Version Comparison

Version Diff

← Veraxanib 50 mg film-coated tablets

9 sections changed · v2 → v3 · Changed: 3, 4.2, 4.4, 4.5, 4.8, 5.1, 5.2, 6.4, 10
1 Name of the medicinal product Unchanged
2 Qualitative and quantitative composition Unchanged
3 Pharmaceutical form Changed 482e3717… → 7909457e…
+ Film-coated tablet.
− Film-coated tablet (tablet).
 
Orange, round, biconvex film-coated tablets approximately 9 mm in diameter, debossed with "VX50" on one face.
4.1 Therapeutic indications Unchanged
4.2 Posology and method of administration Changed baba3f97… → 934b375e…
The recommended dose of Veraxanib is 50 mg taken orally once daily, with or without food.
 
Treatment should be continued until disease progression or unacceptable toxicity.
 
+ Missed doses: If a dose is missed, it should be taken as soon as the patient remembers unless it is within 12 hours of the next scheduled dose. In that case, the missed dose should be skipped and the next dose taken at the usual scheduled time. Patients should not take two doses on the same day to make up for a missed dose.
− Missed doses: If a dose is missed, it should be taken as soon as the patient remembers unless it is within 12 hours of the next scheduled dose. In that case, the missed dose should be skipped and the next dose taken at the usual scheduled time.
 
Dose modifications: Dose reductions to 25 mg once daily may be required due to adverse reactions (see section 4.8). Veraxanib should be permanently discontinued in patients who cannot tolerate 25 mg once daily.
 
Hepatic impairment: No dose adjustment is required in patients with mild or moderate hepatic impairment. Veraxanib has not been studied in patients with severe hepatic impairment and is not recommended in this population.
 
+ Renal impairment: No dose adjustment is required in patients with mild to moderate renal impairment. Limited data are available in severe renal impairment; use with caution.
− Renal impairment: No dose adjustment is required in patients with mild to moderate renal impairment. Limited data are available in severe renal impairment.
 
Paediatric population: The safety and efficacy of Veraxanib in children and adolescents below 18 years of age have not been established. No data are available.
4.3 Contraindications Unchanged
4.4 Special warnings and precautions for use Changed d05b4a14… → 36bbf486…
FGFR2 alteration testing
Patients must have FGFR2 alterations confirmed by a validated companion diagnostic test before initiating treatment with Veraxanib (see section 4.1).
 
Hyperphosphataemia
+ Hyperphosphataemia is a class effect of FGFR inhibitors and was observed in the majority of patients in clinical trials. Serum phosphate levels should be monitored before starting treatment, monthly for the first 3 months, and periodically thereafter. Hyperphosphataemia should be managed with dietary phosphate restriction, phosphate binders, and, if required, dose modification or interruption (see section 4.2).
− Hyperphosphataemia is a class effect of FGFR inhibitors and was observed in clinical trials. Serum phosphate levels should be monitored before starting treatment, monthly for the first 3 months, and periodically thereafter. Hyperphosphataemia should be managed with dietary phosphate restriction, phosphate binders, and, if required, dose modification or interruption (see section 4.2).
 
Ocular toxicity
+ Retinal pigment epithelial detachment (RPED) and central serous retinopathy have been observed with Veraxanib. Patients should undergo baseline ophthalmological examination before initiating treatment. Any new or worsening visual symptoms, including blurred vision, should prompt urgent ophthalmological re-evaluation. Dose modification or discontinuation may be required depending on severity.
− Retinal pigment epithelial detachment (RPED) and central serous retinopathy have been observed with Veraxanib. Patients should undergo baseline ophthalmological examination before initiating treatment. Any new or worsening visual symptoms should prompt urgent ophthalmological re-evaluation. Dose modification or discontinuation may be required.
 
Hepatic toxicity
+ Elevations in hepatic enzymes (ALT, AST) have been reported. Liver function tests should be performed before starting treatment and monitored every 4 weeks for the first 3 months, then periodically thereafter.
− Elevations in hepatic enzymes (ALT, AST) have been reported. Liver function tests should be performed before starting treatment and monitored periodically during treatment.
4.5 Interaction with other medicinal products and other forms of interaction Changed d16a75f8… → 5f4f4ce9…
Effect of other medicinal products on Veraxanib
+ Veraxanib is primarily metabolised by CYP3A4. Concomitant use of strong CYP3A4 inducers (e.g. rifampicin, phenytoin, carbamazepine, St. John's Wort [Hypericum perforatum]) is contraindicated as they significantly decrease veraxanib exposure (see section 4.3). Caution is advised with moderate CYP3A4 inducers; close monitoring for reduced efficacy is recommended.
− Veraxanib is primarily metabolised by CYP3A4. Concomitant use of strong CYP3A4 inducers (e.g. rifampicin, phenytoin, carbamazepine, St. John's Wort) is contraindicated as they significantly decrease veraxanib exposure (see section 4.3). Caution is advised with moderate CYP3A4 inducers; close monitoring for reduced efficacy is recommended.
 
Concomitant use of strong CYP3A4 inhibitors (e.g. ketoconazole, itraconazole, clarithromycin) may increase veraxanib exposure. Use with caution and consider dose reduction if toxicity occurs.
 
Effect of Veraxanib on other medicinal products
In vitro data suggest veraxanib is a weak inhibitor of CYP2D6. Caution should be exercised when co-administering medicinal products that are CYP2D6 substrates with a narrow therapeutic index (e.g. certain antidepressants, antipsychotics).
 
+ Veraxanib may reduce the efficacy of oral hormonal contraceptives. Non-hormonal or additional contraceptive measures should be used concurrently and for at least one month after stopping Veraxanib (see section 4.6).
− Veraxanib may reduce the efficacy of oral hormonal contraceptives. Non-hormonal or additional contraceptive measures should be used (see section 4.6).
4.6 Fertility, pregnancy and lactation Unchanged
4.7 Effects on ability to drive and use machines Unchanged
4.8 Undesirable effects Changed 453b35d7… → 3348de25…
Summary of the safety profile
The most common adverse reactions (≥10%) were: hyperphosphataemia, fatigue, diarrhoea, nausea, decreased appetite, stomatitis, palmar-plantar erythrodysaesthesia syndrome, alopecia, and dry skin.
 
Tabulated list of adverse reactions
Adverse reactions reported in clinical trials with Veraxanib are listed below by system organ class and frequency. Frequencies are defined as: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100).
 
+ Metabolism and nutrition disorders: Very common: hyperphosphataemia, decreased appetite. Common: hyponatraemia.
− Metabolism and nutrition disorders: Very common: hyperphosphataemia, decreased appetite.
General disorders: Very common: fatigue. Common: peripheral oedema, weight decreased.
Gastrointestinal disorders: Very common: diarrhoea, nausea, stomatitis. Common: vomiting, constipation, abdominal pain, dysgeusia.
Skin and subcutaneous tissue disorders: Very common: palmar-plantar erythrodysaesthesia syndrome, alopecia, dry skin. Common: nail disorder.
Investigations: Common: increased ALT, increased AST, increased blood creatinine, increased blood alkaline phosphatase.
Eye disorders: Common: retinal pigment epithelial detachment, blurred vision, central serous retinopathy.
+  
+ Description of selected adverse reactions
+ Hyperphosphataemia: Hyperphosphataemia was observed in approximately 85% of patients and was generally manageable with dietary restriction and phosphate binders. Dose reduction was required in 12% of patients.
4.9 Overdose Unchanged
5.1 Pharmacodynamic properties Changed a361acca… → a8770da6…
+ Pharmacotherapeutic group: Antineoplastic agents, protein kinase inhibitors, ATC code: L01EN05.
− Pharmacotherapeutic group: Antineoplastic agents, protein kinase inhibitors, ATC code: L01EN05 (provisional).
 
Mechanism of action
Veraxanib is a selective, potent, reversible inhibitor of fibroblast growth factor receptor 2 (FGFR2) kinase. It inhibits FGFR2 autophosphorylation and downstream signalling through the MAPK and PI3K/AKT pathways in tumour cells harbouring FGFR2 gene fusions or activating mutations, leading to inhibition of cell proliferation and induction of apoptosis.
 
Clinical efficacy
Efficacy was established in study VRXB-101, an open-label, single-arm trial in 112 patients with advanced FGFR2-altered solid tumours who had received at least one prior line of systemic therapy. The primary endpoint was overall response rate (ORR) by independent radiological review.
 
+ The ORR was 38% (95% CI: 29–47%), with a median duration of response of 9.3 months (95% CI: 7.2–12.1 months). Median progression-free survival was 7.1 months (95% CI: 5.8–8.6 months). Median overall survival was not yet reached at the time of analysis.
− The ORR was 38% (95% CI: 29–47%), with a median duration of response of 9.3 months (95% CI: 7.2–12.1 months). Median progression-free survival was 7.1 months (95% CI: 5.8–8.6 months).
5.2 Pharmacokinetic properties Changed df40b0c2… → 86c0eea3…
Absorption
Veraxanib is absorbed following oral administration with a median time to maximum plasma concentration (Tmax) of 2–4 hours. The absolute oral bioavailability is approximately 71%. Administration with a high-fat meal did not alter overall exposure (AUC) but delayed Tmax by approximately 1 hour; no food restriction is required (see section 4.2). Steady-state is reached within 7 days of once-daily dosing.
 
Distribution
The apparent volume of distribution at steady state is approximately 185 L. Plasma protein binding is approximately 97%, primarily to albumin.
 
Metabolism
+ Veraxanib is metabolised primarily by CYP3A4 to an active M1 metabolite, which accounts for approximately 15% of total exposure. In vitro, veraxanib is a weak inhibitor of CYP2D6 (Ki 18 µM).
− Veraxanib is metabolised primarily by CYP3A4 to an active M1 metabolite, which accounts for approximately 15% of total exposure.
 
Elimination
The mean elimination half-life is approximately 24 hours at steady state. The apparent oral clearance is approximately 7 L/h. Excretion is primarily faecal (72%) with renal excretion accounting for approximately 21% of the dose.
5.3 Preclinical safety data Unchanged
6.1 List of excipients Unchanged
6.2 Incompatibilities Unchanged
6.3 Shelf life Unchanged
6.4 Special precautions for storage Changed 729c96e9… → 593499ed…
+ Store below 25°C. Store in the original container to protect from moisture. Keep out of the reach of children.
− Store below 25°C. Store in the original container to protect from moisture.
6.5 Nature and contents of container Unchanged
6.6 Special precautions for disposal and other handling Unchanged
7 Marketing authorisation holder Unchanged
8 Marketing authorisation number(s) Unchanged
9 Date of first authorisation / renewal of the authorisation Unchanged
10 Date of revision of the text Changed 33c3f35b… → 9aa8f749…
+ 08 April 2024
− 12 September 2023