What are the side effects of lenvatinib (generic name)?

Lenvatinib Side Effects

Lenvatinib commonly causes hypertension, diarrhea, fatigue, proteinuria, rash, hand-foot skin reaction, decreased appetite, weight loss, and hypothyroidism, with almost all patients experiencing at least one side effect during treatment. 1

Common Side Effects

Cardiovascular Effects

• Hypertension is one of the most frequent adverse events (42% of patients), requiring regular blood pressure monitoring and management 1
• Hypertension often occurs during the first few weeks of treatment and may require antihypertensive therapy 1, 2

Gastrointestinal Effects

• Diarrhea affects approximately 39% of patients and can significantly impact quality of life 1
• Anorexia/decreased appetite (34%) and weight loss (31%) are common and require nutritional monitoring 1
• Stomatitis and oral mucositis may occur and require preventive oral hygiene measures 3, 4

Dermatologic Effects

• Hand-foot skin reaction (27%) is less common with lenvatinib than with sorafenib (54%) but still requires monitoring 1
• Rash can occur and may require topical management 1, 3

Endocrine Effects

• Hypothyroidism affects approximately 16% of patients and requires regular thyroid function monitoring 1
• TSH levels should be checked regularly, with endocrinology consultation recommended if TSH exceeds 10 mIU/L or is higher than 5 mIU/L on two separate occasions 1

Renal Effects

• Proteinuria occurs in about 25% of patients 1
• Monitoring is recommended with 24-hour urinary protein or random urinary protein-to-creatinine ratio if dipstick shows 2+ or greater proteinuria 1
• Lenvatinib should be interrupted if 24-hour urinary protein is ≥2 g 1

Other Common Effects

• Fatigue affects approximately 30% of patients 1
• Dysphonia (voice changes) may occur in about 24% of patients 1

Management of Side Effects

Monitoring Recommendations

• Blood pressure should be monitored weekly for the first 2 months, especially in patients with pre-existing hypertension 2
• TSH levels should be monitored monthly 1, 2
• Proteinuria should be regularly assessed 1, 2

Dose Modifications

• For grade 1-2 adverse events, dose interruption is generally not required 5
• For persistent or intolerable grade 2 or grade 3 adverse events, treatment should be interrupted until symptoms improve to grade 0-1 5, 2
• After resolution of symptoms, treatment can be resumed at the same or lower dose 5
• In clinical trials, adverse events frequently led to treatment interruptions (82.4% of patients) and dose reductions (67.8%) 1

Specific Management Strategies

• Hypertension: Initiate or intensify antihypertensive therapy for systolic BP ≥135 mmHg to <160 mmHg or diastolic BP ≥85 mmHg to <100 mmHg 2
• Diarrhea: Initial treatment with loperamide; consider 1-week treatment interruption if diarrhea persists 2
• Proteinuria: Consider angiotensin II receptor blockers or ACE inhibitors for grade 2 proteinuria 2
• Weight loss: Consider nutritional consultation and treatment break if weight loss exceeds 10% of baseline 2
• Skin toxicities: Use moisturizers, emollients, and soap substitutes 2

Special Considerations

Pregnancy and Fertility

• Lenvatinib can cause fetal harm when administered to pregnant women 3
• Women of reproductive potential should use effective contraception during treatment and for 30 days after the last dose 3
• Lenvatinib may impair fertility in both males and females 3

Treatment Efficacy Considerations

• Maintaining the highest possible dose is important for treatment efficacy 5
• Longer treatment interruptions and lower mean dose intensities may diminish the potential benefit of the drug 1
• Adverse events generally occur during the first few weeks of treatment and decrease rapidly after treatment interruption 1

Serious Adverse Events

• Serious adverse events (SAEs) were reported in 43% of lenvatinib-treated patients compared to 30% in sorafenib-treated patients in the REFLECT trial 1
• Patients who discontinued lenvatinib due to SAEs had significantly shorter overall survival than those who continued treatment 1

By recognizing and proactively managing these side effects, clinicians can help patients maintain treatment at optimal doses, potentially improving outcomes while preserving quality of life.