Lenvima

Lenvima Dosage/Direction for Use

lenvatinib

Manufacturer:

Eisai

Distributor:

DKSH
Full Prescribing Info
Dosage/Direction for Use
LENVIMA treatment should be initiated and supervised by a health care professional experienced in the use of anticancer therapies.
If a patient misses a dose, and it cannot be taken within 12 hours, then that dose should be skipped and the next dose should be taken at the usual time of administration.
Treatment should continue as long as clinical benefit is observed or until unacceptable toxicity occurs.
Optimal medical management (i.e. treatment or therapy) for nausea, vomiting, and diarrhoea should be initiated prior to any lenvatinib therapy interruption or dose reduction; however, gastrointestinal toxicity should be actively treated in order to reduce the risk of development of renal impairment or failure (see Renal failure and impairment/Gastrointestinal Toxicity under Precautions).
Posology: Differentiated Thyroid Cancer (DTC): The recommended daily dose of lenvatinib is 24 mg (two 10 mg capsules and one 4 mg capsule) once daily. The daily dose is to be modified as needed according to the dose/toxicity management plan.
Renal Cell Carcinoma (RCC): Lenvatinib in combination with pembrolizumab: Initial dosing regimen: The recommended starting daily dose of lenvatinib is 20 mg (two 10 mg capsules) once daily in combination with pembrolizumab 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks. Refer to the pembrolizumab prescribing information for other pembrolizumab dosing information.
Lenvatinib in combination with everolimus: Initial dosing regimen: The recommended daily dose of lenvatinib is 18 mg (one 10 mg capsule and two 4 mg capsules) once daily in combination with 5 mg of everolimus once daily. The daily doses of lenvatinib and, if necessary, everolimus are to be modified as needed according to the dose/toxicity management plan.
Hepatocellular Carcinoma (HCC): The recommended daily dose of lenvatinib is 8 mg (two 4 mg capsules) once daily for patients with a body weight of <60 kg and 12 mg (three 4 mg capsules) once daily for patients with a body weight of ≥60 kg. Dose adjustments are based only on toxicities observed and not on body weight changes during treatment. The daily dose is to be modified, as needed, according to the dose/toxicity management plan.
Endometrial Carcinoma (EC): The recommended dosage of lenvatinib is 20 mg orally once daily, in combination with pembrolizumab either 200 mg every 3 weeks or 400 mg every 6 weeks, administered as an intravenous infusion over 30 minutes every 3 weeks, until unacceptable toxicity or disease progression.
Refer to the pembrolizumab prescribing information for additional dosing information.
Monitoring, dose medication and discontinuation: Management of adverse reactions may require dose interruption, adjustment, or discontinuation of lenvatinib therapy or the combination therapy (see Precautions). Mild to moderate adverse reactions (e.g., Grade 1 or 2) generally do not warrant interruption of lenvatinib or of the combination, unless intolerable to the patient despite optimal management. Severe (e.g., Grade 3) or intolerable adverse reactions require interruption of lenvatinib or of the combination of medicines until improvement of the reaction to Grade 0-1 or baseline.
Treatment should be discontinued in case of life-threatening reactions (e.g., Grade 4) with the exception of laboratory abnormality judged to be non-life-threatening, in which case they should be managed as severe reactions (e.g., Grade 3).
Dose adjustment and discontinuations for DTC: For lenvatinib related toxicities (see Table 6), upon resolution/improvement of an adverse reaction to Grade 0-1 or baseline, treatment should be resumed at a reduced dose of lenvatinib as suggested in Table 7.
Dose adjustment and discontinuations for RCC: In combination with pembrolizumab: For lenvatinib-related toxicities, upon resolution/improvement of an adverse reaction, treatment should be resumed at a reduced dose as suggested in Table 8. When used in combination with pembrolizumab, one or both medicines should be interrupted as appropriate. Lenvatinib should be withheld, dose reduced, or discontinued as appropriate. Withhold or discontinue pembrolizumab in accordance with the instructions in the prescribing information for pembrolizumab. No dose reductions are recommended for pembrolizumab.
In combination with everolimus: For toxicities thought to be related to everolimus, treatment should be interrupted, reduced to alternate day dosing, or discontinued (see the everolimus prescribing information for advice on specific adverse reactions).
For toxicities thought to be related to both lenvatinib and everolimus, lenvatinib should be reduced (see Table 8) prior to reducing everolimus.
Dose adjustment and Discontinuation for HCC: Management of some adverse reactions may require dose interruption, adjustment, or discontinuation of lenvatinib therapy. Mild to moderate adverse reactions (e.g., Grade 1 or 2) generally do not warrant interruption of lenvatinib, unless intolerable to the patient despite optimal management. Details for monitoring, dose adjustment and discontinuation are provided in Table 9.
Dose adjustment and Discontinuation for EC: For lenvatinib-related toxicities see Table 6. When administering lenvatinib in combination with pembrolizumab, interrupt, dose reduce, or discontinue lenvatinib as appropriate (see table 10). Withhold or discontinue pembrolizumab in accordance with the instructions in the prescribing information for pembrolizumab. No dose reductions are recommended for pembrolizumab. (See Tables 6, 7, 8, 9 and 10.)

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Special populations: DTC: Patients of age ≥75 years, of Asian race, with comorbidities (such as hypertension, and hepatic or renal impairment), or body weight below 60 kg appear to have reduced tolerability to lenvatinib (see Other special populations under Adverse Reactions). All patients other than those with severe hepatic or renal impairment (see as follows) should initiate treatment at the recommended 24 mg dose, following which the dose should be further adjusted on the basis of individual tolerability.
RCC: No data for the combination of lenvatinib and everolimus are available for most of the special populations. The following information is derived from the clinical experience on single agent lenvatinib in patients with differentiated thyroid cancer (DTC).
All patients other than those with severe hepatic or renal impairment (see as follows) should initiate treatment at the recommended dose of 20 mg of lenvatinib daily with pembrolizumab or 18 mg of lenvatinib with 5 mg of everolimus taken once daily as indicated, following which the dose should be further adjusted on the basis of individual tolerability.
HCC: Patients ≥75 years, of white race or female sex or those with worse baseline hepatic impairment (Child-Pugh A score of 6 compared to score of 5) appear to have reduced tolerability to lenvatinib.
HCC patients other than those with moderate and severe hepatic impairment or severe renal impairment should initiate treatment at the recommended starting dose of 8 mg (two 4 mg capsules) for body weight <60 kg and 12 mg (three 4 mg capsules) for body weight ≥60 kg, following which the dose should be further adjusted on the basis of individual tolerability.
Patients with hypertension: Blood pressure should be well controlled prior to treatment with lenvatinib, and should be regularly monitored during treatment (see Precautions). Refer also to Other special populations under Adverse Reactions.
Patients with hepatic impairment: DTC, RCC and EC: No dose adjustments are required on the basis of hepatic function in patients with mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment.
The recommended dosage of lenvatinib for patients with severe hepatic impairment (Child-Pugh C) is: DTC: 14 mg taken orally once daily; RCC: 10 mg taken orally once daily; EC: 10 mg taken orally once daily.
Further dose adjustments may be necessary on the basis of individual tolerability.
Limited data are available for the combination of lenvatinib with pembrolizumab or everolimus in patients with hepatic impairment. Refer to the respective prescribing information for pembrolizumab or everolimus for dosing in patients with hepatic impairment.
HCC: No dose adjustments are required on the basis of hepatic function in patients with HCC and mild hepatic impairment (Child-Pugh A). There are limited data in patients with HCC and moderate hepatic impairment (Child-Pugh B). On the basis of that data, the recommended starting dose in patients with moderate hepatic impairment (Child-Pugh B) is 8 mg, regardless of body weight. Patients with moderate hepatic impairment may require additional monitoring for adverse reactions requiring dose adjustments. The available data do not allow for a dosing recommendation for patients with HCC and severe hepatic impairment (Child-Pugh C).
Patients with renal impairment: DTC, RCC and EC: No dose adjustments are required on the basis of renal function in patients with mild or moderate renal impairment.
The recommended dosage of lenvatinib for patients with severe renal impairment (creatinine clearance less than 30 mL/min calculated by Cockcroft-Gault equation using actual body weight) is: DTC: 14 mg taken orally once daily; RCC: 10 mg taken orally once daily; EC: 10 mg taken orally once daily.
Further dose adjustments may be necessary on the basis individual tolerability. Patients with end-stage renal disease have not been studied, therefore the use of lenvatinib in these patients is not recommended.
Limited data are available for the combination of lenvatinib with pembrolizumab or everolimus in patients with renal impairment. Refer to the respective prescribing information for pembrolizumab or everolimus for dosing in patients with renal impairment.
HCC: No dose adjustments are required on the basis of renal function in HCC patients with mild or moderate renal impairment. The available data do not allow for a dosing recommendation for patients with HCC and severe renal impairment.
Elderly population: No adjustment of starting dose is required on the basis of age. Limited data are available on use in patients aged ≥75 years (see also Other special populations under Adverse Reactions).
Paediatric population: Lenvatinib should not be used in children younger than 2 years of age because of safety concerns identified in animal studies (see Pharmacology: Toxicology: Preclinical safety data under Actions). The safety and efficacy of lenvatinib in children aged 2 to <18 years have not yet been established (see Pharmacology: Pharmacodynamics under Actions). No data are available.
Race: No adjustment of starting dose is required on the basis of race (see Pharmacology: Pharmacokinetics under Actions). Limited data are available on use in patients from ethnic origins other than Caucasian or Asian (see also Other special populations under Adverse Reactions).
Body weight below 60 kg in RCC: No adjustment of starting dose is required on the basis of body weight. Limited data are available on treatment with lenvatinib in combination with everolimus in patients with a body weight below 60 kg with RCC (see also Other special populations under Adverse Reactions).
Patients with high ECOG performance status in RCC: Patients with an ECOG (Eastern Cooperative Oncology Group) performance status of 2 or higher were excluded from the RCC Study 205 (see Pharmacology: Pharmacodynamics under Actions). Patients with a KPS (Karnofsky Performance Status) <70 were excluded from Study 307 (CLEAR). Benefit-risk in these patients has not been evaluated.
Method of administration: Lenvatinib is for oral use. The capsules should be taken at about the same time each day, with or without food (see Pharmacology: Pharmacokinetics under Actions). The capsules should be swallowed whole with water. Caregivers should not open the capsule, in order to avoid repeated exposure to the contents of the capsule.
Alternatively, the lenvatinib capsules may be added without breaking or crushing them to a tablespoon of water or apple juice in a small glass to produce a suspension. The capsules must be left in the liquid for at least 10 minutes and stirred for at least 3 minutes to dissolve the capsule shells. The suspension is to be swallowed. After drinking, the same amount of water or apple juice (one tablespoon) must be added to the glass and swirled a few times. The additional liquid must be swallowed.
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