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近日；美国食品药品监督管理局（FDA）批准了一款巯嘌呤的口服混悬剂Purixan，用于治疗急性淋巴细胞性白血病（ALL）。
巯嘌呤在美国以外市场以Xaluprine为商品名上市，但Nova表示，由于其片剂药物需要根据患者（多数为儿童）人体表面积来调整给药剂量，所以导致问题频频出现。该公司在一份声明中这样表示：“口服混悬剂相比片剂，可以提供更加一致的吸收，允许精确的2mg个体化给药。”
支持该药物批准的临床试验证明，Purixan与巯嘌呤片剂具有生物等效性。欧洲药品管理局（EMA）于2012年3月推荐了这款药物，由于其治疗相对罕见的ALL，该药物在美国被授予了孤儿药资格。
根据美国癌症协会提供的信息，2014年美国将有6020名新的ALL患者被确诊，大约有1440名患者会死于这种疾病，这种疾病始于骨髓中的白细胞，在儿童中较为常见。Nova临床开发主管Hussain Mulla博士说：“我们对于FDA的批准感到非常自豪，这将会有助于改善全球儿童癌症患者的治疗。”
急性淋巴细胞性白血病(ALL)是一种进行性恶性疾病，其特征为大量的类似于淋巴母细胞的未成熟白细胞。这些细胞可在血液、骨髓，淋巴结、脾脏和其它器官中发现。急性淋巴细胞性白血病占儿童急性白血病的80%，发病率高峰在3岁至7岁之间。ALL也可发生于成年人，占所有成年人白血病的20%。
PURIXAN Rx
Pharmacological Class:
Antimetabolite.
Active Ingredient(s):
Mercaptopurine (6-MP) 20mg/mL; oral suspension; contains fruit extract, aspartame.
Company
Rare Disease Therapeutics, Inc.
Indication(s):
Maintenance therapy of acute lymphoblastic leukemia (ALL) as part of a combination regimen.
Pharmacology:
Mercaptopurine is activated by hypoxanthine-guanine phosphoribosyl transferase (HGPRTase) and several enzymes to form 6-thioguanine nucleotides (6-TGNs). Incorporation of 6-TGN into nucleic acids results in cell-cycle arrest and cell death. Mercaptopurine competes with hypoxanthine and guanine for HGPRTase and is itself converted to thioinosinic acid (TIMP). In addition, 6-methylthioinosinate (MTIMP) is formed by the methylation of TIMP. Both TIMP and MTIMP have been reported to inhibit glutamine-5-phosphoribosylpyrophosphate amidotransferase, the first enzyme unique to the de novo pathway for purine ribonucleotide synthesis.
The relative bioavailability of Purixan was compared to mercaptopurine 50mg tablets in 62 healthy patients in a single-dose, two-period, crossover study under fasting conditions. Bioequivalence was demonstrated based on the primary pharmacokinetic parameters AUC(0–t) and AUC(0–∞). Cmax did not demonstrate bioequivalence. The mean Cmax following Purixan administration was 34% higher than the tablet.
Clinical Trials:
The safety and effectiveness of mercaptopurine for the treatment of ALL in pediatric and adult patients have not been established in adequate and well-controlled trials.
The evidence for efficacy of mercaptopurine is derived from the published literature and clinical experience.
Legal Classification:
Rx
Adults & Children:
Shake bottle vigorously for at least 30 seconds. Initially 1.5–2.5mg/kg (50–75mg/m2) per day as a single dose. Monitor subsequent doses to maintain desirable ANC level and adjust for excessive hematological toxicity. Thiopurine-S-methyltransferase (TPMT)-deficient: if homozygous, may require up to a 90% dose reduction; if heterozygous, some may require dose reduction based on toxicities. Renal or hepatic impairment: use lower starting doses; monitor for toxicity. See full labeling.
Warnings/Precautions:
Myelosuppression; monitor CBCs and adjust dose for severe neutropenia and thrombocytopenia. Consider testing for TPMT gene polymorphism in patients who experience repeated severe bone marrow toxicities. Monitor serum transaminase, alkaline phosphatase, and bilirubin levels at weekly intervals when starting therapy, then monthly thereafter; interrupt treatment if evidence of hepatotoxicity occurs. Concomitant other hepatotoxic drugs or with pre-existing liver disease; monitor LFTs more frequently. Immunosuppression. Increased risk of secondary malignancies. Renal or hepatic impairment. Elderly. Pregnancy (Category D); especially 1st trimester, nursing mothers: not recommended.
Interaction(s)
Avoid concomitant allopurinol. Increased risk of bone marrow suppression with allopurinol, aminosalicylate derivatives (eg, olsalazine, mesalamine, sulfasalazine), trimethoprim-sulfamethoxazole. Possibly decreased effectiveness with concomitant warfarin; monitor PT or INR; may need warfarin dose adjustments. Concomitant live virus vaccines: may get suboptimal response and risk of infection.
Adverse Reaction(s)
Myelosuppression (anemia, neutropenia, lymphopenia, thrombocytopenia), nausea, vomiting, anorexia, diarrhea, malaise, rashes, oral lesions, elevated transaminases and bilirubin, intestinal ulceration; hepatotoxicity, embryo-fetal toxicity.
How Supplied:
Susp—100mL
LAST UPDATED:
6/27/2014 | 
