Bdfoie 4/Bdfoie 10 Dosage/Direction for Use

Lenvatinib "Bdfoie 4/Bdfoie 10" treatment should be initiated and supervised by a healthcare professional experienced in the use of anticancer therapies. Optimal medical management (i.e. treatment or therapy) for nausea, vomiting, and diarrhea 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.
Posology: 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.
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.
Dose adjustments and discontinuations for DTC: Management of 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. Severe (e.g., Grade 3) or intolerable adverse reactions require interruption of Lenvatinib until improvement of the reaction to Grade 0-1 or baseline.
For Lenvatinib related toxicities (see Table 3), 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 1. (See Table 1.)

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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 reaction (e.g., Grade 3).
Hepatocellular Carcinoma: 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.
Dose adjustments 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 2. (See Table 2.)

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Grades are based on the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE).
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, until unacceptable toxicity or disease progression.
Refer to the Summary of Product Characteristics (SmPC) for pembrolizumab for additional dosing information.
Dose adjustments and Discontinuation for EC: For lenvatinib-related toxicities see Table 4. When administering Lenvatinib "Bdfoie 4/Bdfoie 10" in combination with pembrolizumab, interrupt, dose reduce, or discontinue Lenvatinib "Bdfoie 4/Bdfoie 10" as appropriate. Withhold or discontinue pembrolizumab in accordance with the instructions in the SmPC for pembrolizumab. No dose reductions are recommended for pembrolizumab. (See Tables 3 and 4.)

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Special Populations: Elderly Population: 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. 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.
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.
Patients with hepatic impairment: DTC: 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.
HCC: 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. Lenvatinib has not been studied in patients with severe hepatic impairment (Child-Pugh C) and is not recommended for use in these patients.
EC: Limited data are available for the combination of lenvatinib with pembrolizumab 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. Please refer to the SmPC for pembrolizumab for dosing in patients with hepatic impairment. Further dose adjustments may be necessary on the basis of individual tolerability.
Patients with renal impairment: DTC: 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 is 14 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.
HCC: 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.
EC: 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 is 10 mg of lenvatinib taken once daily. Please refer to the SmPC for pembrolizumab for dosing in patients with renal impairment. Further dose adjustments may be necessary based on individual tolerability. Patients with end-stage renal disease have not been studied, therefore the use of lenvatinib in these patients is not recommended.
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.
Pediatric population: Lenvatinib should not be used in children younger than 2 years of age because of safety concerns identified in animal studies. The safety and efficacy of Lenvatinib in children aged 2 to <18 years have not yet been established. No data are available.
Race: No adjustment of starting dose is required on the basis of race. Limited data are available on use in patients from ethnic origins other than Caucasian or Asian.
Method of administration: Lenvatinib is for oral use. The capsules should be taken at about the same time each day, with or without food. 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.