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levofloxacin (Levaquin)

Tradename: Levaquin, Leva-pak (50 mg QD for 5 days) levofloxacin is the S-enantiomer of the racemic drug ofloxacin. Indications: - bacterial infections due to susceptible organisms - traveler's diarrhea - tuberculosis, pulmonary tuberculosis - skin or soft tissue infection - diabetic foot infection - anthrax - plague, plague prophylaxis [7] - urinary tract infection - pyelonephritis - nosocomial pneumonia - eye infection - corneal ulcer [7] Dosage: 1) 500-750* mg PO/IV QD 2) 250-750* mg PO BID * 750 mg doses may be required for complicated skin infections, deep wounds, infected ulcers, pneumonia [5] Tabs: 250, 500, 750 mg. Dosage adjustment in renal failure: creatinine clearance dosage 10-50 mL/min* 250 mg every 24-48 hours < 10 mL/min# 250 mg every 48 hours * same dose for continuous arteriovenous hemofiltration # same dose for hemodialysis Pharmacology: 1) rapidly & completely absorbed after oral administration 2) peak plasma concentrations obtained 1-2 hours after oral dosing 3) absolute bioavailability of 500 mg dose is 99% 4) steady-state plasma levels reached in 48 hours after daily dosing 5) plasma concentrations of 5.7 ug/mL (peak) & 0.5 ug/mL (trough) with 500 mg PO QD 6) administration with food delays absorption by about 1 hour & diminished bioavailability by about 14% 7) volume of distribution is 89-112 L a) good penetration into tissues b) blister fluid to plasma ratio is 1 c) lung tissue concentration 2-5 fold plasma concentration 8) protein binding 24-38%, mainly albumin 9) limited metabolism to N-oxide & desmethyl derivatives 10) 87% recovered unchanged in the urine - renal clearance exceeds GFR, suggesting tubular secretion 11) elimination 1/2 life is 6-8 hours (76 hours ESRD) 12) NO significant differences in pharmacokinetics between young & elderly patients Antimicrobial activity: (eradication rate in parenthesis) Gram positive - Streptococcus - Streptococcus group A - Streptococcus group B - Streptococcus group C - Streptococcus group G - Streptococcus pneumonia (95%) - Streptococcus viridans - Streptococcus milleri - Enterococcus faecalis - Staphylococcus aureus (MSSA) (88%) - Staphylococcus aureus (MRSA) (+/-) - Staphylococcus epidermidis Gram negative - Neisseria gonorrhoeae - Neisseria meningitidis - Moraxella catarrhalis (94%) - Haemophilus influenzae (98%) - Haemophilus parainfluenzae [7] - Escherichia coli - Klebsiella species (100%, K pneumoniae) - Enterobacter species - Serratia species - Salmonella species - Shigella species - Proteus mirabilis - Proteus vulgaris - Providencia species - Morganella species - Citrobacter species - Aeromonas species - Acinetobacter species - Pseudomonas aeruginosa - Yersinia enterocolitica - Legionella species - Chlamydophila pnemoniae [7] Atypical bacteria - Chlamydia species - Mycoplasma pneumonia Anaerobes - Clostridium species - Peptostreptococcus species Adverse effects: 1) 3% discontinuation due to adverse effects 2) most common adverse effects: a) gastrointestinal - nausea/vomiting, diarrhea, dyspepsia, abdominal pain, flatulence, constipation, taste disturbance, anorexia, b) skin & mucous membrane - pruritus, rash, urticaria, genital moniliasis, vaginitis c) CNS/psychosomatic - insomnia, dizziness, anxiety, fatigue, malaise, headache, tremor d) other - leukorrhea - acute liver injury [6] - severe hypoglycemia resulting in coma or death, usually in patients with diabetes mellitus taking oral hypglycemic agents &/or insulin [10] - increased risk of nervousness, delirium, disorientation, inattention, or memory impairment [10] - low risk of musculoskeletal complaints in children [9] 3) higher risk of arrhythmia & mortality than amoxicillin [7] Drug interactions: 1) antacids, sucralfate, metal ions & multivitamins may diminish GI absorption of levofloxacin 2) co-administration of an NSAID may increase risk of CNS stimulation & convulsive seizure 3) NO drug interactions with theophylline, warfarin, digoxin, cyclosporine Notes: Physical properties: 1) soluble in water 100 mg/mL pH 0.6-5.8 & 272 mg/mL at pH 6.7 2) forms stable coordination compounds with many metals -> Al+3 > Cu+2 > Zn+2 > Mg+2 > Ca+2

Interactions

drug interactions drug adverse effects of fluoroquinolones

Specific

levofloxacin ophthalmic (Iquix, Quixin)

General

fluoroquinolone

Properties

INHIBITS: DNA gyrase SIZE: MW = 370 G/MOLE MISC-INFO: elimination route KIDNEY LIVER <10%> protein-binding 28-38% 1/2life 6-8 HOURS pregnancy-category C safety in lactation ?

Database Correlations

PUBCHEM correlations

References

  1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
  2. Sanford Guide to antimicrobial therapy 1997
  3. Prescriber's Letter 7(10):57 2000
  4. PDR 2000
  5. Prescriber's Letter 14(3): 2007 Empiric Antibiotic Treatment of Community-Acquired Pneumonia in Adults Detail-Document#: 230302 (subscription needed) http://www.prescribersletter.com
  6. Paterson JM et al Fluoroquinolone therapy and idiosyncratic acute liver injury: a population-based study CMAJ August 13, 2012 PMID: 22891208 http://www.cmaj.ca/content/early/2012/08/13/cmaj.111823.full.pdf+html - Hayashi PH and Chalasani NP Liver injury in the elderly due to fluoroquinolones: Should these drugs be avoided? CMAJ August 13, 2012 PMID: 22891207 http://www.cmaj.ca/content/early/2012/08/13/cmaj.121270
  7. Deprecated Reference
  8. Rao GA et al Azithromycin and Levofloxacin Use and Increased Risk of Cardiac Arrhythmia and Death. Ann Fam Med 2014 vol. 12 no. 2 121-127 PMID: 24615307 http://annfammed.org/content/12/2/121
  9. Bradley JS et al. Assessment of musculoskeletal toxicity 5 years after therapy with levofloxacin. Pediatrics 2014 Jun 2 PMID: 24918220
  10. Jansen Pharmaceuticals