Peringatan Keamanan

Mucositis is dose-limiting toxicity. Folic acid and vitamin B12 supplements do not prevent mucositis from happening.

No specific information is available on the treatment of overdosage of pralatrexate. If an overdose occurs, general supportive measures should be instituted as deemed necessary by the treating healthcare provider. Based on pralatrexate's mechanism of action, consider the prompt administration of leucovorin.L37674

Carcinogenicity studies and fertility studies have not been performed with pralatrexate.L37674Based on findings from animal studies and its mechanism of action see Clinical Pharmacology (12.1), pralatrexate can cause fetal harm when administered to a pregnant woman. There are insufficient data on pralatrexate use in pregnant women to evaluate for a drug-associated risk. Pralatrexate was embryotoxic and fetotoxic in rats and rabbits when administered during organogenesis at doses about 1.2% (0.012 times) of
the clinical dose on an mg/m2 basis. Advise pregnant women of the potential risk to a fetus.L37674

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.L37674

Pralatrexate

DB06813

small molecule approved investigational

Deskripsi

Pralatrexate is an antifolate for the treatment of relapsed or refractory peripheral T-cell lymphoma L37674. Pralatrexate was developed in response due to the inferior responses of patients using the standard therapy for their B-cells counterparts.A246693 Compared to methotrexate, pralatrexate has better accumulation in cancer cells.A246693 Pralatrexate is designed to have a higher affinity for the reduced folate carrier, a protein that is overexpressed in malignant cells and is upregulated by oncogenes.A246703 As such, pralatrexate is thought to have a better therapeutic window compared to other antifolate analogs due to the novel target of RFC.A246703

Pralatrexate was approved by the FDA on September 24, 2009.L37674 It is also being studied for other types of lymphoma and solid malignancy such as non-small-cell lung cancer, breast cancer, and bladder cancer.A246678

Struktur Molekul 2D

Berat 477.4726
Wujud solid

Peta Jejaring Molekuler
Legenda: Obat • Target • Gen • Enzim • (Panah → menunjukkan arah efek / relasi) • Transporter • Carrier

Profil Farmakokinetik

Waktu Paruh (Half-Life) The terminal elimination half-life of pralatrexate was 12-18 hours (coefficient of variance [CV] = 62-120%).[L37674]
Volume Distribusi The steady-state volume of distribution of pralatrexate S- and R-diastereomers is 105 L and 37 L, respectively.[L37674,A7126]
Klirens (Clearance) The total systemic clearance of pralatrexate diastereomers was 417 mL/min (S-diastereomer) and 191 mL/min (R-diastereomer).[L37674]

Absorpsi

With an intravenous formulation, pralatrexate has complete bioavailability.A7126 Pralatrexate demonstrates a dose-proportional and linear pharmacokinetics over a dose range of 30-325 mg/m2.A246678 Upon an intravenous push over 3 to 5 minutes of a starting dose of 30 mg/m2 racemic pralatrexate for dose 1 of cycle 1, Cmax and AUC0-? was estimated to be 5,815 ng/mL and 267,854 ng/mL.min respectively using a noncomparmental pharmacokinetics analysis.L41559,A246678Both pralatrexate diastereomers demonstrates a multiphase decline in plasma concentration with a rapid initial fall followed by a slow terminal phase.A246678 The initial fall is thought to reflect the clearance of pralatrexate by renal and non-renal mechanism , while the slow terminal phase likely represents the return of pralatrexate from deep intracellular compartments, enterohepatic circulation, or after deglutamination.A246678

Metabolisme

While the liver has been shown to metabolize pralatrexate to some extent, pralatrexate is not significantly metabolized by any CYP450 isozymes or glucuronidases in vitro.L37674

Rute Eliminasi

Following a single dose of FOLOTYN 30 mg/m2, approximately 34% of the pralatrexate dose was excreted unchanged into urine. Following a radiolabeled pralatrexate dose, 39% (CV = 28%) of the dose was recovered in urine as unchanged pralatrexate and 34% (CV = 88%) in feces as unchanged pralatrexate and/or any metabolites. 10% (CV = 95%) of the dose was exhaled over 24 hours.L37674

Interaksi Obat

1178 Data
Denosumab The risk or severity of adverse effects can be increased when Denosumab is combined with Pralatrexate.
Etanercept The risk or severity of adverse effects can be increased when Etanercept is combined with Pralatrexate.
Peginterferon alfa-2a The risk or severity of adverse effects can be increased when Peginterferon alfa-2a is combined with Pralatrexate.
Interferon alfa-n1 The risk or severity of adverse effects can be increased when Interferon alfa-n1 is combined with Pralatrexate.
Interferon alfa-n3 The risk or severity of adverse effects can be increased when Interferon alfa-n3 is combined with Pralatrexate.
Peginterferon alfa-2b The risk or severity of adverse effects can be increased when Peginterferon alfa-2b is combined with Pralatrexate.
Anakinra The risk or severity of adverse effects can be increased when Anakinra is combined with Pralatrexate.
Interferon gamma-1b The risk or severity of adverse effects can be increased when Interferon gamma-1b is combined with Pralatrexate.
Interferon alfa-2a The risk or severity of adverse effects can be increased when Interferon alfa-2a is combined with Pralatrexate.
Aldesleukin The risk or severity of adverse effects can be increased when Aldesleukin is combined with Pralatrexate.
Adalimumab The risk or severity of adverse effects can be increased when Adalimumab is combined with Pralatrexate.
Gemtuzumab ozogamicin The risk or severity of adverse effects can be increased when Gemtuzumab ozogamicin is combined with Pralatrexate.
Pegaspargase The risk or severity of adverse effects can be increased when Pegaspargase is combined with Pralatrexate.
Infliximab The risk or severity of adverse effects can be increased when Infliximab is combined with Pralatrexate.
Interferon beta-1b The risk or severity of adverse effects can be increased when Interferon beta-1b is combined with Pralatrexate.
Interferon alfacon-1 The risk or severity of adverse effects can be increased when Interferon alfacon-1 is combined with Pralatrexate.
Rituximab The risk or severity of adverse effects can be increased when Rituximab is combined with Pralatrexate.
Basiliximab The risk or severity of adverse effects can be increased when Basiliximab is combined with Pralatrexate.
Muromonab The risk or severity of adverse effects can be increased when Muromonab is combined with Pralatrexate.
Ibritumomab tiuxetan The risk or severity of adverse effects can be increased when Ibritumomab tiuxetan is combined with Pralatrexate.
Tositumomab The risk or severity of adverse effects can be increased when Tositumomab is combined with Pralatrexate.
Alemtuzumab The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Pralatrexate.
Alefacept The risk or severity of adverse effects can be increased when Alefacept is combined with Pralatrexate.
Efalizumab The risk or severity of adverse effects can be increased when Efalizumab is combined with Pralatrexate.
Antithymocyte immunoglobulin (rabbit) The risk or severity of adverse effects can be increased when Antithymocyte immunoglobulin (rabbit) is combined with Pralatrexate.
Interferon alfa-2b The risk or severity of adverse effects can be increased when Interferon alfa-2b is combined with Pralatrexate.
Daclizumab The risk or severity of adverse effects can be increased when Daclizumab is combined with Pralatrexate.
Phenylalanine The risk or severity of adverse effects can be increased when Phenylalanine is combined with Pralatrexate.
Flunisolide The risk or severity of adverse effects can be increased when Flunisolide is combined with Pralatrexate.
Bortezomib The risk or severity of adverse effects can be increased when Bortezomib is combined with Pralatrexate.
Cladribine Pralatrexate may increase the immunosuppressive activities of Cladribine.
Carmustine The risk or severity of adverse effects can be increased when Carmustine is combined with Pralatrexate.
Amsacrine The risk or severity of adverse effects can be increased when Amsacrine is combined with Pralatrexate.
Bleomycin The risk or severity of adverse effects can be increased when Bleomycin is combined with Pralatrexate.
Chlorambucil The risk or severity of adverse effects can be increased when Chlorambucil is combined with Pralatrexate.
Raltitrexed The risk or severity of adverse effects can be increased when Raltitrexed is combined with Pralatrexate.
Mitomycin The risk or severity of adverse effects can be increased when Mitomycin is combined with Pralatrexate.
Bexarotene The risk or severity of adverse effects can be increased when Bexarotene is combined with Pralatrexate.
Vindesine The risk or severity of adverse effects can be increased when Vindesine is combined with Pralatrexate.
Floxuridine The risk or severity of adverse effects can be increased when Floxuridine is combined with Pralatrexate.
Tioguanine The risk or severity of adverse effects can be increased when Tioguanine is combined with Pralatrexate.
Vinorelbine The risk or severity of adverse effects can be increased when Vinorelbine is combined with Pralatrexate.
Dexrazoxane The risk or severity of adverse effects can be increased when Dexrazoxane is combined with Pralatrexate.
Beclomethasone dipropionate The risk or severity of adverse effects can be increased when Beclomethasone dipropionate is combined with Pralatrexate.
Sorafenib The risk or severity of adverse effects can be increased when Sorafenib is combined with Pralatrexate.
Streptozocin The risk or severity of adverse effects can be increased when Streptozocin is combined with Pralatrexate.
Trifluridine The risk or severity of adverse effects can be increased when Trifluridine is combined with Pralatrexate.
Gemcitabine The risk or severity of adverse effects can be increased when Gemcitabine is combined with Pralatrexate.
Betamethasone The risk or severity of adverse effects can be increased when Betamethasone is combined with Pralatrexate.
Teniposide The risk or severity of adverse effects can be increased when Teniposide is combined with Pralatrexate.
Epirubicin The risk or severity of adverse effects can be increased when Epirubicin is combined with Pralatrexate.
Chloramphenicol The risk or severity of adverse effects can be increased when Chloramphenicol is combined with Pralatrexate.
Lenalidomide The risk or severity of adverse effects can be increased when Lenalidomide is combined with Pralatrexate.
Altretamine The risk or severity of adverse effects can be increased when Altretamine is combined with Pralatrexate.
Zidovudine The risk or severity of adverse effects can be increased when Zidovudine is combined with Pralatrexate.
Cisplatin The risk or severity of adverse effects can be increased when Cisplatin is combined with Pralatrexate.
Oxaliplatin The risk or severity of adverse effects can be increased when Oxaliplatin is combined with Pralatrexate.
Cyclophosphamide The risk or severity of adverse effects can be increased when Cyclophosphamide is combined with Pralatrexate.
Vincristine The risk or severity of adverse effects can be increased when Vincristine is combined with Pralatrexate.
Fluorouracil The risk or severity of adverse effects can be increased when Fluorouracil is combined with Pralatrexate.
Propylthiouracil The risk or severity of adverse effects can be increased when Propylthiouracil is combined with Pralatrexate.
Pentostatin The risk or severity of adverse effects can be increased when Pentostatin is combined with Pralatrexate.
Methotrexate The risk or severity of adverse effects can be increased when Methotrexate is combined with Pralatrexate.
Carbamazepine The risk or severity of adverse effects can be increased when Carbamazepine is combined with Pralatrexate.
Vinblastine The risk or severity of adverse effects can be increased when Vinblastine is combined with Pralatrexate.
Fluticasone propionate The risk or severity of adverse effects can be increased when Fluticasone propionate is combined with Pralatrexate.
Fluocinolone acetonide The risk or severity of adverse effects can be increased when Fluocinolone acetonide is combined with Pralatrexate.
Linezolid The risk or severity of adverse effects can be increased when Linezolid is combined with Pralatrexate.
Imatinib The risk or severity of adverse effects can be increased when Imatinib is combined with Pralatrexate.
Triamcinolone The risk or severity of adverse effects can be increased when Triamcinolone is combined with Pralatrexate.
Clofarabine The risk or severity of adverse effects can be increased when Clofarabine is combined with Pralatrexate.
Prednisone The risk or severity of adverse effects can be increased when Prednisone is combined with Pralatrexate.
Pemetrexed The risk or severity of adverse effects can be increased when Pemetrexed is combined with Pralatrexate.
Fludrocortisone The risk or severity of adverse effects can be increased when Fludrocortisone is combined with Pralatrexate.
Mycophenolate mofetil The risk or severity of adverse effects can be increased when Mycophenolate mofetil is combined with Pralatrexate.
Daunorubicin The risk or severity of adverse effects can be increased when Daunorubicin is combined with Pralatrexate.
Irinotecan The risk or severity of adverse effects can be increased when Irinotecan is combined with Pralatrexate.
Methimazole The risk or severity of adverse effects can be increased when Methimazole is combined with Pralatrexate.
Etoposide The risk or severity of adverse effects can be increased when Etoposide is combined with Pralatrexate.
Dacarbazine The risk or severity of adverse effects can be increased when Dacarbazine is combined with Pralatrexate.
Temozolomide The risk or severity of adverse effects can be increased when Temozolomide is combined with Pralatrexate.
Penicillamine The risk or severity of adverse effects can be increased when Penicillamine is combined with Pralatrexate.
Prednisolone The risk or severity of adverse effects can be increased when Prednisolone is combined with Pralatrexate.
Sirolimus The risk or severity of adverse effects can be increased when Sirolimus is combined with Pralatrexate.
Mechlorethamine The risk or severity of adverse effects can be increased when Mechlorethamine is combined with Pralatrexate.
Azacitidine The risk or severity of adverse effects can be increased when Azacitidine is combined with Pralatrexate.
Carboplatin The risk or severity of adverse effects can be increased when Carboplatin is combined with Pralatrexate.
Methylprednisolone The risk or severity of adverse effects can be increased when Methylprednisolone is combined with Pralatrexate.
Dactinomycin The risk or severity of adverse effects can be increased when Dactinomycin is combined with Pralatrexate.
Cytarabine The risk or severity of adverse effects can be increased when Cytarabine is combined with Pralatrexate.
Azathioprine The risk or severity of adverse effects can be increased when Azathioprine is combined with Pralatrexate.
Doxorubicin The risk or severity of adverse effects can be increased when Doxorubicin is combined with Pralatrexate.
Hydroxyurea The risk or severity of adverse effects can be increased when Hydroxyurea is combined with Pralatrexate.
Busulfan The risk or severity of adverse effects can be increased when Busulfan is combined with Pralatrexate.
Mycophenolic acid The risk or severity of adverse effects can be increased when Mycophenolic acid is combined with Pralatrexate.
Topotecan The risk or severity of adverse effects can be increased when Topotecan is combined with Pralatrexate.
Mercaptopurine The risk or severity of adverse effects can be increased when Mercaptopurine is combined with Pralatrexate.
Thalidomide The risk or severity of adverse effects can be increased when Thalidomide is combined with Pralatrexate.
Melphalan The risk or severity of adverse effects can be increased when Melphalan is combined with Pralatrexate.
Fludarabine The risk or severity of adverse effects can be increased when Fludarabine is combined with Pralatrexate.

Target Protein

Dihydrofolate reductase DHFR
Peptide deformylase, mitochondrial PDF
Folylpolyglutamate synthase, mitochondrial FPGS
Thymidylate synthase TYMS

Referensi & Sumber

Artikel (PubMed)
  • PMID: 23409799
    Shimanovsky A, Dasanu CA: Pralatrexate : evaluation of clinical efficacy and toxicity in T-cell lymphoma. Expert Opin Pharmacother. 2013 Mar;14(4):515-23. doi: 10.1517/14656566.2013.770474. Epub 2013 Feb 14.
  • PMID: 22921318
    Gonen N, Assaraf YG: Antifolates in cancer therapy: structure, activity and mechanisms of drug resistance. Drug Resist Updat. 2012 Aug;15(4):183-210. doi: 10.1016/j.drup.2012.07.002. Epub 2012 Aug 23.
  • PMID: 23032692
    Rodd AL, Ververis K, Karagiannis TC: Safety and efficacy of pralatrexate in the management of relapsed or refractory peripheral T-cell lymphoma. Clin Med Insights Oncol. 2012;6:305-14. doi: 10.4137/CMO.S8536. Epub 2012 Aug 21.
  • PMID: 22394596
    Horwitz SM, Kim YH, Foss F, Zain JM, Myskowski PL, Lechowicz MJ, Fisher DC, Shustov AR, Bartlett NL, Delioukina ML, Koutsoukos T, Saunders ME, O'Connor OA, Duvic M: Identification of an active, well-tolerated dose of pralatrexate in patients with relapsed or refractory cutaneous T-cell lymphoma. Blood. 2012 May 3;119(18):4115-22. doi: 10.1182/blood-2011-11-390211. Epub 2012 Mar 6.
  • PMID: 22332098
    Crider KS, Yang TP, Berry RJ, Bailey LB: Folate and DNA methylation: a review of molecular mechanisms and the evidence for folate's role. Adv Nutr. 2012 Jan;3(1):21-38. doi: 10.3945/an.111.000992. Epub 2012 Jan 5.
  • PMID: 14608107
    Kim YI: Role of folate in colon cancer development and progression. J Nutr. 2003 Nov;133(11 Suppl 1):3731S-3739S. doi: 10.1093/jn/133.11.3731S.
  • PMID: 22729036
    Nunez MI, Behrens C, Woods DM, Lin H, Suraokar M, Kadara H, Hofstetter W, Kalhor N, Lee JJ, Franklin W, Stewart DJ, Wistuba II: High expression of folate receptor alpha in lung cancer correlates with adenocarcinoma histology and EGFR corrected mutation. J Thorac Oncol. 2012 May;7(5):833-40. doi: 10.1097/JTO.0b013e31824de09c.
  • PMID: 17333344
    Assaraf YG: Molecular basis of antifolate resistance. Cancer Metastasis Rev. 2007 Mar;26(1):153-81.
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Contoh Produk & Brand

Produk: 7 • International brands: 0
Produk
  • Folotyn
    Injection • 20 mg/1mL • Intravenous • US • Approved
  • Folotyn
    Injection • 20 mg/1mL • Intravenous • US • Approved
  • Folotyn
    Injection • 40 mg/2mL • Intravenous • US • Approved
  • Folotyn
    Solution • 20 mg / mL • Intravenous • Canada • Approved
  • Folotyn
    Solution • 40 mg / 2 mL • Intravenous • Canada • Approved
  • Pralatrexate
    Injection • 20 mg/1mL • Intravenous • US • Generic • Approved
  • Pralatrexate
    Injection • 40 mg/2mL • Intravenous • US • Generic • Approved

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