The Medical Letter ® On Drugs and Therapeutics Published by The Medical Letter, Inc • 145 Huguenot Street, New Rochelle, NY 10801 • A Nonprofit Publication IN THIS ISSUE (starts on next page) Mumps Outbreak p 21 Intranasal Naloxone for Treatment of Opioid Overdose p 21 Drugs for Gout p 22 Important Copyright Message The Medical Letter® publications are protected by US 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 US 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 FORWARDING OR COPYING IS A VIOLATION OF U.S AND INTERNATIONAL COPYRIGHT LAWS The Medical Letter ® On Drugs and Therapeutics Published by The Medical Letter, Inc • 145 Huguenot Street, New Rochelle, NY 10801 • A Nonprofit Publication Volume 56 (Issue 1438) March 17, 2014 ALSO IN THIS ISSUE Drugs for Gout p 22 Mumps Outbreak An outbreak of mumps has occurred among students at Fordham University in New York All of those who developed mumps had been vaccinated against the disease RECENT OUTBREAKS — Mumps outbreaks in the US have occurred predominantly in vaccinated older teenagers and young adults who are ≥10 years past their last measles-mumps-rubella (MMR) vaccination Primary vaccine failure, close living conditions such as in college dormitories, and waning immunity could be contributing factors The relatively low incidence in older people could be due to a lower level of exposure or superior immunity from natural infection In an outbreak in New York in 20092010, most of the cases occurred in persons who had previously received doses of MMR vaccine; post-exposure prophylaxis with a third dose of the vaccine was followed by a rapid decline in the incidence of disease.1,2 RECOMMENDATIONS — During a mumps outbreak, the Advisory Committee on Immunization Practices (ACIP) recommends vaccination for all persons who might be exposed and not have a history of vaccination or other evidence of immunity.3 For school-age children and older students at risk of exposure, vaccination consists of doses of MMR vaccine at least 28 days apart The CDC recommends considering a third dose of MMR vaccine for control of an outbreak in a highly vaccinated population in a setting with intense exposure, high attack rates, and evidence of ongoing transmission for >2 weeks.4 MMR vaccine is contraindicated during pregnancy, in patients with severe immunodeficiency, and in persons with a history of a severe allergic reaction to any component of the vaccine, including neomycin □ www.medicalletter.org Take CME Exams IU Ogbuanu et al Impact of a third dose of measles-mumps-rubella vaccine on a mumps outbreak Pediatrics 2012; 130:e1567 AP Fiebelkorn et al Mumps postexposure prophylaxis with a third dose of measles-mumps-rubella vaccine, Orange County, New York, USA Emerg Infect Dis 2013; 19:1411 HQ McLean et al Prevention of measles, rubella, congenital rubella syndrome, and mumps, 2013: summary recommendations of the Advisory Committee on Immunization Practices (ACIP) MMWR Recomm Rep 2013; 62(RR-04):1 AP Fiebelkorn et al, in Manual for the surveillance of vaccine-preventable diseases 5th edition, CDC, 2012, chapter Available at: www.cdc.gov/vaccines/pubs/surv-manual/chpt09-mumps.html Accessed March 10, 2014 Intranasal Naloxone for Treatment of Opioid Overdose The recent increase in deaths from heroin overdose in the US has led to renewed interest in the opioid antagonist naloxone, particularly in making it available as an intranasal spray to paramedics and possibly to relatives and close friends of heroin users Intravenous (IV) administration is preferred, but peripheral venous access may be difficult to obtain in IV drug abusers, and exposure to their blood may be hazardous PHARMACOLOGY — Naloxone is a semisynthetic derivative of thebaine that is structurally similar to oxymorphone It acts as a competitive antagonist at opioid receptors in the brain Unlike other opioid antagonists, it has no opioid agonist effects In patients with opioid overdose, naloxone begins to reverse sedation, respiratory depression, and hypotension within 1-2 minutes after IV administration and 2-5 minutes after intramuscular (IM) or subcutaneous (SC) administration It has a half-life of 30-80 minutes in adults, much shorter than that of most opioids; the protective effect may wear off as soon as 45 minutes after IV administration of a low dose.1 ADVERSE EFFECTS — It is not clear whether naloxone has any direct toxicity (seizures, cardiac arrhythmias, and myocardial infarction have been reported), but it can precipitate acute withdrawal symptoms in opioid-dependent patients Acute opioid withdrawal is associated with anxiety, piloerection, yawning, sneezing, FORWARDING OR COPYING IS A VIOLATION OF U.S AND INTERNATIONAL COPYRIGHT LAWS 21 Table Some Clinical Studies of Naloxone for Prehospital Treatment of Opioid Overdose Study Description Results AM Kelly et al2 (n = 155) Prospective, randomized Suspected opioid overdose mg IM or IN (in mL) naloxone Response time IN: vs IM: RR >10 at IN: 63% vs IM: 82% GCS >11 at IN: 57% vs IM: 72% D Kerr et al3 (n = 172) Prospective, randomized Suspected opioid overdose mg IM or IN (in mL) naloxone TM Robertson et al4 (n = 96) Retrospective, EMS records Suspected opioid overdose IN or IV naloxone Response time IN: 8.0 vs IM: 7.9 RR >10 and/or GCS >13 at 10 IN: 72.3% vs IM: 77.5% Response time IN: 12.9 vs IV: 8.1 Increase in RR of >6 or in GCS of >6 IN: 66% vs IV: 56% MA Merlin et al5 Confirmed opioid overdose (n = 96) mg IN or 0.4-2 mg IV Retrospective, naloxone EMS reports Median increase in RR IN: vs IV: Median increase in GCS IN: vs IV: rhinorrhea, nausea, vomiting, diarrhea, and abdominal or muscle cramps, which are uncomfortable but rarely life-threatening DOSAGE FOR OPIOID OVERDOSE — Naloxone hydrochloride is available in the US as 0.4- and 1-mg/mL solutions for IV, IM, or SC administration No singleagent oral formulation and no intranasal formulation is commercially available An initial dose of 0.4-2 mg IV is recommended for adults It can be repeated every 2-3 minutes up to a total of 10 mg If the patient still has not responded, the diagnosis of opioid overdose should be questioned If the patient responds initially, but respiratory depression recurs when the effect of naloxone has worn off, naloxone can be given again as needed Naloxone can be administered intranasally using a mucosal atomizer device A syringe is attached to a spray tip that fragments the medication into a fine mist The usual intranasal dose (off-label) is mg (1 mg per nostril), which can be repeated in 3-5 minutes Table Some Naloxone Formulations Formulation Hospira 0.4 mg/mL mL vial 10 mL vial mL syringe mg/mL mL syringe Amphastar Cost1 $22.00 137.10 15.40 17.00 Approximate acquisition cost (WAC) Source: Analy$ource® Monthly (Selected from FDB MedKnowledge™) March 5, 2014 Reprinted with permission by FDB, Inc All rights reserved ©2014 www.fdbhealth.com/policies/drug-pricingpolicy Actual retail prices may be higher 22 Opiate antagonists: naloxone hydrochloride, in AHFS Drug Information, Bethesda, MD: American Society of Health-System Pharmacists, 2014, page 2259 AM Kelly et al Randomised trial of intranasal versus intramuscular naloxone in prehospital treatment for suspected opioid overdose Med J Aust 2005; 182:24 D Kerr et al Randomized controlled trial comparing the effectiveness and safety of intranasal and intramuscular naloxone for the treatment of suspected heroin overdose Addiction 2009; 104:2067 TM Robertson et al Intranasal naloxone is a viable alternative to intravenous naloxone for prehospital narcotic overdose Prehosp Emerg Care 2009; 13:512 MA Merlin et al Intranasal naloxone delivery is an alternative to intravenous naloxone for opioid overdoses Am J Emerg Med 2010; 28:296 Drugs for Gout Related Article(s) since publication GCS = Glasgow Coma Scale score (graded 0-15); IM = Intramuscular; IN = Intranasal; IV = Intravenous; RR = Respiratory rate Manufacturer CONCLUSION — Naloxone can be life-saving in patients with opioid overdose It is usually injected intravenously, intramuscularly, or subcutaneously, but intranasal administration may be an alternative □ The goals of gout treatment are threefold: treating acute inflammation, preventing flares, and lowering serum urate levels.1,2 ACUTE GOUT — Nonsteroidal anti-inflammatory drugs (NSAIDs) – In most patients without renal disease, peptic ulcer disease, or other contraindications, acute exacerbations of gout can be treated successfully with an NSAID, which should be started as soon as possible after the onset of symptoms and taken regularly (not as needed) until resolution of the flare There is no convincing evidence that indomethacin (Indocin, and others), a traditional choice, is more effective than other NSAIDs such as ibuprofen (Motrin, and others) or naproxen (Naprosyn, and others) In one controlled trial, high doses of the selective cyclooxygenase-2 (COX-2) inhibitor celecoxib (Celebrex; 800 mg once, then 400 mg 12 hours later on day 1, followed by 400 mg bid for days) were as effective as indomethacin 50 mg three times daily.3 Colchicine – Colchicine can be used for patients with contraindications to NSAIDs It should be started in the first 24 hours after the onset of acute symptoms A 1.2-mg dose followed by 0.6 mg one hour later is as effective as higher doses, with less toxicity.4 Diarrhea can occur Colchicine is a myotoxin; neuromyopathy can occur, especially in elderly patients or in those with hepatic or renal dysfunction It is a substrate of CYP3A4 and the efflux transporter P-glycoprotein (P-gp) Fatal toxicity has been reported in patients taking colchicine with a strong CYP3A4 inhibitor such as clarithromycin (Biaxin, and others) or a strong P-gp inhibitor such as cyclosporine (Neoral, and others).5 Myopathy and rhabdomyolysis have been reported in patients taking colchicine with a statin or fibrate The Medical Letter • Volume 56 • Issue 1438 • March 17, 2014 Table Some Drugs for Gout Drug Usual Adult Dosage Cost Anti-Inflammatory Drugs Naproxen – generic Naprosyn (Roche) Colchicine – Colcrys (Takeda) Urate-Lowering Drugs Allopurinol – generic Zyloprim (Prometheus) Febuxostat – Uloric (Takeda) Probenecid – generic Pegloticase – Krystexxa (Savient) Acute: 750 mg, then 250 mg q8h Prophylaxis4: 250 mg bid x weeks Acute: 1.2 mg, then 0.6 mg hour later Prophylaxis4: 0.6 mg once/d or bid x months 100-900 mg once/d5 40-80 mg once/d 500-1000 mg bid mg IV every weeks $0.352 8.653 5.882 145.323 15.45 925.20 2.40 43.80 214.20 36.00 10,780.00 Approximate wholesale acquisition cost (WAC) for day’s treatment of an acute attack, course of prophylaxis, or 30 days of urate lowering at the lowest recommended dosage Source: Analy$ource® Monthly (Selected from FDB MedKnowledge™) March 5, 2014 Reprinted with permission by FDB, Inc All rights reserved ©2014 www.fdbhealth.com/policies/drug-pricing-policy Actual retail prices may be higher Cost of generic naproxen Cost of Naprosyn Not an FDA-approved indication To avoid gout flares, starting dosage should be no more than 100 mg/d and the dose should be increased by 100 mg/d at 2-4 week intervals Doses >300 mg/d should be divided The starting dose should be lowered in patients with moderate to severe renal impairment, but still should be titrated up to a maintenance dose that may be higher than 300 mg Corticosteroids – Short courses of systemic corticosteroids such as prednisone or methylprednisolone given orally or parenterally are effective for treatment of acute flares Intra-articular injection of methylprednisolone or triamcinolone is also considered effective, but randomized controlled trials are lacking.6 Interleukin-1 (IL-1) Inhibitors – Canakinumab (Ilaris),7 which is FDA-approved for treatment of systemic juvenile idiopathic arthritis and is extraordinarily expensive, has also been reported to be effective in relieving gout pain and inflammation.8 Anakinra (Kineret), which is approved for use in rheumatoid arthritis, has also reduced the pain and inflammation of gout and is widely used off-label.9 These drugs may be options for patients with gout who cannot tolerate or have contraindications to NSAIDs, colchicine, and corticosteroids PREVENTION OF FLARES — Prophylaxis with colchicine or an NSAID can prevent flares of acute gout associated with initiation of urate-lowering therapy In older patients or in those with comorbidities such as renal disease or peptic ulcer disease, colchicine is preferred URATE-LOWERING AGENTS — The goal of therapy with urate-lowering drugs is to reduce the serum urate level to