New Drug Introduction: Lenvima / lenvatinib
Pharmacology
Manufacturer
Approval Date
Indications
Contraindications
Warnings and
Precautions
Pregnancy/Lactation
Pharmacokinetics
Pharmacokinetic
drug interactions
Pharmacodynamic
drug interactions
Most Common
Adverse Effects
(≥20%)
Monitoring Efficacy
Lenvatinib is a receptor tyrosine kinase (RTK) inhibitor which inhibits the
kinase activities of vascular endothelial growth factor (VEGF) receptors
VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4). Lenvatinib also
inhibits other RTKs implicated in angiogenesis, tumor growth, and cancer
progression.
Patheon Inc.
02/2015
Treatment of patients with locally-recurrent or metastatic, progressive,
radioactive iodine-refractory differentiated thyroid cancer (DTC)
 Used in conjunction with thyroid-hormone-suppression therapy
None
 Cardiac: hypertension (HTN), cardiac failure, QT prolongation
 Renal: proteinuria, renal failure and impairment
 Hepatic: hepatotoxicity
 Gastrointestinal (GI): GI perforation and fistula formation
 Hematologic/thrombotic: hemorrhagic events, arterial thromboembolic
events
 Endocrine: hypocalcemia, impairment of thyroid stimulating hormone
(TSH) suppression
 Neurologic: reversible posterior leukoencephalopathy syndrome
(RPLS)
 Reproductive: embryofetal toxicity
Pregnancy: Based on its mechanism and data from animal reproduction
studies, lenvatinib can cause fetal harm when used in pregnant women.
Females of reproductive age should use effective contraception while on
lenvatinib and for at least 2 weeks following discontinuation.
Lactation Recommendation: it is not known whether lenvatinib is present in
human milk. Due to the risk for serious adverse reactions in nursing infants,
advise women to discontinue breastfeeding during lenvatinib treatment.
A – Tmax: 1-4 hours. Administration with food delays the Tmax by ~2 hours
D – Protein binding: 98-99%
M – Primarily CYP3A4; also aldehyde oxidase and non-enzymatic
processes
E – Feces (64%), urine (25%). Elimination t1/2: ~28 hours
No known clinically-significant drug interactions
May result in  QTc-prolongation when used with other QTc-prolonging
agents
Hypertension (73%) [16%]
Headache (38%) [11%]
Diarrhea (67%) [17%]
Vomiting (36%) [15%]
Fatigue (67%) [35%]
Proteineuria (34%) [11%]
Arthralgia/myalgia (62%) [28%]
Dysphonia (31%) [5%]
Decreased appetite (54%) [18%]
Abdominal pain (31%) [11%]
Weight decreased (51%) [15%]
Constipation (29%) [15%]
Nausea (47%) [25%]
Oral pain (25%) [2%]
Stomatitis (41%) [8%]
Rash (21%) [3%]
Palmar-plantar erythrodysesthesia
Peripheral edema (21%) [8%]
(32%) [1%]
Radiographic evidence of disease progression
Monitoring Toxicity
Dosing - Initial
Dosing - Usual
Dosing - Max
Renal Adjustment
Hepatic Adjustment
Toxicity Adjustment
Baseline and periodically: blood pressure, proteinuria (urinalysis),
liver/renal function and electrolytes/serum calcium (comprehensive
metabolic panel, magnesium level), TSH levels, QTc interval
(electrocardiogram), left ventricular ejection fraction (echocardiogram);
symptoms of cardiac decompensation, arterial thromboembolic events, GI
perforation/fistula, RPLS
24 mg PO once daily at the same time each day (not to exceed 2 doses
within a 12 hour period)
24 mg PO once daily
24 mg PO once daily
CrCl ≤ 30 mL/min: 14 mg PO once daily
Severe (Child-Pugh C): 14 mg PO once daily
Grade 2/3 adverse reaction or grade 4 laboratory abnormality: interrupt
lenvatinib therapy until resolved, then resume at:
 20 mg PO once daily (1st occurrence)
 14 mg PO once daily (2nd occurrence)
 10 mg PO once daily (3rd occurrence)
Life-threatening HTN, grade 4 cardiac dysfunction, arterial thrombotic
event, hepatic failure, nephrotic syndrome, severe renal impairment, GI
perforation, life-threatening fistula, severe RPLS, grade 4 hemorrhage:
discontinue lenvatinib
Cost: Source: GoodRx.com, accessed 03/14/2015
Dose(s)
Brand– Generic
Lenvima- lenvatinib
Caprelsa®- vandetanib
Nexavar®- sorafenib
24 mg once daily
300 mg once daily
400 mg twice daily
$ (30d)
$14,371
$12,331
$12,588
Summary



Lenvima™, lenvatinib, is an oral receptor tyrosine kinase (RTK) inhibitor indicated for the
treatment of locally-recurrent or metastatic, progressive, radioactive iodine-refractory
differentiated thyroid cancer (DTC).
Lenvatinib is used in conjunction with thyroid-hormone-suppression therapy for DTC that is
refractory to iodine-131 therapy.
The most common adverse effects in lenvatinib-treated patients are hypertension (sometimes
severe), diarrhea, and fatigue.
.
References:
1. http://www.lenvima.com
2. Lenvima package insert. Patheon Inc. February 2015.
3. Schlumberger M, Tahara M, Wirth LJ, et al. Lenvatinib versus placebo in radioiodinerefractory thyroid cancer. N Engl J Med 2015;372(7):621-630.
Date Prepared: 04/07/2015
Editor: Peter G. Koval, Pharm.D., BCPS
Author: Kira Letvak, Pharm.D. Candidate, UNC Eshelman School of Pharmacy