About FDA

Hexaminolevulinate Hydrochloride

On May 28, 2010, the U.S. Food and Drug Administration (FDA) granted approval for hexaminolevulinate hydrochloride (Cysview for Intravesical Solution, Photocure ASA), as an optical imaging agent for use in combination with the Karl Storz Photodynamic Diagnostic D-Light C (PDD) System for cystoscopic detection of non-muscle invasive papillary cancer of the bladder for patients suspected or known to have lesion(s) on the basis of a prior cystoscopy.  The imaging agent is used with the PDD System to perform cystoscopy with the blue light setting (Mode 2) as an adjunct to the white light setting (Mode 1). 

Hexaminolevulinate hydrochloride, a heme precursor, is instilled into the bladder and concentrates within cells with enhanced generation of photoreactive porphyrins as occurs in neoplasia and/or inflammation.  After blue light excitation with the PDD System, the photoreactive bladder mucosa fluoresces red while other mucosa appears blue. 

The approval of hexaminolevulinate hydrochloride with the PDD System was based upon a clinical study that showed a single use of the imaging agent and PDD System resulted in the detection of a greater number of Ta and/or T1 bladder lesions, compared to standard (white light) cystoscopy.  Future clinical trials will assess the safety and efficacy of repetitive use of the product and its use in the detection of carcinoma in situ of the bladder. 

The safety and efficacy of hexaminolevulinate hydrochloride with the PDD System were evaluated in a prospective, multicenter, controlled clinical trial of 779 adult patients.  All patients had previously undergone cystoscopy and were known or suspected of having bladder cancer. Patients randomized to receive hexaminolevulinate hydrochloride had the imaging agent instilled into the bladder prior to cystoscopy.  After evacuation of the agent, bladder lesion mapping was performed initially using the PDD System in the white light mode followed by lesion mapping in the blue light mode.  Control group patients underwent only white light cystoscopy with lesion mapping.  All lesions were biopsied and histologic outcomes (the truth standard) were assessed at a central pathology laboratory.

The trial’s main objective was to demonstrate that more than 10% of patients within the hexaminolevulinate hydrochloride group had at least one Ta or T1 bladder cancer lesion detected only by blue light (i.e., the lesion was not detected with white light).  Within this group, 286 patients had one or more Ta and/or T1 lesion detected with either white light or blue light cystoscopy and 47 (16%) had at least one lesion detected only with blue light (p < 0.001). 

In the controlled clinical study, the imaging agent failed to detect 10% of malignant lesions.  False fluorescence (a false positive result) may also occur.  In the controlled clinical study, biopsies from 23% of fluorescent areas showed neither dysplasia nor carcinoma, if the areas were not also identified during white light cystoscopy.  False fluorescence may result from inflammation, cystoscopic trauma, scar tissue or a prior bladder mucosa biopsy.  The false positive rate for white light was 17%.

Overall, 1,324 patients were exposed to hexaminolevulinate hydrochloride in clinical studies.  Of these patients, 12% reported at least one adverse reaction.  The most common reactions were bladder spasm, dysuria, hematuria and bladder pain.  Within the controlled clinical study, the occurrence of adverse reactions was similar between the study drug and control group.  Hexaminolevulinate hydrochloride is currently marketed in Europe under the tradename Hexvix and in this post-marketing experience, anaphylactoid reactions have been reported.

Training in blue light cystoscopy with the PDD System is essential prior to the use of hexaminolevulinate hydrochloride.  The drug is supplied as a kit that contains the hexaminolevulinate hydrochloride powder (100 mg), a diluent (50 mL) and a Luer Lock urethral catheter adapter.  Following reconstitution, the hexaminolevulinate hydrochloride solution is administered into the bladder via a catheter.  Following retention of the imaging agent for one hour, the bladder is emptied and the PDD System cystoscopy performed in the white light mode followed by the blue light mode.  All suspicious bladder lesions are documented under both white and blue light and the lesions biopsied following completion of the blue light cystoscopy.  The safety and efficacy of repetitive use of hexaminolevulinate hydrochloride have not been assessed. 

Full prescribing information is available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/022555s000lbl.pdf

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).

Page Last Updated: 11/27/2015
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