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; gastrointestinal toxicity should be actively treated in order to reduce the risk of development of renal impairment or failure (see Renal failure and impairment under Precautions).
Posology: 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.
RCC: 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.
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: The recommended dosage of LENVIMA is 20 mg orally once daily, in combination with pembrolizumab 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks, until unacceptable toxicity or disease progression. Refer to the pembrolizumab prescribing information for recommended pembrolizumab dosing information.
Dose adjustment and discontinuations for DTC and RCC: 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.
For lenvatinib related toxicities (see Table 5), 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 6.
For toxicities thought to be related to everolimus, treatment should be interrupted, reduced to alternate day dosing, or discontinued (see the everolimus SmPC for advice on specific adverse reactions).
For toxicities thought to be related to both lenvatinib and everolimus, lenvatinib should be reduced (see Table 7) prior to reducing everolimus.
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 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 8.
Grades are based on the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE). (See Table 5, Table 6, Table 7, Table 8 and Table 9.)

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When administering LENVIMA in combination with pembrolizumab for the treatment of endometrial carcinoma, interrupt one or both drugs or dose reduce LENVIMA as appropriate. No dose reductions are recommended for pembrolizumab. Withhold or discontinue pembrolizumab in accordance with the instructions in the pembrolizumab prescribing information.
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 with the combination 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 18 mg of lenvatinib with 5 mg of everolimus taken once daily, 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: In DTC patients, no adjustment of starting dose is required on the basis of hepatic function in patients with mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment. In patients with severe (Child-Pugh C) hepatic impairment, the recommended starting dose is 14 mg taken once daily. Further dose adjustments may be necessary on the basis of individual tolerability. Refer also to Other special populations under Adverse Reactions.
In RCC or endometrial carcinoma, no data with the combination therapy is available in patients with hepatic impairment. No adjustment of starting dose of the combination is required on the basis of hepatic function in patients with mild (Child Pugh A) or moderate (Child Pugh B) hepatic impairment. In patients with severe (Child Pugh C) hepatic impairment, the recommended starting dose of lenvatinib is 10 mg taken once daily in combination of everolimus (recommended in the everolimus SmPC) taken once daily for RCC and 10 mg once daily for endometrial carcinoma. Further dose adjustments may be necessary on the basis of individual tolerability. The combination therapy should be used in patients with severe hepatic impairment only if the anticipated benefit exceeds the risk. Refer also to Other special populations under Adverse Reactions.
In the patient populations enrolled in the HCC study no dose adjustments were required on the basis of hepatic function in those patients who had mild hepatic impairment (Child-Pugh A). The available very limited data are not sufficient to allow for a dosing recommendation for HCC patients with moderate hepatic impairment (Child-Pugh B). Close monitoring of overall safety is recommended in these patients (see Precautions and Pharmacology: Pharmacokinetics under Actions). Lenvatinib has not been studied in patients with severe hepatic impairment (Child-Pugh C) and is not recommended for use in these patients.
Patients with renal impairment: In the DTC, RCC and endometrial carcinoma patients, no adjustment of starting dose is required on the basis of renal function in patients with mild or moderate renal impairment. In patients with severe renal impairment, the recommended starting dose for DTC is 14 mg, for RCC is 10 mg of lenvatinib with 5 mg of everolimus and for endometrial carcinoma is 10 mg taken once daily. Further dose adjustments may be necessary based on individual tolerability. Patients with end-stage renal disease were not studied, therefore the use of lenvatinib in these patients is not recommended. Refer also to Other special populations under Adverse Reactions.
In the HCC patients, no dose adjustments are required on the basis of renal function in 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 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 (see Pharmacology: Pharmacodynamics under Actions). 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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