The Medical Letter ® on Drugs and Therapeutics Volume 58 ISSUE ISSUE No 1433 1508 Volume 56 November 21, 2016 IN THIS ISSUE Minimed 670G: A Hybrid Closed-Loop Insulin Delivery System .p 147 Lesinurad (Zurampic) for Gout-Associated Hyperuricemia p 148 Drugs for Head Lice .p 150 Important Copyright Message FORWARDING OR COPYING IS A VIOLATION OF U.S AND INTERNATIONAL COPYRIGHT LAWS The Medical Letter, Inc publications are protected by U.S and international copyright laws Forwarding, copying or any distribution of this material is prohibited Sharing a password with a non-subscriber or otherwise making the contents of this site available to third parties is strictly prohibited By accessing and reading the attached content I agree to comply with U.S and international copyright laws and these terms and conditions of The Medical Letter, Inc For further information click: Subscriptions, Site Licenses, Reprints or call customer service at: 800-211-2769 Published by The Medical Letter, Inc • A Nonprofit Organization The Medical Letter publications are protected by US and international copyright laws Forwarding, copying or any other distribution of this material is strictly prohibited For further information call: 800-211-2769 The Medical Letter ® on Drugs and Therapeutics Volume 58 November 21, 2016 Take CME Exams ISSUE ISSUE No 1433 1508 Volume 56 ▶ ALSO IN THIS ISSUE Lesinurad (Zurampic) for Gout-Associated Hyperuricemia p 148 Drugs for Head Lice .p 150 Minimed 670G: A Hybrid ClosedLoop Insulin Delivery System The FDA has approved the Minimed 670G (Medtronic), a hybrid closed-loop insulin delivery system for use in patients ≥14 years old with type diabetes The system uses an algorithm to automatically adjust basal insulin doses based on readings from a continuous glucose monitor (CGM) It fully automates basal insulin delivery in “auto” mode, but is considered a “hybrid” system (not a true “artificial pancreas") because it requires some action by the patient The 670G system is expected to become available in Spring 2017 RELATED DEVICES — The Minimed 630G system was approved in August 2016 and is currently available; it has a less accurate CGM sensor than the 670G and does not automatically adjust insulin doses based on CGM readings The 670G, 630G, and the earlier Minimed 530G all have an automatic suspend feature that alerts the patient and stops insulin delivery for up to hours when glucose readings reach a prespecified low level; pumps with this feature have been shown to reduce the occurrence of hypoglycemia compared to sensor-augmented insulin pumps without this feature.1 The Minimed 640G, which is available in Europe, offers predictive suspension of basal insulin before a low glucose reading is reached continuous glucose readings that are transmitted via radiofrequency signals to the insulin pump every minutes; the pump can display CGM readings and store them for up to days The pump can be set to “auto" or “manual" mode; when it is set to auto mode, an algorithm uses the data from the CGM sensor to automatically adjust or suspend delivery of basal insulin When first using the system, the patient must use manual mode for 48 hours before auto mode can be activated In manual mode, the user can program delivery of insulin at a preselected rate The system automatically stops insulin delivery for up to hours when glucose readings reach, or are predicted to reach, a predetermined low-threshold value to protect against hypoglycemia while in manual mode In either mode, the user must manually enter the estimated amount of carbohydrate to be consumed during a meal and accept bolus prandial doses of insulin suggested by the system If hyperglycemia occurs, the patient is prompted to perform a fingerstick before authorizing bolus correction doses of insulin The patient should not use glucose values from the sensor to make treatment decisions; manual therapy adjustments should be based on fingerstick readings from the blood glucose meter THE NEW DEVICE — The Minimed 670G system consists of a battery-operated insulin pump, a CGM sensor (Guardian Sensor 3), a transmitter (Guardian Link 3), a sensor insertion aid (One-Press Serter), and a blood glucose meter (Contour Next Link 2.4 Meter).2 The patient must also enter blood glucose readings to calibrate the CGM sensor Fingerstick readings can be transmitted wirelessly from the blood glucose meter to the sensor The manufacturer recommends that the user calibrate the device with a fingerstick at least every 12 hours, but preferably times a day The CGM sensor is inserted subcutaneously in the abdomen and taped in place; it is replaced every days The sensor uses interstitial fluid to take CLINICAL STUDIES — Approval of the Minimed 670G system was based on safety endpoints assessed during a single-arm trial, published as a research 147 Published by The Medical Letter, Inc • A Nonprofit Organization The Medical Letter ® letter, in 123 patients 14-75 years old with type diabetes who had been using an insulin pump for at least months After a 2-week run-in period using only the sensor-augmented pump without any of the automated features, patients entered a 3-month athome study period The pump was used in manual mode for the first days of the study period and switched to auto mode on day The percentage of sensor glucose values within the target range (71-180 mg/dL) was 72.2% at the end of the study, compared to 66.7% at baseline There were no reports of severe hypoglycemia or ketoacidosis during the trial There were 24 reports of severe hyperglycemia (glucose concentration >300 mg/dL with blood ketones >0.6 mmol/L or symptoms of nausea, vomiting, or abdominal pain).3 In an early efficacy trial, 21 subjects 14-40 years old staying in a diabetes camp were randomized to the Minimed 670G or to the Minimed 530G After days, mean percent time in the sensor target glucose range (70-180 mg/dL) and the mean percent of meter glucose values in this range were similar in the two groups.4 A single-arm trial of the Minimed 670G in children 7-13 years old is in progress.5 CONCLUSION — The Minimed 670G hybrid closedloop system includes a continuous glucose monitor that communicates with an insulin pump and uses an algorithm to automatically adjust basal insulin delivery It appears to be safe for use in patients ≥14 years old with type diabetes who want a more automated insulin pump, but frequent calibration with fingersticks and manual inputs to determine prandial insulin doses are still required The new device appears to have the potential to improve quality of life for patients with type diabetes Whether it improves glucose control remains to be established ■ MiniMed 530G: an insulin pump with low-glucose suspend automation Med Lett Drugs Ther 2013; 55:97 FDA Minimed 670G system Summary of safety and effectiveness data (SSED) Available at www.accessdata.fda.gov/cdrh_ docs/pdf16/P160017b.pdf Accessed November 10, 2016 RM Bergenstal et al Safety of a hybrid closed-loop insulin delivery system in patients with type diabetes JAMA 2016; 316:1407 TT Ly et al Day and night closed-loop control using the integrated Medtronic hybrid closed-loop system in type diabetes at diabetes camp Diabetes Care 2015; 38:1205 Safety evaluation of the hybrid closed loop (HCL) system in pediatric subjects with type diabetes Available at clinicaltrials gov (NCT02660827) Accessed November 10, 2016 148 Vol 58 (1508) ▶ November 21, 2016 Lesinurad (Zurampic) for GoutAssociated Hyperuricemia The FDA has approved lesinurad (Zurampic – Ironwood), a uric acid transporter (URAT1) inhibitor, for adjunctive treatment of gout-associated hyperuricemia in patients whose serum uric acid levels fail to reach goal with xanthine oxidase inhibitor monotherapy Pronunciation Key Lesinurad: le sin' ure ad Zurampic: zer am' pik STANDARD TREATMENT — Recent guidelines offer conflicting views on the benefits of monitoring serum uric acid levels and the appropriate use of uratelowering therapy in patients with gout,1-3 but most expert clinicians still initially treat gout-associated hyperuricemia with a xanthine oxidase inhibitor such as allopurinol or febuxostat with the goal of reducing the serum uric acid level below 6.0 mg/dL (and preferably below 5.0 mg/dL) The uricosuric drug probenecid can be used for add-on therapy if target serum uric acid levels are not reached with a xanthine oxidase inhibitor alone or for initial therapy in patients who cannot tolerate a xanthine oxidase inhibitor Probenecid is less effective in patients with renal insufficiency (eGFR ≤30 mL/min) Pegloticase, a pegylated urate oxidase enzyme administered intravenously, is highly effective, but it is very expensive and can cause serious side effects Table Uric Acid-Lowering Drugs for Gout Drug Xanthine Oxidase Inhibitors Allopurinol – generic Zyloprim (Prometheus) Febuxostat – Uloric (Takeda) Uricosuric Drugs Lesinurad – Zurampic (Ironwood) Probenecid – generic Urate Oxidase Enzyme Pegloticase – Krystexxa (Savient) Usual Adult Dosage1 100-900 mg PO once/d3 Cost2 40-80 mg PO once/d $8.20 46.40 285.20 200 mg PO once/d4 350.00 500-1000 mg PO bid 45.80 mg IV q2 wks 33,818.405 Dosage adjustment may be needed for patients with renal impairment Approximate WAC for 30 days’ treatment at the lowest usual adult dosage WAC = wholesaler acquisition cost or manufacturer's published price to wholesalers; WAC represents a published catalogue or list price and may not represent an actual transactional price Source: AnalySource® Monthly November 5, 2016 Reprinted with permission by First Databank, Inc All rights reserved ©2016 www.fdbhealth.com/ policies/drug-pricing-policy To avoid gout flares, the starting dose should not be greater than 100 mg/d, with increases of 100 mg/d at 2-4 week intervals Doses >300 mg/d should be divided Taken in the morning with food and water Must only be used in combination with a xanthine oxidase inhibitor Patients taking lesinurad should drink ≥2 liters of liquid per day Cost of two 8-mg doses The Medical Letter Vol 58 (1508) ® Table Pharmacology Class Route Formulation Tmax Metabolism Elimination Half-life (terminal) Uric acid transporter inhibitor Oral 200 mg tablets 1-4 hours Hepatic, mainly by CYP2C9 Urine (63%); feces (32%) ~5 hours including anaphylaxis; it should be reserved for use in patients with severe tophaceous gout that has not responded to treatment with both a xanthine oxidase inhibitor and a uricosuric drug.4 MECHANISM — Lesinurad prevents reuptake of uric acid at the proximal renal tubule by blocking URAT1 It also reduces diuretic-induced hyperuricemia by inhibiting organic anion transporter (OAT4).5 CLINICAL STUDIES — In two double-blind trials, one published (CLEAR 1) and one available only as a poster presentation (CLEAR 2), a total of 1213 patients with serum uric acid levels >6.5 mg/dL and ≥2 gout flares in the previous 12 months despite treatment with allopurinol were randomized to receive add-on therapy with lesinurad 200 or 400 mg/day or placebo Both lesinurad doses significantly increased the percentage of patients who achieved a reduction in serum uric acid level to