Dosing and uses of Levaquin, Levofloxacin Systemic (levofloxacin)
Adult dosage forms and strengths
premix, ready-to-use injection
- 250mg/50mL
- 500mg/100mL
- 750mg/150mL
oral solution
- 25mg/mL
tablet
- 250mg
- 500mg
- 750mg
Community-Acquired Pneumonia
500 mg PO/IV once daily for 7-14 days or 750 mg PO/IV once daily for 5 days
Nosocomial Pneumonia
750 mg PO/IV once daily for 7-14 days
Acute Bacterial Sinusitis
500 mg PO/IV once daily for 10-14 days or 750 mg PO/IV once daily for 5 days
Limitations-of-use: Reserve fluoroquinolones for patients who do not have other available treatment options for acute sinusitis
Acute Bacterial Exacerbation of Chronic Bronchitis
500 mg PO/IV once daily for ≥7 days
Limitations-of-use: Reserve fluoroquinolones for patients who do not have other available treatment options for acute bacterial exacerbation of chronic bronchitis
Inhalational Anthrax
Postexposure therapy
500 mg PO once daily for 60 days, beginning as soon as possible after exposure
Skin/Skin Structure Infections
Uncomplicated: 500 mg PO/IV once daily for 7-10 days
Complicated: 750 mg PO/IV once daily for 7-14 days
Chronic Bacterial Prostatitis
500 mg PO/IV once daily for 28 days
Complicated Urinary Tract Infections & Acute Pyelonephritis
250 mg PO/IV once daily for 10 days or 750 mg PO/IV once daily for 5 days
Uncomplicated Urinary Tract Infections
250 mg PO/IV once daily for 3 days
Limitations-of-use: Reserve fluoroquinolones for patients who do not have other available treatment options for uncomplicated urinary tract infections
Plague
Indicated for treatment and prophylaxis of plague, including pneumonic and septicemic plague, caused by Yersinia pestis in adults and pediatric patients, aged 6 months or older
500 mg PO/IV once daily for 10-14 days
Acne Vulgaris (Off-label)
100 mg PO q8hr for 4 weeks
Epididymitis (Off-label)
500 mg PO qDay for 10 days
Pseudomonas aeruginosa Pulmonary Infections (Orphan)
Treatment of pulmonary infections due to Pseudomonas aeruginosa and other bacteria in patients with cystic fibrosis
Orphan indication sponsor
- Mpex Pharmaceuticals, Inc, 11535 Sorrento Valley Road, San Diego, CA 92121
Dosage modifications
Renal impairment (normal dosage, 750 mg/day)
- CrCl 20-49 mL/min: 750 mg every other day
- CrCl 10-19 mL/min or hemodialysis (HD)/peritoneal dialysis (PD): 750 mg initially, then 500 mg every other day
Renal impairment (normal dosage, 500 mg/day)
- CrCl 20-49 mL/min: 500 mg initially, then 250 mg once daily
- CrCl 10-19 mL/min or HD/PD: 500 mg initially, then 250 mg every other day
Renal impairment (normal dosage, 250 mg/day)
- CrCl 20-49 mL/min: No dosage adjustment required
- CrCl 10-19 mL/min: 250 mg every other day; no dosage adjustment required for uncomplicated urinary tract infection (UTI)
- HD/PD: No data
Dosing Considerations
Susceptible organisms
- Aeromonas hydrophila, Campylobacter jejuni, Citrobacter diversus, Citrobacter freundii, Chlamydia pneumoniae, Enterococcus faecalis, Enterobacter cloacae, Escherichia coli, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Legionella pneumophila, Morganella morganii, Moraxella catarrhalis, Proteus mirabilis, Providencia spp, Pseudomonas aeruginosa, Serratia spp, Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, Ureaplasma urealyticum
- First-line therapy: C jejuni, C freundii, Enterobacter spp; no unanimity on others (eg, A hydrophila, L pneumophila, M morganii)
Pediatric dosage forms and strengths
premix, ready-to-use injection
- 250mg/50mL
- 500mg/100mL
oral solution
- 25mg/mL
tablet
- 250mg
- 500mg
Inhalational Anthrax
Postexposure therapy
≥6 months and <50 kg: 8 mg/kg PO q12hr for 60 days, beginning as soon as possible after exposure; individual dose not to exceed 250 mg
≥6 months and >50 kg: 500 mg PO once daily for 60 days, beginning as soon as possible after exposure
Safety in children for treatment duration >14 days has not been established
Plague
Indicated for treatment and prophylaxis of plague, including pneumonic and septicemic plague, caused by Yersinia pestis in adults and pediatric patients, aged 6 months or older
≥6 months and <50 kg: 8 mg/kg PO/IV q12hr for 10-14 days; individual dose not to exceed 250 mg
≥50 kg: 500 mg PO/IV once daily for 10-14 days
Acute Bacterial Rhinosinusitis (Off-label)
10-20 mg/kg/day PO qDay or divided q12hr
Community Acquired Pneumonia (Off-label)
S. pneumonia
- 6 months - 5 years: 16-20 mg/kg/day PO qDay for 10 days
- 5-16 years: 8-10 mg/kg/day PO qDay for 10 days; not to exceed 750 mg/da
M. pneumoniae, C. trachomatis, C. pneumoniae
- Adolescents with skeletal maturity: 500 mg PO qDay for 10 days; not to exceed 750 mg/day
Levaquin, Levofloxacin Systemic (levofloxacin) adverse (side) effects
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
Warnings
Black box warnings
Fluoroquinolones have been associated with disabling and potentially irreversible serious adverse reactions that have occurred together including: tendinitis and tendon rupture, peripheral neuropathy, and CNS effects
Discontinue the drug immediately and avoid use of systemic fluoroquinolones in patients who experience any of these serious adverse reactions
May exacerbate muscle weakness in patients with myasthenia gravis; fluoroquinolones should be avoided in patients with known history of myasthenia gravis
Serious adverse effects and limitations-of-use
- Both oral and injectable fluroquinolones are associated with disabling side effects involving tendons, muscles, joints, nerves and the central nervous system
- These side effects can occur hours to weeks after exposure to fluoroquinolones and may potentially be permanent
- Because the risk of these serious side effects generally outweighs the benefits for patients with acute bacterial sinusitis, acute exacerbation of chronic bronchitis, and uncomplicated UTIs, that fluoroquinolones should be reserved for use in patients with these conditions who have no alternative treatment options
- For some serious bacterial infections, including anthrax, plague, and bacterial pneumonia among others, the benefits of fluoroquinolones outweigh the risks and it is appropriate for them to remain available as a therapeutic option
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
Central nervous system (CNS) effects, including toxic psychosis, convulsions, increased intracranial pressure (pseudotumor cerebri), anxiety, confusion, depression, and insomnia reported with therapy
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
Pregnancy and lactation
Pregnancy category: C
Lactation: Drug excreted in breast milk; not recommended
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Levaquin, Levofloxacin Systemic (levofloxacin)
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
Administration
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
