Javlor

What Is Javlor and What Is It Used For?

Javlor (vinflunine) is a chemotherapy medicine belonging to the vinca alkaloid class of anticancer drugs. It is used to treat advanced or metastatic transitional cell carcinoma of the urothelial tract – the lining of the bladder and urinary system – in adults whose cancer has progressed after previous platinum-based chemotherapy.

Javlor contains the active substance vinflunine, a third-generation vinca alkaloid that represents an important advancement in the treatment of urothelial cancer. Vinca alkaloids are a well-established class of plant-derived anticancer agents that work by interfering with the internal scaffolding of cancer cells, specifically the microtubule system that is essential for cell division. By disrupting microtubule formation, vinflunine arrests cancer cells during mitosis (cell division) and triggers programmed cell death, known as apoptosis.

Urothelial carcinoma, also known as transitional cell carcinoma (TCC), is the most common type of bladder cancer and accounts for approximately 90% of all bladder malignancies. It arises from the transitional epithelium that lines the urinary tract, including the bladder, ureters, renal pelvis, and urethra. Advanced or metastatic urothelial carcinoma has a poor prognosis, and treatment options after first-line platinum-based chemotherapy have historically been limited.

Javlor was approved by the European Medicines Agency (EMA) for the treatment of advanced or metastatic transitional cell carcinoma of the urothelial tract after failure of a prior platinum-containing regimen. The approval was based on a pivotal phase III randomised controlled trial that demonstrated a statistically significant improvement in overall survival when Javlor was added to best supportive care compared with best supportive care alone. In this trial, median overall survival was 6.9 months in the Javlor group versus 4.6 months in the control group, representing a 22% reduction in the risk of death (hazard ratio 0.78, 95% CI 0.61–0.99).

It is important to understand that Javlor is a cytotoxic chemotherapy drug and is administered exclusively in hospital or specialist clinic settings under the supervision of physicians experienced in the use of anticancer medications. It is given as an intravenous infusion and is not available as an oral medication. Treatment decisions are made by a multidisciplinary oncology team based on the individual patient's disease status, performance status, and organ function.

What Should You Know Before Receiving Javlor?

Before starting Javlor, your oncologist will assess your blood counts, liver function, kidney function, and overall health status. You must not receive Javlor if you have a severe active infection, are breastfeeding, have critically low white blood cell or platelet counts, or are allergic to vinflunine or other vinca alkaloids.

Contraindications

You must not receive Javlor if any of the following apply to you:

• Allergy to vinflunine or other vinca alkaloids (vinblastine, vincristine, vindesine, vinorelbine) – cross-reactivity may occur within this drug class
• Severe infection present or occurring within the past two weeks – as Javlor suppresses the immune system, an active infection could become life-threatening
• Breastfeeding – vinflunine may pass into breast milk and harm the nursing infant
• Low white blood cell count (neutrophils below 1,500/mm³) and/or low platelet count (below 100,000/mm³) – Javlor further suppresses bone marrow function and could cause dangerous levels of blood cell depletion

Warnings and Precautions

Talk to your oncologist before receiving Javlor if you have or have had any of the following conditions:

• Liver problems – vinflunine is metabolised by the liver, and impaired liver function can lead to increased drug exposure and higher risk of toxicity. Dose adjustment may be required
• Kidney problems – patients with moderate to severe renal impairment require a reduced starting dose. Kidney function is routinely assessed before each cycle
• Heart problems – cardiac function should be evaluated before starting treatment, particularly in patients with a history of cardiac disease or prior exposure to cardiotoxic chemotherapy
• Neurological symptoms such as headache, altered mental state that could lead to confusion or coma, seizures, blurred vision, or high blood pressure – these may indicate posterior reversible encephalopathy syndrome (PRES), a rare but serious neurological condition that requires immediate discontinuation of treatment
• Constipation or history of bowel problems – particularly if you are taking opioid pain medications, have abdominal cancer, or have had abdominal surgery. Severe constipation, including paralytic ileus, can occur with vinca alkaloid therapy
• Previous pelvic radiotherapy – your doctor may reduce the starting dose due to reduced bone marrow reserve in the irradiated area

Your blood counts will be checked regularly before and during treatment, as myelosuppression (suppression of blood cell production) is a very common effect of Javlor. This includes monitoring of neutrophils (a type of white blood cell essential for fighting infection), red blood cells, and platelets. If your blood counts fall below safe levels, your doctor may delay treatment, reduce the dose, or discontinue therapy.

Use in Children and Adolescents

Javlor is not intended for use in children and adolescents. The safety and efficacy of vinflunine have not been established in the paediatric population (under 18 years of age). Urothelial carcinoma is exceedingly rare in children, and there are no clinical data to support the use of Javlor in this age group.

Pregnancy and Breastfeeding

Javlor can cause serious harm to an unborn baby. Women of childbearing potential must not become pregnant during treatment and must use highly effective contraception during therapy and for at least 7 months after the last dose. If you become pregnant while receiving Javlor, inform your oncologist immediately so that appropriate monitoring and counselling can be provided regarding the potential risks to the foetus.

Men receiving Javlor should use reliable contraception during treatment and for at least 4 months after the last dose. Vinflunine may cause irreversible infertility in men. Male patients who wish to have children in the future should be offered sperm banking (cryopreservation) before starting treatment. This should be discussed with your oncologist before the first cycle of chemotherapy.

Breastfeeding is contraindicated during Javlor treatment. It is not known whether vinflunine passes into human breast milk, but given its cytotoxic properties, a risk to the breastfed infant cannot be excluded. Women must stop breastfeeding before treatment begins.

Driving and Operating Machinery

Javlor can cause fatigue, dizziness, vertigo, visual disturbances, and fainting – all of which can impair your ability to drive or operate machinery safely. You should not drive or operate heavy machinery without first consulting your doctor. If you experience any of these symptoms, refrain from driving until they have fully resolved.

How Does Javlor Interact with Other Drugs?

Javlor can interact with several medications, particularly those processed by the CYP3A4 liver enzyme system. Strong CYP3A4 inhibitors (such as ketoconazole, itraconazole, and ritonavir) can increase vinflunine levels, while CYP3A4 inducers (such as rifampicin and St. John's Wort) can reduce its effectiveness. Always inform your oncologist about all medications, supplements, and herbal products you are taking.

Vinflunine is primarily metabolised by the liver enzyme CYP3A4. Drugs that inhibit or induce this enzyme can significantly alter vinflunine blood levels, potentially increasing toxicity or reducing efficacy. Additionally, certain drug combinations may increase the risk of specific side effects, particularly constipation and bone marrow suppression.

Major Interactions

Moderate Interactions

Always provide your oncology team with a complete list of all medications you are taking, including prescription drugs, over-the-counter medicines, vitamins, and herbal or dietary supplements. Some interactions may require dose adjustments, timing changes, or substitution with alternative medications to ensure safe and effective Javlor treatment.

What Is the Correct Dosage of Javlor?

The recommended dose of Javlor for adults is 320 mg/m² of body surface area, given as a 20-minute intravenous infusion every 3 weeks. Your oncologist will calculate the exact dose based on your height and weight, and may adjust it based on your age, kidney function, liver function, previous treatments, and any side effects you experience.

Javlor is always administered by qualified healthcare professionals experienced in the use of cytotoxic chemotherapy. The dose is calculated based on your body surface area (BSA), which is determined from your height and weight. Treatment is given in cycles of 21 days (3 weeks), and each cycle consists of a single infusion on day 1.

Standard Adult Dose

Dose Adjustments

Your oncologist may reduce the starting dose or adjust subsequent doses based on the following factors:

Dose Reductions for Toxicity

During treatment, your oncologist may reduce the dose, delay a cycle, or discontinue Javlor if you experience severe side effects. Common reasons for dose modification include:

• Severe neutropenia (very low white blood cell count) or febrile neutropenia (fever with low white cells)
• Severe constipation (grade 3–4, lasting more than 5 days despite laxative use)
• Severe mucositis (inflammation of the mouth lining)
• Other grade 3–4 non-haematological toxicities

Dose reductions are typically made in steps: from 320 to 280 mg/m², then to 250 mg/m². If further dose reduction below 250 mg/m² is needed, discontinuation of treatment is generally recommended.

How Javlor Is Administered

Javlor is a concentrate that must be diluted before administration. It is diluted in a 100 ml bag of sodium chloride 0.9% (normal saline) or glucose 5% solution. The diluted solution is then administered as an intravenous infusion over exactly 20 minutes.

After the Javlor infusion is completed, the vein is flushed with at least an equal volume of sodium chloride 0.9% solution to ensure complete drug delivery and reduce the risk of venous irritation.

What Are the Side Effects of Javlor?

The most common side effects of Javlor are low white blood cell counts (neutropenia), constipation, fatigue, nausea, vomiting, abdominal pain, hair loss, appetite loss, and injection site reactions. Blood counts are monitored before each cycle. Seek immediate medical attention if you develop fever, signs of infection, severe constipation, chest pain, or neurological symptoms.

Like all chemotherapy medicines, Javlor can cause side effects, although not everyone experiences them to the same degree. Most side effects are manageable with supportive care and dose adjustments. Your oncology team will monitor you closely throughout treatment and provide medications to prevent or treat side effects as needed.

If you experience any side effects not listed here, or if any side effect becomes severe, contact your oncology team immediately. Reporting suspected side effects through your national pharmacovigilance system helps ensure ongoing monitoring of the medicine's benefit-risk balance.

How Should Javlor Be Stored?

Javlor must be stored in a refrigerator (2°C–8°C) in its original packaging to protect from light. As a hospital-administered medication, you will not normally be responsible for storing Javlor. The diluted solution should be used immediately after preparation.

Javlor is a specialist hospital medicine, and its storage is managed by trained pharmacy and nursing staff. However, the following storage requirements apply:

• Unopened vials: Store in a refrigerator at 2°C to 8°C (36°F to 46°F). Keep in the original carton to protect from light.
• Diluted solution: The diluted infusion solution should be used immediately after preparation. If not used immediately, chemical and physical stability has been demonstrated for up to 24 hours at 2°C to 8°C and up to 24 hours at 25°C when protected from light. However, from a microbiological standpoint, immediate use is recommended.
• Light sensitivity: Both the concentrate and diluted solution are sensitive to light. The infusion bag should be protected from light until the moment of administration.

Keep all medicines out of the sight and reach of children. Do not use Javlor after the expiry date printed on the vial label (marked “EXP”). Any unused product or waste material must be disposed of in accordance with local requirements for cytotoxic agents.

What Does Javlor Contain?

Each millilitre of Javlor concentrate contains 25 mg of vinflunine (as ditartrate). The only other ingredient is water for injections. Javlor is a clear, colourless to pale yellow solution supplied in glass vials of 2 ml (50 mg), 4 ml (100 mg), or 10 ml (250 mg).

Active Ingredient

The active substance is vinflunine. Each ml of the concentrate contains 25 mg vinflunine (as vinflunine ditartrate). The three available vial sizes contain the following amounts:

• 2 ml vial: 50 mg vinflunine (as ditartrate)
• 4 ml vial: 100 mg vinflunine (as ditartrate)
• 10 ml vial: 250 mg vinflunine (as ditartrate)

Inactive Ingredient

The only other ingredient is water for injections. This simple formulation reflects the high aqueous solubility of vinflunine ditartrate, which does not require additional excipients for dissolution.

Appearance and Packaging

Javlor is a clear, colourless to pale yellow solution, supplied in colourless glass vials closed with a rubber stopper and sealed with an aluminium flip-off cap. The cap colour indicates the vial size:

• Yellow cap: 2 ml vial (50 mg)
• Pink cap: 4 ml vial (100 mg)
• Orange cap: 10 ml vial (250 mg)

Not all pack sizes may be marketed in all countries.

Marketing Authorisation Holder

Javlor is manufactured by Pierre Fabre Médicament, headquartered in Boulogne, France. Additional information about Javlor is available from the European Medicines Agency (EMA) website.

How Does Javlor Work in the Body?

Javlor works by binding to tubulin, a protein that forms microtubules – the structural scaffolding inside cells that is essential for cell division. By preventing microtubule assembly, vinflunine arrests cancer cells during mitosis and triggers programmed cell death (apoptosis). It has a unique interaction with tubulin that distinguishes it from older vinca alkaloids.

Microtubules are dynamic protein structures composed of alpha- and beta-tubulin subunits. They play a critical role in maintaining cell shape, intracellular transport, and most importantly, the formation of the mitotic spindle – the apparatus that separates chromosomes during cell division. Cancer cells, which divide rapidly and uncontrollably, are particularly dependent on functional microtubule dynamics.

Vinflunine binds to tubulin at or near the same binding sites used by other vinca alkaloids. However, its unique bis-fluorinated chemical structure gives it distinct binding characteristics. It inhibits the polymerisation of tubulin into microtubules more potently than it depolymerises existing ones, a profile that differs from classical vinca alkaloids like vincristine and vinblastine. This results in the disruption of the mitotic spindle, arresting cells at the metaphase stage of mitosis and ultimately leading to apoptosis.

In addition to its direct anti-mitotic effect, vinflunine has been shown to have anti-angiogenic properties, meaning it can inhibit the formation of new blood vessels that tumours need to grow and spread. This dual mechanism – disrupting cell division and impairing tumour blood supply – contributes to its anticancer activity in urothelial carcinoma.

Pharmacokinetic Profile

After intravenous administration, vinflunine exhibits linear pharmacokinetics across the therapeutic dose range. It is rapidly and extensively distributed into tissues, with a large volume of distribution (approximately 2,422 litres). Vinflunine is moderately bound to plasma proteins (approximately 66.7%).

Vinflunine is metabolised primarily by the liver enzyme CYP3A4 to produce its main active metabolite, 4-O-deacetyl vinflunine (DVFL). DVFL is pharmacologically active but circulates at lower concentrations than the parent compound. The terminal elimination half-life of vinflunine is approximately 40 hours, with elimination occurring primarily through faecal excretion (approximately two-thirds of the dose) and urinary excretion (approximately one-third).

The pharmacokinetic properties of vinflunine mean that it requires administration only once every three weeks, which minimises the number of hospital visits required during treatment. The prolonged tissue distribution and elimination half-life ensure sustained drug exposure within the tumour between cycles.

Frequently Asked Questions About Javlor