Kathryn G. Smith, PharmD PGY1 Pharmacy Resident Via Christi Hospitals Wichita, Inc Kathryn G. Smith: Nothing to disclose Describe the new updates and rationale for them Relay safety concerns with use of fluoroquinolones (FQ) List appropriate alternatives to FQ July 26, 2016 - FDA approved label changes • Boxed Warning • Warnings and Precautions • Indications and Usage Updated Medication Guides for patients FDA Drug Safety Communication. 2016. Available at: https://www.fda.gov/Drugs/DrugSafety/ucm511530.htm FDA Briefing Document 2015. Available at: https://www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/drugs/anti-infectivedrugsadvisorycommittee/ucm467383.pdf Associated with disabling and potentially permanent side effects • Tendons, muscles, and peripheral and central nervous systems Risk outweighs the benefit • Acute bacterial sinusitis (ABS) • Acute bacterial exacerbation of chronic bronchitis (ABECB) • Uncomplicated urinary tract infections (uUTI) FDA Drug Safety Communication. 2016. Available at: https://www.fda.gov/Drugs/DrugSafety/ucm511530.htm FDA Briefing Document 2015. Available at: https://www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/drugs/anti-infectivedrugsadvisorycommittee/ucm467383.pdf Black Box Warnings • Tendinitis and tendon ruptures • Central nervous system effects • Peripheral neuropathy • Exacerbation of Myasthenia Gravis Warnings and Precautions • Clostridium difficile-associated diarrhea • Photosensitivity • Prolongation of QT interval Daily Med. “Levofloxacin”. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo FDA Briefing Document 2015. Available at: https://www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/drugs/anti-infectivedrugsadvisorycommittee/ucm467383.pdf Use of antibacterial agents inhibits normal flora Risk with nearly all antibacterial agents Mild diarrhea to fatal colitis Modifiable risk factor Antibiotic Class Hazard Ratio Fluoroquinolones 4.0 3rd and 4th generation cephalosporins 3.1 1st and 2nd generation cephalosporins 2.4 β-lactamase inhibitor combinations 2.3 Sulfas 1.9 Penicillins 1.9 Metronidazole 0.3 Stevens, et al. Clin Infect Dis. 2011 FDA Adverse Event Reporting System Identified 178 U.S. cases • November 1997-May 2015 • Previously healthy individuals • FQ to treat ABS, ABECB, or uncomplicated UTI • Lasting longer than a month • Involving two or more body systems FDA Briefing Document 2015. Available at: https://www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/drugs/anti-infectivedrugsadvisorycommittee/ucm467383.pdf FQAD = Fluoroquinolone-associated disability FDA Briefing Document 2015. Available at: https://www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/drugs/anti-infectivedrugsadvisorycommittee/ucm467383.pdf Age: • 74% were 30-59 years old • 17% were ≥60 years old Sex: 78% were female Reported Indication: 47% for cystitis/UTI Onset of AE: 48% within 1-2 days FDA Briefing Document 2015. Available at: https://www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/drugs/anti-infectivedrugsadvisorycommittee/ucm467383.pdf Overall: 23% reported AE ≥ 1 year Mean: 14 months Longest: 9 years FDA Briefing Document 2015. Available at: https://www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/drugs/anti-infectivedrugsadvisorycommittee/ucm467383.pdf Total Disability Reports (n=1122) Total FQAD Cases (n=178) 592 358 136 91 65 19 Levofloxacin Ciprofloxacin Moxifloxacin FDA Briefing Document 2015. Available at: https://www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/drugs/anti-infectivedrugsadvisorycommittee/ucm467383.pdf Percentage of Disability Reports (%) Azithromycin 1.2 Cephalexin 2.7 Amox/Clav 5.1 Doxycycline 6 Amoxicillin 6 Nitrofurantoin 6.7 Cefdinir 6.9 Moxifloxacin 9.9 Gemifloxacin 10.5 Levofloxacin 26.9 Ciprofloxacin 29.3 Ofloxacin 31.1 FDA Briefing Document 2015. Available at: https://www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/drugs/anti-infectivedrugsadvisorycommittee/ucm467383.pdf Levofloxacin (n=91) Ciprofloxacin (n=65) Moxifloxacin (n=19) Musculoskeletal 98% 94% 95% Peripheral 52% 78% 79% Nervous System 38% Neuropsychiatric 74% 66% 65% Senses 30% 31% 30% Cardiovascular 10% 12% 10% Skin 10% 15% 15% FDA Briefing Document 2015. Available at: https://www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/drugs/anti-infectivedrugsadvisorycommittee/ucm467383.pdf Duration ≤4 weeks Bacterial infection suspected: Nasal purulence + severe/persistent symptoms + ≥7-10 days Watchful waiting with symptomatic relief Treatment Prescribe antibiotic failure? -Amoxicillin-Clavulanate 875/125 mg PO BID x 10-14 days* -Azithromycin 2 g x 1 dose or 500 mg PO daily x 3 days -Doxycycline 100 mg PO BID x 10-14 days* -TMP-SMX DS 1 tab BID x 10-14 days* *5-7 day duration may be appropriate for adults Chow AW, et al. Clin Infect Dis. 2012;54(8):e72-e112 Rosenfeld RM, et al. Otolaryng Head Neck. 2015; 152(4) Bartlett JG, et al. (2012). ABX Guide. Burlington, MA: Jones & Bartlett Learning Assess for cardinal symptoms: -Increased dyspnea -Increased sputum volume -Increased sputum purulence Amoxicillin- Age >65 or cardiac clavulanate disease or ≥3 875/125 mg PO exacerbations/year BID x 7 days Doxycycline 100 mg Cefdinir 300 mg PO PO BID x 7 days BID x 7 days Cefuroxime 500 mg Azithromycin 500 mg PO BID x 10 days PO x 1 day, then 250 x 4 days Lee H, Am Fam Physician. 2013 Nov 15;88(10):655-63 -100 mg PO BID x 5 days -Do not use: CrCl <40mL/min -DS 1 tab PO BID x 3 days -Avoid use in ≥65 yo -CrCl >30 mL/min -40% unchanged in urine -40% unchanged in urine -500 mg PO q6-8h x 5-7 days -3 g PO x 1 dose -CrCl >30 mL/min -30-40% bioavailability -80% unchanged in urine -100% unchanged in urine -875/125 mg PO BID x 5-7 days -CrCl >30 mL/min -60% unchanged in urine *Beta-lactams can be considered if other agents cannot be used. Treatment with antibiotics is only indicated if patient is symptomatic or pregnant Gupta K, et al. Clin Infect Dis. 2011;52(5):e103–e120 Bartlett JG, et al. (2012). ABX Guide. Burlington, MA: Jones & Bartlett Learning FQ are associated with severe disabling events Can involve several body systems at once High risk of C. difficile-associated diarrhea Variety of alternative antibacterial options available Education to patients and physicians can be beneficial Kathryn G. Smith, PharmD PGY1 Pharmacy Resident Via Christi Hospitals Wichita, Inc.