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Levofloxacin (Systemic)

Pronunciation

Pronunciation

(lee voe FLOKS a sin)

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Intravenous:

Generic: 250 mg/50 mL (50 mL); 500 mg/100 mL (100 mL); 750 mg/150 mL (150 mL)

Solution, Intravenous [preservative free]:

Levaquin: 250 mg/50 mL (50 mL [DSC]); 500 mg/100 mL (100 mL [DSC]); 750 mg/150 mL (150 mL [DSC])

Generic: 250 mg/50 mL (50 mL); 500 mg/100 mL (100 mL); 750 mg/150 mL (150 mL); 25 mg/mL (20 mL, 30 mL)

Solution, Oral:

Levaquin: 25 mg/mL (480 mL [DSC]) [contains propylene glycol]

Generic: 25 mg/mL (10 mL, 20 mL, 100 mL, 200 mL, 480 mL)

Tablet, Oral:

Levaquin: 250 mg, 500 mg, 750 mg

Generic: 250 mg, 500 mg, 750 mg

Brand Names: U.S.

  • Levaquin

Pharmacologic Category

  • Antibiotic, Fluoroquinolone
  • Antibiotic, Respiratory Fluoroquinolone

Pharmacology

As the S(-) enantiomer of the fluoroquinolone, ofloxacin, levofloxacin, inhibits DNA-gyrase in susceptible organisms thereby inhibits relaxation of supercoiled DNA and promotes breakage of DNA strands. DNA gyrase (topoisomerase II), is an essential bacterial enzyme that maintains the superhelical structure of DNA and is required for DNA replication and transcription, DNA repair, recombination, and transposition.

Absorption

Rapid and complete; levofloxacin oral tablet and solution formulations are bioequivalent

Distribution

Widely distributed in the body, including blister fluid, skin tissue, macrophages, prostate, and lung tissue; CSF concentrations ~15% of serum concentrations

Vd: (Chien 2005):

Infants ≥6 months, Children, and Adolescents ≤16 years: Mean range: 1.44 to 1.57 L/kg; reported values not statistically different between pediatric age subgroups; distribution not age-dependent

Adults: 1.27 L/kg

Metabolism

Minimally hepatic

Excretion

Urine (~87% as unchanged drug, <5% as metabolites); feces (<4%)

Clearance: IV (Chien 2005):

Infants and Children 6 months to 2 years: 0.35 ± 0.13 L/hour/kg

Children 2 to 5 years: 0.32 ± 0.08 L/hour/kg

Children 5 to 10 years: 0.25 ± 0.05 L/hour/kg

Children 10 to 12 years: 0.19 ± 0.05 L/hour/kg

Children 12 to 16 years: 0.18 ± 0.03 L/hour/kg

Adults: 0.15 ± 0.02 L/hour/kg

Time to Peak

1 to 2 hours

Half-Life Elimination

Infants ≥6 months and Children ≤5 years: ~4 hours (Chien 2005)

Children 5 to 10 years: 4.8 hours (Chien 2005)

Children 10 to 12 years: 5.4 hours (Chien 2005)

Children 12 to 16 years: 6 hours (Chien 2005)

Adults: ~6 to 8 hours

Adults, renal impairment: 27 ± 10 hours (CrCl 20 to 49 mL/minute); 35 ± 5 hours (CrCl <20 mL/minute)

Protein Binding

~24% to 38%; primarily to albumin

Special Populations: Renal Function Impairment

Cl is reduced and half-life prolonged in patients with CrCl less than 50 mL/minute.

Use: Labeled Indications

Treatment of community-acquired pneumonia, including multidrug resistant strains of S. pneumoniae (MDRSP); nosocomial pneumonia; chronic bronchitis (acute bacterial exacerbation); acute bacterial rhinosinusitis (ABRS); prostatitis (chronic bacterial), urinary tract infection (uncomplicated or complicated); acute pyelonephritis; skin or skin structure infections (uncomplicated or complicated); reduce incidence or disease progression of inhalational anthrax (postexposure); prophylaxis and treatment of plague (pneumonic and septicemic) due to Y. pestis

Contraindications

Hypersensitivity to levofloxacin, any component of the formulation, or other quinolones

Canadian labeling: Additional contraindications (not in U.S. labeling): History of tendonitis or tendon rupture associated with use of any quinolone antimicrobial agent

Dosing: Adult

Note: Sequential therapy (intravenous to oral) may be instituted based on prescriber's discretion.

Acute bacterial rhinosinusitis: Oral, IV:

Manufacturer's labeling: 750 mg every 24 hours for 5 days or 500 mg every 24 hours for 10-14 days

Alternate recommendations: 500 mg every 24 hours for 5-7 days (Chow 2012)

Anthrax (inhalational): Oral, IV: 500 mg every 24 hours for 60 days, beginning as soon as possible after exposure

Bite wounds (animal/human) (off-label use): Oral, IV: Note: Recommended as an alternative therapy for human bite wound in patients hypersensitive to beta-lactams: 750 mg once daily; in combination with metronidazole or clindamycin (IDSA [Stevens 2014])

Chlamydia trachomatis urogenital infection (alternative to preferred therapy) (off-label use): Oral: 500 mg once daily for 7 days (CDC [Workowski 2015])

Chronic bronchitis (acute bacterial exacerbation): Oral: 500 mg every 24 hours for 7 days; Canadian labeling (not in U.S. labeling) also includes a dosage regimen of 750 mg every 24 hours for 5 days

Diverticulitis, peritonitis (off-label use) (Solomkin, [IDSA] 2010): Oral, IV: 750 mg every 24 hours for 7-10 days; use adjunctive metronidazole therapy

Epididymitis (off-label use; CDC [Workowski 2015]): Oral:

Likely caused by enteric organisms: 500 mg once daily for 10 days

Likely caused by sexually-transmitted chlamydia and gonorrhea and enteric organisms in men who practice insertive anal sex: 500 mg once daily for 10 days in combination with ceftriaxone

Intra-abdominal infection, complicated, community-acquired (in combination with metronidazole) (off-label use) (Solomkin, [IDSA] 2010): IV: 750 mg once daily for 4-7 days (provided source controlled). Note: Avoid using in settings where E. coli susceptibility to fluoroquinolones is <90%.

Pelvic inflammatory disease (in patients allergic to cephalosporins; off-label use): Oral: 500 mg once daily for 14 days with or without concomitant metronidazole; Note: The CDC recommends use as an alternative therapy only if standard parenteral cephalosporin therapy is not feasible and community prevalence of quinolone-resistant gonococcal organisms is low. Culture sensitivity must be confirmed (CDC [Workowski 2015]).

Plague (prophylaxis and treatment): Oral, IV: 500 mg every 24 hours for 10-14 days, beginning as soon as possible after exposure. Note: Dose of 750 mg once daily may be considered if clinically warranted.

Pneumonia: Oral, IV:

Community-acquired (CAP): 500 mg every 24 hours for 7-14 days or 750 mg every 24 hours for 5 days (efficacy of 5-day regimen for MDRSP not established)

Healthcare-associated (HAP): 750 mg every 24 hours for 7-14 days

Prostatitis (chronic bacterial): Oral, IV: 500 mg every 24 hours for 28 days

Skin and skin structure infections: Oral, IV:

Uncomplicated: 500 mg every 24 hours for 7-10 days

Complicated: 750 mg every 24 hours for 7-14 days

Surgical (preoperative) prophylaxis (off-label use): IV: 500 mg within 120 minutes prior to surgical incision (Bratzler 2013)

Surgical site infections (intestinal or genitourinary tract; perineum or axilla) (off-label use): IV: 750 mg every 24 hours, in combination with metronidazole (IDSA [Stevens 2014])

Traveler's diarrhea (off-label use): Oral: 500 mg for one dose (Sanders 2007)

Tuberculosis, drug-resistant tuberculosis, or intolerance to first-line agents (off-label use): Oral: 500-1000 mg every 24 hours (CDC 2003)

Urethritis, nongonococcal (off-label use): Oral: 500 mg every 24 hours for 7 days (CDC [Workowski 2015])

Urinary tract infections: Oral, IV:

Uncomplicated: 250 mg once daily for 3 days

Complicated, including pyelonephritis: 250 mg once daily for 10 days or 750 mg once daily for 5 days

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Acute bacterial rhinosinusitis (off-label use): Oral, IV: 10-20 mg/kg/day divided every 12-24 hours for 10-14 days (maximum: 500 mg daily). Note: Recommended in patients with a type I penicillin allergy, after failure of initial therapy or in patients at risk for antibiotic resistance (eg, daycare attendance, age <2 years, recent hospitalization, antibiotic use within the past month) (Chow 2012).

Anthrax (inhalational, postexposure): Oral, IV

Infants ≥6 months and Children ≤50 kg: 8 mg/kg every 12 hours for 60 days (do not exceed 250 mg/dose), beginning as soon as possible after exposure

Children >50 kg: 500 mg every 24 hours for 60 days, beginning as soon as possible after exposure

Chlamydia trachomatis urogenital infection (alternative to preferred therapy) (off-label use): Adolescents: Refer to adult dosing.

Community-acquired pneumonia (CAP) (IDSA/PIDS 2011): Note: May consider addition of vancomycin or clindamycin to empiric therapy if community-acquired MRSA suspected; alternative to ceftriaxone or cefotaxime in patients not fully immunized for H. influenzae type b and S. pneumoniae, or significant local resistance to penicillin in invasive pneumococcal strains.

Infants ≥6 months and Children ≤4 years:

S. pneumoniae (MICs to penicillin ≤2.0 mcg/mL), mild infection or step-down therapy (alternative to amoxicillin): Oral: 8-10 mg/kg/dose every 12 hours (maximum: 750 mg daily)

S. pneumoniae (MICs to penicillin ≥4.0 mcg/mL):

Moderate-to-severe infection (alternative to ceftriaxone): IV: 8-10 mg/kg/dose every 12 hours (maximum: 750 mg daily)

Mild infection, step-down therapy (preferred): Oral: 8-10 mg/kg/dose every 12 hours (maximum: 750 mg daily)

H. influenzae, moderate-to-severe infection (alternative to ampicillin, ceftriaxone, or cefotaxime): IV: 8-10 mg/kg/dose every 12 hours (maximum: 750 mg daily)

Atypical pathogens, moderate-to-severe infection (alternative to azithromycin) or empiric treatment (alternative to azithromycin +/- beta-lactam; should be limited to macrolide allergic/intolerant patients): Oral, IV: 8-10 mg/kg/dose every 12 hours (maximum: 750 mg daily)

Children 5-16 years:

S. pneumoniae (MICs to penicillin ≤2.0 mcg/mL), mild infection or step-down therapy (alternative to amoxicillin): Oral: 8-10 mg/kg/dose once daily (maximum: 750 mg daily)

S. pneumoniae (MICs to penicillin ≥4.0 mcg/mL):

Moderate-to-severe infection (alternative to ceftriaxone): IV: 8-10 mg/kg/dose once daily (maximum: 750 mg daily)

Mild infection, step-down therapy (preferred): Oral: 8-10 mg/kg/dose once daily (maximum: 750 mg daily)

H. influenzae, moderate-to-severe infection (alternative to ampicillin, ceftriaxone, or cefotaxime): IV: 8-10 mg/kg/dose once daily (maximum: 750 mg daily)

Atypical pathogens:

Moderate-to-severe infection (alternative to azithromycin): Oral, IV: 8-10 mg/kg/dose once daily (maximum: 750 mg daily)

Mild infection, step-down therapy (alternative to azithromycin in adolescents with skeletal maturity): Oral: 500 mg once daily

Plague (prophylaxis and treatment): Infants ≥6 months and Children: Oral, IV:

≤50 kg: 8 mg/kg every 12 hours for 10-14 days (do not exceed 250 mg/dose), beginning as soon as possible after exposure

>50 kg: 500 mg every 24 hours for 10-14 days, beginning as soon as possible after exposure. Note: Dose of 750 mg once daily may be considered if clinically warranted.

Surgical (preoperative) prophylaxis (off-label use): Children ≥1 year: IV: 10 mg/kg within 120 minutes prior to surgical incision (maximum: 500 mg) (Bratzler 2013)

Dosing: Renal Impairment

IV, Oral:

Normal renal function dosing of 250 mg daily:

CrCl 20-49 mL/minute: No dosage adjustment required.

CrCl 10-19 mL/minute: Administer 250 mg every 48 hours (except in uncomplicated UTI, where no dosage adjustment is required).

Hemodialysis/chronic ambulatory peritoneal dialysis (CAPD): No information available.

Normal renal function dosing of 500 mg daily:

CrCl 20-49 mL/minute: Administer 500 mg initial dose, followed by 250 mg every 24 hours.

CrCl 10-19 mL/minute: Administer 500 mg initial dose, followed by 250 mg every 48 hours.

Hemodialysis/chronic ambulatory peritoneal dialysis (CAPD): Administer 500 mg initial dose, followed by 250 mg every 48 hours; supplemental doses are not required following either hemodialysis or CAPD

Normal renal function dosing of 750 mg daily:

CrCl 20-49 mL/minute: Administer 750 mg every 48 hours.

CrCl 10-19 mL/minute: Administer 750 mg initial dose, followed by 500 mg every 48 hours.

Hemodialysis/chronic ambulatory peritoneal dialysis (CAPD): Administer 750 mg initial dose, followed by 500 mg every 48 hours; supplemental doses are not required following either hemodialysis or CAPD.

Normal renal function dosing of 750 or 1000 mg daily (treatment of tuberculosis only) (CDC 2003): CrCl <30 mL/minute: Administer 750 or 1000 mg 3 times per week (in hemodialysis patients administer after dialysis on dialysis days).

Continuous renal replacement therapy (CRRT) (Heintz 2009; Trotman 2005): Drug clearance is highly dependent on the method of renal replacement, filter type, and flow rate. Appropriate dosing requires close monitoring of pharmacologic response, signs of adverse reactions due to drug accumulation, as well as drug concentrations in relation to target trough (if appropriate). The following are general recommendations only (based on dialysate flow/ultrafiltration rates of 1-2 L/hour and minimal residual renal function) and should not supersede clinical judgment:

CVVH: Loading dose of 500-750 mg followed by 250 mg every 24 hours.

CVVHD: Loading dose of 500-750 mg followed by 250-500 mg every 24 hours.

CVVHDF: Loading dose of 500-750 mg followed by 250-750 mg every 24 hours.

Dosing: Hepatic Impairment

IV, Oral: No dosage adjustment provided in manufacturer’s labeling (has not been studied). However, dosage adjustment unlikely due to limited hepatic metabolism.

Reconstitution

Solution for injection: Single-use vials must be further diluted in compatible solution to a final concentration of 5 mg/mL prior to infusion.

Extemporaneously Prepared

Note: Commercial oral solution is available (25 mg/mL)

A 50 mg/mL oral suspension may be made with tablets and a 1:1 mixture of Ora-Plus® and strawberry syrup NF. Crush six 500 mg levofloxacin tablets in a mortar and reduce to a fine powder. Add small portions of the vehicle and mix to a uniform paste; mix while adding the vehicle in incremental proportions to almost 60 mL; transfer to a graduated cylinder, rinse mortar with vehicle, and add quantity of vehicle sufficient to make 60 mL. Label "shake well". Stable for 57 days when stored in amber plastic prescription bottles at room temperature or refrigerated.

VandenBussche HL, Johnson CE, and Fontana EM, et al, "Stability of Levofloxacin in an Extemporaneously Compounded Oral Liquid," Am J Health Syst Pharm, 1999, 56(22):2316-8.10582824

Administration

Oral: Tablets may be administered without regard to meals. Oral solution should be administered 1 hour before or 2 hours after meals. Maintain adequate hydration of patient to prevent crystalluria.

IV: Infuse 250-500 mg IV solution over 60 minutes; infuse 750 mg IV solution over 90 minutes. Too rapid of infusion can lead to hypotension. Avoid administration through an intravenous line with a solution containing multivalent cations (eg, magnesium, calcium). Maintain adequate hydration of patient to prevent crystalluria or cylindruria.

Dietary Considerations

Tablets may be taken without regard to meals. Oral solution should be administered on an empty stomach (1 hour before or 2 hours after a meal). Take 2 hours before or 2 hours after multiple vitamins, antacids, or other products containing magnesium, aluminum, iron, or zinc.

Compatibility

Stable in D5LR, D5NS, D51/2NS with KCl 20 mEq/L, D5W, NS, Plasma-Lyte® 56 in 5% dextrose, sodium lactate (M/6); incompatible with mannitol 20%, sodium bicarbonate 5%.

Y-site administration: Incompatible with acyclovir, alprostadil, azithromycin, furosemide, heparin, indomethacin, nitroglycerin, nitroprusside, pantoprazole, propofol, telavancin.

Storage

Solution for injection:

Vial: Store at room temperature. Protect from light. Diluted solution (5 mg/mL) is stable in NS, D5W, D5NS, D5LR, D51/2NS with 20 mEq/L KCl, Plasma-Lyte 56 in D5, or sodium lactate for 72 hours when stored at room temperature; stable for 14 days when stored under refrigeration. When frozen, stable for 6 months; do not refreeze. Do not thaw in microwave or by bath immersion.

Premixed: Store at ≤25°C (77°F); do not freeze. Brief exposure to 40°C (104°F) does not adversely affect the product. Protect from light.

Tablet, oral solution: Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).

Drug Interactions

Aminolevulinic Acid: Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid. Monitor therapy

Antacids: May decrease the absorption of Quinolone Antibiotics. Of concern only with oral administration of quinolones. Exceptions: Sodium Bicarbonate. Consider therapy modification

BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Monitor therapy

Blood Glucose Lowering Agents: Quinolone Antibiotics may enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Quinolone Antibiotics may diminish the therapeutic effect of Blood Glucose Lowering Agents. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Monitor therapy

Calcium Salts: May decrease the absorption of Quinolone Antibiotics. Of concern only with oral administration of both agents. Exceptions: Calcium Chloride. Consider therapy modification

Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Avoid combination

Corticosteroids (Systemic): May enhance the adverse/toxic effect of Quinolone Antibiotics. Specifically, the risk of tendonitis and tendon rupture may be increased. Monitor therapy

Didanosine: Quinolone Antibiotics may decrease the serum concentration of Didanosine. Didanosine may decrease the serum concentration of Quinolone Antibiotics. Management: Administer oral quinolones at least 2 hours before or 6 hours after didanosine. Monitor for decreased therapeutic effects of quinolones, particularly if doses cannot be separated as recommended. This does not apply to unbuffered enteric coated didanosine. Consider therapy modification

Highest Risk QTc-Prolonging Agents: Moderate Risk QTc-Prolonging Agents may enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Avoid combination

Iron Salts: May decrease the serum concentration of Quinolone Antibiotics. Management: Administer oral quinolones at least several hours before (4 h for moxi- and sparfloxacin, 2 h for others) or after (8 h for moxi-, 6 h for cipro-, 4 h for lome-, 3 h for gemi-, and 2 h for levo-, nor-, or ofloxacin or nalidixic acid) oral iron salts. Exceptions: Ferric Carboxymaltose; Ferric Gluconate; Ferric Hydroxide Polymaltose Complex; Ferric Pyrophosphate Citrate; Ferumoxytol; Iron Dextran Complex; Iron Sucrose. Consider therapy modification

Ivabradine: May enhance the QTc-prolonging effect of Moderate Risk QTc-Prolonging Agents. Avoid combination

Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Monitor therapy

Lanthanum: May decrease the serum concentration of Quinolone Antibiotics. Management: Administer oral quinolone antibiotics at least two hours before or after lanthanum. Consider therapy modification

Magnesium Salts: May decrease the serum concentration of Quinolone Antibiotics. Management: Administer oral quinolones at least several hours before (4 h for moxi- and sparfloxacin, 2 h for others) or after (8 h for moxi-, 6 h for cipro-, 4 h for lome-, 3 h for gemi-, and 2 h for levo-, nor-, or ofloxacin or nalidixic acid) oral magnesium salts. Consider therapy modification

MiFEPRIStone: May enhance the QTc-prolonging effect of Moderate Risk QTc-Prolonging Agents. Avoid combination

Moderate Risk QTc-Prolonging Agents: May enhance the QTc-prolonging effect of other Moderate Risk QTc-Prolonging Agents. Management: Avoid such combinations when possible. Use should be accompanied by close monitoring for evidence of QT prolongation or other alterations of cardiac rhythm. Consider therapy modification

Multivitamins/Minerals (with ADEK, Folate, Iron): May decrease the serum concentration of Quinolone Antibiotics. Specifically, polyvalent cations in multivitamin products may decrease the absorption of orally administered quinolone antibiotics. Management: Interactions can be minimized by administering the oral quinolone at least 2 hours before, or 6 hours after, the dose of a multivitamin that contains polyvalent cations (i.e., calcium, iron, magnesium, selenium, zinc). Consider therapy modification

Multivitamins/Minerals (with AE, No Iron): May decrease the serum concentration of Quinolone Antibiotics. Specifically, minerals in the multivitamin/mineral product may impair absorption of quinolone antibiotics. Management: Interactions can be minimized by administering the oral quinolone at least 2 hours before, or 6 hours after, the dose of a multivitamin that contains polyvalent cations (i.e., calcium, iron, magnesium, selenium, zinc). Consider therapy modification

Mycophenolate: Quinolone Antibiotics may decrease the serum concentration of Mycophenolate. Specifically, quinolones may decrease concentrations of the active metabolite of mycophenolate. Monitor therapy

Nadifloxacin: May enhance the adverse/toxic effect of Quinolone Antibiotics. Avoid combination

Nonsteroidal Anti-Inflammatory Agents: May enhance the neuroexcitatory and/or seizure-potentiating effect of Quinolone Antibiotics. Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Quinolone Antibiotics. Monitor therapy

Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Monitor therapy

Probenecid: May decrease the excretion of Quinolone Antibiotics. Specifically, probenecid may decreased the renal excretion of quinolone antibiotics. Probenecid may increase the serum concentration of Quinolone Antibiotics. Monitor therapy

QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying): May enhance the QTc-prolonging effect of Moderate Risk QTc-Prolonging Agents. Monitor therapy

Quinapril: May decrease the serum concentration of Quinolone Antibiotics. Management: Separate doses of quinapril and oral quinolones by at least 2 hours in order to reduce the risk of interaction. Monitor for reduced efficacy of the quinolone if these products are used concomitantly. Consider therapy modification

Sevelamer: May decrease the absorption of Quinolone Antibiotics. Management: Administer oral quinolones at least 2 hours before or 6 hours after sevelamer. Consider therapy modification

Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Consider therapy modification

Strontium Ranelate: May decrease the serum concentration of Quinolone Antibiotics. Management: In order to minimize any potential impact of strontium ranelate on quinolone antibiotic concentrations, it is recommended that strontium ranelate treatment be interrupted during quinolone therapy. Avoid combination

Sucralfate: May decrease the serum concentration of Quinolone Antibiotics. Management: Administer oral quinolones at least 2 hours before or 6 hours after the sucralfate dose. Greater separation of doses may further lessen the risk for a significant interaction. Consider therapy modification

Tacrolimus (Systemic): LevoFLOXacin (Systemic) may enhance the QTc-prolonging effect of Tacrolimus (Systemic). LevoFLOXacin (Systemic) may increase the serum concentration of Tacrolimus (Systemic). Monitor therapy

Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 3 days after cessation of antibacterial agents. Consider therapy modification

Varenicline: Quinolone Antibiotics may increase the serum concentration of Varenicline. Management: Monitor for increased varenicline adverse effects with concurrent use of levofloxacin or other quinolone antibiotics, particularly in patients with severe renal impairment. International product labeling recommendations vary. Consult appropriate labeling. Monitor therapy

Verteporfin: Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin. Monitor therapy

Vinflunine: May enhance the QTc-prolonging effect of Moderate Risk QTc-Prolonging Agents. Avoid combination

Vitamin K Antagonists (eg, warfarin): Quinolone Antibiotics may enhance the anticoagulant effect of Vitamin K Antagonists. Monitor therapy

Zinc Salts: May decrease the serum concentration of Quinolone Antibiotics. Management: Administer oral quinolones at least several hours before (4 h for moxi- and sparfloxacin, 2 h for others) or after (8 h for moxi-, 6 h for cipro-, 4 h for lome-, 3 h for gemi-, and 2 h for levo-, nor-, or ofloxacin or nalidixic acid) oral zinc salts. Exceptions: Zinc Chloride. Consider therapy modification

Test Interactions

Some quinolones may produce a false-positive urine screening result for opioids using commercially-available immunoassay kits. This has been demonstrated most consistently for levofloxacin and ofloxacin, but other quinolones have shown cross-reactivity in certain assay kits. Confirmation of positive opioid screens by more specific methods should be considered.

Adverse Reactions

1% to 10%:

Cardiovascular: Chest pain (1%), edema (1%)

Central nervous system: Headache (6%), insomnia (4%), dizziness (3%)

Dermatologic: Skin rash (2%), pruritus (1%)

Gastrointestinal: Nausea (7%), diarrhea (5%), constipation (3%), abdominal pain (2%), dyspepsia (2%), vomiting (2%)

Genitourinary: Vaginitis (1%)

Infection: Candidiasis (1%)

Local: Injection site reaction (1%)

Respiratory: Dyspnea (1%)

<1% (Limited to important or life-threatening): Abnormal electroencephalogram, abnormal gait, acute renal failure, ageusia, agranulocytosis, anaphylactoid reaction, anemia (including aplastic and hemolytic), anorexia, anosmia, brain disease (rare), cardiac arrest, cardiac arrhythmia (including ventricular tachycardia/fibrillation and torsade de pointes), casts in urine, Clostridium difficile-associated diarrhea, confusion, convulsions, crystalluria, depression, elevation in serum levels of skeletal-muscle enzymes, eosinophilia, epistaxis, erythema multiforme, esophagitis, exacerbation of myasthenia gravis, gastritis (including gastroenteritis), glossitis, granulocytopenia, hallucination, hepatic failure (some fatal), hepatic insufficiency, hepatitis, hepatotoxicity (idiosyncratic) (Chalasani, 2014), hyperglycemia, hyperkalemia, hyperkinesias, hypersensitivity reaction (including anaphylaxis, angioedema, rash, pneumonitis, and serum sickness), hypertension, hypertonia, hypoacusis, hypoglycemia, hypotension, increased INR, increased intracranial pressure, increased serum alkaline phosphatase, increased serum transaminases, interstitial nephritis, intestinal obstruction, jaundice, leukocytosis, leukopenia, leukorrhea, lymphadenopathy, multiorgan failure, muscle injury, muscle spasm, pancreatitis, pancytopenia, paralysis, paranoia, peripheral neuropathy (may be irreversible), phlebitis, phototoxicity, prolonged prothrombin time, prolonged Q-T interval on ECG, pseudotumor cerebri, psychosis, renal function abnormality, rhabdomyolysis, rupture of tendon, scotoma, seizure, skeletal pain, skin photosensitivity, sleep disorder (including abnormal dreams and nightmares), Stevens-Johnson syndrome, stomatitis, suicidal ideation, syncope, tachycardia, tendonitis, toxic epidermal necrolysis, toxic psychosis, thrombocytopenia (including thrombotic thrombocytopenic purpura), uveitis, vasculitis (leukocytoclastic), vasodilatation, visual disturbances(including diplopia), voice disorder

ALERT: U.S. Boxed Warning

Serious adverse reactions:

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 levofloxacin immediately and avoid the use of fluoroquinolones in patients who experience any of these serious adverse reactions. Because fluoroquinolones have been associated with serious adverse reactions, reserve levofloxacin for use in patients who have no alternative treatment options for the following indications: uncomplicated urinary tract infection, acute bacterial exacerbation of chronic bronchitis, and acute bacterial sinusitis.

Exacerbation of myasthenia gravis:

Fluoroquinolones may exacerbate muscle weakness in patients with myasthenia gravis. Avoid levofloxacin in patients with a known history of myasthenia gravis.

Warnings/Precautions

Concerns related to adverse effects:

• Altered cardiac conduction: Fluoroquinolones may prolong QTc interval; avoid use in patients with a history of QTc prolongation, uncorrected hypokalemia, hypomagnesemia, or concurrent administration of other medications known to prolong the QT interval (including Class Ia and Class III antiarrhythmics, cisapride, erythromycin, antipsychotics, and tricyclic antidepressants).

• Glucose regulation: Fluoroquinolones have been associated with the development of serious, and sometimes fatal, hypoglycemia. These events have occurred most often in elderly patients with diabetes, but have also been reported in patients without a prior history of diabetes. Prompt identification and treatment of hypoglycemia is essential. Individual quinolones may differ in their potential to cause this effect. It was most evident with gatifloxacin (no longer marketed as systemic formulation). Hyperglycemia has also been associated with the use of fluoroquinolones. Patients should be monitored closely for signs/symptoms of disordered glucose regulation.

• Hepatotoxicity: Unrelated to hypersensitivity, severe hepatotoxicity (including acute hepatitis and fatalities) has been reported. Elderly patients may be at greater risk. Discontinue therapy immediately if signs and symptoms of hepatitis occur.

• Hypersensitivity reactions: Severe hypersensitivity reactions, including anaphylaxis, have occurred with quinolone therapy. The spectrum of these reactions can vary widely; reactions may present as typical allergic symptoms (eg, itching, urticaria, rash, edema) after a single dose, or may manifest as severe idiosyncratic dermatologic (eg, Stevens-Johnson, toxic epidermal necrolysis), vascular (eg, vasculitis), pulmonary (eg, pneumonitis), renal (eg, nephritis), hepatic (eg, hepatic failure or necrosis), and/or hematologic (eg, anemia, cytopenias) events, usually after multiple doses. Prompt discontinuation of drug should occur if skin rash or other symptoms arise.

• Phototoxicity: Avoid excessive sunlight and take precautions to limit exposure (eg, loose fitting clothing, sunscreen); may cause moderate-to-severe phototoxicity reactions. Discontinue use if photosensitivity occurs.

• Serious adverse reactions:[US Boxed Warning]: Fluoroquinolones are associated with disabling and potentially irreversible serious adverse reactions that may occur together, including tendinitis and tendon rupture, peripheral neuropathy, and CNS effects. Discontinue levofloxacin immediately and avoid use of fluoroquinolones in patients who experience any of these serious adverse reactions. Patients of any age or without preexisting risk factors have experienced these reactions; may occur within hours to weeks after initiation.

- CNS effects: Fluoroquinolones have been associated with an increased risk of CNS effects including seizures, increased intracranial pressure (including pseudotumor cerebri), and toxic psychosis; may also cause nervousness, agitation, insomnia, anxiety, nightmares, paranoia, dizziness, confusion, tremors, hallucinations, depression, and suicidal thoughts or actions. May occur following the first dose; discontinue immediately and avoid further use of fluoroquinolones in patients who experience these reactions. Use with caution in patients with known or suspected CNS disorder, or risk factors that may predispose to seizures or lower the seizure threshold.

- Peripheral neuropathy: Fluoroquinolones have been associated with an increased risk of peripheral neuropathy; may occur soon after initiation of therapy and may be irreversible; discontinue if symptoms of sensory or sensorimotor neuropathy occur. Avoid use in patients who have previously experienced peripheral neuropathy.

- Tendinitis/tendon rupture: Fluoroquinolones have been associated with an increased risk of tendonitis and tendon rupture in all ages; risk may be increased with concurrent corticosteroids, solid organ transplant recipients, and in patients >60 years of age, but has also occurred in patients without these risk factors. Rupture of the Achilles tendon has been reported most frequently; but other tendon sites (eg, rotator cuff, biceps, hand) have also been reported. Inflammation and rupture may occur bilaterally. Cases have been reported within hours or days of initiation, and up to several months after discontinuation of therapy. Strenuous physical activity, renal failure, and previous tendon disorders may be independent risk factor for tendon rupture. Discontinue at first sign of tendon pain, swelling, inflammation or rupture. Avoid use in patients with a history of tendon disorders or who have experienced tendinitis or tendon rupture.

• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.

Disease-related concerns:

• Myasthenia gravis: [U.S. Boxed Warning]: May exacerbate muscle weakness related to myasthenia gravis; avoid use in patients with known history of myasthenia gravis. Cases of severe exacerbations, including the need for ventilatory support and deaths have been reported.

• Renal impairment: Use with caution in patients with renal impairment; dosage adjustment required. May increase risk of tendon rupture.

• Rheumatoid arthritis: Use with caution in patients with rheumatoid arthritis; may increase risk of tendon rupture.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Elderly: Adverse effects (eg, hepatotoxicity, tendon rupture, QT changes) may be increased in the elderly.

• G6PD deficiency: Hemolytic reactions may (rarely) occur with quinolone use in patients with latent or actual G6PD deficiency.

• Pediatric: Safety of use in pediatric patients for >14 days of therapy has not been studied; increased incidence of musculoskeletal disorders (eg, arthralgia, tendon rupture) has been observed in children.

Dosage form specific issues:

• Benzyl alcohol and derivatives: Some dosage forms may contain benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity ("gasping syndrome") in neonates; the "gasping syndrome" consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer's labeling.

Other warnings/precautions:

• Appropriate use: [US Boxed Warning]: Reserve use of levofloxacin for treatment of acute bacterial sinusitis, acute bacterial exacerbation of chronic bronchitis, or uncomplicated urinary tract infection for patients who have no alternative treatment options because of the risk of disabling and potentially serious adverse reactions (eg, tendinitis and tendon rupture, peripheral neuropathy, CNS effects).

Monitoring Parameters

Evaluation of organ system functions (renal, hepatic, and hematopoietic) is recommended periodically during therapy; the possibility of crystalluria should be assessed; WBC and signs of infection

Pregnancy Risk Factor

C

Pregnancy Considerations

Adverse events have been observed in some animal reproduction studies. Levofloxacin crosses the placenta and can be detected in the amniotic fluid and cord blood (Ozyüncü and Beksac 2010; Ozyüncü and Nemutl, 2010). Information specific to levofloxacin use during pregnancy is limited (Padberg 2014).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience nausea or diarrhea. Have patient report immediately to prescriber signs of kidney problems (urinary retention, hematuria, change in amount of urine passed, or weight gain), signs of Stevens-Johnson syndrome/toxic epidermal necrolysis (red, swollen, blistered, or peeling skin [with or without fever]; red or irritated eyes; or sores in mouth, throat, nose, or eyes), signs of tendon inflammation or rupture (pain, bruising, or swelling in the back of the ankle, shoulder, hand, or other joints), signs of depression (suicidal ideation, anxiety, emotional instability, or confusion), signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice), signs of high blood sugar (confusion, fatigue, increased thirst, increased hunger, polyuria, flushing, fast breathing, or breath that smells like fruit), signs of low blood sugar (dizziness, headache, fatigue, feeling weak, shaking, tachycardia, confusion, increased hunger, or sweating), tinnitus, angina, tachycardia, abnormal heartbeat, dizziness, severe loss of strength and energy, muscle pain, muscle weakness, insomnia, agitation, vision changes, hallucinations, nightmares, seizures, severe headache, shortness of breath, bruising, bleeding, tremors, abnormal gait, vaginitis, thrush, chills, signs of nerve problems (sensitivity to heat or cold; decreased sense of touch; burning, numbness, or tingling; pain, or weakness in the arms, hands, legs, or feet), or signs of Clostridium difficile (C. diff)-associated diarrhea (abdominal pain or cramps, severe diarrhea or watery stools, or bloody stools) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

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