Duzallo(Lesinurad and Allopurinol Tablets)
Duzallo（DUZALLO+lesinurad）-首款固定剂量组合疗法治疗痛风症、高尿酸血
2017年8月21日，FDA批准固定剂量复方药物Duzallo（DUZALLO+lesinurad Ironwood制药）用于治疗痛风高尿酸血症。这是首个服用单一药丸同时解决痛风中高尿酸血症两个病因的固定剂量复方药物，该两种病因分别为血清尿酸产生过度及排泄减少。
该药物作为一种日服一次的口服治疗药物用于与痛风相关的高尿酸血症，适用于仅采用医学上合适日剂量别嘌呤醇不能达到目标血清尿酸（sUA）水平的患者。
别嘌呤醇是一种黄嘌呤氧化酶抑制剂（XOI），它的作用不同于促尿酸排泄剂，如lesinurad。别嘌呤醇旨在减少尿酸（UA）的产生，而lesinurad旨在通过选择性抑制 URAT1 的活性而增加尿酸的肾脏排泄，URAT1 是尿酸的转运体，负责大部分尿酸的肾脏重新吸收。
Duzallo 将以两种规格上市，一种规格药品中含有200mg的 lesinurad 和300mg的别嘌呤醇，另一种规格中含有200mg的lesinurad和200mg 的别嘌呤醇。Ironwood称，Duzallo上市时带有一项黑框警告，提醒该药物有急性肾衰竭风险。
Duzallo(Lesinurad and Allopurinol Tablets)
DUZALLO Rx
Generic Name and Formulations:
Lesinurad, allopurinol 200mg/200mg, 200mg/300mg; tabs.
Company:
Ironwood Pharmaceuticals
Indications for DUZALLO:
Hyperuricemia associated with gout in patients who have not achieved target serum uric acid levels with an appropriate daily dose of allopurinol alone.
Limitations Of use:
Not for treatment of asymptomatic hyperuricemia.
Adult:
Take in the AM with food and water. ≥18yrs: 1 tab daily. Patients on daily allopurinol dose 200mg: initially one 200mg/200mg tab daily; 300mg: initially one 200mg/300mg tab daily; >300mg: initially one tab in place of an equal portion of the total daily allopurinol dose; if <300mg (or <200mg with eCLCr <60mL/min): not recommended.
Children:
<18yrs: not established.
Contraindications:
Severe renal impairment (eCLCr <30mL/min), ESRD, kidney transplant recipients, or dialysis patients. Tumor lysis syndrome or Lesch-Nyhan syndrome.
Warnings/Precautions:
Risk of acute renal failure. Assess renal function prior to initiation and periodically thereafter. Renal impairment (eCLCr <45mL/min): do not initiate. If eCLCr <60mL/min or with serum creatinine (SCr) elevations 1.5–2X pre-treatment value: monitor more frequently; if SCr >2X pre-treatment value: interrupt treatment. Discontinue therapy if eCLCr is persistently <45mL/min. Maintain adequate hydration (2 liters of liquid per day). Give gout flare prophylaxis if patient not currently taking lesinurad. Discontinue immediately if rash occurs. Evaluate liver function if anorexia, weight loss, or pruritus develops. Pre-existing liver disease: perform LFTs periodically. Severe hepatic impairment: not recommended. Females should use additional non-hormonal methods of contraception. Pregnancy. Nursing mothers.
Interactions:
Caution with concomitant moderate CYP2C9 inhibitors (eg, fluconazole, amiodarone) and in CYP2C9 poor metabolizers. Antagonized by moderate CYP2C9 inducers (eg, rifampin, carbamazepine), aspirin >325mg/day. Antagonizes CYP3A substrates (eg, sildenafil, amlodipine). May affect sensitive CYP3A substrates (eg, HMG-CoA reductase inhibitors); monitor. Concomitant epoxide hydrolase inhibitors (eg, valproic acid): not recommended. May reduce efficacy of hormonal contraceptives. Potentiates azathioprine and mercaptopurine toxicity; reduce dose of these by ⅓ to ¼ of usual dose and monitor. Assess PT periodically with concomitant coumarin anticoagulants (eg, dicumarol, warfarin). May potentiate chlorpropamide, cyclosporine. Increased rash with ampicillin, amoxicillin. Monitor renal function with thiazides.
Pharmacological Class:
URAT1 inhibitor + xanthine oxidase inhibitor.
Adverse Reactions:
Headache, influenza, blood creatinine increased, GERD, skin rash; renal events, gout flares, hepatotoxicity, cardiovascular events, drowsiness; rarely: bone marrow depression, severe hypersensitivity reactions (eg, eosinophilia, SJS, TEN).
Generic Availability:
NO
How Supplied:
Tabs—5, 30, 90
Duzallo Now Available for the Treatment of Uncontrolled Gout
Ironwood announced the launch of Duzallo (lesinurad/allopurinol) tablets for the treatment of hyperuricemia associated with gout in patients who have not achieved target serum uric acid levels with a medically appropriate daily dose of allopurinol alone.
Duzallo was approved by the Food and Drug Administration (FDA) in August 2017. The fixed-dose product combines lesinurad, a uric acid transporter 1 (URAT1) inhibitor, with allopurinol, a xanthine oxidase inhibitor in one tablet. Allopurinol reduces the production of uric acid while lesinurad increases renal excretion of uric acid by selectively inhibiting the action of URAT1, the UA transporter responsible for the majority of renal UA reabsorption.
Duzallo is not recommended for the treatment of asymptomatic hyperuricemia. It carries a Boxed Warning stating that acute renal failure has occurred with lesinurad, one of the components of Duzallo. Treatment should be interrupted if serum creatinine levels rise to >2 times the value when lesinurad treatment was initiated.
Duzallo is available as 200mg/200mg and 200mg/300mg strengths in 5-, 30-, and 90-count bottles
