Trifluridine and Tipiracil (Lonsurf) -@-(Sep 2015)- Anti-Cancer Drug
Drug Name:Trifluridine and Tipiracil (Lonsurf) -@-(Sep 2015)- Anti-Cancer Drug
List Of Brands:
Indication Type Description:
Drug Interaction
Indication
Adverse Reaction
Contra-Indications
Dosages/ Overdosage Etc
Patient Information
Pharmacology/ Pharmacokinetics
Pregnancy and lactation
Drug Interaction:
No pharmacokinetic drug-drug interaction studies have been conducted with LONSURF.
Indication:
LONSURF (trifluridine and tipiracil) tablets, for oral use
Initial U.S. Approval: 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.26
Drug Name - Trifluridine and Tipracil
Active Ingredient- Lonsurf
Date of approval - 9/22/2015
FDA-approved use - To treat adults with an advanced form of Corectal
Cancer who are no longer responding to other
therapies
Approved by US FDA on 9/22/2015- (Ref- FDA approved List- 2015)
INDICATIONS AND USAGE
LONSURF is a combination of trifluridine, a nucleoside metabolic inhibitor,
and tipiracil, a thymidine phosphorylase inhibitor, indicated for the treatment
of patients with metastatic colorectal cancer who have been previously treated
with fluoropyrimidine-, oxaliplatin-and irinotecan-based chemotherapy,
an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy.
Adverse Reaction:
The most common adverse reaction (.10%) are anemia, neutropenia,
asthenia/fatigue, nausea, thrombocytopenia, decreased appetite,
diarrhea, vomiting, abdominal pain, and pyrexia.
Contra-Indications:
CONTRAINDICATIONS
None.
WARNINGS AND PRECAUTIONS
.
Severe Myelosuppression: Obtain complete blood counts prior to and on
Day 15 of each cycle. Reduce dose and/or hold LONSURF as clinically
indicated.
.
Embryo-Fetal Toxicity: Fetal harm can occur. Advise women of potential risk
to a fetus.
Dosages/ Overdosage Etc:
INDICATIONS AND USAGE
LONSURF is a combination of trifluridine, a nucleoside metabolic inhibitor,
and tipiracil, a thymidine phosphorylase inhibitor, indicated for the treatment
of patients with metastatic colorectal cancer who have been previously treated
with fluoropyrimidine-, oxaliplatin-and irinotecan-based chemotherapy,
an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy.
DOSAGE AND ADMINISTRATION
Recommended dose: 35 mg/m2/dose orally twice daily on Days 1
through 5 and Days 8 through 12 of each 28-day cycle.
Take LONSURF within 1 hour after completion of morning and evening meals.
DOSAGE FORMS AND STRENGTHS
Tablets:
15 mg trifluridine/6.14 mg tipiracil
20 mg trifluridine/8.19 mg tipiracil
Patient Information:
PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling (Patient Information).
1. Severe Myelosuppression:
Advise the patient to immediately contact their healthcare provider if they experience
signs or symptoms of infection and advise patients to keep all appointments for blood
tests.
2.Gastrointestinal toxicity:
Advise patients to contact their healthcare provider for severe or persistent nausea,
vomiting, diarrhea, or abdominal pain.
3.Administration Instructions:
Advise the patient that LONSURF is available in two strengths and they may receive
both strength tablets to provide the prescribed dose.
Advise the patient of the importance of reading prescription labels carefully and
taking the appropriate number of tablets.
Advise the patient to take LONSURF within 1 hour after eating their morning and
evening meals.
Advise the patient that anyone else who handles their medication should wear gloves.
4.Embryo-Fetal Toxicity:
Advise pregnant women of the potential risk to the fetus. Advise females of reproductive
potential to use effective contraception during treatment with LONSURF.
5.Lactation:
Advise women not to breastfeed during treatment with LONSURF and for one day
following the final dose.
Pharmacology/ Pharmacokinetics:
CLINICAL PHARMACOLOGY
1. Mechanism of Action
LONSURF consists of a thymidine-based nucleoside analog, trifluridine, and the
thymidine phosphorylase inhibitor, tipiracil, at a molar ratio 1:0.5 (weight ratio,
1:0.471). Inclusion of tipiracil increases trifluridine exposure by inhibiting its
metabolism by thymidine phosphorylase.
Following uptake into cancer cells, trifluridine is incorporated into DNA, interferes with
DNA synthesis and inhibits cell proliferation. Trifluridine/tipiracil demonstrated
anti-tumor activity against KRAS wild-type and mutant human colorectal cancer
xenografts in mice.
2. Pharmacokinetics
After twice daily dosing of LONSURF, systemic exposure (area under the concentration
curve, AUC) of trifluridine increased more than dose-proportionally over the dose
range of 15 to 35 mg/m2 . After administration of LONSURF 35 mg/m2 twice daily,
the mean elimination half-life (t1/2 ) of trifluridine was 1.4 hours and of tipiracil
was 2.1 hours after a single dose.
The mean elimination half-life at steady state of trifluridine was 2.1 hours and of
tipiracil was 2.4 hours
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1. Pregnancy
Risk Summary
Based on animal data and its mechanism of action, LONSURF can cause fetal harm
LONSURF caused embryo-fetal lethality and embryo-fetal toxicity in pregnant
rats when given during gestation at doses resulting in exposures lower than
or similar to exposures at the recommended dose in humans.
There are no available data on LONSURF exposure in pregnant women.
Advise pregnant women of the potential risk to a fetus.
In the U.S. general population, the estimated background risk of major birth defects
and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
2. Lactation
Risk Summary
It is not known whether LONSURF or its metabolites are present in human milk.
In nursing rats, trifluridine and tipiracil or their metabolites were present in breast milk.
There are no data to assess the effects of LONSURF or its metabolites on the
breastfed infant or the effects on milk production. Because of the potential for
serious adverse reactions in breastfeeding infants.
Advise women not to breastfeed during treatment with LONSURF and for
one day following the final dose.
3.Pediatric Use
Safety and effectiveness of LONSURF in pediatric patients have not been established.
4. Geriatric Use
In Study 1, 533 patients received LONSURF; 44% were 65 years of age or over,
while 7% were 75 and over.
No overall differences in effectiveness were observed in patients 65 or older versus
younger patients, and no adjustment is recommended for the starting dose of
LONSURF based on age.
