Dosing and uses of Cipro, Cipro XR (ciprofloxacin)
Adult dosage forms and strengths
infusion solution
- 200mg/100mL
- 200mg/20mL
- 400mg/40mL
- 400mg/200mL
oral suspension
- 250mg/5mL
- 500mg/5mL
tablet
- 100mg
- 250mg
- 500mg
- 750mg
tablet, extended release
- 500mg
- 1000mg
Acute Sinusitis
Mild/moderate: 500 mg PO q12hr or 400 mg IV q12hr for 10 days
Limitations-of-use: Reserve fluoroquinolones for patients who do not have other available treatment options for acute sinusitis
Bone & Joint Infections
Mild/moderate: 500 mg PO q12hr or 400 mg IV q12hr for ≥4-6 weeks
Severe/complicated: 750 mg PO q12hr or 400 mg IV q8hr for ≥4-6 weeks
Chronic Bacterial Prostatitis
Indicated for chronic bacterial prostatitis caused by Escherichia coli or Proteus mirabilis
Mild/moderate: 500 mg PO q12hr or 400 mg IV q12hr for 28 days
Infectious Diarrhea
Mild/moderate/severe: 500 mg PO q12hr for 5-7 days
Empirical Therapy in Febrile Neutropenic Patients
Severe: 400 mg IV q8hr for 7-14 days
Intra-abdominal Infections
Complicated: 500 mg PO q12hr or 400 mg IV q12hr for 7-14 days
Lower Respiratory Tract Infections
Mild/moderate: 500 mg PO q12hr or 400 mg IV q12hr for 7-14 days
Severe/complicated: 750 mg PO q12hr or 400 mg IV q8hr for 7-14 days
Limitations-of-use: Reserve fluoroquinolones for patients who do not have other available treatment options for acute bacterial exacerbation of chronic bronchitis
Nosocomial Pneumonia
Mild/moderate/severe: 400 mg IV q8hr for 10-14 days
Skin/Skin Structure Infections
Mild/moderate: 500 mg PO q12hr or 400 mg IV q12hr for 7-14 days
Severe/complicated: 750 mg PO q12hr or 400 mg IV q8hr for 7-14 days
Urinary Tract Infections
Acute uncomplicated: Immediate-release, 250 mg PO q12hr for 3 days; extended-release, 500 mg PO q24hr for 3 days
Mild/moderate: 250 mg PO q12hr or 200 mg IV q12hr for 7-14 days
Severe/complicated: 500 mg PO q12hr or 400 mg IV q12hr for 7-14 days
Limitations-of-use: Reserve fluoroquinolones for patients who do not have other available treatment options for uncomplicated urinary tract infections
Urethral & Cervical Gonococcal Infections
Uncomplicated: 250-500 mg PO once
Anthrax Infection
Postexposure therapy
Inhalation (prophylaxis/postexposure): 500 mg PO q12hr or 400 mg IV q12hr for 60 days
Cutaneous: 500 mg PO q12hr or 400 mg IV q12hr for 60 days
Plague
Indication for treatment and prophylaxis of plague due to Yersinia pestis
500-750 mg PO q12hr x14 days, Or
400 mg IV q8-12hr x 14 days
Bronchiectasis (Orphan)
Orphan indication sponsor
- Aradigm Corporation, 3929 Point Eden Way, Hayward, CA 94545
Noncystic Fibrosis Bronchiectasis (Orphan)
Dry powder for inhalation: Orphan designation for patients with NCFB who suffer from frequent severe acute pulmonary bacterial exacerbations which lead to further inflammation, airway, and lung parenchyma damage
Sponsor
- Bayer HealthCare
Dosage modifications
Renal impairment
- CrCl >50 mL/min: Dose adjustment not necessary
- CrCl 30-50 mL/min: 250-500 mg PO q12hr
- CrCl <30 mL/min: Extended-release, 500 mg PO q24hr
- CrCl 5-29 mL/min: 250-500 mg PO q18hr or 200-400 mg IV q18-24hr
- Some clinicians suggest decreasing dose but not frequency of administration
- Hemodialysis: 0.25-0.5 g PO q12hr or 0.2-0.4 g IV q24hr
- Peritoneal dialysis: 0.25-0.5 g PO q8hr or 0.2-0.4 g IV q24hr
Dosing Considerations
ProQuin XR should be taken with a main meal, preferably evening meaL
Cipro XR may be taken with or without meal; drink fluids liberally
Susceptible organisms
- Aeromonas hydrophila, Bacillus anthracis, Bacteroides fragilis, Campylobacter jejuni, Citrobacter freundii, Citrobacter diversus, Enterobacter cloacae, Enterococcus faecalis, Escherichia coli, Haemophilus ducreyi, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Legionella pneumophila, Morganella morganii, Moraxella catarrhalis, certain mycobacteria, Neisseria gonorrhoeae, Proteus mirabilis, Providencia spp, Pseudomonas aeruginosa, Salmonella typhi, Serratia spp, Shigella spp, methicillin-sensitive Staphylococcus aureus (MSSA), Staphylococcus epidermis, Staphylococcus saprophyticus, Streptococcus pneumoniae, Vibrio cholerae, Yersinia enterocolitica
- First-line therapy: B anthracis, C freundii, C jejuni, Enterobacter spp, Hafnia alvei, S typhi, Salmonella spp, Shigella spp; no unanimity on others (eg, K pneumoniae, M morganii, V cholerae, Y enterocolitica )
Pediatric dosage forms and strengths
infusion solution
- 200mg/100mL
- 200mg/20mL
- 400mg/40mL
- 400mg/200mL
oral suspension
- 250mg/5mL
- 500mg/5mL
tablet
- 250mg
- 500mg
- 750mg
tablet, extended release
- 500mg
- 1000mg
Complicated Urinary Tract Infections or Pyelonephritis
<1 year: Safety and efficacy not established
≥1 year (IV): 6-10 mg/kg q8hr; individual dose not to exceed 400 mg for 10-21 days
≥1 year (PO): 10-20 mg/kg q12hr; individual dose not to exceed 750 mg q12hr for 10-21 days
Cholera
Single dose: 30 mg/kg PO
Multiple doses: 30 mg/kg/day PO divided q12hr for 3 days
Plague
Indication for treatment and prophylaxis of plague due to Yersinia pestis in pediatric patients from birth to 17 years of age
15 mg/kg PO q8-12hr x10-21 days; not to exceed 500 mg/dose, Or
10 mg/kg IV q8-12hr x 10-21 days; not to exceed 400 mg/dose
Inhalational Anthrax (Off-label)
Postexposure therapy
IV: 10 mg/kg q12hr for 60 days; individual dose not to exceed 400 mg
PO: 15 mg/kg q12hr for 60 days; individual dose not to exceed 500 mg
Change antibiotic to amoxicillin as soon as penicillin susceptibility confirmed
Cystic Fibrosis (Off-label)
PO: 40 mg/kg/day divided q12hr; not to exceed 2 g/day
IV: 20-30 mg/kg/day divided q8-12hr; not to exceed 1.2 g/day
Cipro, Cipro XR (ciprofloxacin) adverse (side) effects
1-10%
Nausea (3%)
Abdominal pain (2%)
Diarrhea (2% adults; 5% children)
Increased aminotransferase levels (2%)
Vomiting (1% adults; 5% children)
Headache (1%)
Increased serum creatinine (1%)
Rash (2%)
Restlessness (1%)
<1%
Acidosis
Allergic reaction
Angina pectoris
Anorexia
Arthralgia
Ataxia
Back pain
Bad taste
Blurred vision
Breast pain
Bronchospasm
Diplopia
Dizziness
Drowsiness
Dysphagia
Dyspnea
Flushing
Foot pain
Hallucinations
Hiccups
Hypertension
Hypotension
Insomnia
Irritability
Joint stiffness
Lethargy
Migraine
Nephritis
Nightmares
Oral candidiasis
Palpitation
Photosensitivity
Polyuria
Syncope
Tachycardia
Tinnitus
Tremor
Urinary retention
Vaginitis
Postmarketing Reports
Acute generalized exanthematous pustulosis (AGEP), erythema multiforme, exfoliative dermatitis, fixed eruption, photosensitivity/phototoxicity reaction
Agitation, confusion, delirium
Agranulocytosis, albuminuria, serum cholesterol and TG elevations, blood glucose elevation, hemolytic anemia, marrow depression (life threatening), pancytopenia (life threatening or fatal outcome), potassium elevation (serum)
Anaphylactic reactions (including life-threatening anaphylactic shock), serum sickness like reaction, Stevens-Johnson syndrome
Anosmia, hypesthesia
Constipation, dyspepsia, dysphagia, flatulence, hepatic failure (including fatal cases), hepatic necrosis, jaundice, pancreatitis
Hypertonia, hypotension (postural), increased INR (in patients treated with Vitamin K antagonists), QT prolongation, torsade de pointes, ventricular arrhythmia
Methemoglobinemia
Myasthenia, exacerbation of myasthenia gravis, myoclonus, nystagmus, peripheral neuropathy that may be irreversible, phenytoin alteration (serum), polyneuropathy, psychosis
Myalgia, tendinitis, tendon rupture, toxic epidermal necrolysis (Lyell’s Syndrome), twitching
Infections: Candiduria, vaginal candidiasis, moniliasis (oral, gastrointestinal, vaginal), pseudomembranous colitis
Renal calculi
Vasculitis
Warnings
Black box warnings
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 the drug immediately and avoid use of systemic fluoroquinolones in patients who experience any of these serious adverse reactions
May exacerbate muscle weakness in patients with myasthenia gravis; avoid fluoroquinolones with known history of myasthenia gravis
Serious adverse effects and limitations-of-use
- Both oral and injectable fluroquinolones are associated with disabling side effects involving tendons, muscles, joints, nerves and the central nervous system
- These side effects can occur hours to weeks after exposure to fluoroquinolones and may potentially be permanent
- Because the risk of these serious side effects generally outweighs the benefits for patients with acute bacterial sinusitis, acute exacerbation of chronic bronchitis, and uncomplicated UTIs, that fluoroquinolones should be reserved for use in patients with these conditions who have no alternative treatment options
- For some serious bacterial infections, including anthrax, plague, and bacterial pneumonia among others, the benefits of fluoroquinolones outweigh the risks and it is appropriate for them to remain available as a therapeutic option
Contraindications
Documented hypersensitivity; concurrent tizanidine administration
Cautions
Use in pregnancy, though generally contraindicated for all quinolones, is allowed for life-threatening situations; limited data from use of ciprofloxacin in pregnancy show no higher rate of birth defects than background
Do not use oral suspension in nasogastric tube; to prepare, add microcapsules to diluent
No longer recommended for gonorrhea in United States, because of widespread resistance
Commonly seen adverse reactions include tendinitis, tendon rupture, arthralgia, myalgia, peripheral neuropathy, and central nervous system effects (hallucinations, anxiety, depression, insomnia, severe headaches, and confusion); these reactions can occur within hours to weeks after starting therapy, including in patients of any age or without pre-existing risk factors; discontinue therapy immediately at first signs or symptoms of any serious adverse reaction; in addition, avoid use of fluoroquinolones, in patients who have experienced any serious adverse reactions associated with fluoroquinolones
Peripheral neuropathy: Sensory or sensorimotor axonal polyneuropathy affecting small and/or large axons resulting in paresthesias, hypoesthesias, dysesthesias, and weakness reported; peripheral neuropathy may occur rapidly after initiating and may potentially become permanent
In prolonged therapy, perform periodic evaluations of organ system functions (eg, renal, hepatic, hematopoietic); adjust dose in renal impairment; superinfections may occur with prolonged or repeated antibiotic therapy; discontinue use immediately if signs and symptoms of hepatitis occur
Not drug of first choice in pediatrics (except in anthrax), because of increased incidence of adverse events in comparison with control subjects, including arthropathy; no data exist on dosing for pediatric patients with renal impairment (ie, CrCl <50 mL/min)
Fluoroquinolones are associated with increased risk of tendinitis and tendon rupture in all ages; this risk is further increased in older patients (usually >60 years); in patients taking corticosteroids; and in kidney, heart, or lung transplant recipients; discontinue therapy immediately at first signs or symptoms of any serious adverse reaction; in addition, avoid use of fluoroquinolones, in patients who have experienced any serious adverse reactions associated with fluoroquinolones
Convulsions, increased intracranial pressure (including pseudotumor cerebri), and toxic psychosis are reported with fluoroquinolones; psychotic reactions have progressed to suicidal ideations or thoughts and self-injurious behavior
Avoid IV administration in patients who have known QT prolongation, carry risk factors for prolonged QT, or are taking class 1A or class III antiarrhythmic drugs
Crystalluria may occur; urine alkalinity may increase risk; ensure adequate hydration during therapy
Serious and sometimes fatal hypoglycemia reported with fluoroquinolone use; hyperglycemia also reported; monitor patients closely for signs/symptoms of abnormal glucose levels
Moderate-to-severe phototoxicity reactions reported; avoid excessive sunlight and take precautions to limit exposure; discontinue use if phototoxicity occurs
Use with caution in patients with history of seizures taking concurrent therapy that lowers seizure threshold; risk increases rarely when administered concomitantly with NSAIDs
Acute onset of retinal detachment increased 4.5-fold with oral fluoroquinolones in a single case-controlled study - JAMA 2012;307(13):1414-1419; another study disputes these findings (relative risk, 1.29) - JAMA 2013;310(20):2184-2190
Serious and fatal reactions have reported in patients receiving concurrent administration of ciprofloxacin and theophylline; if concomitant use cannot be avoided, monitor serum levels of theophylline and adjust dosage as appropriate
Clostridium difficile-associated diarrhea (CDAD) has been reported; if CDAD suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued; appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated
Prescribing antibiotics in absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to patient and increases risk of development of drug-resistant bacteria
Pregnancy and lactation
Pregnancy category: C
Lactation: Drug enters breast milk; use not recommended (American Academy of Pediatrics Committee states that drug is compatible with nursing)
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Cipro, Cipro XR (ciprofloxacin)
Mechanism of action
Inhibits relaxation of DNA; inhibits DNA gyrase in susceptible organisms; promotes breakage of double-stranded DNA
Absorption
Bioavailability (PO): ~50-85%
Peak plasma time (PO): Immediate-release, 0.5-2 hr; extended-release, 1-2.5 hr
Distribution
Distributed widely throughout body; tissue concentrations often exceed serum concentrations, especially in kidneys, gallbladder, liver, lungs, gynecologic tissue, and prostatic tissue; cerebrospinal fluid (CSF) concentration is 10% in noninflamed meninges and 14-37% in inflamed meninges; crosses placenta; enters breast milk
Protein bound: 20-40%
Vd: 2.1-2.7 L/kg
Metabolism
Metabolized in liver
Enzyme inhibitor: CYP1A2
Elimination
Half-life: 2-5 hr (children); 3-5 hr (adults)
Excretion: Urine (30-50%), feces (15-43%)
Administration
IV Incompatibilities
Additive: Aminophylline, amoxicillin, amoxicillin-clavulanate, amphotericin, ampicillin-sulbactam, ceftazidime, cefuroxime, clindamycin, floxacillin, heparin, piperacillin, sodium bicarbonate, ticarcillin
Y-site: Aminophylline, ampicillin-sulbactam, azithromycin, cefepime, dexamethasone sodium phosphate, furosemide, heparin, hydrocortisone sodium succinate, magnesium sulfate(?), methylprednisolone sodium succinate, phenytoin, potassium phosphates, propofol, sodium bicarbonate(?), sodium phosphates, total parenteral nutrition formulations, warfarin
IV Compatibilities
Solution: Compatible with most IV fluids
Additive: Amikacin, aztreonam, dobutamine, dopamine, fluconazole, gentamicin, lidocaine, linezolid, metronidazole (ready-to-use form is compatible; hydrochloride form in vial is incompatible), midazolam, potassium chloride, tobramycin
Y-site: Amiodarone, calcium gluconate, clarithromycin, digoxin, diphenhydramine, dobutamine, dopamine, linezolid, lorazepam, midazolam, promethazine, quinupristin/dalfopristin, tacrolimus
IV Administration
Infuse 1-2 mg/mL (diluted in D5W or NS) into large vein over 60 minutes
When administering intermittently through Y-site, temporarily discontinue primary solution
Stability
Stable at concentration of 0.5-2 mg/mL in D5W or NS for 14 days at room temperature or refrigerated
