Lenvima

Name: Lenvima

Pharmacology

Mechanism of Action

Receptor tyrosine kinase (RTK) inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4)

Also inhibits other RTKs that have been implicated in pathogenic angiogenesis, tumor growth, and cancer progression in addition to their normal cellular functions, including fibroblast growth factor (FGF) receptors FGFR1, 2, 3, and 4; the platelet-derived growth factor receptor alpha (PDGFR-alpha), KIT, and RET

Absorption

Orally administered

Peak plasma time: 1-4 hr after PO administration

Administration with food does not affect the extent of absorption but can delay the mean peak plasma time from 2 hr to 4 hr

Distribution

Protein bound: 98-99%

Substrate of P-gp and BCRP

Metabolism

Metabolized by the CYP3A enzymes and aldehyde oxidase

Elimination

Half-life: 28 hr

Excretion (10 days after single dose): 64% feces; 25% urine

Lenvima Dosage

Follow all directions on your prescription label. Do not use this medicine in larger or smaller amounts or for longer than recommended.

You may take lenvatinib with or without food.

Take the medicine at the same time each day.

Call your doctor if you are sick with vomiting or diarrhea. Prolonged illness can lead to dehydration and kidney failure while you are taking lenvatinib.

Lenvatinib is usually given until your body no longer responds to the medication.

While using lenvatinib, you will need frequent blood and urine tests. Your blood pressure will need to be checked often.

Store at room temperature away from moisture and heat.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Take the missed dose as soon as you remember. If you are more than 12 hours late, skip the missed dose. Do not take extra medicine to make up the missed dose.

Side Effects of Lenvima

Serious side effects have been reported with Lenvima. See the "Lenvima Precautions" section.

Common side effects of Lenvima include the following:

  • high blood pressure (hypertension)
  • fatigue
  • diarrhea
  • joint and muscle pain (arthralgia/myalgia)
  • decreased appetite
  • decreased weight
  • nausea
  • inflammation of the lining of the mouth (stomatitis)
  • headache
  • vomiting
  • excess protein in the urine (proteinuria)
  • swelling and pain in the palms, hands and/or the soles of the feet
  • stomach pain
  • changes in voice volume or quality

This is not a complete list of Lenvima side effects. Ask your doctor or pharmacist for more information.

Tell your doctor if you have any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

What is the most important information I should know about lenvatinib?

Some people taking lenvatinib have developed a perforation (a hole or tear) or a fistula (an abnormal passageway) within the stomach or intestines. Get emergency medical help if you have severe stomach pain, or if you feel like you are choking and gagging when you eat or drink.

Call your doctor at once if you have signs of serious side effects, including: severe chest pain, shortness of breath, swelling in your ankles, numbness or weakness, confusion, severe headache, problems with speech or vision, seizure (convulsions), unusual bleeding, coughing up blood, dark urine, clay-colored stools, or jaundice (yellowing of the skin or eyes).

Lenvima Pharmacokinetics

Absorption

Bioavailability

Following oral administration, peak plasma concentrations usually attained within 1–4 hours.1

Systemic exposure and peak plasma concentrations appear to increase in a proportional manner following single or repeated administration of lenvatinib 3.2–32 mg once daily.1

Food

Food decreases rate (time to peak concentration delayed by 2 hours) but does not substantially affect extent of absorption.1

Special Populations

Total exposure in individuals with mild (Clcr 60–89 mL/minute) and moderate renal impairment (Clcr 30–59 mL/minute) similar compared with individuals with normal renal function and was approximately 20% higher in those with severe renal impairment (Clcr <30 mL/minute).1 5

End-stage renal disease: Pharmacokinetics not studied.1

Mild (Child-Pugh class A), moderate (Child-Pugh class B), or severe (Child-Pugh class C) hepatic impairment: Dose-adjusted total exposure was 119, 107, or 180% higher, respectively, compared with individuals with normal hepatic function.1

Distribution

Extent

Not known whether lenvatinib is distributed into human milk.1 Lenvatinib and its metabolites distribute into milk in rats at concentrations higher than maternal plasma.1

Plasma Protein Binding

98–99%.1

Elimination

Metabolism

Primarily metabolized by CYP3A4, aldehyde oxidase, and nonenzymatic processes.1 5

Elimination Route

Eliminated in feces (approximately 64%) and urine (approximately 25%).1

Half-life

Approximately 28 hours.1

Special Populations

In a pharmacokinetic population analysis, age, gender, and race did not have a substantial effect on apparent clearance.1

Stability

Storage

Oral

Capsules

25°C (may be exposed to 15–30°C).1

Uses For Lenvima

Lenvatinib is used to treat progressive, differentiated thyroid cancer that can no longer be treated with radioactive iodine and has already spread to different parts of the body. This medicine is used in combination with everolimus to treat advanced kidney cancer in patients who have received other treatments. It interferes with the growth of cancer cells, which are eventually destroyed by the body. Lenvatinib is an antineoplastic (cancer) medicine.

This medicine is available only with your doctor's prescription.

Dosage forms and strengths

4 mg hard capsule: A yellowish-red body and yellowish-red cap, marked in black ink with “Є” on the cap and “LENV 4 mg” on the body.

10 mg hard capsule: A yellow body and yellowish-red cap, marked in black ink with “Є” on the cap and “LENV 10 mg” on the body.

Lenvima dosing information

Usual Adult Dose for Thyroid Cancer:

24 mg orally once a day
Duration of therapy: Until disease progression or unacceptable toxicity occurs

Use: Treatment of patient with locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer.

What happens if I miss a dose?

Take the missed dose as soon as you remember. If you are more than 12 hours late, skip the missed dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

What should I avoid while taking Lenvima?

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

For Healthcare Professionals

Applies to lenvatinib: oral capsule

Cardiovascular

Very common (10% or more): Hypertension (73%)
Common (1% to 10%): Hypotension, QT prolongation, arterial thromboembolic event, cardiac dysfunction (cardiac failure, decreased ventricular function, pulmonary edema)[Ref]

Renal

Very common (10% or more): Proteinuria (34%), renal impairment (14%)
Common (1% to 10%): Increased creatinine, renal failure[Ref]

Hematologic

Very common (10% or more): Hemorrhagic events (35%)
Common (1% to 10%): Decreased platelet count

Hepatic

Common (1% to 10%): Hyperbilirubinemia, increased alkaline phosphatase, increased ALT, increased AST
Very rare (less than 0.01%): Hepatic failure, acute hepatitis[Ref]

Gastrointestinal

Very common (10% or more): Diarrhea (67%), nausea (47%), stomatitis (41%), vomiting (36%), abdominal pain (31%), constipation (29%), oral pain (25%), dry mouth (17%), dyspepsia (13%)
Common (1% to 10%): GI perforation/fistula, increased serum amylase, increased lipase[Ref]

Nervous system

Very common (10% or more): Headache (38%), dysgeusia (18%), dizziness (15%)
Common (1% to 10%): Reversible posterior leukoencephalopathy syndrome[Ref]

Endocrine

Very common (10% or more): TSH suppression impairment (up to 88%)

Metabolic

Very common (10% or more): Decreased appetite (54%), weight decreased (51%)
Common (1% to 10%): Dehydration, hypoalbuminemia, hypomagnesemia, hypoglycemia, hypocalcemia, hypercalcemia, hyperkalemia, hypercholesterolemia[Ref]

Dermatologic

Very common (10% or more): Palmar-plantar erythrodysesthesia (32%), rash (21%), alopecia (12%)
Common (1% to 10%): Hyperkeratosis[Ref]

Genitourinary

Very common (10% or more): Urinary tract infections (11%)[Ref]

Immunologic

Very Common (10% or more): Dental and oral infections (10%)[Ref]

Musculoskeletal

Very common (10% or more): Arthralgia/myalgia (62%)[Ref]

Other

Very common (10% or more): Fatigue (67%), peripheral edema (21%)

Psychiatric

Very common (10% or more): Insomnia (12%)[Ref]

Respiratory

Very common (10% or more): Dysphonia (31%), cough (24%), epistaxis (12%)
Common (1% to 10%): Pulmonary embolism[Ref]

Some side effects of Lenvima may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

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