Lenvima^® (Capsules) Instructions for Use

Marketing Authorization Holder

Eisai Europe, Limited (United Kingdom)

Manufactured By

PATEON, Inc. (Canada)

Or

Kawashima Plant Of Eisai Co., Ltd. (Japan)

Labeled By

EISAI MANUFACTURING, LTD. (United Kingdom)

Packaging and Quality Control Release

EISAI MANUFACTURING, LTD. (United Kingdom)

Or

PHARMSTANDARD-UfaVITA, JSC (Russia)

ATC Code

L01EX08 (Lenvatinib)

Active Substance

Lenvatinib (Rec.INN registered WHO)

Dosage Forms

	Lenvima®	Capsules 4 mg: 30 pcs.
		Capsules 10 mg: 30 pcs.

Dosage Form, Packaging, and Composition

Capsules size №4, with cap and body of red-orange color, with applied black ink sign “Є” on the cap and “LENV 4 mg” on the body, containing granules of white or almost white color.

Auxiliary substances: calcium carbonate, mannitol, microcrystalline cellulose, hypromellose, low-substituted hypromellose, talc; capsule shell: hypromellose, titanium dioxide, dye iron oxide yellow (E172), dye iron oxide red (E172); ink: shellac, dye iron oxide black (E172), potassium hydroxide, propylene glycol.

10 pcs. – blisters (3) – carton packs.

Places of opening of the pack are glued with two transparent protective stickers.

Capsules size №4, with cap of red-orange color and body of yellow color, with applied black ink sign “Є” on the cap and “LENV 10 mg” on the body, containing granules of white or almost white color.

Auxiliary substances: calcium carbonate, mannitol, microcrystalline cellulose, hypromellose, low-substituted hypromellose, talc; capsule shell: hypromellose, titanium dioxide, dye iron oxide yellow (E172), dye iron oxide red (E172); ink: shellac, dye iron oxide black (E172), potassium hydroxide, propylene glycol.

10 pcs. – blisters (3) – carton packs.

Places of opening of the pack are glued with two transparent protective stickers.

Clinical-Pharmacological Group

Antitumor drug. Protein kinase inhibitor

Pharmacotherapeutic Group

Antineoplastic agents; protein kinase inhibitors; other protein kinase inhibitors

Indications

• Differentiated Thyroid Cancer (DTC): Treatment of adult patients with progressive, locally recurrent or metastatic, radioactive iodine-refractory differentiated thyroid cancer.
• Renal Cell Carcinoma (RCC): First-line treatment of adult patients with advanced renal cell carcinoma in combination with pembrolizumab.
• Hepatocellular Carcinoma (HCC): Treatment of adult patients with unresectable hepatocellular carcinoma who have not received prior systemic therapy.
• Endometrial Carcinoma (EC): Treatment of adult patients with advanced endometrial carcinoma that is mismatch repair proficient (pMMR) or not microsatellite instability-high (MSI-H), in combination with pembrolizumab, in patients who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.

Contraindications

• Hypersensitivity: Known hypersensitivity to lenvatinib or to any of the excipients.
• Pregnancy: Lenvima is contraindicated during pregnancy due to the potential for fetal harm based on mechanism of action and animal reproduction studies.
• Severe Hepatic Impairment: Contraindicated in patients with severe hepatic impairment (Child-Pugh class C).
• Uncontrolled Hypertension: Patients with uncontrolled hypertension despite optimal antihypertensive therapy should not initiate Lenvima treatment.

Dosage Regimen

The recommended dosage of Lenvima varies depending on the indication and combination therapy. The dose must be individualized based on clinical response and tolerability.

For Differentiated Thyroid Cancer (DTC): The recommended dosage is 24 mg orally once daily. For Renal Cell Carcinoma (RCC): The recommended dosage is 20 mg orally once daily in combination with pembrolizumab. For Hepatocellular Carcinoma (HCC): The recommended dosage is 12 mg (for patients with a body weight ≥60 kg) or 8 mg (for patients with a body weight <60 kg) orally once daily. For Endometrial Carcinoma (EC): The recommended dosage is 20 mg orally once daily in combination with pembrolizumab.

Capsules should be swallowed whole with a glass of water, with or without food. If a dose is missed, it can be taken if it is within 12 hours of the usual time; if more than 12 hours have passed, the missed dose should be skipped and the next dose taken at the regular time. Do not take two doses at the same time to make up for a missed dose.

Dose modifications (interruption or dose reduction) are recommended to manage adverse drug reactions. The dose may be reduced in 4 mg (using the 4 mg capsule) or 10 mg (using the 10 mg capsule) decrements. For HCC, the dose may be reduced from 12 mg to 8 mg, or from 8 mg to 4 mg daily. Treatment should be continued until disease progression or unacceptable toxicity occurs.

Adverse Reactions

The safety profile of Lenvima is characterized by class-effects common to VEGF pathway inhibitors and other multi-kinase inhibitors. The most common adverse reactions (occurring in ≥20% of patients) include hypertension, fatigue, diarrhea, arthralgia/myalgia, decreased appetite, vomiting, nausea, stomatitis/oral inflammation, weight loss, abdominal pain, headache, constipation, dysphonia, proteinuria, palmar-plantar erythrodysesthesia syndrome, hypothyroidism, and rash.

Serious adverse reactions have been reported and may require dose interruption, reduction, or discontinuation of therapy. These include cardiac dysfunction (including cardiac failure and left ventricular dysfunction), arterial thromboembolic events (such as myocardial infarction and cerebrovascular accident), hepatotoxicity (including hepatic encephalopathy and hepatic failure), renal impairment or failure, gastrointestinal perforation or fistula formation, QT interval prolongation, hypocalcemia, reversible posterior leukoencephalopathy syndrome (RPLS), hemorrhagic events, and impaired wound healing.

Laboratory abnormalities commonly observed include decreased platelet count, decreased white blood cell count, increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), increased alkaline phosphatase, hypocalcemia, hypokalemia, and hyponatremia. Routine monitoring of blood counts, electrolytes, liver function, renal function, and thyroid function is essential during treatment.

Drug Interactions

Lenvatinib is primarily metabolized by CYP3A4 and aldehyde oxidase and is a substrate of the efflux transporter P-glycoprotein (P-gp). Concomitant use with strong CYP3A4 inducers (e.g., rifampicin, phenytoin, carbamazepine, St. John’s Wort) may decrease lenvatinib plasma concentrations and should be avoided. If concomitant use is unavoidable, the dose of Lenvima may need to be increased as recommended, with careful monitoring for reduced efficacy.

Concomitant use with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir) may increase lenvatinib plasma concentrations. Patients should be monitored more closely for adverse reactions, and a dose reduction of Lenvima may be necessary.

Lenvatinib may prolong the QT interval. Caution is advised when co-administering Lenvima with other drugs known to prolong the QT interval (e.g., certain antiarrhythmics, antipsychotics, antibiotics) or drugs that may cause electrolyte abnormalities, as this may increase the risk of Torsade de Pointes. Serum electrolytes, including potassium, magnesium, and calcium, should be monitored and corrected prior to and during treatment.

Due to the risk of hypertension, patients should be monitored closely when Lenvima is used concomitantly with other antihypertensive agents, and adjustments to antihypertensive therapy may be required.

Overdose

There is no specific antidote for lenvatinib overdose. Management of overdose should consist of general supportive measures, including close monitoring for signs and symptoms of adverse reactions.

In the event of a suspected overdose, Lenvima should be immediately discontinued. Given the pharmacokinetic profile of lenvatinib, hemodialysis is not expected to be effective in enhancing its elimination due to high plasma protein binding. Treatment should be symptomatic and supportive, with particular attention to managing severe hypertension, cardiac dysfunction, renal impairment, and other potential severe adverse reactions. Patients should be advised to store the medication properly and out of reach of children to prevent accidental ingestion.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.