fluoroquinolones

REMS

PO: IV: Treatment of the following bacterial infections:
- Urinary tract infections (UTIs), 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).

Contraind./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);
History of tendon disorders, including tendinitis or tendon rupture;
History of peripheral neuropathy;
Patients with or at ↑ risk for aortic aneurysm (use only if no alternatives);
Moxifloxacin: Concurrent use of Class IA antiarrhythmics (disopyramide, quinidine, procainamide) or Class III antiarrhythmics (amiodarone, sotalol) (↑ risk of QTc interval prolongation and torsades 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 (delafloxacin, moxifloxacin, ofloxacin);
Lactation: Avoid breastfeeding during treatment and for 2 days after final dose (for ciprofloxacin and levofloxacin, applies for all indications other than postexposure prophylaxis of inhalational anthrax);
Pedi: Use only for treatment of anthrax, plague, and complicated UTIs in children 1–17 yr due to possible arthropathy.

Use Cautiously in:

Known or suspected CNS disorder;
Depression;
Renal impairment (dose ↓ if CCr ≤50 mL/min for ciprofloxacin, levofloxacin, ofloxacin);
Cirrhosis (levofloxacin, moxifloxacin);
Concurrent use of corticosteroids, strenuous exercise, or rheumatoid arthritis (↑ risk of tendinitis/tendon rupture);
Kidney, heart, or lung transplant patients (↑ risk of tendinitis/tendon rupture);
Diabetes;
Moxifloxacin: Concurrent use of erythromycin, antipsychotics, and tricyclic antidepressants (↑ risk of QTc prolongation and torsades de pointes);
Moxifloxacin: Bradycardia;
Moxifloxacin: Acute myocardial ischemia;
Delafloxacin: Severe renal impairment (dose ↓ if eGFR 15–29 mL/min) (IV diluent may accumulate and ↑ serum creatinine) (↑ risk of tendon rupture in renal failure);
OB: Use during pregnancy only if potential maternal benefit outweighs potential fetal risk (ciprofloxacin and levofloxacin only);
Lactation: Can be used while breastfeeding for postexposure prophylaxis of anthrax if potential maternal benefit justifies potential risk to infant (ciprofloxacin and levofloxacin only);
Geri: ↑risk of adverse reactions in older adults.

Adv. Reactions/Side Effects ⬆ ⬇

CV: AORTIC ANEURYSM/DISSECTION, myocardial ischemia, QT interval prolongation (levofloxacin, moxifloxacin), TORSADES DE POINTES, vasodilation

Derm: ACUTE GENERALIZED EXANTHEMATOUS PUSTULOSIS, photosensitivity, rash, STEVENS-JOHNSON SYNDROME (SJS)

Endo: hyperglycemia, hypoglycemia

GI: diarrhea, nausea, ↑liver enzymes (ciprofloxacin, moxifloxacin), abdominal pain, CLOSTRIDIOIDES DIFFICILE-ASSOCIATED DIARRHEA (CDAD), HEPATOTOXICITY (CIPROFLOXACIN), vomiting

GU: vaginitis

Local: phlebitis

MS: arthralgia, myalgia, tendinitis, tendon rupture

Neuro: dizziness, headache, insomnia, ↑INTRACRANIAL PRESSURE (INCLUDING PSEUDOTUMOR CEREBRI), acute psychoses, agitation, anxiety, attention disturbances, confusion, depression, drowsiness, hallucinations, light-headedness, memory impairment, nightmares, paranoia, peripheral neuropathy, SEIZURES, SUICIDAL THOUGHTS/BEHAVIORS, toxic psychosis, tremor

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS)

Interactions ⬆ ⬇

Drug-drug:

Ciprofloxacin may ↑ tizanidine levels and risk of hypotension and sedation; concurrent use contraindicated.
QT interval-prolonging medications may ↑ risk of QT interval prolongation and torsades de pointes; avoid concurrent use.
Ciprofloxacin may ↑ theophylline levels and risk of CNS toxicity; avoid concurrent use; if concurrent use cannot be avoided, closely monitor serum theophylline levels.
Ciprofloxacin may ↑ levels and risk of toxicity of CYP1A2 substrates, including ropinirole, clozapine, olanzapine, and zolpidem; avoid concurrent use with zolpidem.
Antacids, iron salts, bismuth subsalicylate, sucralfate, sevelemer, lanthanum, and zinc salts may ↓ absorption of fluoroquinolones; separate administration of medications.
May ↑ levels of and risk of bleeding from warfarin.
Ciprofloxacin may alter levels and the effects of phenytoin.
Probenecid may ↑ levels and risk of toxicity.
May ↑ risk of nephrotoxicity from cyclosporine.
Concurrent use of ciprofloxacin with NSAIDs may ↑ risk of seizures.
Corticosteroids may ↑ risk of tendon rupture.
May ↑ risk of hypoglycemia when used with antidiabetic agents.

Drug-Natural Products:

Fennel↓ the absorption of ciprofloxacin.

Drug-Food:

Absorption is impaired by concurrent tube feeding (because of metal cations).
Absorption is ↓ if taken with dairy products or calcium-fortified juices.

Availability ⬆ ⬇

Ciprofloxacin

(Generic available)

Immediate-release tablets: 100 mg; 250 mg; 500 mg; 750 mg
Oral suspension strawberry flavor: 250 mg/5 mL; 500 mg/5 mL
Premixed infusion: 200 mg/100 mL D5W; 400 mg/200 mL D5W
Solution for injection: 10 mg/mL
In combination with:
dexamethasone (generic only); fluocinolone (Otovel); hydrocortisone (Cipro HC) (see Combination Drugs).

Delafloxacin

Tablets: 450 mg
Lyophilized powder for injection: 300 mg/vial

Levofloxacin

(Generic available)

Tablets: 250 mg; 500 mg; 750 mg
Oral solution: 25 mg/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
Premixed infusion: 400 mg/250 mL 0.8% NaCl

Ofloxacin

(Generic available)

Tablets: 200 mg; 300 mg; 400 mg

Route/Dosage ⬆ ⬇

Ciprofloxacin

PO (Adults ): Most infections: 500–750 mg every 12 hr. Complicated UTIs: 500 mg every 12 hr for 7–14 days. Uncomplicated UTIs: 250 mg every 12 hr for 3 days. Gonorrhea: 250-mg single dose. Inhalational anthrax (postexposure) or cutaneous anthrax: 500 mg every 12 hr for 60 days; Plague: 500–750 mg every 12 hr for 14 days.
PO (Children 1–17 yr): Complicated UTIs: 10–15 mg/kg every 12 hr (max = 750 mg/dose) for 10–21 days. Inhalational anthrax (postexposure) or cutaneous anthrax: 10–15 mg/kg every 12 hr (max = 500 mg/dose) for 60 days; Plague: 15 mg/kg every 8–12 hr (max = 500 mg/dose) for 14 days.
IV (Adults ): Most infections: 400 mg every 12 hr. Complicated UTIs: 400 mg every 12 hr for 7–14 days. Uncomplicated UTIs: 200 mg every 12 hr for 7–14 days. Inhalational anthrax (postexposure): 400 mg every 12 hr for 60 days; Plague: 400 mg every 8–12 hr for 14 days.
IV (Children 1–17 yr): Inhalational anthrax (postexposure): 10 mg/kg every 12 hr (not to exceed 400 mg/dose) for 60 days; Complicated UTIs: 6–10 mg/kg every 8 hr (max = 400 mg/dose) for 10–21 days; Plague: 10 mg/kg every 8–12 hr (max = 400 mg/dose) for 10–21 days.

Renal Impairment

PO (Adults ): CCr 30–50 mL/min: 250–500 mg every 12 hr; CCr 5–29 mL/min: 250–500 mg every 18 hr.
IV (Adults ): CCr 5–29 mL/min: 200–400 mg every 18–24 hr.

Delafloxacin

IV (Adults ): 300 mg every 12 hr for 5–14 days (for acute bacterial skin and skin structure infections) or 5–10 days (for community-acquired pneumonia [CAP]) or 300 mg every 12 hr followed by switching to oral regimen (at dose stated below) for a total of 5–14 days (for acute bacterial skin and skin structure infections) or 5–10 days (for CAP).
PO (Adults ): 450 mg every 12 hr for 5–14 days (for acute bacterial skin and skin structure infections) or 5–10 days (for CAP).

Renal Impairment

IV (Adults ): eGFR 15–29 mL/min: 200 mg every 12 hr for 5–14 days (for acute bacterial skin and skin structure infections) or 5–10 days (for CAP) or 200 mg every 12 hr followed by switching to oral regimen (450 mg every 12 hr) for a total of 5–14 days (for acute bacterial skin and skin structure infections) or 5–10 days (for CAP); eGFR <15 mL/min: Not recommended.

Levofloxacin

PO IV (Adults ): Most infections: 250–750 mg every 24 hr; Inhalational anthrax (postexposure): 500 mg once daily for 60 days.
PO IV (Children >50 kg): Inhalational anthrax (postexposure): 500 mg once daily for 60 days; Plague: 500 mg once daily for 10–14 days.
PO IV (Children <50 kg and ≥6 mo): 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 every 48 hr; CCr 10–19 mL/min: 750 mg initially, then 500 mg every 48 hr; Normal renal function dosing of 500 mg/day: CCr 20–49 mL/min: 500 mg initially then 250 mg every 24 hr; CCr 10–19 mL/min: 500 mg initially then 250 mg every 48 hr. Normal renal function dosing of 250 mg/day: CCr 10–19 mL/min: 250 mg every 48 hr.

Moxifloxacin

PO IV (Adults ): Bacterial sinusitis: 400 mg once daily for 10 days; CAP: 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 every 12 hr. Prostatitis: 300 mg every 12 hr for 6 wk. Uncomplicated UTIs: 200 mg every 12 hr for 3–7 days. Complicated UTIs: 200 mg every 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 every 24 hr; CCr <20 mL/min: 50% of the usual dose every 24 hr.

US Brand Names ⬆ ⬇

ciprofloxacin : Cipro, ~~Cipro XR,~~

delafloxacin: Baxdela,

levofloxacin: ~~Levaquin,~~

moxifloxacin : ~~Avelox,~~

ofloxacin : ~~Floxin~~

Action ⬆ ⬇

Inhibit bacterial DNA synthesis by inhibiting DNA gyrase.

Therapeutic effects:

Death of susceptible bacteria.

Spectrum:

Broad activity includes many gram-positive 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.

Classifications ⬆ ⬇

Therapeutic Classification: anti-infectives

Pharmacologic Classification: Fluoroquinolones

Pharmacokinetics ⬆ ⬇

Absorption: Well absorbed after oral administration (ciprofloxacin: 70%; delafloxacin: 59%; moxifloxacin: 90%; levofloxacin: 99%; ofloxacin: 98%).

Distribution: Widely distributed. High tissue and urinary levels are achieved. Ciprofloxacin and ofloxacin enter breast milk.

Metabolism/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; 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); levofloxacin: 8 hr; moxifloxacin: 12 hr; ofloxacin: 5–7 hr (all are ↑ in renal impairment).

Time/Action Profile ⬆ ⬇

( blood levels)

ROUTE	ONSET	PEAK	DURATION
Ciprofloxacin: PO	rapid	1–2 hr	12 hr
Ciprofloxacin: IV	rapid	end of infusion	12 hr
Delafloxacin: PO	rapid	1 hr	12 hr
Delafloxacin: IV	rapid	end of infusion	12 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

Patient/Family Teaching ⬆ ⬇

Explain the purpose and side effects of fluoroquinolones. Instruct to take medication as directed at evenly spaced times and to finish drug completely, even if feeling better. Take missed doses as soon as possible, unless almost time (within 6 hr for ciprofloxacin; 8 hr for moxifloxacin) for next dose. Do not double doses. Advise that sharing of this medication may be dangerous. Advise patient to read Patient Information before starting therapy.
Instruct the patient to notify health care provider if symptoms do not improve.
Advise patients to notify health care provider immediately if they are taking theophylline.
Encourage patient to maintain a fluid intake of ≥1500–2000 mL/day to prevent crystalluria.
Advise that antacids or medications containing iron or zinc will ↓ absorption. Ciprofloxacin, levofloxacin, and ofloxacin should be taken ≥2 hr before (4 hr for moxifloxacin) or 2 hr after (6 hr for ciprofloxacin, and delafloxacin, 8 hr for moxifloxacin) these products.
May cause dizziness and drowsiness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
Advise patient to notify health care provider of any personal or family history of QTc prolongation or proarrhythmic conditions such as recent hypokalemia, significant bradycardia, or recent myocardial ischemia or if fainting spells or palpitations occur.
Advise patient to report signs/symptoms of superinfection (furry overgrowth on the tongue, vaginal itching or discharge, loose or foul-smelling stools).
Instruct patient to notify health care provider immediately if diarrhea, abdominal cramping, fever, or bloody stools occur and not to treat with antidiarrheals without consulting health care provider.
Advise patient to immediately report signs and symptoms of hepatotoxicity (fatigue, nausea, upper abdominal pain, yellowing of skin or eyes, dark urine, light-colored stools).
Advise patients and family to call 911 and seek urgent treatment for signs and symptoms of hypersensitivity reactions (difficulty breathing; chest tightness; hives; rash; feeling light-headed; itching; swelling of the face, lips, tongue, or throat).
Caution patient to use sunscreen and protective clothing to prevent phototoxicity reactions during and for 5 days after therapy. Notify health care provider if a sunburn-like reaction or skin eruption occurs.
Instruct patients being treated for gonorrhea that partners also must be treated.
Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care provider before taking other medications.
Instruct patient to notify health care provider immediately if serious CNS effects (seizures, agitation, insomnia, anxiety, nightmares, paranoia, dizziness, confusion, tremors, hallucinations, depression, suicidal ideations/thoughts); peripheral neuropathy (pain, burning, tingling, numbness, weakness, other alterations in sensation); or tendon (shoulder, hand, Achilles, other) pain, swelling, or inflammation occur.
Inform patient that fluoroquinolones may cause worsening of myasthenia gravis symptoms (muscle weakness, breathing problems). Advise patient to notify health care provider immediately if symptoms occur.
Rep: Advise patient to notify health care provider if pregnancy is planned or suspected. Advise women of reproductive potential to use effective contraception during delafloxacin, moxifloxacin, and ofloxacin therapy and to avoid breastfeeding during therapy with delafloxacin, moxifloxacin, ofloxacin and during and for 2 days after last dose of ciprofloxacin or levofloxacin.

section name header

Indications ⬇

Contraind./Precautions ⬆ ⬇

Adv. Reactions/Side Effects ⬆ ⬇

Interactions ⬆ ⬇

Availability ⬆ ⬇

Route/Dosage ⬆ ⬇

US Brand Names ⬆ ⬇

Action ⬆ ⬇

Classifications ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Patient/Family Teaching ⬆ ⬇

Pronunciation ⬆