Cysview

Pregnancy Category: C

Lactation: Unknown whether distributed in breast milk, caution advised

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

Mechanism of Action

Hexaminolevulinate is an ester of aminolevulinic acid, a heme precursor; used as photoactive intermediate protoporphyrin IX (PpIX) and other photoactive porphyrins (PAPs); PpIX and PAPs referentially accumulate in neoplastic cells and are detected at light wavelengths of 360-450 to distinguish between cancerous and normal tissue

Pharmacokinetics

Half-Life: Biphasic; 39 minutes initial half-life, 76 hr terminal half-life

Absorption: 7% following 1 hr instillation

Metabolism: Rapidly by human blood

Bioavailability: 7% (intravesical)

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur:

• Blood in the urine
• burning while urinating
• difficult or painful urination
• frequent urge to urinate
• lower stomach pain or spasm

• Bloody or cloudy urine
• cough
• difficulty with breathing or swallowing
• dizziness
• fast heartbeat
• fever
• hives
• itching
• nausea
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• reddening of the skin, especially around the ears
• shortness of breath
• skin rash
• tightness in the chest
• unusual tiredness or weakness
• wheezing

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

• Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using Cysview while you are pregnant.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

• If you need to store this medicine at home, talk with your doctor, nurse, or pharmacist about how to store it.

Cysview is an optical imaging agent indicated for use in the cystoscopic detection of non-muscle invasive papillary cancer of the bladder among patients suspected or known to have lesion(s) on the basis of a prior cystoscopy. Cysview is used with the Karl Storz D-Light C Photodynamic Diagnostic (PDD) system to perform cystoscopy with the blue light setting (Mode 2) as an adjunct to the white light setting (Mode 1).

Limitations of Use

Cysview is not:

• a replacement for random bladder biopsies or other procedures used in the detection of bladder cancer [see Warnings and Precautions (5.2)].
• for repetitive use. The potential risks associated with repetitive exposure, including sensitization and adverse effects of blue light have not been evaluated [see Warnings and Precautions (5.1)].

Anaphylaxis

Anaphylaxis, including anaphylactoid shock, has been reported following administration of Cysview [see Adverse Reactions (6.2)]. Prior to and during use of the Cysview, have trained personnel and therapies available for the treatment of anaphylaxis. The safety of repetitive Cysview exposures has not been evaluated.

Failed Detection

Cysview may fail to detect some bladder tumors, including malignant lesions. Cysview is not a replacement for random biopsies or any other procedure usually performed in the cystoscopic evaluation for cancer. In the controlled clinical trial, Cysview failed to detect 10% of lesions confirmed as malignant within the study drug group [see Clinical Studies (14)]. Do not perform cystoscopy with blue light alone as malignant lesions can be missed unless the bladder is initially examined under white light [see Dosage and Administration (2.5)].

False Fluorescence

Fluorescent areas detected during blue light cystoscopy may not indicate a bladder mucosal lesion. In the controlled clinical study, biopsies from one of every four fluorescent areas showed neither dysplasia nor carcinoma, if the areas were not also identified during white light cystoscopy [see Clinical Studies (14)]. In addition to these false detections, fluorescent areas within the bladder mucosa may result from inflammation, cystoscopic trauma, scar tissue or bladder mucosal biopsy from a previous cystoscopic examination. The presence of urine and/or blood within the bladder may interfere with the detection of tissue fluorescence. To enhance the diagnostic utility of Cysview with the Karl Storz D-Light C PDD System:

• ensure the bladder is emptied of urine prior to the instillation of fluids at cystoscopy;
• biopsy/resect bladder mucosal lesions only following completion of both white light and blue light cystoscopy;

Anaphylaxis has been reported following exposure to Cysview [see Warnings and Precautions (5.1)].

Clinical Study 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.

In six clinical trials, safety data were obtained from 1,324 patients, aged 32 to 96 years with a median age of 69 years, all primarily Caucasian and approximately 75% male. All patients were evaluated after a single instillation of 50 mL solution of Cysview. Of these patients, 161 (12.2%) patients reported at least one adverse reaction. The most common adverse reaction was bladder spasm (reported in 2.2% of the patients) followed by dysuria, hematuria, and bladder pain. No patients experienced anaphylaxis. In the controlled clinical study, adverse reactions were similar in nature and rate between the study drug group and the control group [see Clinical Studies (14)].

Postmarketing Experience

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Anaphylactoid shock, hypersensitivity reactions, bladder pain, cystitis and abnormal urinalysis have been reported during post-marketing use of Cysview.

Cysview contains hexaminolevulinate hydrochloride, an optical imaging drug that in solution form is instilled intravesically for use with photodynamic blue light cystoscopy as an adjunct to white light cystoscopy. The chemical formula for hexaminolevulinate hydrochloride is C11H21NO3∙HCl. Its molecular weight is 251.76 and it has the following structural formula:

Cysview (hexaminolevulinate hydrochloride) for Intravesical Solution is intended for intravesical administration only after reconstitution with the supplied 50 mL DILUENT. Cysview (hexaminolevulinate hydrochloride) for Intravesical Solution and DILUENT for Cysview are supplied together as a kit. Cysview (hexaminolevulinate hydrochloride) for Intravesical Solution is supplied as a sterile, non-pyrogenic, freeze-dried, white to off-white or pale yellow, powder containing 100 mg of hexaminolevulinate hydrochloride (equivalent of 85 mg of hexaminolevulinate) in a 10 mL clear glass vials. The DILUENT for Cysview is a sterile, non-pyrogenic solution (pH 6) containing 0.61 mg/ mL disodium hydrogen phosphate, 0.58 mg/mL of potassium dihydrogen phosphate, 7.02 mg/mL of sodium chloride, hydrochloric acid, sodium hydroxide, and water for injection. It is a clear, colorless solution, free from visible particles, and is provided in a 50 mL polypropylene vial.

The reconstituted solution of Cysview contains 2 mg/ml of hexaminolevulinate hydrochloride and is colorless to pale yellow. It is free from visible particles and has a pH between 5.7 and 6.2.

Ask patients if they have:

• a diagnosis or a family history of porphyria
• allergy to aminolevulinic acid or prior exposure to Cysview
• gross hematuria
• had BCG immunotherapy or chemotherapy within the bladder.

Inform patients that Cysview should be retained in the bladder for 1 hour from instillation of Cysview to the start of the cystoscopic procedure. If the patient cannot hold Cysview for 1 hour, but needs to void and expel Cysview from the bladder, he or she may void and should then inform a health care professional.