Hexvix

What Is Hexvix and What Is It Used For?

Hexvix (hexaminolevulinat) is a diagnostic medicine that is instilled into the bladder to help urologists detect bladder cancer more effectively during cystoscopy. It is not a treatment – it is used solely for diagnostic purposes as part of a procedure known as blue light cystoscopy or photodynamic diagnosis (PDD).

Bladder cancer is one of the most common urological malignancies worldwide, with an estimated 600,000 new cases diagnosed each year according to the World Health Organization (WHO). Early and accurate detection is critical because it directly influences treatment outcomes and survival rates. However, certain types of bladder cancer – particularly flat lesions such as carcinoma in situ (CIS) – can be very difficult to see using conventional white light cystoscopy.

This is where Hexvix plays a vital role. The active substance in Hexvix is hexaminolevulinat, a photosensitising agent that is preferentially taken up by rapidly dividing cells, including cancer cells in the bladder lining. Once inside these cells, hexaminolevulinat is metabolised through the haem biosynthesis pathway into photoactive porphyrins, primarily protoporphyrin IX (PpIX). These porphyrins accumulate in neoplastic tissue at much higher concentrations than in normal bladder mucosa.

During the cystoscopy procedure, the urologist uses a special cystoscope equipped with both white light and blue light (wavelength 360–450 nm) capabilities. Under blue light illumination, the accumulated porphyrins in tumour cells emit a distinctive red-pink fluorescence, making cancerous lesions clearly visible against the normal blue-appearing bladder wall. This dramatic contrast allows the urologist to identify tumours and suspicious areas that may have been completely invisible under standard white light examination.

Clinical evidence strongly supports the use of Hexvix-enhanced blue light cystoscopy. Multiple randomised controlled trials and meta-analyses have demonstrated that this technique detects significantly more papillary tumours and, more importantly, up to 30–40% more flat lesions (CIS) compared to white light cystoscopy alone. The European Association of Urology (EAU) guidelines on non-muscle-invasive bladder cancer (NMIBC) recommend photodynamic diagnosis with hexaminolevulinat when available, particularly for initial evaluation and during transurethral resection of bladder tumours (TURBT).

What Should You Know Before Receiving Hexvix?

Before receiving Hexvix, inform your doctor if you have porphyria, a current urinary tract infection, have recently undergone BCG treatment or bladder surgery, or if you are pregnant or breastfeeding. These conditions may prevent you from receiving Hexvix or affect the accuracy of the diagnostic results.

Although Hexvix is a diagnostic agent rather than a systemic treatment medication, there are important factors your healthcare team must consider before administering it. Because Hexvix is given directly into the bladder and acts locally, systemic side effects are rare. However, certain conditions can interfere with the safety of the procedure or the reliability of the diagnostic results.

Contraindications

You should not receive Hexvix if any of the following apply to you:

• Allergy to hexaminolevulinat or to any of the other ingredients in the product, including the solvent used to dissolve the powder. If you have experienced an allergic reaction to Hexvix in the past, you must not receive it again.
• Porphyria – a rare, inherited group of blood disorders that affect the body's ability to produce haem. Because Hexvix works by being converted into porphyrins through the haem biosynthesis pathway, patients with porphyria may experience a dangerous accumulation of porphyrins, leading to severe symptoms such as abdominal pain, skin sensitivity, and neurological complications.

Warnings and Precautions

Talk to your doctor or nurse before receiving Hexvix if you have or have recently had any of the following:

• Urinary tract infection (UTI) or a burning sensation when urinating – active infection and inflammation of the bladder lining can cause false-positive fluorescence, making it harder for the urologist to distinguish between infected/inflamed tissue and cancerous tissue. Your doctor may choose to treat the infection first and reschedule the procedure.
• Recent BCG (Bacillus Calmette–Guérin) treatment – BCG is an immunotherapy instilled into the bladder to treat superficial bladder cancer. The intense inflammatory response caused by BCG can persist for several weeks and may interfere with the accuracy of fluorescence cystoscopy. Most urologists recommend waiting at least 90 days after BCG treatment before performing Hexvix-enhanced cystoscopy.
• Recent bladder surgery – surgical manipulation of the bladder wall can cause local inflammation and tissue changes that may produce false-positive fluorescence results. Your doctor will determine the appropriate waiting period before the Hexvix procedure can be performed.

It is important to note that these conditions do not make Hexvix itself dangerous; rather, they can compromise the diagnostic accuracy of the blue light cystoscopy by causing non-cancerous tissue to fluoresce. Your urologist will weigh the benefits of proceeding with the examination against the risk of inaccurate results and will make the best clinical decision for your individual circumstances.

Pregnancy and Breastfeeding

If you are pregnant, think you might be pregnant, planning to become pregnant, or breastfeeding, you should inform your doctor before receiving Hexvix. The safety of hexaminolevulinat during pregnancy and lactation has not been established in clinical studies. While systemic absorption of Hexvix from the bladder is minimal, your doctor will carefully assess the risks and benefits before proceeding. In most cases, the diagnostic procedure can be postponed until after pregnancy and breastfeeding unless there is an urgent clinical need.

Driving and Operating Machinery

Hexvix itself is not expected to impair your ability to drive or use machines. However, the cystoscopy procedure may cause temporary discomfort, and if sedation or anaesthesia is used during the procedure, you should follow your doctor's advice regarding when it is safe to drive. Some patients may experience mild dizziness or discomfort after cystoscopy, so it is advisable to arrange for someone to drive you home after the procedure, especially if it is your first cystoscopy.

Other Medicines and Hexvix

Tell your doctor if you are taking, have recently taken, or might take any other medicines. Because Hexvix is administered locally into the bladder and has minimal systemic absorption, significant drug interactions are not expected. However, your doctor should be aware of all medications you are taking, particularly those that may affect the urinary tract or the haem biosynthesis pathway.

There are no known clinically significant interactions with common prescription or over-the-counter medications. Unlike many systemic drugs, Hexvix does not undergo hepatic metabolism via cytochrome P450 enzymes and is not expected to affect the blood levels or efficacy of other medications you may be taking.

How Is Hexvix Used During Cystoscopy?

Hexvix is prepared and administered by trained healthcare professionals in a hospital or clinic setting. It is instilled into the bladder through a catheter and retained for approximately 60 minutes before cystoscopic examination under both white and blue light.

Hexvix is always prepared, handled, and administered by specially trained and authorised healthcare professionals. You will not need to prepare or administer it yourself. The entire procedure typically takes place in a hospital urology department or an outpatient clinic equipped with a compatible blue light cystoscope.

Preparation of the Solution

Hexvix is supplied as a powder (containing 85 mg of hexaminolevulinat) together with a pre-filled syringe containing 50 ml of solvent. A healthcare professional reconstitutes the powder by adding approximately 10 ml of the solvent to the vial, shaking gently to ensure complete dissolution, and then drawing the dissolved solution back into the syringe. The final reconstituted solution contains hexaminolevulinat at a concentration of 1.7 mg/ml (8 mmol/l). The solution should be clear to slightly opalescent and colourless to pale yellow. Once reconstituted, the solution must be used within 2 hours and should be stored at 2–8°C if not used immediately.

The Procedure Step by Step

The Hexvix-enhanced cystoscopy procedure follows a systematic protocol to ensure optimal diagnostic results:

1. Catheter insertion: A thin, flexible tube (urinary catheter) is gently inserted through the urethra into the bladder. This may cause brief discomfort but is generally well tolerated.
2. Bladder emptying: Any residual urine in the bladder is drained through the catheter to ensure the Hexvix solution comes into direct contact with the entire bladder wall.
3. Hexvix instillation: The reconstituted Hexvix solution (approximately 50 ml) is instilled into the bladder through the catheter using the pre-filled syringe.
4. Retention period: The solution is retained inside the bladder for approximately 60 minutes. During this time, the hexaminolevulinat is absorbed by the bladder lining cells, with preferential uptake by neoplastic (cancerous) cells. You may be asked to change position periodically to ensure the solution bathes all surfaces of the bladder.
5. Bladder emptying: After the retention period, the bladder is emptied through the catheter to remove the Hexvix solution.
6. Cystoscopic examination: The urologist inserts a cystoscope (a thin instrument with a camera and light source) through the urethra into the bladder. The examination is first performed under standard white light, followed by examination under blue light (360–450 nm). Under blue light, any tumour tissue containing accumulated porphyrins will emit a red-pink fluorescence, making it clearly visible.
7. Biopsy or resection: If suspicious areas are identified (either under white or blue light), the urologist may take biopsies or perform a transurethral resection of the lesion(s) during the same procedure.

If More Hexvix Is Used Than Intended

If Hexvix is retained in the bladder for longer than 60 minutes, or if a larger amount of solution is used than intended, no additional adverse effects are expected. The safety profile of Hexvix remains favourable even with extended contact times. However, if you have any concerns, speak with your doctor or nurse. Clinical studies have shown that retention times up to 3 hours do not significantly increase the risk of adverse effects, though the fluorescence quality may diminish after approximately 90 minutes.

What Are the Side Effects of Hexvix?

Most side effects associated with Hexvix are related to the cystoscopy procedure itself rather than the Hexvix solution. Common side effects include bladder spasms, blood in the urine, pain during urination, and nausea. These are typically mild and resolve within a few days. Serious side effects are rare.

Like all medicines, Hexvix can cause side effects, although not everybody experiences them. It is important to understand that many of the side effects listed below are associated with the cystoscopy examination technique rather than with Hexvix itself. The addition of Hexvix as a complementary procedure to standard cystoscopy is generally well tolerated. When side effects do occur, they are usually not serious and do not last long.

Most of these side effects are directly attributable to the mechanical and procedural aspects of cystoscopy – catheter insertion, bladder distension, and tissue manipulation – rather than to the chemical properties of Hexvix. Studies comparing blue light cystoscopy with Hexvix to standard white light cystoscopy have shown no significant difference in the overall incidence or severity of adverse events between the two approaches.

If you experience any side effects that concern you, or if any side effect becomes severe or persistent, contact your doctor or nurse. It is also important to report any suspected side effects to your national pharmacovigilance authority, as post-marketing surveillance helps to continually monitor the safety profile of medicines.

Managing Common Side Effects

After the Hexvix cystoscopy procedure, you can take several steps to manage common side effects:

• Drink plenty of fluids: Increasing your fluid intake helps flush the bladder and urethra, reducing irritation and helping to clear any blood in the urine more quickly.
• Pain relief: Over-the-counter pain relievers such as paracetamol (acetaminophen) can help with procedural discomfort. Avoid aspirin or ibuprofen if you have blood in the urine, as these may increase bleeding.
• Rest: Most patients can resume normal activities the day after the procedure, but listen to your body and rest if needed.
• Monitor symptoms: Mild blood in the urine and burning during urination typically resolve within 24–48 hours. If these symptoms persist beyond 3 days or worsen, contact your healthcare team.

How Should Hexvix Be Stored?

Hexvix is stored and handled by healthcare professionals. The unopened powder and solvent have no special storage requirements. Once reconstituted, the solution must be stored at 2–8°C and used within 2 hours.

As a patient, you will not need to store or handle Hexvix yourself, as it is always prepared and administered in a clinical setting. However, the following storage information is relevant for healthcare facilities:

• Unopened product: The powder and pre-filled syringe have no special storage requirements and can be stored at room temperature. Keep the product out of the sight and reach of children.
• After reconstitution: The prepared solution should be stored in a refrigerator (2–8°C) and must be used within 2 hours of preparation. Chemical and physical stability of the solution has been demonstrated for 2 hours at 2–8°C.
• Expiry date: Do not use Hexvix after the expiry date stated on the outer packaging. The expiry date refers to the last day of the stated month.
• Disposal: Hexvix is for single use only. Any unused solution must be discarded. Healthcare staff are responsible for proper storage, handling, and disposal of the product.

From a microbiological perspective, the reconstituted product should ideally be used immediately after preparation. If not used immediately, the in-use storage time and conditions are the responsibility of the healthcare professional and should normally not exceed 2 hours at 2–8°C.

What Does Hexvix Contain?

Hexvix contains 85 mg of hexaminolevulinat hydrochloride as the active ingredient, packaged with a 50 ml solvent for reconstitution. The product is supplied as a powder in a vial together with a pre-filled syringe.

Active Ingredient

The active substance is hexaminolevulinat (as the hydrochloride salt). Each vial contains 85 mg of hexaminolevulinat. When reconstituted with the supplied solvent, the resulting solution has a concentration of 1.7 mg/ml (8 mmol/l). Hexaminolevulinat is a synthetic derivative of aminolevulinic acid (ALA), which is a naturally occurring precursor in the haem biosynthesis pathway. The hexyl ester modification improves cellular uptake compared to ALA itself, resulting in higher intracellular porphyrin accumulation and stronger fluorescence in neoplastic tissue.

Other Ingredients (Excipients)

The other ingredients in Hexvix are:

• Disodium phosphate dihydrate (buffering agent)
• Potassium dihydrogen phosphate (buffering agent)
• Sodium chloride (isotonicity agent)
• Hydrochloric acid (pH adjustment)
• Sodium hydroxide (pH adjustment)
• Water for injections (solvent)

Appearance and Packaging

Each Hexvix package contains:

• One vial with a white to off-white or pale yellow powder containing 85 mg hexaminolevulinat
• One pre-filled syringe (with or without a Mini-Spike transfer device) containing 50 ml of clear, colourless solvent

When reconstituted, the solution is clear to slightly opalescent and colourless to pale yellow. The reconstituted solution is sterile and intended for single use only.

What Does the Clinical Evidence Say About Hexvix?

Multiple randomised controlled trials and meta-analyses have demonstrated that blue light cystoscopy with Hexvix detects more bladder tumours – particularly flat lesions such as carcinoma in situ – than standard white light cystoscopy alone, leading to more complete resections and potentially improved patient outcomes.

The clinical evidence supporting the use of Hexvix in blue light cystoscopy is robust and has been built through decades of research. The pivotal clinical trials that led to regulatory approval involved thousands of patients across multiple centres in Europe and North America.

Improved Detection Rates

The landmark phase III clinical trial published in the Journal of Urology demonstrated that blue light cystoscopy with hexaminolevulinat detected at least one additional bladder tumour in approximately 29% of patients compared to white light cystoscopy alone. The improvement was most pronounced for carcinoma in situ (CIS), the most aggressive form of flat bladder cancer, where detection rates improved by approximately 30–40%.

A subsequent meta-analysis by Burger et al. (2013), published in European Urology, analysed data from 12 studies involving over 2,200 patients and confirmed that Hexvix-enhanced blue light cystoscopy significantly improved the detection of both papillary tumours (Ta/T1) and CIS. The analysis also showed that the use of blue light cystoscopy was associated with a reduction in recurrence rates at 12 and 24 months follow-up, suggesting that improved initial detection leads to more complete tumour resection.

Guideline Recommendations

Based on the accumulated clinical evidence, several major urological associations have incorporated photodynamic diagnosis with hexaminolevulinat into their clinical guidelines:

Impact on Patient Outcomes

Beyond improved detection, the clinical significance of Hexvix-enhanced cystoscopy extends to meaningful patient outcomes. A prospective, randomised trial by Stenzl et al. (2010) showed that patients who underwent blue light cystoscopy with Hexvix experienced a significantly longer time to tumour recurrence compared to those examined with white light alone. At 9 months follow-up, the recurrence rate was 47% in the white light group compared to 34% in the blue light group.

These findings have been corroborated by real-world evidence from large registry studies and institutional series, consistently demonstrating that the adoption of blue light cystoscopy with Hexvix is associated with improved quality of TURBT, reduced residual tumour rates, and better long-term disease management. While the procedure does not directly treat cancer, the enhanced detection enables urologists to perform more thorough resections, which is the foundation of effective bladder cancer management.

Frequently Asked Questions About Hexvix