levofloxacin (Rx)

1-10%

Nausea (7%)

Headache (6%)

Diarrhea (5%)

Insomnia (4%)

Constipation (3%)

Dizziness (3%)

Dyspepsia (2%)

Rash (2%)

Vomiting (2%)

Chest pain (1%)

Dyspnea (1%)

Edema (1%)

Fatigue (1%)

Injection-site reaction (1%)

Moniliasis (1%)

Pain (1%)

Pruritus (1%)

Vaginitis (1%)

<1%

Cardiac: Cardiac arrest, palpitation, ventricular tachycardia, arrhythmia

Nervous system: Tremor, convulsions, paresthesia, vertigo, hypertonia, hyperkinesias, abnormal gait, somnolence, syncope

Metabolic: Hypoglycemia, hyperglycemia, hyperkalemia

Blood/lymphatic system: Anemia, thrombocytopenia, granulocytopenia

Musculoskeletal/connective tissue: Arthralgia, tendonitis, myalgia, skeletal pain

Gastrointestinal (GI): Gastritis, stomatitis, pancreatitis, esophagitis, gastroenteritis, glossitis, pseudomembranous/C difficile colitis

Hepatobiliary: Abnormal hepatic function, increased hepatic enzymes, increased alkaline phosphatase

Psychiatric: Anxiety, agitation, confusion, depression, hallucinations, nightmares, sleep disorder, anorexia, abnormal dreaming

Other: Immune hypersensitivity reaction, acute renal failure, urticaria, phlebitis, epistaxis

Postmarketing Reports

Cardiac: Prolonged QT interval, torsades de pointes, tachycardia

Musculoskeletal/connective tissue: Tendon rupture, muscle injury, rhabdomyolysis

Skin/subcutaneous tissue: Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, photosensitivity/phototoxicity, leukocytoclastic vasculitis

Renal and urinary disorders: Interstitial nephritis

Vascular disorders: Vasodilation

Blood/lymphatic system: Pancytopenia, aplastic anemia, leukopenia, hemolytic anemia, eosinophilia

Hepatobiliary: Hepatic failure, hepatitis, jaundice

Psychiatric: Psychosis, paranoia, suicidal ideation, isolated reports of suicide attempts

Nervous system: Exacerbation of myasthenia gravis, anosmia, ageusia, parosmia, dysgeusia, peripheral neuropathy, abnormal electroencephalogram (EEG), dysphonia, isolated reports of encephalopathy, pseudotumor cerebri

Central nervous system effects (hallucinations, anxiety, depression, insomnia, severe headaches, and confusion)

Respiratory, thoracic and mediastinal disorders: Isolated reports of allergic pneumonitis

Immune system disorders: Hypersensitivity reactions, sometimes fatal including: anaphylactic/anaphylactoid reactions, anaphylactic shock, angioneurotic edema, serum sickness

Eye disorders: Uveitis, vision disturbance (including diplopia), visual acuity reduced, vision blurred, scotoma

Otologic: Hypoacusis, tinnitus

General disorders and administration site conditions: Multiorgan failure, pyrexia

Contraindications

Documented hypersensitivity

Cautions

Anaphylactic reactions and allergic skin reactions, serious, occasionally fatal, may occur after first dose

Use caution in hematologic and renal toxicities

Hepatotoxicity reported with therapy

Peripheral neuropathy: Sensory or sensorimotor axonal polyneuropathy affecting small and/or large axons resulting in paresthesias, hypoesthesias, dysesthesias, and weakness reported; peripheral neuropathy may occur rapidly after initiating and may potentially become permanent

Associated with increased risk of central nervous system (CNS) effects, including convulsions, toxic psychoses, increased intracranial (including pseudotumor cerebri); fluoroquinolones may also cause central nervous system stimulation which may lead to tremors, restlessness, anxiety, lightheadedness, confusion, hallucinations, paranoia, depression, nightmares, and insomnia; suicidal thoughts, and attempted or completed suicide may also occur, especially in patients with medical history of depression, or underlying risk factor for depression; these reactions may occur following the first dose; if reactions occur during therapy, discontinue and institute appropriate measures; use with caution in patients with known or suspected central nervous system (CNS) disorders that may predispose them to seizures or lower the seizure threshold (e.g., severe cerebral arteriosclerosis, epilepsy) or in the presence of other risk factors that may predispose them to seizures or lower the seizure threshold (e.g., certain drug therapy, renal dysfunction)

Commonly seen adverse reactions include tendinitis, tendon rupture, arthralgia, myalgia, peripheral neuropathy, and central nervous system effects (hallucinations, anxiety, depression, insomnia, severe headaches, and confusion); these reactions can occur within hours to weeks after starting therapy, including in patients of any age or without pre-existing risk factors; discontinue therapy immediately at first signs or symptoms of any serious adverse reaction; in addition, avoid use of fluoroquinolones, in patients who have experienced any serious adverse reactions associated with fluoroquinolones

Risk of developing fluoroquinolone-associated tendinitis and tendon rupture is increased in patients over 60 years of age, in patients taking corticosteroid drugs, and in patients with kidney, heart or lung transplants; other factors that may independently increase risk of tendon rupture include strenuous physical activity, renal failure, and previous tendon disorders such as rheumatoid arthritis

Use with caution in patients with known or suspected disorders that predispose to seizures or take medications that will lower seizure threshold

May increase risk of tendon rupture in aptients with rheumatoid arthritis; use caution

Excessive sunlight may result in moderate-to-severe phototoxicity

Fatal hypoglycemia reported in elderly patients with or without diabetes; prompt treatment when symptoms are present is essential

May cause C difficile-associated colitis

Prolonged use may result in fungal or bacterial superinfection

Prolongation of QT interval and isolated cases of torsades de pointes; avoid use in patients with known QT prolongation, those with hypokalemia, and those taking other QT-prolonging drugs

May produce false-positive urine opiate screens

No longer recommended for gonorrhea in United States, because of widespread resistance

In prolonged therapy, perform periodic evaluations of organ system function (eg, renal, hepatic, hematopoietic); adjust dosage in renal impairment; superinfections may occur with prolonged or repeated antibiotic therapy

Pediatric patients may experience increased incidence of musculoskeletal disorders (eg, arthralgia, arthritis, tendinopathy, gait abnormality)

Acute onset of retinal detachment increased 4.5-fold with oral fluoroquinolones in a single case-controlled study - JAMA 2012;307(13):1414-1419; another study disputes these findings (relative risk, 1.29) - JAMA 2013;310(20):2184-2190

Clostridium difficile-associated diarrhea (CDAD) has been reported; if CDAD suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued; appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated

Prescribing antibiotics in absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to patient and increases risk of development of drug-resistant bacteria

Mechanism of Action

L-stereoisomer of parent compound ofloxacin; D-isomer form is inactive

Inhibits DNA gyrase activity, which in turn promotes breakage of DNA strands

Good monotherapy with extended coverage against Pseudomonas spp, as well as excellent activity against pneumococcus

Absorption

Well absorbed

Bioavailability: 99%

Peak serum time: 1-2 hr

Distribution

Cerebrospinal fluid (CSF) concentrations ~15% of serum levels; high concentrations achieved in prostate, gynecologic tissues, sinus, breast milk, saliva

Vd: 74-112 L

Metabolism

Limited metabolism in humans

Elimination

Half-life: 6-8 hr

Excretion: Urine (primarily as unchanged drug); after oral administration, 87% is recovered as unchanged drug in urine within 48 hr, and <4% is recovered in feces in 72 hr

Oral Administration

Administer without regard to food

Oral solution should be taken 1 hour before or 2 hours after eating

IV Incompatibilities

Y-site: Acyclovir, alprostadil, furosemide, heparin, indomethacin, insulin (at 100 U/mL + 5 mg/mL levofloxacin), nitroglycerin, propofol, sodium nitroprusside

IV Compatibilities

Additive: Linezolid

Y-site: Amikacin, aminophylline, ampicillin, bivalirudin, caffeine, cefotaxime, cimetidine, clindamycin, dexamethasone, dexmedetomidine, dobutamine, dopamine, epinephrine, fenoldopam, fentanyl, gentamicin, lactated hetastarch, insulin (at 1 U/mL + 5 mg/mL levofloxacin), isoproterenol, lidocaine, linezolid, lorazepam, metoclopramide, oxacillin, pancuronium, penicillin G sodium, phenobarbital, phenylephrine, sodium bicarbonate, vancomycin

IV Preparation

Premixed: No further preparation needed

Single-use vials: Dilute in 50-100 mL D5W or NS or D5/NS solution for injection to 5 mg/mL; alternative solutions include sodium lactate, Plasma-Lyte, D5/lactated Ringer, D5/NS and potassium chloride

Reconstituted solution should be clear, slightly yellow, and free of particulate matter

Reconstituted drug is stable for 72 hours at room temperature, 14 days when refrigerated in plastic containers, and 6 months when frozen

Thaw at room temperature or in refrigerator only

IV Administration

Give by IV infusion only, not bolus; rapid or bolus administration has been associated with hypotension and must be avoided

Infuse 250-500 mg over 60 minutes or 750 mg over 90 minutes

Avoid using IV line with solution containing multivalent cations (ie, magnesium, calcium)

Compatible with potassium additives