FARYDAK*
Manufacturer DetailsNOVARTIS INC
Novartis Pharmaceuticals Corp
Compositions:
Lenvatinib-mg,
Lenvatinib-mg,
| Strength | Rate | Packing Style |
|---|---|---|
| mg | 0.00 | 10s tablets |
List of Related Indications:
- For the treatment of Patients with Multiple Myeloma(MM), who have received at least 2 Prior Regimens,including Bortezomib and an Immunomodulatory Agent
List Of Drugs:
- Lenvatinib- Lenvima-@- (Feb 2015) - Anti-cancer
Indication Type Description:
Drug Interaction
Indication
Adverse Reaction
Contra-Indications
Dosages/ Overdosage Etc
Patient Information
Pharmacology/ Pharmacokinetics
Pregnancy and lactation
Drug Interaction:
Effect of Other Drugs on Lenvatinib
No dose adjustment of LENVIMA is recommended when co-administered with CYP3A,
Pglycoprotein (P-gp), and breast cancer resistance protein (BCRP) inhibitors
and CYP3A and P-gp inducers
Indication:
LENVIMA (lenvatinib) capsules, for oral use
Initial U.S. Approval: 2015
Proprietary Name- LENVIMA
Established Name- Lenvatinib
Applicant- Eisai Inc.
Indication- For the treatment of Patients with Locally recurrent or
Metastatic, Progressive ,Radioactive Iodinerefractory
Differentiated Thyroid Cancer
Approval Date- 2/13/2015
Approved by U.S.FDA on 30-06-2015 (Ref- FDA approved List- 2015)
NEW MOLECULAR ENTITY AND NEW THERAPEUTIC BIOLOGICAL
PRODUCTS APPROVED FOR 2015
Certain drugs are classified as New molecular Emtities- NME- for FDA review
Many of these products contain active moieties that have not been approved
by FDA previously, either as a single ingredient or as part of a combination
products; these products frequently provide important new therapies for the
patients.
Some drugs are characterized as NMEs for administrative purposes ,but
nonetheless contain certain active moieties in products that have been
previously approved by FDA. For example, CDER classifies biological
products submitted in an application under section 351(a) of the Public
Service Act as NME for purposes of FDA review, regardless of whether
the agency previously approved a related active moiety in a different
product.
FDAs classification of a drug as an -NME- for review purposes is distinct
from FDAs determination of whether a drug is a - New Chemical Entity or - NCE-
within the meaning of the Federal Food,Drug, and Cosmetic Act
No.5
Drug Name - Lenvatinib
Active Ingredient- Lenvima
Date of approval - 2/13/2015
FDA-approved use - To treat patients with progressive Differentiated Thyroid Cancer(DTC) whose disease progressed
despite receiving radioactive iodine therapy
(Radioactive Iodine Refractory Disease)
Approved by US FDA on 2/13/2015- (Ref- FDA approved List- 2015)
INDICATIONS AND USAGE
LENVIMA is indicated for the treatment of patients with locally recurrent or metastatic
progressive, radioactive iodine-refractory differentiated thyroid cancer (DTC).
Adverse Reaction:
The following adverse reactions are reported:
Hypertension
Cardiac Dysfunction
Arterial Thromboembolic Events
Hepatotoxicity
Proteinuria
Renal Failure and Impairment
Gastrointestinal Perforation and Fistula Formation
QT Interval Prolongation
Hypocalcemia
Reversible Posterior Leukoencephalopathy Syndrome
Hemorrhagic Events
Contra-Indications:
CONTRAINDICATIONS
None.
WARNINGS AND PRECAUTIONS
1. Hypertension
Discontinue LENVIMA for life-threatening hypertension.
2. Cardiac Dysfunction
Monitor patients for clinical symptoms or signs of cardiac decompensation.
Withhold LENVIMA for development of Grade 3 cardiac dysfunction until improved
to Grade 0 or 1 or baseline.
Either resume at a reduced dose or discontinue LENVIMA
depending on the severity and persistence of cardiac dysfunction.
3. Arterial Thromboembolic Events
Discontinue LENVIMA following an arterial thrombotic event.
The safety of resuming LENVIMA after an arterial thromboembolic event has not been
established and LENVIMA has not been studied in patients who have had an arterial
thromboembolic event within the previous 6 months
4. Hepatotoxicity
Monitor liver function before initiation of LENVIMA, then every 2 weeks for the first 2 months,
and at least monthly thereafter during treatment.
Withhold LENVIMA for the development of Grade 3 or greater liver impairment until
resolved to Grade 0 to 1 or baseline. Either resume at a reduced dose or discontinue
LENVIMA depending on the severity and persistence of hepatotoxicity.
Discontinue LENVIMA for hepatic failure
5. Proteinuria
Monitor for proteinuria before initiation of, and periodically throughout treatment.
If urine dipstick proteinuria greater than or equal to 2+ is detected, obtain a 24 hour
urine protein. Withhold LENVIMA for .2 grams of proteinuria/24 hours and resume
at a reduced dose when proteinuria is <2 gm/24 hours.
Discontinue LENVIMA for nephrotic syndrome .
6. Renal Failure and Impairment
Withhold LENVIMA for development of Grade 3 or 4 renal failure/impairment until
resolved to Grade 0 to 1 or baseline. Either resume at a reduced dose or discontinue
LENVIMA depending on the severity and persistence of renal impairment.
7. Gastrointestinal Perforation and Fistula Formation
Discontinue LENVIMA in patients who develop gastrointestinal perforation or
life-threatening fistula
8. QT Interval Prolongation
Monitor and correct electrolyte abnormalities in all patients.
Withhold LENVIMA for the development of Grade 3 or greater QT interval
prolongation. Resume LENVIMA at a reduced dose when QT prolongation resolves
to Grade 0 or 1 or baseline].
9. Hypocalcemia
Monitor blood calcium levels at least monthly and replace calcium as necessary
during LENVIMA treatment. Interrupt and adjust LENVIMA dosing as necessary
depending on severity, presence of ECG changes, and persistence of hypocalcemia
10. Reversible Posterior Leukoencephalopathy Syndrome
Across clinical studies in which 1108 patients received LENVIMA, there were 3 reported
events of reversible posterior leukoencephalopathy syndrome (RPLS).
Confirm the diagnosis of RPLS with MRI. Withhold for RPLS until fully resolved.
Upon resolution, resume at a reduced dose or discontinue LENVIMA depending
on the severity and persistence of neurologic symptoms.
11. Hemorrhagic Events
Withhold LENVIMA for the development of Grade 3 hemorrhage until resolved to
Grade 0 to 1. Either resume at a reduced dose or discontinue LENVIMA depending
on the severity and persistence of hemorrhage.
Discontinue LENVIMA in patients who experience Grade 4 hemorrhage .
12. Impairment of Thyroid Stimulating Hormone Suppression
Monitor TSH levels monthly and adjust thyroid replacement medication as needed
in patients with DTC.
13. Embryofetal Toxicity
Based on its mechanism of action and data from animal reproduction studies,
LENVIMA can cause fetal harm when administered to a pregnant woman.
In animal reproduction studies, oral administration of lenvatinib during organogenesis
at doses below the recommended human dose resulted in embryotoxicity,
fetotoxicity, and teratogenicity in rats and rabbits. Advise pregnant women of the potentia
risk to a fetus.
Advise females of reproductive potential to use effective contraception during
treatment with LENVIMA and for at least 2 weeks following completion of therapy
Dosages/ Overdosage Etc:
INDICATIONS AND USAGE
LENVIMA is indicated for the treatment of patients with locally recurrent or metastatic
progressive, radioactive iodine-refractory differentiated thyroid cancer (DTC).
DOSAGE AND ADMINISTRATION
Recommended Dose
The recommended daily dose of LENVIMA is 24 mg (two 10 mg capsules and
one 4 mg capsule) orally taken once daily with or without food
Continue LENVIMA until disease progression or until unacceptable toxicity occurs.
Take LENVIMA at the same time each day.
If a dose is missed and cannot be taken within 12 hours, skip that dose and take
the next dose at the usual time of administration
Patient Information:
PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling (Patient Information).
Hypertension:
Advise patients to undergo regular blood pressure monitoring and to contact their health care provider if blood pressure is elevated
Cardiac Dysfunction:
Advise patients that LENVIMA can cause cardiac dysfunction and to immediately contact
their healthcare provider if they experience any clinical symptoms of cardiac dysfunction
such as shortness of breath or swelling of ankles
Arterial Thrombotic Events
Advise patients to seek immediate medical attention for new onset chest pain or acute
neurologic symptoms consistent with myocardial infarction or stroke
Hepatotoxicity:
Advise patients that they will need to undergo lab tests to monitor for liver function and to
report any new symptoms indicating hepatic toxicity or failure
Proteinuria and Renal Failure/Impairment:
Advise patients that they will need to undergo regular lab tests to monitor for kidney
function and protein in the urine
Gastrointestinal perforation or fistula formation:
Advise patients that LENVIMA can increase the risk of gastrointestinal perforation
or fistula and to seek immediate medical attention for severe abdominal pain
.
Hemorrhagic Events:
Advise patients that LENVIMA can increase the risk for bleeding and to contact
their health care provider for bleeding or symptoms of severe bleeding
.
Embryofetal Toxicity:
Advise females of reproductive potential of the potential risk to a fetus and to inform
their healthcare provider of a known or suspected pregnancy
Advise females of reproductive potential to use effective contraception during
treatment with LENVIMA and for at least 2 weeks following completion of therapy .
Lactation:
Advise nursing women to discontinue breastfeeding during treatment with
LENVIMA .
Manufactured by:
Patheon Inc.
Mississauga, Ontario, Canada
Distributed by:
Eisai Inc.
Woodcliff Lake, NJ 07677
LENVIMA™ is a trademark of Eisai R&D Management Co., Ltd.
Pharmacology/ Pharmacokinetics:
CLINICAL PHARMACOLOGY
1 Mechanism of Action
Lenvatinib is a receptor tyrosine kinase (RTK) inhibitor that inhibits the kinase activities
of vascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR),
and VEGFR3 (FLT4).
Lenvatinib 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 (PDGFRá), KIT, and RET.
2. Pharmacokinetics
Absorption: After oral administration of LENVIMA, time to peak plasma concentration
(Tmax) typically occurred from 1 to 4 hours post-dose.
Administration with food did not affect the extent of absorption, but decreased the rate
of absorption and delayed the median Tmax from 2 hours to 4 hours.
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1. Pregnancy
Risk Summary
Based on its mechanism of action and data from animal reproduction studies,
LENVIMA can cause fetal harm when administered to a pregnant woman
There are no available human data informing the drug-associated risk.
Advise pregnant women of the potential risk to a fetus.
2. Lactation
Risk Summary
It is not known whether LENVIMA is present in human milk. However, lenvatinib and its
metabolites are excreted in rat milk at concentrations higher than in maternal plasma
Because of the potential for serious adverse reactions in nursing infants from LENVIMA,
advise women to discontinue breastfeeding during treatment with LENVIMA
3. Pediatric Use
The safety and effectiveness of LENVIMA in pediatric patients have not been established.
4. Geriatric Use
Of 261 patients who received LENVIMA in Study 1, 118 (45.2%) were greater than or
equal to 65 years of age and 29 (11.1%) were greater than or equal to 75 years of age.
No overall differences in safety or effectiveness were observed between these subjects
and younger subjects.
