may have come in contact with ADSTILADRIN in accordance with local biosafety guidelines applicable for handling and disposal of the biohazard waste.
Disclaimer: Do not rely on openFDA or Phanrmacy Near Me to make decisions regarding medical care. While we make every effort to ensure that data is accurate, you should assume all results are unvalidated. Source: OpenFDA, Healthporta Drugs API