Indications
PO, IV: Treatment of the following bacterial infections:
Urinary tract infections including cystitis and prostatitis
(ciprofloxacin, levofloxacin, ofloxacin) (should be used
for acute uncomplicated cystitis only when there are no
other alternative treatment options), Gonorrhea (may not
be considered first-line agents due to increasing resistance),
Gynecologic infections (ciprofloxacin, ofloxacin),
Respiratory tract infections including acute sinusitis,
acute exacerbations of chronic bronchitis, and pneumonia
(should be used for acute sinusitis or acute bacterial
exacerbations of chronic bronchitis only when there are
no other alternative treatment options), Skin and skin
structure infections (delafloxacin, levofloxacin, moxifloxacin,
ciprofloxacin, ofloxacin), Bone and joint infections
(ciprofloxacin), Infectious diarrhea (ciprofloxacin), Intra-
abdominal infections (ciprofloxacin, moxifloxacin).
Febrile neutropenia (ciprofloxacin). Postexposure treatment
of inhalational anthrax (ciprofloxacin, levofloxacin).
Treatment and prophylaxis of plague (ciprofloxacin,
levofloxacin, moxifloxacin).
Action
Inhibit bacterial DNA synthesis by inhibiting DNA gyrase.
Therapeutic Effects: Death of susceptible bacteria.
Spectrum: Broad activity includes many grampositive
pathogens: Staphylococci including
methicillin-resistant Staphylococcus aureus, Staphylococcus
epidermidis, Staphylococcus saprophyticus,
Streptococcus pneumoniae, Streptococcus pyogenes,
and Bacillus anthracis. Gram-negative spectrum notable for activity against: Escherichia coli, Klebsiella, Enterobacter,
Salmonella, Shigella, Proteus, Providencia,
Morganella morganii, Pseudomonas aeruginosa,
Serratia, Haemophilus, Acinetobacter, Neisseria gonorrhoeae,
Moraxella catarrhalis, Campylobacter, and
Yersinia pestis. Additional spectrum includes: Chlamydia
pneumoniae, Legionella pneumoniae, and
Mycoplasma pneumoniae
Pharmacokinetics
Absorption: Well absorbed after oral administration
(ciprofloxacin—70%; delafloxacin—59%; moxifloxacin—
90%; gemifloxacin—71%; levofloxacin—
99%; ofloxacin—98%).
Distribution: Widely distributed. High tissue and urinary
levels are achieved. All agents appear to cross the
placenta. Ciprofloxacin and ofloxacin enter breast milk.
Metabolism and Excretion: Ciprofloxacin—
15% metabolized by the liver, 40–50% excreted unchanged
by the kidneys; delafloxacin—primarily undergoes
glucuronidation; 50–65% excreted unchanged
by the kidneys; 28–48% excreted unchanged in feces;
gemifloxacin—minimal metabolism, 61% excreted unchanged
in feces, 36% excreted unchanged in urine; levofloxacin—
87% excreted unchanged in urine, small
amounts metabolized; moxifloxacin—mostly metabolized
by the liver, 20% excreted unchanged in urine, 25%
excreted unchanged in feces; ofloxacin—70–80% excreted
unchanged by the kidneys.
Half-life: Ciprofloxacin—4 hr; delafloxacin—3.7
hr (IV); 4.2–8.5 hr (PO); gemifloxacin—7 hr; levofloxacin—
8 hr; moxifloxacin—12 hr; ofloxacin—
5–7 hr (all areqin renal impairment).
TIME/ACTION PROFILE (blood levels)
ROUTE ONSET PEAK DURATION
Ciprofloxacin—
PO
rapid 1–2 hr 12 hr
Ciprofloxacin—
POER
rapid 1–4 hr 24 hr
Ciprofloxacin—
IV
rapid end of infusion
12 hr
Delafloxacin—
PO
rapid 1 hr 12 hr
Delafloxacin—
IV
rapid end of infusion
12 hr
Gemifloxacin—
PO
rapid 0.5–2 hr 24 hr
Levofloxacin—
PO
rapid 1–2 hr 24 hr
Levofloxacin—
IV
rapid end of infusion
24 hr
Moxifloxacin—
PO
within 1 hr 1–3 hr 24 hr
Moxifloxacin—
IV
rapid end of infusion
24 hr
Ofloxacin—
PO
rapid 1–2 hr 12 hr
Ofloxacin—
IV
rapid end of infusion
12 hr
Contraindications/Precautions
Contraindicated in: Hypersensitivity. Cross-sensitivity
among agents within class may occur; History of
myasthenia gravis (may worsen symptoms including
muscle weakness and breathing problems); Gemifloxacin
and moxifloxacin: Concurrent use of Class IA
antiarrhythmics (disopyramide, quinidine, procainamide)
or Class III antiarrhythmics (amiodarone, sotalol)
(qrisk of QTc interval prolongation and torsade de
pointes); Known QT interval prolongation or concurrent
use of agents causing prolongation; Ciprofloxacin:
Concurrent use with tizanidine; Delafloxacin:
End-stage renal disease (eGFR 15 mL/min); OB: Do
not use unless potential benefit outweighs potential fetal
risk; Pedi: Use only for treatment of anthrax, plague,
and complicated UTIs in children 1–17 yrs due to possible
arthropathy.
Use Cautiously in: Seizure disorder; Depression;
Renal impairment (dosepif CCr 50 mL/min for ciprofloxacin,
levofloxacin, ofloxacin; 40 mL/min for
gemifloxacin); Cirrhosis (levofloxacin, moxifloxacin);
Gemifloxacin and moxifloxacin: Concurrent use of
erythromycin, antipsychotics, and tricyclic antidepressants
(qrisk of QTc prolongation and torsades de
pointes); Gemifloxacin and moxifloxacin: Bradycardia;
Gemifloxacin and moxifloxacin: Acute myocardial
ischemia; Delafloxacin: Severe renal impairment
(dosepif eGFR 15–29 mL/min) (IV diluent may accumulate
andqSCr) (qrisk of tendon rupture in renal
failure); Concurrent use of corticosteroids (qrisk of
tendinitis/tendon rupture); Kidney, heart, or lung transplant
patients (qrisk of tendinitis/tendon rupture);
Rheumatoid arthritis (qrisk of tendon rupture); Diabetes;
Lactation: Safety not established except for treatment
of anthrax; Geri:qrisk of adverse reactions.
Adverse Reactions/Side Effects
CNS: ELEVATED INTRACRANIAL PRESSURE (including
pseudotumor cerebri), SEIZURES, SUICIDAL THOUGHTS/
BEHAVIORS, dizziness, headache, insomnia, acute psychoses,
agitation, confusion, depression, drowsiness,
hallucinations, lightheadedness, nightmares, paranoia,
toxic psychosis. CV: gemifloxacin, levofloxacin,
moxifloxacin—TORSADE DE POINTES, QT interval prolongation,
vasodilation. GI: HEPATOTOXICITY (CIPROFLOXACIN),
CLOSTRIDIUM DIFFICILE-ASSOCIATED DIARRHEA
(CDAD), diarrhea, nausea, abdominal pain,qliver enzymes
(ciprofloxacin, moxifloxacin), vomiting. GU:
vaginitis. Derm: STEVENS-JOHNSON SYNDROME, acute
generalized exanthematous pustulosis, photosensitivity,
rash. Endo: hyperglycemia, hypoglycemia. Local:
phlebitis at IV site. MS: arthralgia, myalgia, tendinitis,
tendon rupture. Neuro: peripheral neuropathy,
tremor. Misc: hypersensitivity reactions including ANAPHYLAXIS,
STEVENS-JOHNSON SYNDROME.
Interactions
Drug-Drug: Concurrent use of amiodarone, disopyramide,
erythromycin, procainamide, dofetilide, quinidine, some antipsychotics, sotalol, or
tricyclic antidepressantsqrisk of torsade de pointes
in susceptible individuals (avoid concurrent use). Ciprofloxacinqserum
theophylline levels and may lead
to toxicity. Administration with magnesium and aluminum-
containing antacids, iron salts, bismuth
subsalicylate, sucralfate, didanosine, and zinc
saltspabsorption of fluoroquinolones. Mayqthe effects
of warfarin. Ciprofloxacin mayplevels and effectiveness
of phenytoin. Levels of fluoroquinolones may
bepby antineoplastics. Cimetidine may interfere
with elimination of fluoroquinolones. Beneficial effects
of ciprofloxacin may be antagonized by nitrofurantoin.
Probenecidprenal elimination of fluoroquinolones.
Mayqrisk of nephrotoxicity from cyclosporine.
Concurrent use of ciprofloxacin with foscarnet
mayqrisk of seizures. Concurrent therapy with corticosteroids
mayqthe risk of tendon rupture. Mayq
risk of hypoglycemia when used with antidiabetic
agents.
Drug-Natural Products: Fennelpthe absorption
of ciprofloxacin.
Drug-Food: Absorption is impaired by concurrent
tube feeding (because of metal cations). Absorption
ispif taken with dairy products or calcium-fortified
juices.
Route/Dosage
Ciprofloxacin
PO (Adults): Most infections—500–750 mg q 12
hr. Complicated urinary tract infections—500 mg q
12 hr for 7–14 days (immediate-release); or 1000 mg
q 24 hr for 7–14 days (extended-release). Uncomplicated
urinary tract infections—250 mg every 12 hr
for 3 days (immediate-release) or 500 mg every 24 hr
for 3 days (extended-release). Gonorrhea—250-mg
single dose. Inhalational anthrax (postexposure) or
cutaneous anthrax—500 mg every 12 hr for 60 days;
Plague—500–750 mg q 12 hr for 14 days.
PO (Children 1–17 yr): Complicated urinary tract
infections—10–15 mg/kg q 12 hr (not to exceed
750 mg/dose) for 10–21 days. Inhalational anthrax
(postexposure) or cutaneous anthrax—10–15 mg/
kg q 12 hr (not to exceed 500 mg/dose) for 60 days;
Plague—15 mg/kg q 8–12 hr (maximum: 500 mg/
dose) for 10–21 days.
IV (Adults): Most infections—400 mg q 12 hr.
Complicated urinary tract infections—400 mg q 12
hr for 7–14 days. Uncomplicated urinary tract infections—
200 mg q 12 hr for 7–14 days. Inhalational
anthrax (post exposure)—400 mg q 12 hr for 60
days; Plague—400 mg q 8–12 hr for 14 days.
IV (Children 1–17 yr): Inhalational anthrax (post
exposure)—10 mg/kg q 12 hr (not to exceed 400 mg/
dose) for 60 days; Complicated urinary tract infections—
6–10 mg/kg q 8 hr (not to exceed 400 mg/
dose) for 10–21 days; Plague—10 mg/kg q 8–12 hr
(maximum: 400 mg/dose) for 10–21 days.
Renal Impairment
PO (Adults): CCr 30–50 mL/min—250–500 mg q
12 hr; CCr 5–29 mL/min—250–500 mg q 18 hr
(immediate-release) or 500 mg q 24 hr (extended-release).
IV (Adults): CCr 5–29 mL/min—200–400 mg q
18–24 hr.
Delafloxacin
IV (Adults): 300 mg every 12 hr for 5–14 days or 300
mg every 12 hr followed by switching to oral regimen
(at dose stated below) for a total of 5–14 days.
PO (Adults): 450 mg every 12 hr for 5–14 days.
Renal Impairment
IV (Adults): eGFR 15–29 mL/min—200 mg every
12 hr or 200 mg every 12 hr followed by switching to
oral regimen (450 mg every 12 hr); eGFR 15 mL/
min—Not recommended.
Gemifloxacin
PO (Adults): Acute bacterial exacerbation of
chronic bronchitis—320 mg once daily for 5 days;
Community-acquired pneumonia (CAP) caused by
Klebsiella pneumoniae, Moraxella catarrhalis, and
multidrug resistant strains of S. pneumonia—320
mg once daily for 7 days. Community-acquiredpneumonia
(CAP) caused by S. pneumonia, Haemophilus
influenzae, Mycoplasma pneumoniae, or Chlamydia
pneumonia, and multidrug resistant strains of
S. pneumonia—320 mg once daily for 5 days.
Renal Impairment
PO (Adults): CCr 40 mL/min—160 mg once daily
for 5 days.
Levofloxacin
PO, IV (Adults): Most infections—250–750 mg q
24 hr; inhalational anthrax (postexposure)—500
mg once daily for 60 days.
PO, IV (Children 50 kg): Inhalational anthrax
(postexposure)—500 mg daily for 60 days; Plague—
500 mg daily for 10–14 days.
PO, IV (Children 50 kg and 6mo): Inhalational
anthrax (postexposure)—8 mg/kg (max: 250
mg/dose) every 12 hr for 60 days. Plague—8 mg/kg
(max: 250 mg/dose) every 12 hr for 10–14 days;
Other infections—10 mg/kg/dose every 24 hr (max:
500 mg/dose).
Renal Impairment
PO, IV (Adults): Normal renal function dosing of
750 mg/day: CCr 20–49 mL/min—750 mg q 48 hr;
CCr 10–19 mL/min—750 mg initially, then 500 mg q
48 hr; Normal renal function dosing of 500 mg/day: CCr 20–49 mL/min—500 mg initially then 250 mg q
24 hr; CCr 10–19 mL/min—500 mg initially then
250 mg q 48 hr. Normal renal function dosing of 250
mg/day: CCr 10–19 mL/min—250 mg q 48 hr.
Moxifloxacin
PO, IV (Adults): Bacterial sinusitis—400 mg once
daily for 10 days; Community-acquired pneumonia—
400 mg once daily for 7–14 days. Acute bacterial
exacerbation of chronic bronchitis—400 mg
once daily for 5 days. Complicated intra-abdominal
infection—400 mg once daily for 5–14 days. Skin/
skin structure infections—400 mg/day for 7–21
days. Treatment/prevention of plague—400 mg
once daily for 10–14 days.
Ofloxacin
PO (Adults): Most infections—400 mg q 12 hr.
Prostatitis—300 mg q 12 hr for 6 wk. Uncomplicated
urinary tract infections—200 mg q 12 hr for
3–7 days. Complicated urinary tract infections—
200 mg q 12 hr for 10 days. Gonorrhea—400-mg single
dose.
Renal Impairment
PO, IV (Adults): CCr 20–50 mL/min—100% of the
usual dose q 24 hr; CCr 20 mL/min—50% of the
usual dose q 24 hr.
Availability
Ciprofloxacin (generic available)
Tablets: 100 mg, 250 mg, 500 mg, 750 mg. Cost: Generic—
100 mg $20.22/6, 250 mg $7.51/30, 500 mg
$15.38/30, 750 mg $278.41/50. Extended-release
tablets: 500 mg, 1000 mg. Cost: Generic—500 mg
$489.94/50, 1000 mg $557.80/50. Oral suspension
(strawberry flavor): 250 mg/5 mL, 500 mg/5 mL.
Cost: Generic—250 mg/5 mL $123.24/100 mL, 500
mg/5 mL $144.28/100 mL. Solution for injection: 10
mg/mL. Premixed infusion: 200 mg/100 mL D5W,
400 mg/200 mL D5W. In combination with: hydrocortisone
(Cipro HC) (see Appendix B).
Delafloxacin
Lyophilized powder for injection: 300 mg/vial.
Tablets: 450 mg.
Gemifloxacin (generic available)
Tablets: 320 mg. Cost: $239.20/5.
Levofloxacin (generic available)
Tablets: 250 mg, 500 mg, 750 mg. Cost: Generic—
500 mg $13.77/50, 750 mg $24.22/20. Oral solution:
25 mg/mL. Cost: Generic—$579.42/480 mL. Solution
for injection: 25 mg/mL. Premixed infusion:
250 mg/50 mL D5W, 500 mg/100 mL D5W, 750 mg/
150 mL D5W.
Moxifloxacin (generic available)
Tablets: 400 mg. Cost: $769.58/30. Premixed infusion:
400 mg/250 mL 0.8% NaCl.
Ofloxacin (generic available)
Tablets: 200 mg, 300 mg, 400 mg. Cost: Generic—
200 mg $239.20/50, 300 mg $284.66/50, 400 mg
$600.36/100.
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