INTERACTIONS Avoid coadministration with probenecid or nonsteroidal anti-inflammatory drugs. If coadministration is unavoidable, monitor for increased risk of adverse reactions. ( 7.1 )
7.1 Effects of Other Drugs on Pralatrexate Injection Coadministration of Pralatrexate injection with probenecid increased pralatrexate plasma concentrations <span class="opacity-50 text-xs">[see Clinical Pharmacology ( 12.3 )]</span> , which may increase the risk of adverse reactions. Avoid coadministration with probenecid or nonsteroidal anti-inflammatory drugs. If coadministration is unavoidable, monitor for increased risk of adverse reactions.
AND PRECAUTIONS Myelosuppression : Monitor complete blood counts and omit and/or reduce dose based on ANC and platelet count. ( 2.4 , 5.1 ) Mucositis : Monitor at least weekly. Omit and/or reduce dose for grade 2 or higher mucositis. ( 2.4 , 5.2 ) Dermatologic reactions : Reactions, including fatal reactions, occurred and may be progressive and increase in severity with further treatment. Monitor closely and withhold or discontinue pralatrexate injection based on severity. ( 2.4 , 5.3 ) Tumor lysis syndrome : Monitor patients who are increased risk and treat promptly. ( 5.4 ) Hepatic toxicity : Monitor for liver function tests. Omit until recovery, adjust or discontinue therapy based on severity. ( 2.4 , 5.5 ) Risk of increased toxicity with renal impairment : Avoid pralatrexate injection in patients with end stage renal disease with or without dialysis. If the potential benefit of administration justifies the potential risk, monitor renal function and reduce the pralatrexate injection dose based on adverse reactions. ( 2.3 , 2.4 , 5.6 ) Embryo-fetal toxicity : Can cause fetal harm. Advise patients of the potential risk to a fetus and to use an effective method of contraception. ( 5.7 , 8.1 , 8.3 )
5.1 Myelosuppression Pralatrexate injection can cause myelosuppression, manifested by thrombocytopenia, neutropenia, and/or anemia. Administer vitamin B 12 and instruct patients to take folic acid to reduce the risk of treatment-related myelosuppression [ see Dosage and Administration (2.1) ] . Monitor complete blood counts and omit and/or reduce the dose based on ANC and platelet count prior to each dose [ see Dosage and Administration (2.4) ] .
5.2 Mucositis Pralatrexate injection can cause mucositis [ see Adverse Reactions (6.1) ] . Administer vitamin B 12 and instruct patients to take folic acid to reduce the risk of mucositis [ see Dosage and Administration (2.1) ] . Monitor for mucositis weekly and omit and/or reduce the dose for grade 2 or higher mucositis [ see Dosage and Administration (2.4) ] .
5.3 Dermatologic Reactions Pralatrexate injection can cause severe dermatologic reactions, which may result in death. These dermatologic reactions have been reported in clinical studies (2.1% of 663 patients) and post marketing experience, and have included skin exfoliation, ulceration, and toxic epidermal necrolysis (TEN) [ see Adverse Reactions (6.1 , 6.2) ] . They may be progressive and increase in severity with further treatment and may involve skin and subcutaneous sites of known lymphoma. Monitor closely for dermatologic reactions. Withhold or discontinue pralatrexate injection based on severity [ see Dosage and Administration (2.4) ] .
5.4 Tumor Lysis Syndrome Pralatrexate injection can cause tumor lysis syndrome (TLS). Monitor patients who are at increased risk of TLS and treat promptly.
5.5 Hepatic Toxicity Pralatrexate injection can cause hepatic toxicity and liver function test abnormalities [ see Adverse Reactions (6.1) ] . 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 (2.4) ] .
5.6 Risk of Increased Toxicity with Renal Impairment Patients with severe renal impairment (eGFR 15 to < 30 mL/min/1.73 m 2 based on MDRD) may be at greater risk for increased exposure and adverse reactions. Reduce pralatrexate injection dosage in patients with severe renal impairment [ see Dosage and Administration (2.3) ] . Serious adverse reactions, including TEN and mucositis, were reported in patients with end stage renal disease (ESRD) undergoing dialysis who were administered pralatrexate injection. Avoid pralatrexate injection in patients with ESRD with or without dialysis. If the potential benefit of administration justifies the potential risk, monitor renal function and reduce the pralatrexate injection dose based on adverse reactions [ see Dosage and Administration (2.3) ] .
5.7 Embryo-Fetal Toxicity Based on findings in animals and its mechanism of action, pralatrexate injection can cause fetal harm when administered to a pregnant woman. Pralatrexate injection was embryotoxic and fetotoxic in rats and rabbits. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with pralatrexate injection and for 6 months after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with pralatrexate injection and for 3 months after the last dose [ see Use in Specific Populations (8.1 , 8.3) ] .