"Sabahaddin Akman, owner of the Istanbul, Turkey, firm Ozay Pharmaceuticals, has pleaded guilty to charges of smuggling misbranded and adulterated cancer treatment drugs into the United States.
Akman pleaded guilty in the U.S. District Court"...
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 [see DOSAGE AND ADMINISTRATION and ADVERSE REACTIONS].
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 [see DOSAGE AND ADMINISTRATION and ADVERSE 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 [see ADVERSE REACTIONS and Use In Specific Populations].
Tumor Lysis Syndrome
FOLOTYN can cause tumor lysis syndrome (TLS). Monitor patients who are at increased risk of TLS and treat promptly.
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 [see DOSAGE AND ADMINISTRATION and Use In Specific Populations].
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 [see DOSAGE AND ADMINISTRATION, ADVERSE REACTIONS, Use in Specific Populations, and CLINICAL PHARMACOLOGY].
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 [see Use in Specific Populations].
Patient Counseling Information
See FDA-approved labeling (PATIENT INFORMATION).
Patients should be instructed to read the Patient Information carefully.
Need for Folic Acid and Vitamin B12
Low Blood Cell Counts
Inform patients of the risk of low blood cell counts and to immediately contact their physician should any signs of infection develop, including fever. Inform patients to contact their physician if bleeding or symptoms of anemia occur.
Inform patients of the signs and symptoms of mucositis. Instruct patients on ways to reduce the risk of its development, and on ways to maintain nutrition and control discomfort from mucositis if it occurs.
Fatal Dermatologic Reactions
Advise patients about the risks for and the signs and symptoms of dermatologic reactions. Instruct patients to immediately notify their physician if any skin reactions occur [see WARNINGS AND PRECAUTIONS].
Tumor Lysis Syndrome
Inform patients about the risk of and the signs and symptoms of tumor lysis syndrome. Patients should be instructed to notify their physician if they experience these symptoms [see WARNINGS AND PRECAUTIONS].
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) [see DRUG INTERACTIONS].
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.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenicity studies have not been performed with pralatrexate.
Pralatrexate did not cause mutations in the Ames test or the Chinese hamster ovary cell chromosome aberration assay. Nevertheless, these tests do not reliably predict genotoxicity for this class of compounds. Pralatrexate did not cause mutations in the mouse micronucleus assay.
Impairment of Fertility
No fertility studies have been performed.
Use In Specific Populations
Pregnancy Category D [see WARNINGS AND PRECAUTIONS]
FOLOTYN can cause fetal harm when administered to a pregnant woman. Pralatrexate was embryotoxic and fetotoxic in rats at IV doses of 0.06 mg/kg/day (0.36 mg/m²/day or about 1.2% of the clinical dose on a mg/m² basis) given on gestation days 7 through 20. Treatment with pralatrexate caused a dose-dependent decrease in fetal viability manifested as an increase in late, early, and total resorptions. There was also a dose-dependent increase in post-implantation loss. In rabbits, IV doses of 0.03 mg/kg/day (0.36 mg/m²/day) or greater given on gestation days 8 through 21 also caused abortion and fetal lethality. This toxicity manifested as early and total resorptions, post-implantation loss, and a decrease in the total number of live fetuses. 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.
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 FOLOTYN to the mother.
Pediatric patients were not included in clinical studies with FOLOTYN. The safety and effectiveness of FOLOTYN in pediatric patients have not been established.
In the PTCL efficacy study, 36% of patients (n = 40) were 65 years of age and over. No overall differences in efficacy and safety were observed in patients based on age (< 65 years compared with ≥ 65 years). Due to the contribution of renal excretion to overall clearance of pralatrexate (approximately 34%), age-related decline in renal function may lead to a reduction in clearance and a commensurate increase in plasma exposure. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Since elderly patients may be at higher risk, monitor more closely. Omit dose and subsequently adjust or discontinue therapy for exposure related toxicity [see DOSAGE AND ADMINISTRATION, WARNINGS AND PRECAUTIONS, Use In Specific Populations, and CLINICAL PHARMACOLOGY].
The safety, efficacy and pharmacokinetics of FOLOTYN have not been evaluated in patients with hepatic impairment. Patients with the following laboratory values were excluded from the pralatrexate lymphoma clinical trials: total bilirubin > 1.5 mg/dL; aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 × upper limit of normal (ULN); and AST or ALT > 5 × ULN if documented hepatic involvement with lymphoma. Treatment with FOLOTYN can cause hepatic toxicity and liver function test abnormalities [see DOSAGE AND ADMINISTRATION and WARNINGS AND PRECAUTIONS].
The safety, efficacy and pharmacokinetics of FOLOTYN have not been evaluated in patients with renal impairment.
The risk for toxicity may be greater when administering FOLOTYN to patients with moderate-to-severe impairment due to the contribution of renal excretion (approximately 34%) to the overall clearance of pralatrexate. Serious adverse drug reactions, including TEN and mucositis have been reported in patients with ESRD undergoing dialysis. Monitor patients for renal function and for systemic toxicity due to increased drug exposure and adjust dosing accordingly. Avoid the use of FOLOTYN in patients with end stage renal disease undergoing dialysis unless the potential benefit justifies the potential risk [see DOSAGE AND ADMINISTRATION, WARNINGS AND PRECAUTIONS, ADVERSE REACTIONS, and CLINICAL PHARMACOLOGY].
Last reviewed on RxList: 6/7/2012
This monograph has been modified to include the generic and brand name in many instances.
Additional Folotyn Information
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