The medical letter on drugs and therapeutics december 5 2016

In Brief: PPIs and Torsades de Pointes Therapeutics (AZCERT) has recently added the proton pump inhibitors (PPIs) omeprazole (Prilosec, and others), esomeprazole (Nexium, and others), lansoprazole (Prevacid,... Ciprofloxacin/Fluocinolone (Otovel) for Otitis Media with Tympanostomy Tubes The FDA has approved Otovel (Arbor), a combination of the fluoroquinolone antibiotic ciprofloxacin 0.3% and the corticosteroid fluocinolone acetonide 0.025%, for otic treatment of acute... Ameluz for Actinic Keratoses The FDA has approved a 10% nanoemulsion gel formulation of the porphyrin-based photosensitizer aminolevulinic acid hydrochloride (ALA; Ameluz – Biofrontera) for use in combination with a... Sublingual Nitroglycerin Powder (GoNitro) The FDA has approved a sublingual powder formulation of nitroglycerin (GoNitro – Espero) for prevention or acute relief of an attack of angina pectoris. It is the first powder... In Brief: Phentermine (Lomaira) for Weight Loss The FDA has approved Lomaira (KVK Tech), an 8-mg tablet formulation of phentermine that can be taken up to three times daily before meals, as an adjunct to lifestyle modifications for... Addendum: Statins for Primary Prevention of Cardiovascular Disease In our recent article on Lipid-Lowering Drugs,1 we said that statins can reduce the risk of first cardiovascular events and death (primary prevention) in patients at high risk for atherosclerotic...

The Medical Letter ® on Drugs and Therapeutics Volume 58 ISSUE ISSUE No 1433 1509 Volume 56 December 5, 2016 IN THIS ISSUE In Brief: PPIs and Torsades de Pointes .p 153 Ciprofloxacin/Fluocinolone (Otovel) for Otitis Media with Tympanostomy Tubes p 153 Ameluz for Actinic Keratoses p 155 Sublingual Nitroglycerin Powder (GoNitro) p 156 In Brief: Phentermine (Lomaira) for Weight Loss p 158 Addendum: Statins for Primary Prevention of Cardiovascular Disease p 158 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 December 5, 2016 Take CME Exams ISSUE ISSUE No 1433 1509 Volume 56 ALSO IN THIS ISSUE Ameluz for Actinic Keratoses p 155 Sublingual Nitroglycerin Powder (GoNitro) p 156 In Brief: Phentermine (Lomaira) for Weight Loss p 158 Addendum: Statins for Primary Prevention of Cardiovascular Disease p 158 IN BRIEF PPIs and Torsades de Pointes The Arizona Center for Education and Research on Therapeutics (AZCERT) has recently added the proton pump inhibitors (PPIs) omeprazole (Prilosec, and others), esomeprazole (Nexium, and others), lansoprazole (Prevacid, and others), and pantoprazole (Protonix, and generics) to its lists of Drugs with Conditional Risk of Torsades de Pointes (TdP) and Drugs to Avoid in Patients with Congenital Long QT Syndrome.1 PPIs not directly cause prolongation of the QT interval, but they can cause hypomagnesemia, which is often accompanied by hypocalcemia and hypokalemia and can result in cardiac repolarization disturbances such as QT interval prolongation.2 Reports have described cases of QT interval prolongation and TdP associated with severe PPIinduced hypomagnesemia.3,4 TdP has also been reported in patients taking a PPI concomitantly with drugs that directly prolong the QT interval.5,6 The newer PPIs dexlansoprazole (Dexilant) and rabeprazole (Aciphex, and generics) have not been linked to QT interval prolongation or TdP to date, but they can cause hypomagnesemia Serum magnesium levels should be monitored periodically in patients taking a PPI for an extended period of time (>2 weeks) If possible, extended PPI therapy should be avoided in patients who require treatment with drugs that carry a known risk of TdP7 and in those with long QT syndrome If extended PPI therapy must be used with a drug that prolongs the QT interval, close monitoring of magnesium levels and the QT interval is recommended ■ AZCERT New drugs added to CredibleMeds drugs lists November 2, 2016 Available at: www.crediblemeds.org/blog/news-drugsadded-qtdrugs-lists Accessed November 22, 2016 In brief: PPIs and hypomagnesemia Med Lett Drugs Ther 2011; 53:25 EJ Hoorn et al A case series of proton pump inhibitor-induced hypomagnesemia Am J Kidney Dis 2010; 56:112 BA Hansen and Ø Bruserud Hypomagnesemia as a potentially lifethreatening adverse effect of omeprazole Oxf Med Case Reports 2016; 2016:147 H Asajima et al Lansoprazole precipitated QT prolongation and torsade de pointes associated with disopyramide Eur J Clin Pharmacol 2012; 68:331 JN Bibawy et al Pantoprazole (proton pump inhibitor) contributing to torsades de pointes storm Circ Arrhythm Electrophysiol 2013; 6:e17 RL Woosley and KA Romero QT drugs list Available at: www.crediblemeds.org Accessed November 22, 2016 ▶ Ciprofloxacin/Fluocinolone (Otovel) for Otitis Media with Tympanostomy Tubes The FDA has approved Otovel (Arbor), a combination of the fluoroquinolone antibiotic ciprofloxacin 0.3% and the corticosteroid fluocinolone acetonide 0.025%, for otic treatment of acute otitis media with tympanostomy tubes (AOMT) in children ≥6 months old It is the second fluoroquinolone/corticosteroid combination to be approved for this indication; ciprofloxacin 0.3%/ dexamethasone 0.1% (Ciprodex) has been available for many years In December 2015, a suspension of ciprofloxacin 6% (Otiprio) was approved for otic treatment of bilateral otitis media with effusion in children undergoing tympanostomy tube placement.1 Pronunciation Key Ciprofloxacin: sip” roe flox’ a sin Otovel: oh' toe vel Fluocinolone acetonide: floo” oh sin’ oh lone a seet’ oh nide STANDARD TREATMENT — Insertion of tympanostomy tubes is a common surgical procedure for children who experience recurrent acute otitis media or otitis media with effusion Otorrhea, primarily due to bacterial infection, is the most common complication of tympanostomy tubes Topical antibiotics are preferred over oral antibiotics for treatment of uncomplicated acute tympanostomy tube otorrhea because they have been shown to be more effective, safer, and less likely to promote bacterial resistance.2 Addition of topical corticosteroids may increase cure rates.3 MECHANISM OF ACTION — Ciprofloxacin is active against most strains of the pathogens that typically cause AOMT, including Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, and Pseudomonas aeruginosa.2 Corticosteroids such as fluocinolone acetonide have anti-inflammatory effects that can reduce middle ear secretions 153 Published by The Medical Letter, Inc • A Nonprofit Organization The Medical Letter Vol 58 (1509) ® Table AOMT Clinical Trials Drug Regimen Median Time to Cessation of Otorrhea Trial (n=331) Ciprofloxacin/ fluocinolone acetonide 3.75 days* Ciprofloxacin Otorrhea Cessation Rate at Day 22 79%* 7.69 days 67% Fluocinolone acetonide N.R 48% Trial (n=331) Ciprofloxacin/ fluocinolone acetonide 4.94 days* 78%* Ciprofloxacin 6.83 days 69% N.R 44% Fluocinolone acetonide N.R = No results available because the number of patients with otorrhea exceeded the number without otorrhea at day 22 *Statistically significant difference vs ciprofloxacin or fluocinolone acetonide alone PHARMACOKINETICS — Analyses of blood samples from 30 children months to 12 years old with AOMT who were treated with Otovel for days in the clinical trials found detectable plasma concentrations of ciprofloxacin in only one sample, which was taken from a patient with bilateral AOMT; all of the other samples were from children with unilateral AOMT Fluocinolone acetonide was not detected in any blood samples CLINICAL STUDIES — Ciprofloxacin 0.3%/fluocinolone acetonide 0.025% was compared to its individual components in two unpublished, randomized, doubleblind trials (summarized in the package insert) in 662 patients months to 12 years old with AOMT The median duration of treatment was days In both trials, the median time to cessation of otorrhea (the primary endpoint) was significantly shorter with the combination than with ciprofloxacin or fluocinolone acetonide alone Significantly more patients treated with ciprofloxacin/fluocinolone acetonide had no otorrhea by day 22 compared to those who received either drug alone (Table 1) December 5, 2016 In another trial, 590 patients ≥7 years old with diffuse otitis externa (swimmer’s ear) were randomized to combination treatment with ciprofloxacin 0.3%/ fluocinolone acetonide 0.025% or to ciprofloxacin 0.3% monotherapy.4 The dosage for both treatments was 4-6 drops instilled into the ear canal every hours for days Clinical cure (score of for symptoms of otalgia, edema, and otorrhea at the end of treatment), the primary endpoint, was reported in 80% of patients who received ciprofloxacin/fluocinolone acetonide, compared to 71% of those who received ciprofloxacin alone, a statistically significant difference The combination has not been approved by the FDA for treatment of acute otitis externa ADVERSE EFFECTS — Both ciprofloxacin and fluocinolone acetonide are well tolerated when administered topically Use of the combination is contraindicated in patients with viral or fungal infections of the external ear canal PREGNANCY AND LACTATION — Systemic absorption of ciprofloxacin/fluocinolone acetonide following otic administration is negligible Use of the combination is not expected to result in exposure of the fetus or the breastfed infant to either drug DOSAGE AND ADMINISTRATION — Otovel is available in single-dose vials that deliver the equivalent of ciprofloxacin 0.75 mg and fluocinolone acetonide 0.0625 mg in 0.25 mL of solution The recommended dosage is instillation of one vial into the affected ear(s) twice daily for days To prevent dizziness resulting from instillation of a cold solution, Otovel vials should be warmed by holding them in the palm of the hand for 1-2 minutes before use With the child's head tilted to the side, the caregiver should empty the contents of the vial into the affected ear and press the tragus times with a pumping motion to aid delivery of the Table Some Otic Fluoroquinolone Products for Otitis Media Drug Formulations Dosage Cost1 $283.20 Ciprofloxacin 6% – Otiprio2 (Otonomy) 60 mg/1 mL single-use vial3 0.1 mL in each ear once, intratympanically Ciprofloxacin 0.3%/dexamethasone 0.1% – Ciprodex4 (Alcon) 7.5 mL bottle drops in affected ear bid x days Ciprofloxacin 0.3%/fluocinolone acetonide 0.025% – Otovel4 (Arbor) 0.25 mL single-dose vial5 0.25 mL in affected ear bid x days Ofloxacin 0.3%4 – generic 5, 10 mL bottles drops in affected ear bid x 10 days 192.90 198.00 131.50 Approximate WAC for the smallest-size bottle or vial 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 FDA-approved for treatment of children with bilateral otitis media with effusion who are undergoing tympanostomy tube placement Includes sufficient syringes and needles to treat both ears FDA-approved for treatment of acute otitis media in children with tympanostomy tubes Ciprodex is also approved for treatment of acute otitis externa Ofloxacin 0.3% is also approved for treatment of otitis externa and of chronic suppurative otitis media in patients with perforated tympanic membranes Sold in cartons containing 14 single-dose vials 154 The Medical Letter Vol 58 (1509) ® drug to the middle ear The child should not move his or her head for minute after administration CONCLUSION — An otic solution containing ciprofloxacin 0.3% and fluocinolone acetonide 0.025% (Otovel) is more effective than either of its components alone in decreasing otorrhea in children with acute otitis media with tympanostomy tubes How it compares with other otic fluoroquinolone products for this indication remains to be determined ■ ▶ Ameluz for Actinic Keratoses The FDA has approved a 10% nanoemulsion gel formulation of the porphyrin-based photosensitizer aminolevulinic acid hydrochloride (ALA; Ameluz – Biofrontera) for use in combination with a narrowband red light photodynamic therapy (PDT) lamp (BFRhodoLED) for treatment of actinic keratoses (AKs) of mild to moderate severity on the face and scalp A 20% ALA solution (Levulan Kerastick) approved for use in combination with blue light PDT (BLU-U) has been available in the US since 2002.1 Pronunciation Key Aminolevulinic acid: a mee" noe lev" ue lin' ik as' id Ameluz: am' e looz" ACTINIC KERATOSES — Common in older, lighterskinned persons with a long history of sun exposure, AKs are gritty, scaly, red- or flesh-colored papules or plaques caused by UV radiation-induced abnormal keratinocyte proliferation AKs commonly regress and reappear, and most only cause cosmetic harm, but they are considered precancerous with a risk of progression to squamous cell carcinoma.2 STANDARD TREATMENT — Few studies directly comparing the various treatments for AKs are available Liquid nitrogen cryosurgery is the most commonly used technique; it is effective, but can cause hypopigmentation Field therapy with topical fluorouracil (5-FU) or imiquimod (Aldara, Zyclara, and generics) is effective, but requires weeks to months December 5, 2016 Ciprofloxacin (Otiprio) for tympanostomy tube insertion Med Lett Drugs Ther 2016; 58:69 RM Rosenfeld et al Clinical practice guideline: tympanostomy tubes in children Otolaryngol Head Neck Surg 2013; 149 (1 Suppl):S1 J Chee et al Topical versus oral antibiotics, with or without corticosteroids, in the treatment of tympanostomy tube otorrhea Int J Pediatr Otorhinolaryngol 2016; 86:183 J Lorente et al Ciprofloxacin plus fluocinolone acetonide versus ciprofloxacin alone in the treatment of diffuse otitis externa J Laryngol Otol 2014; 128:591 of treatment and can cause disfiguring erythema, vesicles, and ulceration Topical ingenol mebutate gel (Picato) is also effective and requires only 2-3 days of treatment Ingenol can cause severe local reactions, which are usually of shorter duration than those caused by 5-FU or imiquimod; it has also been associated with severe allergic reactions, including anaphylaxis, and with herpes zoster reactivation Diclofenac gel (Solaraze) is relatively well tolerated but only modestly effective, and requires months of application Use of Levulan Kerastick and BLU-U is highly effective and well tolerated, with skin inflammation usually lasting only about a week after treatment.2-5 MECHANISM — ALA is a prodrug that is metabolized to protoporphyrin IX (PpIX) when applied to skin under occlusion Activation of PpIX by red light causes formation of reactive oxygen species that damage and destroy the treated cells CLINICAL STUDIES — FDA approval of Ameluz and the BF-RhodoLED lamp was based on three randomized trials including a total of 299 patients with 4-8 mild to moderate AK lesions on the face, forehead, or scalp who received red light treatment with either ALA or the drug vehicle Complete clearance of AK lesions 12 weeks after the last treatment, the primary endpoint, occurred in 183 of 212 patients (86%) who received ALA and in 14 of 87 patients (16%) who received the vehicle alone.6-8 In a follow-up study that included responders from two of the trials, 69% and 53% of those who had Table Aminolevulinic Acid (ALA) Formulations Time Between Application and PDT PDT Light Color PDT Duration Cost1 10% gel hours Red (~635 nm) 10 minutes $270.00 20% solution 14-18 hours Blue (~410 nm) 16.7 minutes Name Formulation Ameluz (Biofrontera) Levulan Kerastick (Dusa) 330.00 PDT = photodynamic therapy Approximate WAC for one dosage unit Cost of PDT not included 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 155 The Medical Letter ® received ALA and red light PDT remained completely clear for 12 months after the last treatment.9 In one network meta-analysis, 5-FU was found to have the highest rate of complete clearance, followed by ALA/PDT and then imiquimod.10 In another, which distinguished between ALA dosage forms, Ameluz had better clearance rates than 5-FU, and imiquimod had better rates than Levulan Kerastick.11 ADVERSE EFFECTS — Application-site erythema, pain/burning, and irritation occurred in most patients receiving ALA/PDT in the randomized clinical trials; 30% of patients reported severe pain/burning Other application-site adverse effects reported in ≥10% of patients receiving the active treatment and more frequently than with the vehicle included edema, pruritus, scabbing, exfoliation, induration, and vesicles Most reactions were mild to moderate in severity and lasted for 1-4 days, but some persisted for >2 weeks Patients treated with ALA gel should avoid exposure to sunlight for 48 hours after application Eyelid edema and mucous membrane inflammation can occur Patients with coagulation disorders were excluded from clinical trials Practitioners should take care to avoid bleeding during preparation of lesions for treatment, and bleeding must be stopped before the gel is applied DRUG INTERACTIONS — Concomitant use of photosensitizing drugs such as thiazide diuretics, fluoroquinolones, or tetracyclines could exacerbate the phototoxic effect of PDT DOSAGE AND ADMINISTRATION — Ameluz is supplied in 2-g tubes, which should be refrigerated and used within 12 weeks after opening A 1-mm layer of gel should be applied to the affected lesions or field and to a 5-mm radius of surrounding skin, avoiding the eyes, nose, mouth, and ears No more than g of gel should be applied per treatment After allowing the gel to dry for 10 minutes, the treated areas should be occluded for hours and then illuminated with the BF-RhodoLED lamp, which delivers 37 J/cm2 of red light (~635 nm) within 10 minutes Both the patient and the provider must wear protective eye equipment during PDT Lesions that have not resolved may be retreated once, months after the initial dose CONCLUSION — The combination of the new gel formulation of aminolevulinic acid (Ameluz) and red 156 Vol 58 (1509) December 5, 2016 light photodynamic therapy is effective for treatment of actinic keratoses on the face and scalp and better tolerated than 5-FU or imiquimod Whether it offers any advantage over Levulan Kerastick, an older aminolevulinic acid formulation that uses blue light photodynamic therapy, remains to be established ■ New treatments for actinic keratoses Med Lett Drugs Ther 2002; 44:57 JA Siegel et al Current perspective on actinic keratosis: a review Br J Dermatol 2016 August (epub) B Berman et al Pharmacotherapy of actinic keratosis Expert Opin Pharmacother 2009; 10:3015 Ingenol mebutate (Picato) for actinic keratoses Med Lett Drugs Ther 2012; 54:35 FDA Drug Safety Communication: FDA warns of severe adverse events with application of Picato (ingenol mebutate) gel for skin conditions requires label changes Available at: www.fda.gov/ Drugs/DrugSafety/ucm459142.htm Accessed November 22, 2016 RM Szeimies et al Photodynamic therapy with BF-200 ALA for the treatment of actinic keratosis: results of a prospective, randomized, double-blind, placebo-controlled phase III study Br J Dermatol 2010; 163:386 T Dirschka et al Photodynamic therapy with BF-200 ALA for the treatment of actinic keratosis: results of a multicentre, randomized, observer-blind phase III study in comparison with a registered methyl-5-aminolaevulinate cream and placebo Br J Dermatol 2012; 166:137 U Reinhold et al A randomized, double-blind, phase III, multicentre study to evaluate the safety and efficacy of BF-200 ALA (Ameluz®) vs placebo in the field-directed treatment of mild-to-moderate actinic keratosis with photodynamic therapy (PDT) when using the BF-RhodoLED® lamp Br J Dermatol 2016; 175:696 T Dirschka et al Long-term (6 and 12 months) follow-up of two prospective, randomized, controlled phase III trials of photodynamic therapy with BF-200 ALA and methyl aminolaevulinate for the treatment of actinic keratosis Br J Dermatol 2013; 168:825 10 AK Gupta and M Paquet Network meta-analysis of the outcome ‘participant complete clearance’ in nonimmunosuppressed participants of eight interventions for actinic keratosis: a follow-up on a Cochrane review Br J Dermatol 2013; 169:250 11 S Vegter and K Tolley A network meta-analysis of the relative efficacy of treatments for actinic keratosis of the face or scalp in Europe PLoS One 2014; 9:e96829 ▶ Sublingual Nitroglycerin Powder (GoNitro) The FDA has approved a sublingual powder formulation of nitroglycerin (GoNitro – Espero) for prevention or acute relief of an attack of angina pectoris It is the first powder formulation of nitroglycerin to become available in the US Most patients with angina use sublingual nitroglycerin tablets (Nitrostat, and generics) Translingual spray formulations of nitroglycerin (NitroMist, Nitrolingual Pumpspray, and generics) are also available.1 The Medical Letter Vol 58 (1509) ® December 5, 2016 Table Some Nitroglycerin Formulations Drug Formulations Tmax Usual Dosage1 Cost2 Sublingual powder – GoNitro (Espero) 0.4 mg single-use packets (12, 36, 96 packets/box) 1-2 packets, then packet q5 PRN $653.30 Sublingual tablets – generic Nitrostat (Pfizer) 0.3, 0.4, 0.6 mg tabs (100 tabs/package)3 6.4-7.2 0.3-0.6 mg q5 PRN 38.20 43.60 Translingual spray – generic Nitrolingual Pumpspray (Espero) 0.4 mg/spray (60, 200 sprays/unit) 7.5 1-2 sprays, then spray q5 PRN4 279.30 401.70 Translingual aerosol spray – generic NitroMist (Akrimax) 0.4 mg/spray (90, 230 sprays/unit) 1-2 sprays, then spray q5 PRN4 279.00 633.30 Maximum dose is dosage units or 1.2 mg in a 15-minute period Approximate WAC for 96 packets of sublingual powder, 100 0.4-mg sublingual tabs, 200 translingual sprays, or 230 translingual aerosol sprays 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 The 0.4-mg tablets are also supplied in packages containing bottles of 25 tablets The dose should be sprayed onto or under the tongue CLINICAL STUDIES — In an unpublished, randomized, double-blind, crossover trial in 51 patients with exertional angina pectoris (summarized in the package insert), doses of nitroglycerin powder ranging from 200-1600 mcg produced significant, dose-related increases in exercise tolerance, time to onset of angina, and time to ST-segment depression, compared to placebo No clinical studies comparing nitroglycerin sublingual powder with other formulations of the drug are available ADVERSE EFFECTS — As with other nitroglycerin formulations, headache (which may be severe and persistent), flushing, dizziness, postural hypotension, and paresthesia can occur with use of nitroglycerin sublingual powder DRUG INTERACTIONS — Concurrent use of nitroglycerin with antihypertensive drugs can result in additive hypotensive effects Phosphodiesterase type (PDE5) inhibitors such as sildenafil (Revatio, and generics; Viagra) prevent the breakdown of cyclic guanosine monophosphate (cGMP), prolonging nitrate-induced vasodilation and hypotension; their use with nitroglycerin is contraindicated Use of nitroglycerin with ergot derivatives should be avoided because nitroglycerin can decrease first-pass metabolism of dihydroergotamine and ergotamine can precipitate angina pectoris DOSAGE AND ADMINISTRATION — GoNitro is supplied in single-use packets containing 0.4 mg of nitroglycerin The packets should be stored at room temperature At the onset of an anginal attack, the contents of one or two packets should be placed under the tongue and allowed to dissolve, preferably with the patient in a sitting position An additional packet can be used every minutes as needed, up to a maximum of packets in a 15-minute period If angina does not begin to subside within minutes or completely resolve within 15 minutes, the patient should seek immediate medical attention.2 The contents of one packet can be dissolved under the tongue 5-10 minutes before physical activity to prevent an acute attack of angina STABILITY — Nitroglycerin is a volatile compound; its degradation can be accelerated by exposure to heat or light Sublingual nitroglycerin tablets are dispensed in a tightly sealed amber glass bottle to prevent degradation and loss of potency Patients are usually instructed to discard unused tablets to 12 months after first opening the bottle Because GoNitro is supplied in single-use packets, use of one dosage unit does not affect the stability of others According to the manufacturer, unopened packets have an expiration date of up to 24 months from the date of manufacture CONCLUSION — Sublingual nitroglycerin powder (GoNitro) packets offer a very expensive alternative to nitroglycerin sublingual tablets (Nitrostat, and generics), with no demonstrated advantage in efficacy ■ NitroMist nitroglycerin spray for angina Med Lett Drugs Ther 2011; 53:23 SD Fihn et al 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons J Am Coll Cardiol 2012; 60:e44 157 The Medical Letter Vol 58 (1509) ® Addendum: Statins for Primary Prevention of Cardiovascular Disease (Med Lett Drugs Ther 2016; 58:133) IN BRIEF Phentermine (Lomaira) for Weight Loss The FDA has approved Lomaira (KVK Tech), an 8-mg tablet formulation of phentermine that can be taken up to three times daily before meals, as an adjunct to lifestyle modifications for weight loss It is only approved for short-term use (a few weeks) in adults with a body mass index (BMI) ≥30 kg/m2, or with a BMI ≥27 kg/m2 in addition to a weight-related comorbidity such as hypertension, dyslipidemia, or diabetes Phentermine has been available alone and in combination with topiramate for years.1 Table Phentermine Products Drug December 5, 2016 Formulations Usual Dosage Cost1 Phentermine2 – generic 15, 30, 37.5 mg caps; 37.5 mg 37.5 mg tabs once/d3 Adipex-P4 (Teva) mg tabs mg tid5 Lomaira4 (KVK Tech) $10.50 63.50 43.50 Phentermine/ topiramate ER – Qsymia6 (Vivus) 186.00 7.5/46, 15/92 mg ER caps7 7.5/46 15/92 mg once/d8 ER = extended-release Approximate WAC for 30 days’ treatment at the lowest usual 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 Only approved for short-term use (a few weeks) Taken before breakfast or 1-2 hours after breakfast A branded generic Taken 30 minutes before meals, up to three times daily Approved for chronic weight management Also available in 3.75/23 mg and 11.25/69 mg capsules, which are intended for use only during titration Taken before breakfast Lomaira was approved by the FDA under an abbreviated new drug application (ANDA) and is considered a generic drug Its approval was based on the results of earlier phentermine trials No studies are available comparing the efficacy and safety of Lomaira to standard doses of phentermine or to any other drug approved for weight loss Like other sympathomimetic amines approved for weight loss, Lomaira is classified as a schedule IV controlled substance All sympathomimetics can increase heart rate, raise blood pressure, and cause nervousness and insomnia.2 Phentermine is contraindicated for use in patients with cardiovascular disease, hyperthyroidism, glaucoma, or a history of drug abuse, and in pregnant women It should not be used while taking, and for 14 days after stopping, a monoamine oxidase (MAO) inhibitor because of the risk of hypertensive crisis ■ Diet, drugs, and surgery for weight loss Med Lett Drugs Ther 2015; 57:21 SZ Yanovski and JA Yanovski Long-term drug treatment for obesity: a systematic and clinical review JAMA 2014; 311:74 In our recent article on Lipid-Lowering Drugs,1 we said that statins can reduce the risk of first cardiovascular events and death (primary prevention) in patients at high risk for atherosclerotic cardiovascular disease (CVD) and significantly reduce the incidence of cardiovascular events in patients at lower risk for CVD Now the United States Preventive Services Task Force (USPSTF) has issued new recommendations on the appropriate use of statins for primary prevention of CVD.2 The USPSTF states that clinicians should periodically screen all persons 40-75 years old for cardiovascular risk factors and evaluate their 10-year risk of CVD using the ACC/AHA Pooled Cohort Equation.3 It recommends starting low- to moderate-intensity statin therapy (lowintensity statin therapy lowers LDL-cholesterol 10% Initiate low- to moderate-intensity statin therapy3 7.5-10% Selectively offer low- to moderateintensity statin therapy3,4 Any Evidence insufficient to recommend initiating statin therapy >75 years Dyslipidemia, diabetes, hypertension, or smoking Calculated using the ACC/AHA Pooled Cohort Equation (tools.acc.org/ ASCVD-Risk-Estimator) Low-intensity statin therapy lowers LDL-cholesterol