Drug Interaction:
Co-administration with probenecid, NSAIDs, and trimethoprim/sulfamethaxazole
may result in delayed renal clearance.
Indication:
Proprietary Name- Folotyn
Established Name - Pralatrexate Injection
Applicant- Allos Therapeutics Inc.
Indication-
Treatment of patients with Refractory Peripheral T-Cell Lymphoma (PTCL)
Dosage-
30mg/m2 administered as an intervenous push over 3-5 min2 once weekly for
6 weeks in 7-weekly cycles
Approved by FDA 24-9- 2009 (Ref- FDA approved List- 2009)
Adverse Reaction:
Most common adverse reactions are mucositis, thrombocytopenia, nausea,
and fatigue. Most common serious adverse reactions are pyrexia, mucositis,
sepsis, febrile neutropenia, dehydration, dyspnea, and thrombocytopenia.
Contra-Indications:
CONTRAINDICATIONS
None.
PRECAUTIONS
.
Thrombocytopenia, neutropenia, and anemia may occur.
Monitor blood counts and omit or modify dose for hematologic toxicities.
.
Mucositis may occur. If Grade 2 mucositis is observed, omit or modify dose.
.
FOLOTYN can cause fetal harm. Women should avoid becoming pregnant
while being treated with FOLOTYN, and pregnant women should be informed
of the potential harm to the fetus.
.
Use caution in patients with moderate to severe renal function impairment.
.
Elevated liver function test abnormalities may occur. If liver function test abnormalities
are Grade 3, omit or modify dose.
Dosages/ Overdosage Etc:
Indication-
Treatment of patients with Refractory Peripheral T-Cell Lymphoma (PTCL)
INDICATIONS AND USAGE-
FOLOTYN is a folate analogue metabolic inhibitor indicated for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma (PTCL).
This indication is based on overall response rate. Clinical benefit such as
improvement in progression free survival or overall survival has not been demonstrated.
DOSAGE AND ADMINISTRATION
The recommended dose of FOLOTYN is 30 mg/m2 administered as an intravenous
push over 3 to 5 minutes once weekly for 6 weeks in 7-week cycles.
Supplement patients with vitamin B12 1 mg intramuscularly every 8-10 weeks and
folic acid 1.0-1.25 mg orally on a daily basis.
Treatment interruption or dose reduction to 20 mg/m2 may be needed
to manage adverse drug reactions.
Patient Information:
1. Need for Folic Acid and Vitamin B12
Patients treated with FOLOTYN must be instructed to take folic acid and
Vitamin B12 as a prophylactic measure to potentially reduce possible
side effects .
.2 Mucositis
Physicians should discuss with patients the signs and symptoms of mucositis.
Patients should be instructed on ways to reduce the risk of its development,
and/or ways to maintain nutrition and control discomfort from mucositis
if it occurs.
3 Low Blood Cell Counts
Patients should be adequately informed of the risk of low blood cell counts
and instructed to immediately contact their physician should any signs of
infection develop including fever. Patients should also be instructed to contact
their physician if bleeding or symptoms of anemia occur.
4 Concomitant Medications
Patients should be instructed to inform their physician if they are taking
any concomitant medications including prescription drugs
(such as trimethoprim/sulfamethoxazole) and nonprescription drugs
(such as nonsteroidal anti-inflammatory drugs)
5 Pregnancy/Nursing
Patients should be instructed to tell their physician if they are pregnant or
plan to become pregnant due to the risk of fetal harm.
Patients should be instructed to tell their physician if they are nursing.
Pharmacology/ Pharmacokinetics:
1 Mechanism of Action
Pralatrexate is a folate analogue metabolic inhibitor that competitively inhibits
dihydrofolate reductase. It is also a competitive inhibitor for polyglutamylation
by the enzyme folylpolyglutamyl synthetase. This inhibition results in the depletion
of thymidine and other biological molecules the synthesis of which depends
on single carbon transfer.
2 Pharmacokinetics
Absorption
The pharmacokinetics of pralatrexate administered as a single agent at a dose
of 30 mg/m2 administered as an intravenous push over 3-5 minutes once
weekly for 6 weeks in 7-week cycles have been evaluated in 10 patients with PTCL
Excretion
A mass balance study has not been performed. The mean fraction of unchanged
pralatrexate diastereomers excreted in urine following a pralatrexate dose
of 30 mg/m2 administered as an intravenous push over 3-5 minutes was
31% (S-diastereomer) (CV = 47%) and 38% (R-diastereomer) (CV = 45%),
respectively
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1. Pregnancy
Pregnancy Category D
FOLOTYN can cause fetal harm when administered to a pregnant woman.
2. Nursing Mothers
It is not known whether pralatrexate is excreted in human milk.
Because many drugs are excreted in human milk, and because of the potential
for serious adverse reactions in nursing infants from this drug, a decision
should be made whether to discontinue nursing or to discontinue FOLOTYN,
taking into account the importance of drug to the mother.
3. Pediatric Use
Pediatric patients were not included in clinical studies with FOLOTYN.
The safety and effectiveness in pediatric patients have not been established.
4 Geriatric Use
No overall differences in efficacy and safety were observed in patients based
on age (< 65 years compared with . 65 years).
No dosage adjustment is required in elderly patients with normal renal function
Manufacturer Details