Lenvatinib

About Lenvatinib

• Lenvatinib gained its initial FDA approval in February 2015 for treating advanced thyroid cancer, specifically differentiated thyroid cancer. Following this, it obtained approval for advanced renal cell carcinoma (RCC) in May 2016. 
• Subsequently, in August 2018, it received approval for the treatment of unresectable hepatocellular carcinoma (HCC). Later, in September 2019, Lenvatinib secured approval for advanced endometrial carcinoma (EC) when used in combination with pembrolizumab.
• Lenvatinib, a kinase inhibitor, is indicated for the treatment of various cancers. In Differentiated Thyroid Cancer (DTC), it is used for patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory DTC. 
• In Renal Cell Carcinoma (RCC), this medicine is prescribed in combination with pembrolizumab as a first-line treatment for adult patients with advanced RCC. 
• Additionally, it is administered with everolimus for the treatment of adult patients with advanced RCC following one prior antiangiogenic therapy. 
• For Hepatocellular Carcinoma (HCC), this medicine is recommended as a first-line treatment for patients with unresectable HCC. 
• In the case of Endometrial Carcinoma (EC) that is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), Lenvatinib is combined with pembrolizumab for patients experiencing disease progression after prior systemic therapy in any setting and is not suitable for curative surgery or radiation.
• Lenvatinib, effectively blocking enzymes called tyrosine kinases found in receptors like VEGF, FGFR, and RET receptors within cancer cells. 
• These enzymes facilitate processes such as cell division and the formation of new blood vessels. By inhibiting them, it disrupts the formation of new blood vessels, thereby cutting off the blood supply essential for cancer cell growth and reducing their proliferation. Additionally, it may modulate the activity of the body’s immune system, altering its natural defenses.

Strength: 

Lenvatinib capsules are available in strengths of  10 mg and 4 mg.

Recommended Dosage:

Lenvatinib capsules offer the option of being swallowed whole or dissolved in a small amount of liquid. If choosing to dissolve the capsules, place them into one tablespoon of water or apple juice without breaking or crushing them. Allow the capsules to sit in the liquid for a minimum of 10 minutes. Stir the mixture for at least three minutes. 

After consuming the mixture, add tablespoon of water or apple juice to the glass, swirl the contents a few times, and then drink the water or apple juice to ensure the entire dose is taken. Consult your doctor for more details on the dosage of medicine. 

• For Differentiated Thyroid Cancer (DTC), the recommended dosage is 24 mg orally once daily until disease progression or unacceptable toxicity.
• Renal Cell Carcinoma (RCC), for first-line treatment of advanced RCC, the suggested dosage is 20 mg orally once daily in combination with pembrolizumab 200 mg administered intravenously over 30 minutes every 3 weeks, up to 2 years or until disease progression or unacceptable toxicity. After completing the combination therapy period, Lenvatinib may be continued as a single agent until disease progression or unacceptable toxicity.
• For previously treated RCC, the recommended dosage is 18 mg in combination with 5 mg everolimus orally once daily until disease progression or unacceptable toxicity.
• Regarding Hepatocellular Carcinoma (HCC), the recommended dosage of the medicine is based on actual body weight, with 12 mg for patients greater than or equal to 60 kg or 8 mg for patients less than 60 kg, taken orally once daily until disease progression or unacceptable toxicity.
• In Endometrial Carcinoma (EC), the suggested dosage is 20 mg orally once daily in combination with pembrolizumab 200 mg administered intravenously over 30 minutes every 3 weeks until unacceptable toxicity or disease progression.
• Dosage adjustments are necessary for patients with severe renal or hepatic impairment when using the medicine for Differentiated Thyroid Cancer (DTC), Renal Cell Carcinoma (RCC), or Endometrial Carcinoma. 
• For those with severe renal impairment (creatinine clearance less than 30 mL/min), the recommended dosages are as follows: 14 mg orally once daily for DTC, and 10 mg orally once daily for both RCC and endometrial carcinoma. 
• Similarly, for individuals with severe hepatic impairment (Child-Pugh C), the recommended dosages are 14 mg orally once daily for DTC, and 10 mg orally once daily for both RCC and endometrial carcinoma. 
• These adjustments aim to optimize treatment efficacy and minimize risks associated with impaired renal or hepatic function. It is essential to consider individual patient conditions and consult with healthcare professionals for appropriate dosage modifications.

Important:

Before initiating treatment, it’s crucial to inform your doctor about all your preexisting conditions and other relevant health histories. If you experience any adverse effects, seek medical attention immediately. If you forget to take a dose of Lenvatinib, take it as soon as you remember. However, if your next scheduled dose is within 12 hours, skip the missed dose and resume your regular dosing schedule.

Warnings & Precaution:

• Blood pressure should be monitored and controlled before and during treatment, with consideration given to withholding medication for Grade 3 hypertension and discontinuing it for Grade 4 hypertension. 
• Clinical signs of cardiac dysfunction should be closely watched for, and the medicine may need to be withheld or discontinued if Grade 3 or 4 dysfunction is detected. 
• Following an arterial thromboembolic event, discontinuation of the treatment is recommended. 
• Liver function should be monitored regularly, and the medicine may need to be withheld or discontinued for Grade 3 or 4 hepatotoxicity, or in cases of hepatic failure. 
• Renal failure or impairment warrants consideration for withholding or discontinuing Lenvatinib. 
• Proteinuria should be monitored, and the medication may need to be withheld for significant proteinuria or discontinued for nephrotic syndrome. 
• Severe diarrhea should be promptly managed, with this medicine potentially being withheld or discontinued based on severity. 
• Patients developing Grade 3 or 4 fistula or gastrointestinal perforation should discontinue the medicine. 
• Electrolyte abnormalities and prolonged QT interval should be monitored, with the medicine being withheld for QT interval greater than 500 ms or a 60 ms or greater increase in baseline QT interval. 
• Blood calcium levels should be monitored monthly, with calcium replacement as necessary, and consideration given to withholding or discontinuing of the medicine is based on the severity of hypocalcemia. 
• This medicine should be withheld until reversible posterior leukoencephalopathy syndrome (RPLS) is resolved, and discontinuation may be necessary. 
• Hemorrhagic events may require withholding or discontinuation of the medicine. Thyroid function should be monitored regularly, and caution should be exercised regarding wound healing and osteonecrosis of the jaw. 
• Patients should be informed about the potential risk of embryo-fetal toxicity and advised to use effective contraception during the treatment due to the risk of fetal harm. 
• These warnings and precautions are critical for the safe and effective use of the therapy.

Common Lenvatinib Side Effects:

• Fatigue or tiredness
• Weakness
• Loss of appetite
• Weight loss
• Diarrhea
• Nausea and vomiting
• High blood pressure
• Mouth sores
• Headache
• Muscle or joint pain
• Skin rash
• Swelling in your arms or legs (edema)
• Difficulty sleeping
• Bleeding, including nosebleeds or heavy menstrual bleeding
• Changes in taste
• Hair loss
• Changes in your voice
• Hoarseness
• Constipation
• Liver problems
• Kidney problems
• Heart problems
• Pancreatitis

Use in Specific Population

• Lenvatinib, carries the potential for fetal harm if administered to pregnant women, based on its mechanism of action and data from animal reproduction studies. The presence of the medicine in human milk is not known, and due to the risk of serious adverse reactions in breastfed infants, women should verify their pregnancy status before starting the treatment.
• For females of reproductive potential, effective contraception should be used during the treatment and for at least 30 days after the final dose. Additionally, the medicine may affect fertility in both males and females of reproductive potential.
• Regarding pediatric use, the safety and efficacy of the medicine have not been established in pediatric patients. However, no significant differences in safety or effectiveness were noted between pediatric and adult subjects. This medicine has not undergone studies in patients with end-stage renal disease.
• In cases of severe hepatic impairment, the dosage of the medicine should be reduced for patients with differentiated thyroid cancer (DTC), renal cell carcinoma (RCC), or endometrial carcinoma.
• It is advisable for breastfeeding mothers to discontinue breastfeeding during the treatment and for at least one week after the final dose to prevent potential harm to the infant.

Storage and Handling 

• Store Lenvatinib capsules at the temperature of 20°C to 25°C (68°F to 77°F).
• Do not freeze the medicine. 
• Keep the medicine away from pets and children.