Kisplyx (Lenvatinib)
Tyrosine Kinase Inhibitor for Advanced Renal Cell Carcinoma
Quick Facts About Kisplyx
Key Takeaways
- Kisplyx (lenvatinib) is a multi-kinase inhibitor used in combination therapy for advanced renal cell carcinoma (kidney cancer)
- It is given with pembrolizumab as first-line treatment or with everolimus after prior VEGF-targeted therapy failure
- The most common side effects are hypertension, diarrhoea, fatigue, decreased appetite, and hand-foot syndrome
- Regular blood pressure monitoring, liver function tests, and urine protein checks are required during treatment
- Highly effective contraception is mandatory during treatment and for at least one month after the last dose
What Is Kisplyx and What Is It Used For?
Kisplyx is a prescription medicine containing the active substance lenvatinib, a potent multi-targeted tyrosine kinase inhibitor (TKI). It belongs to a class of anticancer agents that work by selectively blocking specific enzymes called receptor tyrosine kinases (RTKs). These enzymes play a crucial role in the formation of new blood vessels (angiogenesis) that tumours need to grow and spread, as well as in direct tumour cell proliferation.
Lenvatinib specifically targets several key signalling pathways implicated in cancer progression. It inhibits vascular endothelial growth factor receptors (VEGFR1, VEGFR2, and VEGFR3), fibroblast growth factor receptors (FGFR1 through FGFR4), platelet-derived growth factor receptor alpha (PDGFRα), as well as RET and KIT proto-oncogene receptors. By simultaneously blocking multiple pathways, lenvatinib disrupts the complex signalling network that drives tumour angiogenesis and cancer cell survival.
In clinical practice, Kisplyx is authorised for two distinct treatment regimens in advanced renal cell carcinoma (RCC). As a first-line treatment, it is used in combination with pembrolizumab (a PD-1 immune checkpoint inhibitor) for adult patients with advanced RCC who have not received prior systemic therapy. This combination was supported by the landmark KEYNOTE-581/CLEAR trial, which demonstrated significant improvements in progression-free survival, overall survival, and objective response rate compared to sunitinib monotherapy.
The second approved indication is in combination with everolimus (an mTOR inhibitor) for adult patients with advanced RCC following one prior anti-angiogenic (VEGF-targeted) therapy. The HOPE-205 study demonstrated superior progression-free survival for the lenvatinib plus everolimus combination compared to everolimus alone, establishing this regimen as a viable option after first-line treatment failure.
The mechanism by which Kisplyx exerts its antitumour effect is multifaceted. By cutting off the blood supply that cancer cells depend upon for oxygen and nutrients, the drug effectively starves the tumour. Simultaneously, by blocking RTK-mediated intracellular signalling cascades, it directly inhibits cancer cell proliferation and survival. When combined with immunotherapy (pembrolizumab) or mTOR inhibition (everolimus), the complementary mechanisms provide enhanced antitumour activity compared to either agent alone.
What Should You Know Before Taking Kisplyx?
Before starting treatment with Kisplyx, your doctor will conduct a thorough medical assessment to determine whether this medication is appropriate for you. Several important factors must be considered, and certain conditions may require dose adjustments, additional monitoring, or alternative treatment approaches. It is essential to discuss your complete medical history openly with your healthcare team.
Contraindications
You must not take Kisplyx if you have a known hypersensitivity (allergy) to lenvatinib or any of the other ingredients in the capsules, including calcium carbonate, mannitol, microcrystalline cellulose, hydroxypropylcellulose, low-substituted hydroxypropylcellulose, and talc. Signs of an allergic reaction may include skin rash, itching, swelling of the face or throat, and difficulty breathing.
Kisplyx is also strictly contraindicated during breastfeeding. Lenvatinib is excreted in breast milk and may cause serious harm to the nursing infant. Breastfeeding must be discontinued during treatment and should not be resumed after the last dose without medical guidance.
Warnings and Precautions
Inform your doctor before taking Kisplyx if any of the following apply to you, as special precautions or closer monitoring may be necessary:
- High blood pressure (hypertension): Lenvatinib commonly causes significant blood pressure elevation. Your blood pressure should be well controlled before starting treatment and monitored regularly throughout therapy. Antihypertensive medication may need to be initiated or adjusted.
- Heart problems or stroke: Arterial thromboembolic events, including myocardial infarction and cerebrovascular accident, have been reported. Patients with a history of cardiovascular events require careful risk-benefit assessment.
- Liver or kidney disease: Hepatotoxicity, including fatal liver failure, has been reported. Patients with severe hepatic or renal impairment may require dose reductions (10 mg once daily).
- Recent surgery or planned surgery: Kisplyx can impair wound healing. Treatment should be interrupted before major surgical procedures and resumed only when the wound has healed adequately.
- History of aneurysm or arterial dissection: Lenvatinib may increase the risk of arterial wall weakening. Patients with a history of or risk factors for aneurysms should be carefully evaluated.
- Jaw bone problems: Osteonecrosis of the jaw has been reported, particularly in patients also receiving bisphosphonates or other antiresorptive agents. A dental examination is recommended before starting treatment.
- Age over 75 years: Elderly patients may be at increased risk of certain adverse effects and may require closer monitoring.
- Body weight under 60 kg: Lower body weight may affect drug exposure and could necessitate dose adjustments.
Stiffness or weakness on one side of the body, severe headache, seizures, confusion, speech difficulties, or vision changes (signs of stroke or brain haemorrhage). Chest pain, shortness of breath, rapid or irregular heartbeat, bluish discolouration of the lips or fingers (signs of heart problems or blood clots). Severe abdominal pain (possible bowel perforation). Black, tarry, or bloody stools or coughing up blood (signs of internal bleeding).
Pregnancy and Breastfeeding
Kisplyx can cause serious harm to a developing baby and must not be taken during pregnancy. Women of childbearing potential must use highly effective contraception during treatment with Kisplyx and for at least one month after the last dose. If you become pregnant while taking Kisplyx, inform your doctor immediately. Your healthcare team will discuss whether treatment should continue, taking into account the potential risks to the foetus and the benefits of continued cancer treatment.
Breastfeeding is contraindicated during Kisplyx treatment. The active substance lenvatinib is excreted in breast milk and may cause serious adverse effects in the nursing infant. The decision to discontinue breastfeeding or to discontinue Kisplyx therapy should take into account the importance of the drug to the mother.
Driving and Using Machines
Kisplyx may cause side effects such as dizziness and fatigue that can impair your ability to drive or operate machinery. If you experience these symptoms, you should avoid driving or using machines until you feel well enough to do so safely.
How Does Kisplyx Interact with Other Drugs?
Drug interactions are an important consideration when taking Kisplyx. Lenvatinib is primarily metabolised through cytochrome P450 3A4 (CYP3A4) and aldehyde oxidase pathways, and it can both be affected by other drugs and influence the metabolism of co-administered medications. It is essential to tell your doctor or pharmacist about all medicines you are taking, have recently taken, or might take, including prescription drugs, over-the-counter medications, vitamins, supplements, and herbal preparations.
While no formal dose adjustment is required based on current pharmacokinetic data for most drug combinations, several interaction categories warrant clinical awareness and careful monitoring. The most clinically significant interactions are detailed in the table below.
| Interacting Drug/Class | Effect | Clinical Significance | Recommendation |
|---|---|---|---|
| Pembrolizumab | Enhanced antitumour activity; additive toxicity profile | Approved combination | Close monitoring for immune-related and TKI-related adverse events |
| Everolimus | Synergistic antitumour effect; overlapping toxicity | Approved combination | Monitor for additive hepatotoxicity and myelosuppression |
| Strong CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir) | May increase lenvatinib plasma concentrations | Moderate | Use with caution; monitor for increased toxicity |
| Strong CYP3A4 inducers (rifampicin, carbamazepine, phenytoin) | May decrease lenvatinib plasma concentrations | Moderate | Avoid if possible; consider alternative agents |
| QT-prolonging drugs (amiodarone, sotalol, haloperidol) | Additive risk of QT interval prolongation | High | ECG monitoring; correct electrolyte imbalances before starting |
| NSAIDs (ibuprofen, naproxen) | Increased risk of gastrointestinal perforation and bleeding | Moderate | Use with caution; consider alternatives for pain management |
| Anticoagulants (warfarin, heparin) | Increased risk of haemorrhage | Moderate to High | Monitor closely for signs of bleeding; adjust anticoagulant dose as needed |
Major Interactions
The most significant drug interactions with Kisplyx involve medications that prolong the QT interval. Lenvatinib itself has been associated with QT prolongation, and combining it with other QT-prolonging agents can further increase the risk of serious cardiac arrhythmias, including torsades de pointes. Before starting Kisplyx, your doctor should review your current medication list for QT-prolonging drugs and perform baseline ECG monitoring. Electrolyte imbalances (particularly low potassium, magnesium, and calcium) should be corrected prior to initiating treatment, as these can exacerbate QT prolongation.
Concurrent use of anticoagulants and antiplatelet agents also warrants careful attention, as lenvatinib is associated with an increased risk of haemorrhagic events. Patients receiving warfarin or other anticoagulants should have their coagulation parameters monitored more frequently, and dose adjustments may be necessary.
Minor Interactions
Interactions with CYP3A4 inhibitors and inducers are generally considered of moderate clinical significance for lenvatinib. Although strong CYP3A4 inhibitors such as ketoconazole may increase lenvatinib exposure, the magnitude of the effect is relatively modest based on pharmacokinetic studies. Nevertheless, clinicians should be vigilant for signs of increased toxicity when these agents are used together. Strong CYP3A4 inducers like rifampicin may reduce lenvatinib efficacy, and alternative medications should be considered where possible.
What Is the Correct Dosage of Kisplyx?
Kisplyx dosing follows precise guidelines determined by the combination therapy regimen, the patient's organ function, and tolerability. Treatment should be initiated and supervised by a physician experienced in the administration of anticancer therapies. The capsules are available in 4 mg and 10 mg strengths, allowing flexible dose adjustments.
Adults
With Pembrolizumab (First-Line)
The recommended starting dose of Kisplyx is 20 mg once daily (two 10 mg capsules), taken at approximately the same time each day with or without food. Pembrolizumab is administered as 200 mg intravenously every 3 weeks or 400 mg every 6 weeks over a 30-minute infusion. Treatment continues as long as clinical benefit is observed or until unacceptable toxicity occurs.
With Everolimus (After Prior VEGF Therapy)
The recommended starting dose of Kisplyx is 18 mg once daily (one 10 mg capsule and two 4 mg capsules), combined with everolimus 5 mg once daily as a tablet. Treatment continues until disease progression or unacceptable toxicity.
Severe Hepatic or Renal Impairment
For patients with severe liver or kidney problems, the recommended dose is 10 mg once daily (one 10 mg capsule) regardless of the combination partner. Your doctor will determine the appropriate pembrolizumab dose separately.
| Regimen | Kisplyx Dose | Combination Partner | Notes |
|---|---|---|---|
| First-line with pembrolizumab | 20 mg once daily | Pembrolizumab 200 mg IV q3w or 400 mg IV q6w | Two 10 mg capsules |
| Second-line with everolimus | 18 mg once daily | Everolimus 5 mg once daily | One 10 mg + two 4 mg capsules |
| Severe hepatic/renal impairment | 10 mg once daily | As per regimen | One 10 mg capsule |
How to Take the Capsules
Kisplyx capsules should be swallowed whole with water and should not be opened to avoid exposure to the capsule contents. They can be taken with or without food. If you cannot swallow the capsules whole, a liquid preparation can be made by following these steps:
- Place the whole capsules for your prescribed dose (up to 5 capsules) in a small container (approximately 20 ml) or an oral syringe (20 ml). Do not split or crush the capsules.
- Add 3 ml of liquid (water, apple juice, or milk). Wait 10 minutes for the capsule shell to dissolve, then stir or shake for 3 minutes until the capsules have fully dissolved.
- Drink the liquid mixture from the container or use the oral syringe to take it directly into the mouth or via a nasogastric tube.
- Add another 2 ml of liquid to the container or syringe, swirl or shake, and take this rinse. Repeat this step at least twice to ensure all medication is consumed.
If the liquid preparation is not used immediately, it can be stored in a covered container in a refrigerator (2°C to 8°C) for a maximum of 24 hours. Shake the mixture for 30 seconds before use after refrigeration. Discard after 24 hours.
Children and Adolescents
Kisplyx is not recommended for use in children and adolescents under 18 years of age. There is insufficient data on safety and efficacy in this population, and no paediatric indications have been approved by regulatory authorities.
Elderly Patients
No specific dose adjustment is required based on age alone. However, elderly patients (over 75 years) may be more susceptible to certain adverse effects, particularly hypertension, fatigue, and renal impairment. Closer monitoring and proactive dose modifications are recommended in this population.
Missed Dose
If you miss a dose and there are 12 hours or more until the next scheduled dose, take the missed dose as soon as you remember, then continue with your normal dosing schedule. If there are fewer than 12 hours until the next dose, skip the missed dose entirely and take the next dose at the regular time. Do not take a double dose to compensate for a missed one.
Overdose
If you take more Kisplyx than prescribed, contact your doctor or pharmacist immediately. Take the medication packaging with you to help identify the dose taken. Overdose may result in an intensification of known adverse effects, particularly severe hypertension, gastrointestinal toxicity, and hepatic dysfunction. There is no specific antidote for lenvatinib; treatment of overdose is supportive.
What Are the Side Effects of Kisplyx?
Like all medicines, Kisplyx can cause side effects, although not everybody gets them. The side effect profile may vary depending on whether Kisplyx is used in combination with pembrolizumab or everolimus. Many side effects are manageable with dose modifications and supportive care. Your doctor will monitor you closely throughout treatment and may adjust your dose or temporarily interrupt therapy to manage adverse reactions.
The following side effects have been reported with Kisplyx in clinical trials and post-marketing surveillance. They are grouped by frequency to help you understand how likely each side effect is.
When Used Alone or in Combination
Very Common
- High blood pressure (hypertension)
- Diarrhoea, nausea, vomiting, constipation, abdominal pain, indigestion
- Decreased appetite and weight loss
- Fatigue and weakness
- Hand-foot syndrome (palmar-plantar erythrodysaesthesia) – redness, pain and swelling of hands and feet
- Rash and hair loss
- Bleeding events (most commonly nosebleeds)
- Mouth sores, dry mouth, altered taste
- Headache, dizziness
- Hoarseness
- Back pain, joint and muscle pain
- Swelling in the legs (peripheral oedema)
- Proteinuria (protein in the urine)
- Hypothyroidism (underactive thyroid)
- Low platelet count and low white blood cell count
- Abnormal liver function tests
- Low potassium, calcium, and magnesium levels
- High cholesterol levels
- Elevated lipase and amylase (digestive enzymes)
- Abnormal kidney function tests and kidney failure
- Sleep difficulties
Common
- Dehydration
- Heart palpitations
- Heart problems or blood clots in the lungs (pulmonary embolism)
- Low blood pressure
- Stroke or transient ischaemic attack (mini-stroke)
- Pancreatitis (inflammation of the pancreas)
- Gallbladder inflammation (cholecystitis)
- Colitis (inflammation of the large intestine)
- Liver failure or hepatotoxicity
- Anal fistula
- Bloating and flatulence
- Dry skin, skin thickening, and itching
- Wound healing problems
- Urinary tract infections
- Adrenal insufficiency (decreased hormone production by adrenal glands)
- Gastrointestinal perforation (hole in the stomach or intestine)
- General feeling of being unwell
Uncommon
- Painful infection or irritation near the anus (perianal abscess)
- Splenic infarction (severe upper abdominal pain with fever and chills)
- Pneumothorax (air leakage from lung to chest cavity causing breathing difficulty)
- Osteonecrosis of the jaw (jawbone damage)
- Liver failure with jaundice, confusion, or loss of consciousness
- Fistula formation (abnormal connections between organs or to the skin)
Rare
- Tumour lysis syndrome (TLS) – a potentially life-threatening condition caused by the rapid breakdown of cancer cells, leading to kidney problems and electrolyte imbalances
Aneurysms (weakening of blood vessel walls) and arterial dissections (tears in blood vessel walls) have been reported after marketing authorisation. If you notice any new or unusual symptoms, inform your doctor promptly.
Tumour Lysis Syndrome (TLS)
During cancer treatment, substances from the breakdown of dying tumour cells may leak into the bloodstream, leading to tumour lysis syndrome. This is a cluster of metabolic complications that can affect kidney function and be life-threatening. Your doctor will monitor you for signs of TLS and may prescribe preventive treatment to reduce the risk. Symptoms include nausea, shortness of breath, irregular heartbeat, muscle cramps, seizures, cloudy urine, and fatigue. Contact your doctor immediately if you experience any of these symptoms.
Reporting Side Effects
If you experience any side effects, including those not listed in this guide, talk to your doctor, pharmacist, or nurse. You can also report side effects directly to your national medicines regulatory authority. By reporting side effects, you can help provide more information on the safety of this medicine.
How Should You Store Kisplyx?
Proper storage of Kisplyx is essential to maintain the effectiveness and safety of the medication. The capsules should be stored at a temperature not exceeding 25°C (77°F). Keep the capsules in the original packaging (blister pack) to protect them from moisture, as lenvatinib capsules are moisture-sensitive.
Always keep this medicine out of sight and reach of children. Do not use Kisplyx after the expiry date printed on the carton and blister after “EXP.” The expiry date refers to the last day of the stated month. Do not dispose of medicines via wastewater or household waste. Ask your pharmacist about how to dispose of medicines you no longer use. These measures help to protect the environment.
If you prepare a liquid mixture from the capsules but do not use it immediately, store it in a covered container in the refrigerator (2°C to 8°C) for a maximum of 24 hours. Shake the mixture for 30 seconds when removed from the refrigerator before use. If not consumed within 24 hours, the liquid preparation must be discarded.
What Does Kisplyx Contain?
Understanding the composition of your medication is important, particularly if you have known allergies to specific pharmaceutical ingredients. Kisplyx capsules contain the following ingredients:
Active substance: Lenvatinib (as mesilate). Kisplyx 4 mg hard capsules contain 4 mg of lenvatinib. Kisplyx 10 mg hard capsules contain 10 mg of lenvatinib.
Other ingredients (excipients): Calcium carbonate, mannitol, microcrystalline cellulose, hydroxypropylcellulose, low-substituted hydroxypropylcellulose, and talc. The capsule shell contains hypromellose, titanium dioxide (E171), yellow iron oxide (E172), and red iron oxide (E172). The printing ink contains shellac, black iron oxide (E172), potassium hydroxide, and propylene glycol.
Appearance and Pack Sizes
Kisplyx 4 mg capsules have a yellowish-red body and cap, approximately 14.3 mm long, printed with “Ε” in black ink on the cap and “LENV 4 mg” on the body. Kisplyx 10 mg capsules have a yellow body and yellowish-red cap, approximately 14.3 mm long, printed with “Ε” on the cap and “LENV 10 mg” on the body. The capsules are supplied in aluminium foil-sealed blisters in cartons of 30, 60, or 90 hard capsules. Not all pack sizes may be marketed.
The marketing authorisation holder is Eisai GmbH, Edmund-Rumpler-Strasse 3, 60549 Frankfurt am Main, Germany. Kisplyx is authorised in the European Union and is available in many countries worldwide under the supervision of qualified oncology specialists.
Frequently Asked Questions About Kisplyx
Kisplyx (lenvatinib) is used in combination with pembrolizumab as a first-line treatment for adults with advanced renal cell carcinoma (kidney cancer). It is also used in combination with everolimus for adults with advanced renal cell carcinoma that has progressed after prior VEGF-targeted therapy. Kisplyx is not used as a single agent for kidney cancer; it is always given as part of a combination regimen.
Both Kisplyx and LENVIMA contain the same active substance, lenvatinib. The difference lies in their approved indications. Kisplyx is specifically authorised for the treatment of advanced renal cell carcinoma (kidney cancer) in combination with pembrolizumab or everolimus. LENVIMA is authorised for differentiated thyroid cancer, hepatocellular carcinoma (liver cancer), and endometrial carcinoma. The different brand names help differentiate between indications and dosing regimens.
Treatment with Kisplyx typically continues for as long as you are benefiting from it and the side effects remain manageable. Your doctor will regularly assess the response to treatment through imaging studies and clinical evaluations. Treatment may be temporarily interrupted or the dose reduced to manage side effects, and it is permanently discontinued if the disease progresses or side effects become unacceptable despite dose adjustments. There is no predetermined maximum treatment duration.
Yes, Kisplyx capsules can be taken with or without food. Food does not significantly affect the absorption of lenvatinib. The most important consideration is to take the capsules at approximately the same time each day to maintain consistent drug levels in your body. Swallow the capsules whole with water, and do not open or crush them.
Regular monitoring is essential during Kisplyx treatment. Your doctor will check your blood pressure at each visit and may prescribe antihypertensive medications. Blood tests are performed regularly to assess liver function, kidney function, thyroid function, blood cell counts, and electrolyte levels (potassium, calcium, magnesium). Urine tests for proteinuria are also conducted. ECG monitoring may be required if you are taking other medications that affect heart rhythm. Report any new symptoms promptly to your healthcare team.
In the KEYNOTE-581/CLEAR trial, the combination of lenvatinib plus pembrolizumab demonstrated a median progression-free survival of 23.9 months compared to 9.2 months with sunitinib alone as first-line therapy for advanced RCC. The objective response rate was 71% with the lenvatinib-pembrolizumab combination versus 36% with sunitinib. In the second-line setting, the lenvatinib plus everolimus combination also showed significant improvements in progression-free survival compared to everolimus alone (14.6 months vs 5.5 months).
References
- European Medicines Agency (EMA). Kisplyx (lenvatinib) – Summary of Product Characteristics. Last updated 2025. Available at: ema.europa.eu/kisplyx
- Motzer RJ, Alekseev B, Rha SY, et al. Lenvatinib plus pembrolizumab or everolimus for advanced renal cell carcinoma (CLEAR/KEYNOTE-581). N Engl J Med. 2021;384(14):1289-1300. doi:10.1056/NEJMoa2035716
- Motzer RJ, Hutson TE, Glen H, et al. Lenvatinib, everolimus, and the combination in patients with metastatic renal cell carcinoma: a randomised, phase 2, open-label, multicentre trial (HOPE-205). Lancet Oncol. 2015;16(15):1473-1482. doi:10.1016/S1470-2045(15)00290-9
- National Comprehensive Cancer Network (NCCN). Clinical Practice Guidelines in Oncology: Kidney Cancer. Version 4.2025. Available at: nccn.org
- European Society for Medical Oncology (ESMO). Renal Cell Carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2024;35(8):692-706.
- World Health Organization (WHO). WHO Model List of Essential Medicines – 23rd List, 2023. Geneva: WHO; 2023.
- Choueiri TK, Eto M, Motzer RJ, et al. Lenvatinib plus pembrolizumab versus sunitinib as first-line treatment of patients with advanced renal cell carcinoma (CLEAR): extended follow-up. Lancet Oncol. 2023;24(3):228-238. doi:10.1016/S1470-2045(23)00049-9
- Schlumberger M, Tahara M, Wirth LJ, et al. Lenvatinib versus placebo in radioiodine-refractory thyroid cancer. N Engl J Med. 2015;372(7):621-630. doi:10.1056/NEJMoa1406470
About Our Medical Team
This article has been written and reviewed by the iMedic Medical Editorial Team, which includes board-certified specialists in oncology, clinical pharmacology, and internal medicine. Our editorial process follows international standards for medical content creation:
All information is sourced from peer-reviewed clinical trials, international treatment guidelines (EMA, NCCN, ESMO), and expert consensus statements. We follow the GRADE framework for assessing the quality of evidence.
Every article undergoes multi-stage review by qualified medical professionals, including specialist oncologists with clinical experience in renal cell carcinoma treatment. Content is regularly updated to reflect the latest evidence.
iMedic operates without pharmaceutical industry funding or sponsorship. Our content is free from commercial influence, ensuring unbiased and objective medical information for patients and caregivers.
This page meets WCAG 2.2 Level AAA standards, ensuring it is fully accessible to all users, including those using screen readers, keyboard navigation, and other assistive technologies.