Lenvacent4 mg

Lenvatinib mesylate is an oral multi-targeted tyrosine kinase inhibitor indicated, under specialist oncology direction, for:

• Radioactive iodine-refractory differentiated thyroid cancer (DTC), as a single agent
• Unresectable or advanced hepatocellular carcinoma (HCC), as first-line treatment, either as a single agent or in combination with pembrolizumab
• Advanced renal cell carcinoma (RCC), in combination with everolimus (after one prior anti-angiogenic therapy) or with pembrolizumab (first-line)
• Advanced endometrial carcinoma, in combination with pembrolizumab, in patients whose disease has progressed following prior systemic therapy and who are not candidates for curative surgery or radiation

Contains lenvatinib (as Lenvacent 4 mg) as the active ingredient, available as oral capsules, commonly in 4 mg and 10 mg strengths.

Lenvatinib is an oral targeted cancer therapy that blocks multiple receptors involved in tumour blood vessel growth (angiogenesis) and cancer cell proliferation, including VEGF, FGFR, PDGFRα, RET, and KIT receptors. By cutting off the blood supply tumours need to grow and by directly inhibiting cancer cell signalling, lenvatinib slows the progression of several cancers, including thyroid, liver, kidney, and endometrial cancer, often used in combination with other targeted or immunotherapy agents. Its anti-angiogenic mechanism is also responsible for its most common and clinically significant side effects, particularly high blood pressure, protein in the urine, and bleeding risk, which require regular monitoring throughout treatment.

Therapeutic Class: Targeted Anticancer Agent (Antineoplastic)

Lenvatinib inhibits vascular endothelial growth factor receptors (VEGFR1-3), which prevents tumour angiogenesis (new blood vessel formation), while its inhibition of fibroblast growth factor receptors (FGFR1-4), platelet-derived growth factor receptor alpha, RET, and KIT further reduces tumour cell proliferation and survival through multiple pathways. This broad receptor profile gives lenvatinib activity across several tumour types but also accounts for its characteristic side-effect profile, particularly cardiovascular effects (hypertension) related to VEGF pathway inhibition.

• Taken orally, once daily, at approximately the same time each day, with or without food
• Swallow the capsule whole with water
• Blood pressure should be well controlled before starting treatment
• If a dose is missed and it is more than 12 hours until the next scheduled dose, take the missed dose as soon as remembered; if less than 12 hours remain, skip the missed dose

The following should be assessed by the treating oncology team:

• Other antihypertensive medicines: may need adjustment given lenvatinib's own significant blood-pressure-raising effect; blood pressure should be well controlled before and monitored throughout treatment.
• Anticoagulants: lenvatinib increases bleeding risk, and combined use with anticoagulants requires closer monitoring.
• QT-prolonging medicines: lenvatinib can prolong the QT interval; caution is needed when combined with other drugs affecting cardiac conduction.
• Other agents affecting thyroid function: lenvatinib commonly causes hypothyroidism; thyroid function should be monitored and thyroid hormone replacement adjusted as needed.
• NSAIDs and corticosteroids: may add to gastrointestinal risk when combined with lenvatinib.

Very common side effects

• Hypertension (high blood pressure) - occurs in a majority of patients, and can be severe
• Fatigue
• Diarrhoea
• Decreased appetite, nausea
• Palmar-plantar erythrodysesthesia (hand-foot syndrome)
• Proteinuria (protein in the urine)
• Weight loss
• Joint and muscle pain (arthralgia/myalgia)
• Stomatitis (mouth sores)

Serious side effects (require prompt medical attention)

• Severe or malignant hypertension: monitor blood pressure regularly, particularly early in treatment; severe or uncontrolled hypertension requires dose interruption or reduction.
• Cardiac dysfunction: signs of heart failure (shortness of breath, swelling, fatigue) require prompt evaluation; discontinue for Grade 4 cardiac dysfunction.
• Arterial thromboembolic events: signs of heart attack or stroke - chest pain, weakness on one side, slurred speech - require immediate emergency care.
• Hepatotoxicity: yellowing of the skin or eyes, dark urine, right-sided abdominal pain; liver function is monitored throughout treatment.
• Renal impairment and proteinuria: reduced urination, swelling; kidney function and urine protein are monitored regularly.
• Gastrointestinal perforation or fistula formation: severe abdominal pain requires urgent evaluation.
• Haemorrhage: unusual bleeding or bruising, blood in stool or urine, coughing up blood - can be serious.
• QT prolongation: palpitations, dizziness, fainting.
• Reversible posterior leukoencephalopathy syndrome (RPLS, rare): headache, seizures, confusion, visual disturbances - requires prompt evaluation and discontinuation.
• Hypothyroidism - very common, requiring monitoring and thyroid hormone replacement as needed.

Pregnancy

Lenvatinib can cause fetal harm based on its mechanism of action and animal data. Pregnancy status should be verified before starting treatment, and effective contraception is required for patients of reproductive potential during treatment and for a defined period afterward, as advised by the treating oncologist.

Breastfeeding

Breastfeeding is not recommended during lenvatinib treatment and for a period afterward, given the potential for serious adverse effects in a nursing infant.

• Hypertension: control blood pressure adequately before starting treatment; monitor regularly, particularly during the first 2 months, and manage promptly with antihypertensive therapy or dose modification as needed.
• Cardiac dysfunction: monitor for signs of heart failure; discontinue for severe cardiac events.
• Hepatotoxicity, renal impairment, and proteinuria: monitor liver function, renal function, and urine protein regularly throughout treatment.
• Bleeding risk: use with caution in patients with tumours invading major blood vessels or with other risk factors for serious bleeding.
• Gastrointestinal perforation and fistula: evaluate promptly for severe abdominal pain.
• QT prolongation and electrolyte monitoring: monitor ECG and electrolytes periodically, particularly in patients with risk factors.
• Thyroid function: monitor regularly, given the high incidence of hypothyroidism; thyroid hormone replacement should be adjusted as needed.
• This medicine should only be prescribed and monitored by a physician experienced in the use of targeted cancer therapies.

Overdose would be expected to increase the risk and severity of known toxicities, particularly severe hypertension, cardiac dysfunction, and bleeding. There is no specific antidote; management is supportive, provided in a specialist facility, with close monitoring of blood pressure, cardiac and renal function, and bleeding risk, under the direct management of the oncology treatment team.

Store at controlled room temperature (generally 20-25°C, with excursions permitted between 15-30°C), protected from moisture, in the original container. Keep out of reach of children, given the potency of this oncology medicine.

• Body weight (hepatocellular carcinoma dosing): Requires weight-based starting dose selection (12 mg for ≥60 kg, 8 mg for <60 kg) to achieve comparable outcomes across weight ranges.
• Hepatic impairment: Dose adjustment is required for moderate to severe impairment; use with close monitoring, per the treating oncologist's assessment.
• Renal impairment: Dose adjustment may be needed in severe impairment; monitor renal function closely throughout treatment, given lenvatinib's own renal toxicity potential.
• Elderly: May have an increased incidence of certain adverse events, including hypertension and fatigue; used with the same dosing approach, with careful monitoring.

Treatment continues for as long as the cancer responds and the patient tolerates therapy, or until disease progression or unacceptable toxicity occurs, as determined by the treating oncologist through periodic reassessment of disease response and side effects, including regular blood pressure, liver, kidney, and thyroid function monitoring.

Drug Class: Multi-targeted receptor tyrosine kinase inhibitor (VEGFR, FGFR, PDGFRα, RET, KIT)

Lenvatinib blocks multiple receptor tyrosine kinases that tumours rely on both to grow their own blood supply (angiogenesis, via VEGF receptors) and to directly drive cancer cell proliferation (via FGFR, PDGFRα, RET, and KIT receptors). By cutting off blood supply and disrupting these growth signals simultaneously, lenvatinib slows or halts tumour growth across the several cancer types for which it is approved.

Lenvatinib is primarily used in adult oncology practice for the cancers listed under indications; safety and effectiveness in pediatric patients have not been well established for most indications, and any pediatric use would occur under specialist pediatric oncology supervision as part of a specific treatment protocol.