Pralatrexate

Pralatrexate
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alberto Plate [2]

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Overview

Pralatrexate is an antimetabolite, antineoplastic agent that is FDA approved for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma (PTCL). Common adverse reactions include edema, constipation, nausea, anemia, neutropenia, thrombocytopenia, cough and fatigue.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

There is limited information regarding Pralatrexate FDA-Labeled Indications and Dosage (Adult) in the drug label.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Pralatrexate in adult patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Pralatrexate in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

There is limited information regarding Pralatrexate FDA-Labeled Indications and Dosage (Pediatric) in the drug label.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Pralatrexate in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Pralatrexate in pediatric patients.

Contraindications

None

Warnings

Bone Marrow Suppression

• FOLOTYN can cause bone marrow suppression, manifested by thrombocytopenia, neutropenia, and/or anemia. Monitor complete blood counts and omit and/or reduce the dose based on ANC and platelet count prior to each dose as outlined in Section 2.2 TABLE 2. Administer vitamin B12 and instruct patients to take folic acid to reduce the risk of treatment-related hematological toxicity.

Mucositis

• FOLOTYN can cause mucositis. Monitor for mucositis weekly and if ≥ Grade 2 mucositis is observed, omit and/or reduce the dose as outlined in Section 2.2 TABLE 1. Administer vitamin B12 and instruct patients to take folic acid to reduce the risk of mucositis.

Dermatologic Reactions

• FOLOTYN can cause severe dermatologic reactions, which may result in death. These dermatologic reactions have been reported in clinical studies (14/663 patients [2.1%]) and post marketing experience, and have included skin exfoliation, ulceration, and toxic epidermal necrolysis (TEN). They may be progressive and increase in severity with further treatment, and may involve skin and subcutaneous sites of known lymphoma. Monitor patients with dermatologic reactions closely, and if severe, withhold or discontinue FOLOTYN.

Tumor Lysis Syndrome

• FOLOTYN can cause tumor lysis syndrome (TLS). Monitor patients who are at increased risk of TLS and treat promptly.

Hepatic Toxicity

• FOLOTYN can cause hepatic toxicity and liver function test abnormalities. Persistent liver function test abnormalities may be indicators of hepatic toxicity and require dose modification or discontinuation. Monitor liver function tests. Omit dose until recovery, adjust or discontinue therapy based on the severity of the hepatic toxicity.

Risk of Increased Toxicity in the Presence of Impaired Renal Function

• Patients with moderate to severe renal function impairment may be at greater risk for increased exposure and toxicity. Monitor patients for renal function and systemic toxicity and adjust dosing accordingly.
• Serious adverse drug reactions including toxic epidermal necrolysis and mucositis were reported in patients with end stage renal disease (ESRD) undergoing dialysis who were administered FOLOTYN therapy. Avoid FOLOTYN use in patients with end stage renal disease including those undergoing dialysis unless the potential benefit justifies the potential risk.

Embryo-Fetal Toxicity

• FOLOTYN can cause fetal harm when administered to a pregnant woman. FOLOTYN was embryotoxic and fetotoxic in rats and rabbits. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.

Adverse Reactions

Clinical Trials Experience

The following serious adverse reactions are described below and elsewhere in the labeling:

• Bone Marrow Suppression
• Mucositis
• Dermatologic Reactions
• Tumor Lysis Syndrome
• Hepatic Toxicity

The most common adverse reactions observed in patients with peripheral T-cell lymphoma (PTCL) treated with FOLOTYN were mucositis, thrombocytopenia, nausea, and fatigue.

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. The safety of FOLOTYN was evaluated in 111 PTCL patients in a single-arm clinical study in which patients received a starting dose of 30 mg/m2 once weekly for 6 weeks in 7-week cyc

Most Frequent Adverse Reactions

TABLE 4 summarizes the most frequent adverse reactions, regardless of causality, using the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI CTCAE, version 3.0).

Serious Adverse Events

• Forty-four percent of patients (n = 49) experienced a serious adverse event while on study or within 30 days after their last dose of FOLOTYN. The most common serious adverse events (> 3%), regardless of causality, were pyrexia, mucositis, sepsis, febrile neutropenia, dehydration, dyspnea, and thrombocytopenia. One death from cardiopulmonary arrest in a patient with mucositis and febrile neutropenia was reported in this trial. Deaths from mucositis, febrile neutropenia, sepsis, and pancytopenia occurred in 1.2% of patients treated on all FOLOTYN trials at doses ranging from 30 to 325 mg/m2.

Discontinuations

• Twenty-three percent of patients (n = 25) discontinued treatment with FOLOTYN due to adverse reactions. The adverse reactions reported most frequently as the reason for discontinuation of treatment were mucositis (6%, n = 7) and thrombocytopenia (5%, n = 5).

Dose Modifications

• The target dose of FOLOTYN was 30 mg/m2 once weekly for 6 weeks in 7-week cycles. The majority of patients (69%, n = 77) remained at the target dose for the duration of treatment. Overall, 85% of scheduled doses were administered.

Postmarketing Experience

There is limited information regarding Pralatrexate Postmarketing Experience in the drug label.

Drug Interactions

There is limited information regarding Pralatrexate Drug Interactions in the drug label.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): There is no FDA guidance on usage of Pralatrexate in women who are pregnant.
Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Pralatrexate in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Pralatrexate during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Pralatrexate in women who are nursing.

Pediatric Use

There is no FDA guidance on the use of Pralatrexate in pediatric settings.

Geriatic Use

There is no FDA guidance on the use of Pralatrexate in geriatric settings.

Gender

There is no FDA guidance on the use of Pralatrexate with respect to specific gender populations.

Race

There is no FDA guidance on the use of Pralatrexate with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Pralatrexate in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Pralatrexate in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Pralatrexate in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Pralatrexate in patients who are immunocompromised.

Administration and Monitoring

Administration

There is limited information regarding Pralatrexate Administration in the drug label.

Monitoring

There is limited information regarding Pralatrexate Monitoring in the drug label.

IV Compatibility

There is limited information regarding the compatibility of Pralatrexate and IV administrations.

Overdosage

There is limited information regarding Pralatrexate overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.

Pharmacology

There is limited information regarding Pralatrexate Pharmacology in the drug label.

Mechanism of Action

There is limited information regarding Pralatrexate Mechanism of Action in the drug label.

Structure

There is limited information regarding Pralatrexate Structure in the drug label.

Pharmacodynamics

There is limited information regarding Pralatrexate Pharmacodynamics in the drug label.

Pharmacokinetics

There is limited information regarding Pralatrexate Pharmacokinetics in the drug label.

Nonclinical Toxicology

There is limited information regarding Pralatrexate Nonclinical Toxicology in the drug label.

Clinical Studies

There is limited information regarding Pralatrexate Clinical Studies in the drug label.

How Supplied

There is limited information regarding Pralatrexate How Supplied in the drug label.

Storage

There is limited information regarding Pralatrexate Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Pralatrexate Patient Counseling Information in the drug label.

Precautions with Alcohol

Alcohol-Pralatrexate interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

There is limited information regarding Pralatrexate Brand Names in the drug label.

Look-Alike Drug Names

There is limited information regarding Pralatrexate Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

Pralatrexate

File:Pralatrexate.png
Identifiers
IUPAC name N-[4-[1-[(2,4-Diamino-6-pteridinyl)methyl] -3-butynyl]benzoyl]-L-glutamic acid
CAS Number	146464-95-1
PubChem CID	725808
E number	{{#property:P628}}
ECHA InfoCard	{{#property:P2566}}
Chemical and physical data
Formula	C23H23N7O5
Molar mass	477.47 g/mol

Pralatrexate (rINN), also known as 10-propargyl-10-deazaaminopterin, common name PDX, is a drug candidate being studied for the treatment of cancer. PDX is a folate analog inhibitor of dihydrofolate reductase. As of July 2005, it is undergoing Phase 1 and Phase 2 clinical trials for treatment of non-Hodgkin lymphoma and non-small cell lung cancer.

External links

• Allos Therapeutics Information on PDX