507050

research-article2013

AOPXXX10.1177/1060028013507050Annals of PharmacotherapyHost and Sloan

Case Report

Orofacial Dyskinesia Associated With the Use of Levofloxacin

Annals of Pharmacotherapy 2014, Vol. 48(1) 142­–144 © The Author(s) 2013 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/1060028013507050 aop.sagepub.com

Brian D. Host, PharmD, BCPS1, and Walker Sloan, MD1

Abstract Objective: To describe a case of orofacial dyskinesia in a patient treated with levofloxacin for acute diverticulitis. Case Summary: A 77-year-old woman with mild renal insufficiency was admitted with acute diverticulitis. She was initiated on levofloxacin 500 mg IV daily and metronidazole 500 mg IV every 8 hours. On day 4 of treatment, she experienced involuntary, rhythmic facial grimacing accompanied by periodic cervical muscular contractures. Her speech became dysarthric, interrupted by uncontrolled facial and tongue movements, all findings consistent with orofacial dyskinesia. Antibiotics were discontinued, and symptoms resolved after administration of diphenhydramine and lorazepam IV. Discussion: Fluoroquinolone-associated central nervous system (CNS) toxicities are infrequently observed. They are most commonly associated with ciprofloxacin and are thought to be related to inhibition of γ-aminobutyric acid receptors and activation of N-methyl-d-aspartate receptors. Orofacial dyskinesia has previously been reported primarily with second-generation fluoroquinolones, with only a single case report implicating a third-generation fluoroquinolone. To our knowledge, we report the second case of orofacial dyskinesia with a third-generation fluoroquinolone, the first such case associated with levofloxacin. The orofacial dyskinesia experienced in this case was categorized as probably related to levofloxacin, as assessed by the Naranjo adverse drug reaction probability assessment tool. Contributing factors likely included age and renal function. Conclusions: Although rare, CNS toxicities such as orofacial dyskinesia have been reported with levofloxacin. Patients on fluoroquinolones of advanced age and with renal insufficiency should be monitored closely for such toxicities. Keywords fluoroquinolone, levofloxacin, dyskinesia, chorea

Background Fluoroquinolone antibiotics are commonly prescribed to treat infections of respiratory, gastrointestinal, and urinary sources. Commonly reported adverse effects with the fluoroquinolone class include both gastrointestinal and central nervous system (CNS) effects.1-3 More rarely, musculoskeletal and cardiovascular effects have been reported.1,2,4,5 We report here a case of orofacial dyskinesia associated with the use of levofloxacin in a patient treated for acute diverticulitis.

Case Report A 77-year-old, 84-kg woman was hospitalized for newonset abdominal pain. Initial labs revealed leukocytosis (white blood cell count = 11.22 × 103/µL, 78.5% neutrophils) and mild renal insufficiency (blood urea nitrogen = 27 mg/dL; serum creatinine [SCr] = 1.3 mg/dL; baseline SCr = 1 mg/dL). Other laboratory values were within

normal limits. A computed tomography scan confirmed a suspected diagnosis of acute diverticulitis. The patient had significant medical comorbidities, including gout, hypothyroidism, hypertension, atrial fibrillation ( status post pacemaker placement), coronary artery disease ( status post coronary artery bypass graft), diastolic heart failure, deepvein thrombosis/pulmonary embolism ( status post inferior vena cava filter placement), and peripheral neuropathy. There was no personal or family history of neurological disorders. She was initiated on empirical antibiotics consisting of levofloxacin 500 mg intravenous piggyback daily and metronidazole 500 mg intravenous piggyback every 8 hours. Concurrent medications included allopurinol 300 mg 1

Baptist Health Lexington, KY, USA

Corresponding Author: Brian Host, Department of Pharmacy, Baptist Health Lexington, 1740 Nicholasville Rd, Lexington, KY, 40503, USA. Email: [email protected]

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Host and Sloan orally daily, diltiazem CD 240 mg orally daily, famotidine 40 mg orally daily, furosemide 20 mg orally daily, levothyroxine 88 µg orally daily, and paroxetine 20 mg orally daily. Warfarin therapy was withheld secondary to international normalized ratio being 7.07. Clinically, the patient improved, although her renal function worsened despite gentle IV fluid hydration and adequate urine output. Serum creatinine peaked on hospital day 4 at 1.6 mg/dL. On hospital day 5, her SCr improved to 1.4 mg/dL; however, she was described that morning as being confused with waxing and waning level of orientation. That evening, nearly 24 hours after her previous dose of intravenous levofloxacin, nursing staff reported patient “twitching” and “spasms.” On further examination, profound involuntary and rhythmic facial grimacing was observed, accompanied by periodic cervical muscular contractures. The patient remained alert, but speech became dysarthric, interrupted by uncontrolled facial and tongue movements, all findings consistent with orofacial dyskinesia. Neurology consultation was made, and antibiotics were discontinued. One-time doses of diphenhydramine 25 mg IV and lorazepam 0.5 mg IV were administered. By the following morning, all facial spasms had resolved, with no subsequent recurrence. The patient was started on amoxicillin/clavulanate 875 mg/125 mg orally twice daily and was discharged home on hospital day 6.

Discussion A wide range of CNS effects have been reported in the literature, with an estimated incidence of 1% to 2% in patients taking fluoroquinolones. Observed effects have included psychosis, seizures, nonconvulsive status epilepticus, myoclonus, ataxia, dysarthria, and chorea.6-8 Such effects have most commonly been associated with ciprofloxacin and are thought to be related to fluoroquinolone inhibition of γ-aminobutyric acid (GABA) receptors and activation of N-methyl-d-aspartate receptors. Established risk factors for CNS-related effects include advanced age and impaired renal function. It is interesting to note that CNS penetration of fluoroquinolones does not predict CNS-related adverse effects.6,8 Orofacial dyskinesias consist of abnormal, involuntary movements that effect the tongue, lips, palate, and jaw and have rarely been reported with ciprofloxacin, ofloxacin, and moxifloxacin.9-14 Onset of symptoms with reported cases have varied, ranging from hours after administration of the first dose10 up to day 5 of therapy.9 Individuals have ranged in age from 43 to 84 years, with approximately half of those affected experiencing renal dysfunction. Although symptoms have generally been transient and resolve on discontinuation of fluoroquinolone therapy,10,11 orofacial dyskinesia has reportedly persisted from days to weeks.13,14 No specific antidote has been identified, although

conflicting evidence exists for the administration of anticholinergic therapy.9,11 Rates of CNS-related adverse events with levofloxacin are considered to be equivalent to those observed with the fluoroquinolone class. Levofloxacin is noted to have a bulky side-chain structure, making it less likely to bind GABA receptors when compared with agents such as ciprofloxacin.15 As mentioned previously, orofacial dyskinesia has previously been reported primarily with second-generation fluoroquinolones (ciprofloxacin and ofloxacin), with only a single case report implicating a third-generation fluoroquinolone (moxifloxacin). To our knowledge, we report the second case of orofacial dyskinesia with a third-generation fluoroquinolone, the first such case associated with levofloxacin. The orofacial dyskinesia experienced in this case was categorized as probably related to levofloxacin (score of 6), as assessed by the Naranjo adverse drug reaction probability assessment tool.16 Patient-specific risk factors for this reaction include advanced age and mild, acute kidney injury. Dyskinesia resolved on drug withdrawal and treatment with a single dose of a benzodiazepine and an anticholinergic agent. Because the patient was initiated on both levofloxacin and metronidazole simultaneously, it may be difficult to assign causality to levofloxacin because metronidazole has also previously been reported to cause CNS toxicity.17-20 The CNS effects of metronidazole manifest as cerebellar ataxia, characterized by imbalance, gait disturbance, peripheral neuropathy, and dysarthria. Our patient did not experience such effects, and her symptoms were consistent with reported fluoroquinolone CNS toxicities. Additionally, use of paroxetine has also been associated with dystonic reactions involving the face or mouth.21-23 The majority of such reactions occur within the first few days to a month of treatment, and our patient had been on paroxetine for >2 years. Therefore, we believe that this patient experienced a probable levofloxacin-associated orofacial dyskinesia. Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding The author(s) received no financial support for the research, authorship, and/or publication of this article.

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14. Mittal SO, Machado DG, Jabbari B. Orofacial dyskinesia after moxifloxacin treatment: a case with normal hepatorenal function and review of literature. Clin Neuropharmacol. 2012;35:292-294. doi:10.1097/WNF.0b013e31826ba0eb. 15. Liu HH. Safety profile of the fluoroquinolones: focus on levofloxacin. Drug Saf. 2010;33:353-369. doi:10.2165/11536360. 16. Naranjo CA, Busto U, Sellers EM, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. 1981;30:239-245. doi:10.1038/clpt.1981.154. 17. Lawford R, Sorrell TC. Amebic abscess of the spleen complicated by metronidazole-induced neurotoxicity: case report. Clin Infect Dis. 1994;19:346-348. 18. Patel K, Green-Hopkins I, Lu S, Tunkel AR. Cerebellar ataxia following prolonged use of metronidazole: case report and literature review. Int J Infect Dis. 2008;12:e111-e114. doi:10.1016/j.ijid.2008.03.006. 19. Graves TD, Condon M, Loucaidou M, Perry RJ. Reversible metronidazole-induced cerebellar toxicity in a multiple transplant recipient. J Neurol Sci. 2009;285:238-240. doi:10.1016/j.jns.2009.06.011. 20. Moosa AN, Perkins D. Neurological picture: MRI of metronidazole induced cerebellar ataxia. J Neurol Neurosurg Psychiatry. 2010;81:754-755. doi:10.1136/jnnp.2008.165308. 21. Caley CF. Extrapyramidal reactions and the selective serotoninreuptake inhibitors. Ann Pharmacother. 1997;31:1481-1489. 22. Gerber PE, Lynd LD. Selective serotonin-reuptake inhib itor-induced movement disorders. Ann Pharmacother. 1998;32:692-698. 23. Draper B, Berman K. Tolerability of selective serotonin reuptake inhibitors: issues relevant to the elderly. Drugs Aging. 2008;25:501-519.

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Orofacial dyskinesia associated with the use of levofloxacin.

To describe a case of orofacial dyskinesia in a patient treated with levofloxacin for acute diverticulitis...
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