Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Clinical Alert MARCH 2016 Updated Guidance for Hepatitis C Virus (HCV) and Expanded Indications The American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) updated their guidance on the management of HCV infection. Among several important updates, considerations for patients with HIV/HCV co-infection, decompensated cirrhosis (Child-Pugh B or C), HCV infection post-liver transplant, and severe renal impairment are specifically addressed. AASLD/IDSA recommend a number of direct-acting antiviral all-oral regimens to treat HCV genotype (GT) 1 infection that provide sustained virologic response (SVR) rates exceeding 90%, including elbasvir/grazoprevir (Zepatier®; Merck), a new fixed-dose combination of an NS5A inhibitor and HCV NS3/4A protease inhibitor. Regimens vary based on the HCV subtype and prescence of cirrhosis. In addition, detection of NS5A resistance-associated variants (RAVs) is one of the strongest pre-treatment predictors of treatment outcome with NS5A-containing regimens, such as elbasvir/grazoprevir, in patients with GT 1a infection. NS5A RAVs that cause a 5-fold decrease in NS5A inhibitor activity can significantly reduce SVRs of NS5A-containing regimens in patients with genotype 1a. AASLD/IDSA recommend RAV testing, particularly at the M28, Q30, L31, and Y93 positions, prior to selecting an HCV antiviral regimen in patients with GT 1a. At the population level, approximately 10% to 15% of patients with GT 1 and no prior exposure to NS5A inhibitors will test positive for HCV NS5A RAVs at baseline. Recommendations for elbasvir/grazoprevir follow the Food and Drug Administration (FDA) approved indications, including as a first-line option for most patients with GTs 1 and 4; AASLD/IDSA also suggest this agent as an alternative for treatment-naïve GT 1a patients with high fold-change NS5A RAVs, either without cirrhosis or with compensated cirrhosis (Child-Pugh A). In February, the FDA expanded the patient populations for Gilead’s oral fixed-dose combination, ledipasvir/sofosbuvir (Harvoni®), and Bristol-Myers Squibb’s, daclatasvir (Daklinza™). The expanded populations are included in the guidelines, however some recommended regimens may differ between FDA and AASLD/IDSA. Ledipasvir/sofosbuvir is now indicated for GT 1- or 4-infected liver transplant recipients without cirrhosis or with compensated cirrhosis and for GT 1-infected patients with decompensated cirrhosis. Ledipasvir/sofosbuvir is approved in combination with ribavirin (RBV) for 12 weeks for these expanded indications. The FDA expanded the patient populations for daclatasvir (Daklinza) to include patients with GT 1 and compensated cirrhosis and patient with GTs 1 or 3 with decompensated cirrhosis, recurrent HCV post-liver transplant or HIV-coinfection. It is approved in combination with sofosbuvir for 12 weeks for all indications; the addition of RBV is recommended if decompensated cirrhosis or recurrence post-liver transplant occurs in patients with GT 1 or 3 and if compensated cirrhosis is present in patients with GT 3. Increased Risk of Dementia Associated with Proton Pump Inhibitors A large observational study identified a link between the use of proton pump inhibitors (PPIs) and an increased risk of dementia in the elderly. PPIs, such as esomeprazole, lansoprazole, omeprazole, pantoprazole, and rabeprazole, are widely used to treat upper gastrointestinal tract acid-related disorders such as gastroesophageal reflux Drug Information Highlights •AstraZeneca announced a voluntary recall of 3 lots of Tudorza® Pressair® (aclidinium bromide) used for maintenance treatment of chronic obstructive pulmonary disease (COPD). The recall involves the 60 dose-count devices only. The counter ring for some devices was not initially set to “60” in the viewing window, which can potentially result in the device locking by reaching “0” prior to 60 doses being dispensed. The affected products include Lot# 1144394, Lot# 1145539, and Lot# 1145868, all of which were distributed between July 2015 and September 2015. AstraZeneca has instructed to stop distribution of the 3 lots immediately and arrange for return to Stericycle by calling (866) 367-5604. No other lots are being recalled at this time. For more information call (800) 237-8898. •Following recommendations from its advisory panel, the FDA declined to approve Merck’s lipid-lowering agents, ezetimibe (Zetia®) and ezetimibe/simvastatin (Vytorin®), for risk reduction of cardiovascular (CV) events (CV death, nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina, or need for revascularization) in patients with coronary artery disease. The supplemental applications for CV risk reduction were based on results from the IMPROVE-IT study. In their Complete Response Letter (CRL), the agency stated that ezetimibe failed to demonstrate an effect on CV morbidity and mortality given either alone or in combination with simvastatin. Merck is reviewing the CRL to determine their next steps. •The American College of Physicians (ACP) published updated depression treatment guidelines for adults. Second-generation antidepressants (SGAs) are often initially prescribed for patients with depression; however ACP found no significant difference between SGAs and cognitive behavioral therapy (CBT) in treatment response. ACP states that CBT is a reasonable approach for initial treatment and advises that clinicians should select either SGA or CBT to treat patients with major depressive disorder (MDD) and further suggest that selection should consider treatment effects, adverse effects, cost, accessibility, and patient preferences. The complete guidelines can be accessed at http://annals.org. Editorial Staff Maryam Tabatabai, PharmD Carole Kerzic, RPh Editor in Chief Executive Editor 1 March 2016 Lara Frick, PharmD, BCPS, BCPP, CGP Deputy Editor Raquel Holmes, RPh, MHM, AAHIV Deputy Editor Leslie Pittman, PharmD Eileen Zimmer, PharmD, MBA Deputy Editor Deputy Editor disease (GERD) and gastric ulcers. The study was conducted between 2004 and 2011 and included data from the largest German public health insurer. A total of 73,679 patients aged 75 years and older who did not have dementia at baseline were identified. Of these patients, 4% used PPIs regularly (e.g. at least one prescription per quarter) during at least one 12- to 18-month interval during the study period. After adjusting for confounders, including age, depression, stroke, and polypharmacy (≥ 5 drugs), the study reported a 44% higher risk of developing dementia (95% confidence interval, 1.36 to 1.52; p<0.001) in patients who regularly used a PPI. The effect of occasional PPI use was also examined and was associated with a 16% increased risk of dementia (95% CI, 1.13 to 1.19). Although reasons for the increase in dementia with PPI use are unclear, researchers suggest that some PPIs may cross the blood-brain barrier and may increase amyloid levels in the brain. The effect of PPIs on vitamin B12 deficiency, a known influence on cognitive decline, was not included in this study. In addition, the socio-economic status of patients was not taken into account. Finally, to establish a causal relationship of PPI use on the incidence of dementia, randomized, prospective clinical trials are needed. Appropriate Antibiotic Use for Respiratory Tract Infections Pipeline News: Upcoming Prescription Drug User Fee Acts (PDUFA) Dates •March 2016: ixekizumab; subcutaneous (SC) interleukin 17A; moderate to severe plaque psoriasis; Lilly. •March 2016: emtricitabine/rilpivirine/tenofovir alafenamide fumarate; oral antiretroviral; HIV infection; Gilead/Janssen. •March 29, 2016: Xadago®; safinamide; oral once-daily alpha-aminoamide; adjunct for early-, mid- and late-stage Parkinson’s disease; Meiji Eika/Newron. •March 30, 2016: reslizumab; IV anti-IL-5 monoclonal antibody; moderate to severe asthma with eosinophilia not controlled with inhaled corticosteroids; Teva. •April 1, 2016: dronabinol oral solution; cannabinoid; chemotherapy-induced nausea and vomiting, cachexia or an unexplained significant weight loss in AIDS; Insys. •First Half, 2016: Remsima™; infliximab, biosimilar to Remicade®; IV TNF-alpha inhibitor; rheumatoid arthritis and all other Remicade approved indications; Celltrion/Pfizer/Hospira. Acute respiratory tract infection (ARTI) results in more outpatient physician visits and antibiotic prescriptions than any other condition. Antibiotics are often prescribed inappropriately for ARTI contributing to antibiotic resistance, medication-related adverse events, and excess costs. The American College of Physicians (ACP) and Centers for Disease Control and Prevention (CDC) have collaborated to offer recommendations on the appropriate use of antibiotics for ARTIs, which may include acute uncomplicated bronchitis, pharyngitis, acute rhinosinusitis, and the common cold. Recommendations provided are limited to healthy and immunocompetent adults without chronic lung disease (e.g., cystic fibrosis, bronchiectasis, chronic obstructive pulmonary disease). In general, antibiotic use provides no benefit in cases of acute bronchitis or the common cold; patients may find relief from symptoms with the use of cough suppressants, expectorants, antihistamines, and decongestants. Antibiotics may have limited benefit in cases of acute rhinosinusitis for symptoms lasting longer than 10 days, severe symptoms (e.g., fever > 39⁰C, purulent nasal discharge, or facial pain) lasting longer than 3 consecutive days, or if symptoms worsen after initially improving. Recommended oral regimens are amoxicillin-clavulanate (500/125 mg three times daily or 875/125 mg twice daily) or amoxicillin 500 mg twice daily for 5 to 7 days. For patients diagnosed with pharyngitis and positive streptococcal infection, antibiotics may decrease the length of illness and prevent further complications, such as acute rheumatic fever. If acute group A streptococcal pharyngitis has been confirmed, patients should be treated with a narrow-spectrum antibiotic for 10 days. Recommended oral treatment regimens for patients without penicillin allergy include: penicillin V (250 mg four times daily or 500 mg twice daily) or amoxicillin (50 mg/kg once daily or 25 mg/kg twice daily) for 10 days. The complete guidance, including in-depth prescribing strategies and alternative treatment options for persons with penicillin allergies, can be accessed at http://annals.org. Benefits and Risks of Long-Term Bisphosphonate Therapy An American Society for Bone and Mineral Research (ASBMR) task force has provided guidance regarding bisphosphonate (BP) therapy duration for patients with osteoporosis. The recommendations are based primarily on 2 trials, FLEX (Fracture Intervention Trial Longterm Extension) and HORIZON extension which provided evidence for long-term BP use. The task force advises healthcare professionals (HCPs) to reassess the benefits and risks of BP therapy after 5 years of oral or 3 years of intravenous (IV) therapy. Benefit includes continued reduction in the risk of vertebral fracture. Risks, although infrequent, include jaw osteonecrosis (ONJ) and atypical femoral fracture. Unlike ONJ, the risk of atypical femoral fracture increases with BP therapy duration. Oral or intravenous BP therapy for up to 10 years and 6 years, respectively, should be considered for older women (70 to 75 years of age) at high risk of fracture, with a history of major osteoporotic fracture (e.g., hip, spine or multiple other fractures) before or during BP therapy. Periodic evaluations to reassess the benefits and risks of therapy are still recommended throughout treatment. After 3 to 5 years of BP therapy, a 2 to 3 year drug holiday may be considered in women without history of major osteoporotic fracture or high fracture risks. The task force discloses that that their approach for long-term BP therapy is based on limited evidence and applies only for reduction of vertebral fracture in a predominantly Caucasian postmenopausal female population. Clinical judgement is still essential. This approach, with certain modifications, may also apply to men with osteoporosis and patients with glucocorticoid-induced osteoporosis (GIO), although less evidence is available. If glucocorticoid therapy is discontinued in patients with GIO, bisphosphonate therapy may be discontinued depending on the presence of certain risk factors. If the risk of fracture remains elevated, BP therapy should be continued; however, current GIO guidelines do not provide recommendations on duration. Both men with osteoporosis and women with GIO who have received BP therapy for over 5 years and still require bone-protective therapy may consider switching to teriparatide (Forteo®). Men with GIO who continue to receive glucocorticoids may benefit from continuation of BP therapy. 2 March 2016 Recent FDA Approvals Generic Name Trade Name dexlansoprazole FDA Status Description Applicant Dexilant™ SoluTab Dexlansoprazole delayed-release (DR) orally disintegrating tablet (Dexilant SoluTab) has received approval for the treatment of heartburn associated with gastroesophageal reflux disease (GERD) and for maintaining healing of erosive esophagitis (EE) in adults. The recommended dosing for healed EE maintenance is 30 mg once daily for up to 6 months and for symptomatic non-erosive GERD, the dose is 30 mg once daily for 4 weeks. Dexilant SoluTab should be taken at least 30 minutes prior to a meal. Dexilant is also available as 30 and 60 mg DR capsules that carry the additional indication of healing of all grades of EE. Two 30 mg Dexilant SoluTabs are not interchangeable with one 60 mg Dexilant DR capsule. Takeda FDA NDA approval 01/26/2016 sumatriptan succinate Onzetra™ Xsail™ The FDA has approved sumatriptan nasal powder (Onzetra Xsail), a triptan for acute treatment of migraine, with or without aura, in adults. It is not indicated for migraine attack prophylaxis or for the treatment of cluster headache. Available as a capsule in a disposable nosepiece, it is for use only with the Xsail breath-powered delivery device. The recommended dose is 22 mg, administered by use of 1 nosepiece (11 mg) in each nostril. A second dose may be taken after at least 2 hours have passed if migraine has not resolved. A maximum of 2 doses may be given in a 24-hour period. Avanir FDA NDA approval 01/27/2016 amphetamine Adzenys XR-ODT™ The central nervous system stimulant amphetamine extended-release (Adzenys XR-ODT) was approved in an orally disintegrating tablet formulation for the treatment of attention deficit hyperactivity disorder (ADHD) in patients 6 years and older. The recommended starting dose is 6.3 mg once daily for patients 6 to 17 years of age and 12.5 mg once daily for adults, both dosed in the morning. Amphetamine products should not be substituted on a milligram-per-milligram basis due to differences in pharmacokinetics and amphetamine base compositions. Adzenys XR-ODT is a schedule II controlled substance and is approved in a variety of strengths ranging from 3.1 mg to 18.8 mg. Neos FDA NDA approval 01/28/2016 sumatriptan succinate Zembrace™ SymTouch™ Injection The self-administered sumatriptan succinate injection (Zembrace SymTouch) was FDA approved for the acute treatment of migraine, with or without aura, in adults. It is not indicated for migraine prophylaxis. Available as a 3 mg prefilled, single-dose disposable autoinjector, the recommended dose is 3 mg injected SC. The maximum cumulative daily dose is 12 mg and each 3 mg injection should be separated by at least 1 hour. Dr. Reddys FDA NDA approval 01/28/2016 fosaprepitant dimeglumine Emend® for injection The agency has approved the use of fosaprepitant dimeglumine as a single 150 mg IV dose, in combination with other antiemetic agents, for the prevention of delayed nausea and vomiting in adults receiving initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC). Fosaprepitant dimeglumine for injection is a substance P/neurokinin-1 (NK1) receptor antagonist. It is available as 150 mg lyophilized powder for reconstitution and is dosed as a single 150 mg IV infusion administered over 20 to 30 minutes approximately 30 minutes prior to giving chemotherapy. Fosaprepitant dimeglumine for injection, in combination with other antiemetic agents, is also indicated for acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC), including high-dose cisplatin. Merck FDA sNDA approval 02/01/2016 betamethasone dipropionate Sernivo™ Betamethasone dipropionate spray for topical use (Sernivo) was approved for the treatment of mild to moderate plaque psoriasis in adults. The high potency corticosteroid was approved as a 0.05% spray and should be applied to the affected skin areas twice daily as directed. The face, scalp, axilla, groin and other intertriginous areas should be avoided. Treatment should be discontinued when control is achieved with duration not exceeding 4 weeks. Promius FDA NDA approval 02/05/2016 brivaracetam Briviact® The FDA has approved the anticonvulsant brivaracetam (Briviact) as adjunctive therapy in the treatment of partial-onset seizures in patients 16 years of age and older with epilepsy. Brivaracetam was approved in 5 tablet strengths ranging from 10 to 100 mg, a 10 mg/mL oral solution and as a 50 mg/5 mL single-dose vial for IV injection. The recommended starting dosage is 50 mg twice daily to be adjusted as needed based on patient tolerability. The injection formulation may be used when oral administration is not an option. Brivaracetam is scheduled to receive classification by the Drug Enforcement Administration (DEA) within the next 90 days, after which time it will become available for distribution. UCB FDA NDA approval 02/19/2016 Contact: Dona Jones, Executive Assistant, [email protected] https://www1.magellanrx.com/magellan-rx/publications/pharmacy-clinical-alerts.aspx © 2016, Magellan Health, All Rights Reserved. 3 March 2016 References http://annals.org http://archneur.jamanetwork.com www.empr.com www.fda.gov http://jnnp.bmj.com www.medscape.com http://nn.neurology.org