Ofloxacin

Antibiotic Class:

Quinolone

Antimicrobial Spectrum:

Gram positive bacteria:  methicillin-susceptible Staphylococcus epidermidis, Staphylococcus saprophyticus

Gram negative bacteria:  Enterobacteriaceae, H. influenzae, other Haemophilus spp., N. gonorrhoeae, N. meningitides, M. catarrhalis, P. aeruginosa,

Mechanism of Action:

Inhibition of topoisomerase (DNA gyrase) enzymes, which inhibits relaxation of supercoiled DNA and promotes breakage of double stranded DNA.

Pharmacodynamics:

Fluoroquinolones produce both concentration-dependent  (peak:MIC), and a combination of concentration and time-dependent killing (AUC:MIC).

Pharmacokinetics:

400mg dose; Cmax: 1.5mg/ml; Volume of distribution: 1.7 L/kg; Table 2  

Adverse Effects:

CNS:  headache, insomnia, dizziness; hallucinations, depression, psychotic reactions (rare)

Connective tissue:  tendon injury

Renal:  interstitial nephritis

Cardiovascular:  QTC prolongation, torsades de pointes, arrhythmias

Dosage:

Oral: 200mg, 300mg, 400mg tablet

Intravenous: 200mg/50ml

Opthalmic/Otic: 0.3% solution

Adults:

Chronic bronchitis: 400 mg PO/IV every 12 hr x 10 days

Community-acquired pneumonia: 400 mg PO/IV every 12 hr x 10 days

Cystitis: (E. coli, K. pneumoniae) 200 mg PO/IV every 12 hr x 3 days

Cystitis: (other approved organisms) 200 mg PO/IV every 12 hr x 7 days

Gonorrhea: 400 mg IV or ORALLY as a single dose

Nongonococcal cervicitis/urethritis: 300 mg PO/IV every 12 hr x 7 days

Pelvic inflammatory disease: 400 mg PO/IV every 12 hr x 10-14 days

Prostatitis: 300 mg PO/IV every 12 hr for 6 weeks

Skin/skin structure infection: 400 mg PO/IV every 12 hr x 10 days

Urinary tract infection, complicated: 200 mg PO/IV every 12 hr x 10 days

Conjunctivitis: Day 1 and 2, 1-2 drops in affected eye every 2-4 hr; day 3-7, 1-2 drops 4 times a day

Corneal ulcers: Day 1 and 2, 1-2 drops in affected eye every 30 minutes while awake; day 3-7, 1-2 drops every hour while awake; day 7-9, 1-2 drops 4 times a day

Otitis externa: 10 drops into affected ear once a day x 7 days

Otitis media with perforated Tympanic membranes: 10 drops into affected ear twice a day x 14 days

Pediatric:

Conjunctivitis: (1 year of age and older) Day 1 and 2, 1-2 drops in affected eye every 2-4 hr; day 3-7, 1-2 drops 4 times a day

Corneal ulcers: (1 year of age and older) Day 1 and 2, 1-2 drops in affected eye(s) every 30 minutes while awake; day 3-7, 1-2 drops every hour while awake; day 7-9, 1-2 drops 4 times a day

Otitis externa: (6 months-13 years of age) 5 drops in affected ear once a day for 7 days; (13 years and older) 10 drops into affected ear(s) once a day x 7 days

Otitis media, acute with tympanostomy tubes: (1-12 years of age) 5 drops in affected ear twice a day x 10 days

Otitis media, chronic suppurative with perforated Tympanic membranes: (12 years and older) 10 drops in affected ear twice a day x 14 days

Table 4

Disease state based dosing:

Renal failure: CrCl < 20 mL/min, one-half the usual dose q24 hr

Hepatic failure: severe hepatic impairment (cirrhosis), maximum of 400 mg q24 hr

Contraindications/Warnings/Precautions:

Precautions: 

Drug Interactions:

Divalent cations:  aluminum, magnesium zinc, iron, calcium, antacids, sucralfate reduced bioavailability of quinolones (can cause therapeutic failure)

Theophylline, caffeine, xanthines: clearance of these is inhibited with fluoroquinolones

Pregnancy:

Category C: Risk unknown. Human studies inadequate.

Monitoring Requirements:

Therapeutic:  Culture and sensitivities, signs and symptoms of infection

Toxic:  Urinalysis, BUN, SCr, AST and ALT, Physicial examination: encephalopathic changes

Brand names/Manufacturer:

APO-OFLOX (Apotex CANADA, MALAYSIA)

EXOCIN (Allergan - UNITED KINGDOM, ITALY, SOUTH AFRICA, IRELAND, DENMARK, PORTUGAL, FINLAND, SPAIN, GREECE)

FLOXAL - (Riel AUSTRIA, GERMANY, SWITZERLAND, HUNGARY, CZECH REPUBLIC)

FLOXIN (ORTHO MCNEIL PHARMACEUTICAL USA, CANADA)

INOFLOX (Biomedis, SINGAPORE, MALAYSIA)

OCUFLOX (Allergan USA, CANADA, MEXICO)

OFLOX (Basics GERMANY, CHILE, AUSTRIA)

TARIVID (Aventis - UNITED KINGDOM, IRELAND, JAPAN, NETHERLANDS, SOUTH AFRICA, SWEDEN, SWITZERLAND, BELGIUM, NORWAY, AUSTRIA, DENMARK, PORTUGAL, HONG KONG, ISRAEL, GERMANY, THAILAND, FINLAND, MALAYSIA, HUNGARY, CZECH REPUBLIC)

ZANOCIN (Ranbaxy MALAYSIA, HUNGARY, CZECH REPUBLIC)