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Ciprofloxacin

GENERAL
US BOXED WARNING:
SERIOUS SIDE EFFECTS INCLUDING TENDINITIS, TENDON RUPTURE, PERIPHERAL NEUROPATHY, CNS EFFECTS, AND EXACERBATION OF MYASTHENIA GRAVIS:
-Fluoroquinolones (including this drug) have been associated with disabling and potentially irreversible serious side effects that have occurred together (including tendinitis and tendon rupture, peripheral neuropathy, CNS effects). This drug should be discontinued immediately and use of fluoroquinolones (including this drug) should be avoided in patients with any of these serious side effects.
-Fluoroquinolones (including this drug) may exacerbate muscle weakness in patients with myasthenia gravis. This drug should be avoided in patients with known history of myasthenia gravis.
-Since fluoroquinolones (including this drug) have been associated with serious side effects, this drug should be reserved for use in patients with no alternative treatment options for acute exacerbation of chronic bronchitis, acute uncomplicated cystitis/uncomplicated urinary tract infections (acute cystitis), or acute sinusitis.
Extended-release tablets: Safety and efficacy have not been established in patients younger than 18 years.
US FDA pregnancy category: C
If given w/ dairy or calcium may decrease absorption, otherwise no food effects
Volume of Distribution: 1.8 to 3 L/kg; widely distributed throughout body, distributes well into most tissues and body fluids. 
EXCRETION: Primarily renal, partial biliary, intestine.  Urine excretion complete w/in 24hrs
IV: 50% to 70% of dose in urine and about 15% of dose in feces (within 5 days) as unchanged drug
PO: About 40% to 50% of dose in urine and about 20% to 35% of dose in feces (within 5 days) as unchanged drug
Proquin(R) XR: After 500 mg dose, 26.9% in urine (over 24 hours) as unchanged drug; 
SUSCEPTIBILITIES
​UTI: E coli, K pneumoniae, E cloacae, S marcescens, P mirabilis, P rettgeri, M morganii, C koseri, C freundii, P aeruginosa, S epidermidis (methicillin-susceptible), S saprophyticus, or Enterococcus faecalis
PYELONEPHRITIS (UNCOMPLICATED): E coli
CYSTITIS (UNCOMPLICATED):  E coli, S saprophyticus,  K pneumoniae, P mirabilis, E faecalis
PROSTATITIS:
E coli or P mirabilisINTRA-ABDOMINAL INFECTIONS: In combination with metronidazole, for Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis, Klebsiella pneumoniae, or Bacteroides fragilis
JOINT & BONE INFECTIONS: Enterobacter cloacae, Serratia marcescens, or P aeruginosa
NOSOCOMIAL PNEUMONIA:  Haemophilus influenzae or K pneumoniae
PNEUMONIA:
E coli, K pneumoniae, E cloacae, P mirabilis, P aeruginosa, H influenzae, H parainfluenzae, or S pneumoniae; for the treatment of AECB due to Moraxella catarrhalis
SKIN & STRUCTURAL INFECTION E coli, K pneumoniae, E cloacae, P mirabilis, P vulgaris, Providencia stuartii, Morganella morganii, Citrobacter freundii, P aeruginosa, Staphylococcus aureus (methicillin-susceptible), S epidermidis (methicillin-susceptible), or S pyogenesSome isolates of P aeruginosa may develop resistance relatively quickly during therapy.  Can also treat salmonella, typhoid, tularemia, meningococcal prophylaxis, cholera, traveller's diarrhea, chancroid (see below), granuloma inguinale (see below), anthrax prophylaxis and treatment, plague,  shigella  
MONITORING
Culture and susceptibility (periodically during therapy); syphilis serology in gonorrhea patients (at diagnosis and 3 months after therapy)
Renal: Renal function in elderly patients  ​
MECHANISM
Topoisomerase (DNA gyrase) inhibitor, bactericidal.
MEDICATION INTERACTIONS
Methotrexate - do not use
theophylline - Avoid if at all possible
Warfarin - do not give unless able to monitor INR

May increase concentration of drugs metabolized by CYP450 1A2 theophylline, caffeine, methylxanthines, tizanidine, ropinirole, olanzapine, duloxetine, clozapine,  agomelatine
CONTRAINDICATIONS
  • Hypersensitivity to the active component, other quinolones, or any of the ingredients; coadministration with tizanidine
  • Coumadin without inability to monitor INR
See warnings/precautions and side effects below
WARNINGS/PRECAUTIONS
CARDIOVASCULAR - Prolongation of the QT Interval/Cardiac Disorders:
DERMATOLOGIC - Photosensitivity/Phototoxicity, SJS
MUSCULOSKELETAL -  Tendinitis, Tendon Rupture
NERVOUS - dizziness, Peripheral Neuropathy,  CNS effects (hallucinations, anxiety, depression, insomnia, severe headaches, confusion); Exacerbation of Myasthenia Gravis:
OTHERS - vasculitis, arthralgia, myalgia, serum sickness, allergic pneumonitis, interstitial nephritis, acute renal insufficiency or failure, hepatitis, jaundice, acute hepatic necrosis or failure, anemia (including hemolytic and aplastic), thrombocytopenia (including thrombotic thrombocytopenic purpura), leukopenia, agranulocytosis, pancytopenia, and/or other hematologic abnormalities.
HEPATIC - Hepatotoxicity:
GI - C. diff
METABOLIC - Hypoglycemia:
SIDE EFFECTS
General Most common PO - nausea, diarrhea, abnormal liver function tests, vomiting, and rash;  IV - nausea, diarrhea, vomiting, injection and infusion site reactions, rash, and increased transaminases (transient).

Gastrointestinal
Common (1% to 10%): Nausea, diarrhea, vomiting, dyspepsia
Uncommon (0.1% to 1%): Abdominal pains/discomfort, gastrointestinal (GI) pains, flatulence
Rare (0.01% to 0.1%): Elevated amylase, antibiotic-associated colitis, pancreatitis
Frequency not reported: Clostridium difficile-associated diarrhea, constipation, GI bleeding, ileus, intestinal perforation, dry mouth, oral ulceration, epigastric pain, dysphagia, elevated lipase, painful oral mucosa, heartburn, acid reflux, aggravated irritable bowel syndrome, lower abdominal pain
Postmarketing reports: GI candidiasis, oral candidiasis, pseudomembranous colitis

Dermatologic
Common (1% to 10%): Rash
Uncommon (0.1% to 1%): Pruritus, urticaria
Rare (0.01% to 0.1%): Angioedema, photosensitivity reactions, sweating/hyperhidrosis, petechiae, blistering
Very rare (less than 0.01%): Erythema multiforme, erythema nodosum, Stevens-Johnson syndrome (potentially life-threatening), toxic epidermal necrolysis (potentially life-threatening)
Frequency not reported: Exfoliative dermatitis, purpura, burning, phototoxicity reaction, dry skin, maculopapular rash, skin disorder, vesiculobullous rash, erythema, hyperpigmentation, cutaneous candidiasis, bullous pemphigoid, vesicles, lobular panniculitis, photoinduced acute exanthematous pustulosis, drug reaction with eosinophilia and systemic symptoms (DRESS)
Postmarketing reports: Acute generalized exanthematous pustulosis, fixed eruption

Nervous system
Common (1% to 10%): Headache, dizziness/lightheadedness, central nervous system disturbance
Uncommon (0.1% to 1%): Sleep disorders, taste disorders, seizures (including status epilepticus), dysesthesia, paresthesia, vertigo, hearing loss
Rare (0.01% to 0.1%): Syncope, hypoesthesia, tremor, tinnitus, migraine, olfactory nerve disorders, smell disorders, hearing impaired
Very rare (less than 0.01%): Disturbed coordination, intracranial hypertension, benign intracranial hypertension/pseudotumor cerebri, exacerbation of myasthenia gravis, hyperesthesia
Frequency not reported: Unresponsiveness, ataxia, hypertonia, anosmia, nystagmus, taste perversion/bad taste, somnolence/drowsiness, incoordination, disturbance in attention, dyskinesia, myasthenia gravis, paresis, aseptic meningitis, cerebral thrombosis, grand mal convulsion, dysphasia, lethargy, sensory axonal polyneuropathy, sensorimotor axonal polyneuropathy
Postmarketing reports: Taste loss, peripheral neuropathy (may be irreversible), polyneuropathy

Hematologic
Common (1% to 10%): Eosinophilia
Uncommon (0.1% to 1%): Thrombocytopenia, thrombocythemia
Rare (0.01% to 0.1%): Leukopenia, anemia, neutropenia, leukocytosis, pancytopenia, bone marrow depression, abnormal prothrombin level
Very rare (less than 0.01%): Hemolytic anemia, agranulocytosis
Frequency not reported: Decreased hematocrit, decreased platelet counts, increased platelet counts, prolonged prothrombin time, decreased prothrombin, bleeding diathesis, decreased hemoglobin, decreased leukocyte count, increased atypical lymphocyte count, immature WBCs, increased blood monocytes, elevated sedimentation rate, elevated eosinophil counts, lymphadenopathy
Postmarketing reports: Methemoglobinemia, increased INR, prothrombin time prolonged or decreased

Hepatic

Common (1% to 10%): Abnormal liver function tests, increased transaminases
Uncommon (0.1% to 1%): Elevated bilirubin, hepatic impairment, cholestatic icterus/cholestatic jaundice, jaundice
Rare (0.01% to 0.1%): Hepatitis, liver necrosis
Very rare (less than 0.01%): Hepatic failure
Frequency not reported: Elevated AST, elevated ALT, elevated GGT

Psychiatric
Common (1% to 10%): Restlessness
Uncommon (0.1% to 1%): Psychomotor hyperactivity/agitation, confusion, disorientation, hallucinations
Rare (0.01% to 0.1%): Anxiety reaction, abnormal dreams, depression, psychotic reactions
Frequency not reported: Depersonalization, insomnia, manic reaction, nightmares, paranoia, phobia, toxic psychosis, nervousness, self-injurious behavior, suicidal ideations/thoughts, attempted suicide, completed suicide, catatonia, mania (including hypomania)
Postmarketing reports: Delirium

Genitourinary
Common (1% to 10%): Vaginal candidiasis
Rare (0.01% to 0.1%): Hematuria, crystalluria
Frequency not reported: Albuminuria, cylindruria, frequent urination, hemorrhagic cystitis, vaginitis, dysmenorrhea, candiduria, polyuria, urethral bleeding, urinary retention, urinary tract infection, fungal vaginosis, bacterial vaginitis, dysuria, abnormal urine odor, female genital pruritus, vaginal infection, urinary frequency, micturition urgency, vaginal pruritus

Local
Common (1% to 10%): Local IV site reactions, injection and infusion site reactions (e.g., phlebitis, thrombophlebitis)
Frequency not reported: Injection site irritation and induration with IV infusion

Musculoskeletal
Uncommon (0.1% to 1%): Musculoskeletal pain (e.g., extremity pain, back pain, chest pain), arthralgia
Rare (0.01% to 0.1%): Myalgia, arthritis, increased muscle tone and cramping, tendon rupture (mainly Achilles tendon)
Very rare (less than 0.01%): Tendinitis, muscular weakness
Frequency not reported: Arthropathy (including suspected reversible cases), joint stiffness, elevated serum creatine phosphokinase, abnormal joint exam, joint sprains, arthrosis, bone pain, decreased range of motion in a joint (knee, elbow, ankle, hip, wrist, shoulder), jaw pain, neck pain, gout flare-up, joint swelling, muscle spasms, night cramps, knee inflammation
Postmarketing reports: Myoclonus, myasthenia, twitching

Cardiovascular
Uncommon (0.1% to 1%): Tachycardia, vasodilatation, hypotension
Rare (0.01% to 0.1%): Vasculitis
Frequency not reported: Angina pectoris, cardiopulmonary arrest, myocardial infarction, hypertension, palpitation, bradycardia, arrhythmia, atrial flutter, cardiac murmur, cardiovascular collapse, ventricular ectopy, ventricular bigeminy, abdominal aortic bruit, postural hypotension
Postmarketing reports: QT prolongation/ECG QT prolonged, torsade de pointes, ventricular arrhythmia

Other 1
Uncommon (0.1% to 1%): Candida infections, mycotic superinfections, pain, fever, malaise/feeling unwell, asthenia, edema
Very rare (less than 0.01%): Gait disturbance/abnormal gait
Frequency not reported: Irritability, flushing, thirst, elevated serum calcium, elevated serum potassium, elevated triglycerides, decreased serum albumin, decreased serum potassium, decreased total serum protein, elevated serum theophylline, serum phenytoin altered, chills, swelling, breast pain, achiness, weakness, fatigue, suprapubic pain, rigors, tenderness, fungal infection, increased body temperature
Postmarketing reports: Elevated serum cholesterol

Metabolic
Uncommon (0.1% to 1%): Elevated blood alkaline phosphatase, decreased appetite/anorexia, decreased food intake
Rare (0.01% to 0.1%): Hyperglycemia, hypoglycemia
Frequency not reported: Elevated LDH, elevated uric acid, elevated blood glucose, decreased uric acid, decreased blood glucose, acidosis, symptomatic hypoglycemia

Renal
Uncommon (0.1% to 1%): Renal impairment, renal failure
Rare (0.01% to 0.1%): Tubulointerstitial nephritis
Frequency not reported: Elevated serum creatinine, renal calculi, elevated BUN, decreased BUN, abnormal kidney function, allergic interstitial nephritis, nephritis, myoglobin-associated acute kidney injury/failure

Ocular
Uncommon (0.1% to 1%): Visual disturbances (e.g., chromatopsia, diplopia, photopsia)
Very rare (less than 0.01%): Visual color distortions
Frequency not reported: Decreased visual acuity, blurred vision, cataracts, multiple punctate lenticular opacities, eye pain

Hypersensitivity
Rare (0.01% to 0.1%): Allergic reactions, anaphylactic shock (life-threatening), allergic edema
Very rare (less than 0.01%): Anaphylactic reaction, serum sickness-like reaction
Frequency not reported: Anaphylactoid reactions, necrotizing vasculitis, cutaneous vasculitis

Respiratory
Rare (0.01% to 0.1%): Dyspnea (including asthmatic condition)
Frequency not reported: Bronchospasm, hemoptysis, laryngeal edema, respiratory arrest, epistaxis, hiccough, pulmonary edema, pleural effusion, pulmonary embolism, respiratory distress, wheeze, cough, upper respiratory tract infection, pharyngitis, nasopharyngitis

Endocrine
Frequency not reported: Gynecomastia

Immunologic
Frequency not reported: Jarisch-Herxheimer reaction
Antibiotic-associated colitis with possible fatal outcome was reported very rarely.
The onset of pseudomembranous colitis symptoms has been reported during or after antimicrobial treatment.
Photosensitivity was seen most often when patients were exposed to intense sun (e.g., as when used to treat or prevent travelers' diarrhea).
Erythema nodosum, Stevens-Johnson syndrome (potentially life-threatening), and TEN (potentially life-threatening) have also been reported during postmarketing experience.
Seizures have been reported in 2 patients given this drug and foscarnet. 
Cases of sensory or sensorimotor axonal polyneuropathy (affecting small and/or large axons) resulting in paresthesias, hypoesthesias, dysesthesias, and weakness have been reported.
Nystagmus, anosmia, hyperesthesia, hypoesthesia, hypertonia, intracranial hypertension, and exacerbation of myasthenia gravis have also been reported during postmarketing experience.
Pancytopenia (life-threatening or fatal outcome) and bone marrow depression (life-threatening) were reported very rarely; also reported during postmarketing experience.
Increased INR was reported in patients treated with vitamin K antagonists.
Liver necrosis very rarely progressed to life-threatening hepatic failure. Liver necrosis and hepatic failure (including fatal cases) have also been reported during postmarketing experience.
Depression and psychotic reactions (both potentially culminating in self-injurious behavior such as suicidal ideations/thoughts and attempted or completed suicide) have been reported.
Agitation, confusion, and toxic psychosis have also been reported during postmarketing experience.
Crystalluria has been reported in patients with alkaline urine and did not necessarily lead to nephrotoxicity. At physiological urinary pH, the risk of crystalluria was considered minor.
Vaginal candidiasis has also been reported during postmarketing experience.
Local IV site reactions occurred more often if the infusion time was 30 minutes or less. These reactions have appeared as local skin reactions and resolved quickly when infusion was completed.
Injection site irritation and induration have been reported with IV infusion time 30 minutes or less (instead of the recommended 1 hour) or when a small vein in the back of the hand was used.

Tendinitis with subsequent tendon rupture has been documented in numerous case reports. One patient with chronic renal failure developed bilateral Achilles tendon rupture after 4 days of ciprofloxacin therapy. Although renal transplant patients and those with end-stage renal disease tend to have an increased risk of Achilles tendinitis and rupture over the general population, quinolone use has been shown to further increase that risk (12% in quinolone-treated patients versus 7% in nonquinolone-treated patients).

Multiple cases of achilles tendon rupture had been reported to the US FDA. Some ruptures have also occurred in the hand or shoulder. Other risk factors identified included age and corticosteroid use.

Musculoskeletal side effects reported in pediatric patients included arthralgia, abnormal gait, abnormal joint exam, joint sprains, leg pain, back pain, arthrosis, bone pain, pain, myalgia, arm pain, and decreased range of motion in a joint (knee, elbow, ankle, hip, wrist, shoulder).
Myalgia, tendinitis, and tendon rupture have also been reported during postmarketing experience.
Torsade de pointes was reported mainly in patients with risk factors for QT prolongation.
Vasculitis has also been reported during postmarketing experience.
Elevated serum theophylline has been reported in patients receiving theophylline concomitantly.
Gait disturbance and elevated serum potassium have also been reported during postmarketing experience.
Quinolone class antibiotics have been associated with symptomatic hypoglycemia.
Allergic interstitial nephritis resulting in nonoliguric renal failure has been described in numerous case reports. Several cases included symptoms of rash, fever, and arthralgia and were accompanied by eosinophilia and eosinophiluria. Cases of allergic interstitial nephritis often responded to short courses of corticosteroid therapy.

Quinolone class antibiotics have been associated with cataracts and multiple punctate lenticular opacities.

Allergic reactions ranged from urticaria to anaphylactic reactions, including life-threatening anaphylactic shock.
DOSAGE
ADULT

Urinary Tract Infection
IV: 200 to 400 mg IV q8-12h x7-14d 
Oral: Immediate-release: 250 to 500 mg PO q12h x7-14d; 
Oral: Extended-release: (uncomplicated)  500 mg PO q24h x3d 
Oral: Extended-release: (complicated) 1000 mg  PO q24h x7-14d
Indication (UTIs) due to E coli, K pneumoniae, E cloacae, S marcescens, P mirabilis, P rettgeri, M morganii, C koseri, C freundii, P aeruginosa, S epidermidis (methicillin-susceptible), S saprophyticus, or Enterococcus faecalis
​
Pyelonephritis
Oral: 1000 mg PO q24h x7-14d
Indication: For the treatment of acute uncomplicated pyelonephritis due to E coli

Cystitis
Immediate-release: 250 mg PO q12h x3d
Extended-release: 500 mg PO q12h x3d
*drug should be saved for treatment of acute uncomplicated cystitis/uncomplicated UTI (acute cystitis) in patients with no alternative treatment options.
INDICATION: uncomplicated E coli, S saprophyticus,  K pneumoniae, P mirabilis, E faecalis

Prostatitis
IV: 400 mg IV q12h x28d
Oral: 500 mg PO q12h x28d
Indication: E coli or P mirabilis

Gonococcal Infection -- Uncomplicated
250 mg PO x1
**Not recommended for treatment of gonococcal infections in the US due to resistance; dual therapy with ceftriaxone and azithromycin is the recommended regimen for treatment of gonorrhea in the US.

Chancroid
500 mg PO BID x3d
*Sexual partner(s) should also be evaluated/treated
**There are better treatment regimens

Granuloma Inguinale
750 mg orally twice a day BID x3wks or more until lesions healed
*Sexual partner(s) should also be evaluated/treated
**There are better treatment regimens

Surgical Prophylaxis
400 mg IV once, starting within 120 minutes before surgical incision

Intraabdominal Infection
IV: 400 mg IV q12h x7-14d
Oral: 500 mg PO  q12h x7-14d
INDICATION: In combination with metronidazole, for treatment of complicated intraabdominal infections due to Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis, Klebsiella pneumoniae, or Bacteroides fragilis

Joint & Bone Infection
IV: 400 mg IV q8-12h x4-8wks
Oral: 500 to 750 mg PO q12h x4-8wks
INDICATION: For treatment of bone and joint infections due to Enterobacter cloacae, Serratia marcescens, or P aeruginosa

Nosocomial Pneumonia
400 mg IV q8h x10-14d 
*Initial empiric treatment with broad-spectrum coverage according to the hospital's and/or ICU's antibiogram is recommended if multidrug-resistant organisms are suspected.
*INDICATION: Haemophilus influenzae or K pneumoniae

Pneumonia
IV: 400 mg IV q8-12h x7-14d
Oral: 500 to 750 mg po q12h x7-14d
INDICATION: For treatment of lower respiratory tract infections due to E coli, K pneumoniae, E cloacae, P mirabilis, P aeruginosa, H influenzae, H parainfluenzae, or S pneumoniae; for the treatment of AECB due to Moraxella catarrhalis

Skin and Structure Infection
IV: 400 mg IV q8-12h x7-14d
Oral: 500 to 750 mg PO q12h x7-14d
Duration of therapy: 7 to 14 days
INDICATION to E coli, K pneumoniae, E cloacae, P mirabilis, P vulgaris, Providencia stuartii, Morganella morganii, Citrobacter freundii, P aeruginosa, Staphylococcus aureus (methicillin-susceptible), S epidermidis (methicillin-susceptible), or S pyogenes
*animal bites = ok for Pasteurella, doesn't cover some anaerobes & MRSA

Surgical Site Infection
Incisional surgical site infection: IV 400mg q12h or PO 750mg q12h
Infection after animal bite:   IV 400mg q12h or PO 500-750mg q12h  
*Use with metronidazole if after intestinal/genitourinary tract surgery, surgery of axilla or perineum
*coverage for MRSA may be needed

PEDIATRIC
In patients younger than 18 years, this drug is only US FDA-approved for complicated UTIs, prevention of inhalation anthrax (postexposure), and plague

Pyelonephritis
>1yr  
IV: 6 to 10 mg/kg IV q8h, (max dose 400mg/dose) x10-12d
PO: 10 to 20 mg/kg PO  q12h, (max dose: 750mg/dose)
*Not DOC in pediatric patients b/c side effects.
Indication: For treatment of complicated UTIs and pyelonephritis due to E coli

Urinary Tract Infection
>1yr
IV: 6 to 10 mg/kg IV q8h, (max dose 400mg/dose) x10-21d
PO: 10 to 20 mg/kg PO  q12h, (max dose: 750mg/dose)  x10-21d
*Not DOC in pediatric patients b/c side effects.  

Surgical Prophylaxis
>1yr
10 mg/kg IV x1 (max dose 400mg/dose)
*review local antibiotogram

RENAL DOSING

Adults:
IV:
CrCl 5 to 29 mL/min: 200 to 400 mg IV q18-24h

PO:
Immediate-release:
CrCl 30 to 50 mL/min: 250 to 500 mg PO q12h
CrCl 5 to 29 mL/min: 250 to 500 mg PO q18h

Extended-release:
Cipro(R) XR:
CrCl 30 mL/min or less: 500 mg PO q24h

Proquin(R) XR:
Mild to moderate renal dysfunction: No adjustment recommended.
Severe renal dysfunction: Data not available

Pediatric Patients:
CrCl < 50 mL/min: Data not available

*Patients with severe infections and severe renal dysfunction may be given an oral dose of 750 mg (immediate-release) at the intervals above and should be monitored closely

DIALYSIS

Hemodialysis, peritoneal dialysis (ADULTS):
IV: Data not available
Oral: Immediate-release: 250 to 500 mg orally every 24 hours

Extended-release:
Cipro(R) XR: 500 mg orally every 24 hours
Proquin(R) XR: Data not available

*Dose should be administered after dialysis.
OTHER NOTES
Infuse IV doses over at least 60 minutes
Proquin(R) XR with a main meal, preferably the evening meal; others formulas does not matter
Do not administer suspension through feeding or nasogastric tubes.
May administer oral doses with meals that include dairy products (like milk, yogurt) or calcium-fortified juices; do not administer with such products alone.
Administer oral doses at least 2 hours before or 6 hours after magnesium/aluminum antacids, polymeric phosphate binders (e.g., sevelamer, lanthanum carbonate), sucralfate, buffered didanosine, other highly buffered drugs, or other products containing calcium, iron, or zinc; administer Proquin(R) XR at least 4 hours before or 2 hours after such products.
INTERESTING STUDIES
Animal studies and human studies suggest an association between Ciprofloxacin and aortic pathology. (1,2,3,4)
AKI - Large study showed odds ratio of 1.48 of AKI after treatment with ciprofloxacin in patients >65yrs  compared w/ amoxicillin with. ​(5)



GENERAL
US BOXED WARNING:
SERIOUS SIDE EFFECTS INCLUDING TENDINITIS, TENDON RUPTURE, PERIPHERAL NEUROPATHY, CNS EFFECTS, AND EXACERBATION OF MYASTHENIA GRAVIS:
-Fluoroquinolones (including this drug) have been associated with disabling and potentially irreversible serious side effects that have occurred together (including tendinitis and tendon rupture, peripheral neuropathy, CNS effects). This drug should be discontinued immediately and use of fluoroquinolones (including this drug) should be avoided in patients with any of these serious side effects.
-Fluoroquinolones (including this drug) may exacerbate muscle weakness in patients with myasthenia gravis. This drug should be avoided in patients with known history of myasthenia gravis.
-Since fluoroquinolones (including this drug) have been associated with serious side effects, this drug should be reserved for use in patients with no alternative treatment options for acute exacerbation of chronic bronchitis, acute uncomplicated cystitis/uncomplicated urinary tract infections (acute cystitis), or acute sinusitis.
Extended-release tablets: Safety and efficacy have not been established in patients younger than 18 years.
US FDA pregnancy category: C
If given w/ dairy or calcium may decrease absorption, otherwise no food effects
Volume of Distribution: 1.8 to 3 L/kg; widely distributed throughout body, distributes well into most tissues and body fluids. 
EXCRETION: Primarily renal, partial biliary, intestine.  Urine excretion complete w/in 24hrs
IV: 50% to 70% of dose in urine and about 15% of dose in feces (within 5 days) as unchanged drug
PO: About 40% to 50% of dose in urine and about 20% to 35% of dose in feces (within 5 days) as unchanged drug
Proquin(R) XR: After 500 mg dose, 26.9% in urine (over 24 hours) as unchanged drug; 
SUSCEPTIBILITIES


UTI: E coli, K pneumoniae, E cloacae, S marcescens, P mirabilis, P rettgeri, M morganii, C koseri, C freundii, P aeruginosa, S epidermidis (methicillin-susceptible), S saprophyticus, or Enterococcus faecalis
PYELONEPHRITIS (UNCOMPLICATED): E coli
CYSTITIS (UNCOMPLICATED):  E coli, S saprophyticus,  K pneumoniae, P mirabilis, E faecalis
PROSTATITIS:
E coli or P mirabilis
INTRA-ABDOMINAL INFECTIONS: In combination with metronidazole, for Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis, Klebsiella pneumoniae, or Bacteroides fragilis
JOINT & BONE INFECTIONS: Enterobacter cloacae, Serratia marcescens, or P aeruginosa
NOSOCOMIAL PNEUMONIA:  Haemophilus influenzae or K pneumoniae
PNEUMONIA:
E coli, K pneumoniae, E cloacae, P mirabilis, P aeruginosa, H influenzae, H parainfluenzae, or S pneumoniae; for the treatment of AECB due to Moraxella catarrhalis
SKIN & STRUCTURAL INFECTION E coli, K pneumoniae, E cloacae, P mirabilis, P vulgaris, Providencia stuartii, Morganella morganii, Citrobacter freundii, P aeruginosa, Staphylococcus aureus (methicillin-susceptible), S epidermidis (methicillin-susceptible), or S pyogenes
Some isolates of P aeruginosa may develop resistance relatively quickly during therapy.  Can also treat salmonella, typhoid, tularemia, meningococcal prophylaxis, cholera, traveller's diarrhea, chancroid (see below), granuloma inguinale (see below), anthrax prophylaxis and treatment, plague,  shigella  
MONITORING
Culture and susceptibility (periodically during therapy); syphilis serology in gonorrhea patients (at diagnosis and 3 months after therapy)
Renal: Renal function in elderly patients  
MECHANISM Topoisomerase (DNA gyrase) inhibitor, bactericidal.
MEDICATION INTERACTIONS
Methotrexate - do not use
theophylline - Avoid if at all possible
May increase concentration of drugs metabolized by CYP450 1A2 theophylline, caffeine, methylxanthines, tizanidine, ropinirole, olanzapine, duloxetine, clozapine,  agomelatine
CONTRAINDICATIONS
Hypersensitivity to the active component, other quinolones, or any of the ingredients; coadministration with tizanidine
WARNINGS/PRECAUTIONS:

CARDIOVASCULAR - Prolongation of the QT Interval/Cardiac Disorders:
DERMATOLOGIC - Photosensitivity/Phototoxicity, SJS
MUSCULOSKELETAL -  Tendinitis, Tendon Rupture
NERVOUS - dizziness, Peripheral Neuropathy,  CNS effects (hallucinations, anxiety, depression, insomnia, severe headaches, confusion); Exacerbation of Myasthenia Gravis:
OTHERS - vasculitis, arthralgia, myalgia, serum sickness, allergic pneumonitis, interstitial nephritis, acute renal insufficiency or failure, hepatitis, jaundice, acute hepatic necrosis or failure, anemia (including hemolytic and aplastic), thrombocytopenia (including thrombotic thrombocytopenic purpura), leukopenia, agranulocytosis, pancytopenia, and/or other hematologic abnormalities.
HEPATIC - Hepatotoxicity:
GI - C. diff
METABOLIC - Hypoglycemia:


SIDE EFFECTS


DOSAGE




Lactation (Top)

Comments:
-The effects in the nursing infant are unknown; potential risk of serious side effects (including articular damage) in the nursing infant.
-This drug is considered compatible with breastfeeding by the American Academy of Pediatrics.


Side Effects (Top)

General Most common PO - nausea, diarrhea, abnormal liver function tests, vomiting, and rash;  IV - nausea, diarrhea, vomiting, injection and infusion site reactions, rash, and increased transaminases (transient).

Gastrointestinal
Common (1% to 10%): Nausea, diarrhea, vomiting, dyspepsia
Uncommon (0.1% to 1%): Abdominal pains/discomfort, gastrointestinal (GI) pains, flatulence
Rare (0.01% to 0.1%): Elevated amylase, antibiotic-associated colitis, pancreatitis
Frequency not reported: Clostridium difficile-associated diarrhea, constipation, GI bleeding, ileus, intestinal perforation, dry mouth, oral ulceration, epigastric pain, dysphagia, elevated lipase, painful oral mucosa, heartburn, acid reflux, aggravated irritable bowel syndrome, lower abdominal pain
Postmarketing reports: GI candidiasis, oral candidiasis, pseudomembranous colitis

Dermatologic
Common (1% to 10%): Rash
Uncommon (0.1% to 1%): Pruritus, urticaria
Rare (0.01% to 0.1%): Angioedema, photosensitivity reactions, sweating/hyperhidrosis, petechiae, blistering
Very rare (less than 0.01%): Erythema multiforme, erythema nodosum, Stevens-Johnson syndrome (potentially life-threatening), toxic epidermal necrolysis (potentially life-threatening)
Frequency not reported: Exfoliative dermatitis, purpura, burning, phototoxicity reaction, dry skin, maculopapular rash, skin disorder, vesiculobullous rash, erythema, hyperpigmentation, cutaneous candidiasis, bullous pemphigoid, vesicles, lobular panniculitis, photoinduced acute exanthematous pustulosis, drug reaction with eosinophilia and systemic symptoms (DRESS)
Postmarketing reports: Acute generalized exanthematous pustulosis, fixed eruption

Nervous system
Common (1% to 10%): Headache, dizziness/lightheadedness, central nervous system disturbance
Uncommon (0.1% to 1%): Sleep disorders, taste disorders, seizures (including status epilepticus), dysesthesia, paresthesia, vertigo, hearing loss
Rare (0.01% to 0.1%): Syncope, hypoesthesia, tremor, tinnitus, migraine, olfactory nerve disorders, smell disorders, hearing impaired
Very rare (less than 0.01%): Disturbed coordination, intracranial hypertension, benign intracranial hypertension/pseudotumor cerebri, exacerbation of myasthenia gravis, hyperesthesia
Frequency not reported: Unresponsiveness, ataxia, hypertonia, anosmia, nystagmus, taste perversion/bad taste, somnolence/drowsiness, incoordination, disturbance in attention, dyskinesia, myasthenia gravis, paresis, aseptic meningitis, cerebral thrombosis, grand mal convulsion, dysphasia, lethargy, sensory axonal polyneuropathy, sensorimotor axonal polyneuropathy
Postmarketing reports: Taste loss, peripheral neuropathy (may be irreversible), polyneuropathy

Hematologic
Common (1% to 10%): Eosinophilia
Uncommon (0.1% to 1%): Thrombocytopenia, thrombocythemia
Rare (0.01% to 0.1%): Leukopenia, anemia, neutropenia, leukocytosis, pancytopenia, bone marrow depression, abnormal prothrombin level
Very rare (less than 0.01%): Hemolytic anemia, agranulocytosis
Frequency not reported: Decreased hematocrit, decreased platelet counts, increased platelet counts, prolonged prothrombin time, decreased prothrombin, bleeding diathesis, decreased hemoglobin, decreased leukocyte count, increased atypical lymphocyte count, immature WBCs, increased blood monocytes, elevated sedimentation rate, elevated eosinophil counts, lymphadenopathy
Postmarketing reports: Methemoglobinemia, increased INR, prothrombin time prolonged or decreased

Hepatic

Common (1% to 10%): Abnormal liver function tests, increased transaminases
Uncommon (0.1% to 1%): Elevated bilirubin, hepatic impairment, cholestatic icterus/cholestatic jaundice, jaundice
Rare (0.01% to 0.1%): Hepatitis, liver necrosis
Very rare (less than 0.01%): Hepatic failure
Frequency not reported: Elevated AST, elevated ALT, elevated GGT

Psychiatric
Common (1% to 10%): Restlessness
Uncommon (0.1% to 1%): Psychomotor hyperactivity/agitation, confusion, disorientation, hallucinations
Rare (0.01% to 0.1%): Anxiety reaction, abnormal dreams, depression, psychotic reactions
Frequency not reported: Depersonalization, insomnia, manic reaction, nightmares, paranoia, phobia, toxic psychosis, nervousness, self-injurious behavior, suicidal ideations/thoughts, attempted suicide, completed suicide, catatonia, mania (including hypomania)
Postmarketing reports: Delirium

Genitourinary
Common (1% to 10%): Vaginal candidiasis
Rare (0.01% to 0.1%): Hematuria, crystalluria
Frequency not reported: Albuminuria, cylindruria, frequent urination, hemorrhagic cystitis, vaginitis, dysmenorrhea, candiduria, polyuria, urethral bleeding, urinary retention, urinary tract infection, fungal vaginosis, bacterial vaginitis, dysuria, abnormal urine odor, female genital pruritus, vaginal infection, urinary frequency, micturition urgency, vaginal pruritus

Local
Common (1% to 10%): Local IV site reactions, injection and infusion site reactions (e.g., phlebitis, thrombophlebitis)
Frequency not reported: Injection site irritation and induration with IV infusion

Musculoskeletal
Uncommon (0.1% to 1%): Musculoskeletal pain (e.g., extremity pain, back pain, chest pain), arthralgia
Rare (0.01% to 0.1%): Myalgia, arthritis, increased muscle tone and cramping, tendon rupture (mainly Achilles tendon)
Very rare (less than 0.01%): Tendinitis, muscular weakness
Frequency not reported: Arthropathy (including suspected reversible cases), joint stiffness, elevated serum creatine phosphokinase, abnormal joint exam, joint sprains, arthrosis, bone pain, decreased range of motion in a joint (knee, elbow, ankle, hip, wrist, shoulder), jaw pain, neck pain, gout flare-up, joint swelling, muscle spasms, night cramps, knee inflammation
Postmarketing reports: Myoclonus, myasthenia, twitching

Cardiovascular
Uncommon (0.1% to 1%): Tachycardia, vasodilatation, hypotension
Rare (0.01% to 0.1%): Vasculitis
Frequency not reported: Angina pectoris, cardiopulmonary arrest, myocardial infarction, hypertension, palpitation, bradycardia, arrhythmia, atrial flutter, cardiac murmur, cardiovascular collapse, ventricular ectopy, ventricular bigeminy, abdominal aortic bruit, postural hypotension
Postmarketing reports: QT prolongation/ECG QT prolonged, torsade de pointes, ventricular arrhythmia

Other 1
Uncommon (0.1% to 1%): Candida infections, mycotic superinfections, pain, fever, malaise/feeling unwell, asthenia, edema
Very rare (less than 0.01%): Gait disturbance/abnormal gait
Frequency not reported: Irritability, flushing, thirst, elevated serum calcium, elevated serum potassium, elevated triglycerides, decreased serum albumin, decreased serum potassium, decreased total serum protein, elevated serum theophylline, serum phenytoin altered, chills, swelling, breast pain, achiness, weakness, fatigue, suprapubic pain, rigors, tenderness, fungal infection, increased body temperature
Postmarketing reports: Elevated serum cholesterol

Metabolic
Uncommon (0.1% to 1%): Elevated blood alkaline phosphatase, decreased appetite/anorexia, decreased food intake
Rare (0.01% to 0.1%): Hyperglycemia, hypoglycemia
Frequency not reported: Elevated LDH, elevated uric acid, elevated blood glucose, decreased uric acid, decreased blood glucose, acidosis, symptomatic hypoglycemia

Renal
Uncommon (0.1% to 1%): Renal impairment, renal failure
Rare (0.01% to 0.1%): Tubulointerstitial nephritis
Frequency not reported: Elevated serum creatinine, renal calculi, elevated BUN, decreased BUN, abnormal kidney function, allergic interstitial nephritis, nephritis, myoglobin-associated acute kidney injury/failure

Ocular
Uncommon (0.1% to 1%): Visual disturbances (e.g., chromatopsia, diplopia, photopsia)
Very rare (less than 0.01%): Visual color distortions
Frequency not reported: Decreased visual acuity, blurred vision, cataracts, multiple punctate lenticular opacities, eye pain

Hypersensitivity
Rare (0.01% to 0.1%): Allergic reactions, anaphylactic shock (life-threatening), allergic edema
Very rare (less than 0.01%): Anaphylactic reaction, serum sickness-like reaction
Frequency not reported: Anaphylactoid reactions, necrotizing vasculitis, cutaneous vasculitis

Respiratory
Rare (0.01% to 0.1%): Dyspnea (including asthmatic condition)
Frequency not reported: Bronchospasm, hemoptysis, laryngeal edema, respiratory arrest, epistaxis, hiccough, pulmonary edema, pleural effusion, pulmonary embolism, respiratory distress, wheeze, cough, upper respiratory tract infection, pharyngitis, nasopharyngitis

Endocrine
Frequency not reported: Gynecomastia

Immunologic
Frequency not reported: Jarisch-Herxheimer reaction
Antibiotic-associated colitis with possible fatal outcome was reported very rarely.
The onset of pseudomembranous colitis symptoms has been reported during or after antimicrobial treatment.
Photosensitivity was seen most often when patients were exposed to intense sun (e.g., as when used to treat or prevent travelers' diarrhea).
Erythema nodosum, Stevens-Johnson syndrome (potentially life-threatening), and TEN (potentially life-threatening) have also been reported during postmarketing experience.
Seizures have been reported in 2 patients given this drug and foscarnet. 
Cases of sensory or sensorimotor axonal polyneuropathy (affecting small and/or large axons) resulting in paresthesias, hypoesthesias, dysesthesias, and weakness have been reported.
Nystagmus, anosmia, hyperesthesia, hypoesthesia, hypertonia, intracranial hypertension, and exacerbation of myasthenia gravis have also been reported during postmarketing experience.
Pancytopenia (life-threatening or fatal outcome) and bone marrow depression (life-threatening) were reported very rarely; also reported during postmarketing experience.
Increased INR was reported in patients treated with vitamin K antagonists.
Liver necrosis very rarely progressed to life-threatening hepatic failure. Liver necrosis and hepatic failure (including fatal cases) have also been reported during postmarketing experience.
Depression and psychotic reactions (both potentially culminating in self-injurious behavior such as suicidal ideations/thoughts and attempted or completed suicide) have been reported.
Agitation, confusion, and toxic psychosis have also been reported during postmarketing experience.
Crystalluria has been reported in patients with alkaline urine and did not necessarily lead to nephrotoxicity. At physiological urinary pH, the risk of crystalluria was considered minor.
Vaginal candidiasis has also been reported during postmarketing experience.
Local IV site reactions occurred more often if the infusion time was 30 minutes or less. These reactions have appeared as local skin reactions and resolved quickly when infusion was completed.
Injection site irritation and induration have been reported with IV infusion time 30 minutes or less (instead of the recommended 1 hour) or when a small vein in the back of the hand was used.

Tendinitis with subsequent tendon rupture has been documented in numerous case reports. One patient with chronic renal failure developed bilateral Achilles tendon rupture after 4 days of ciprofloxacin therapy. Although renal transplant patients and those with end-stage renal disease tend to have an increased risk of Achilles tendinitis and rupture over the general population, quinolone use has been shown to further increase that risk (12% in quinolone-treated patients versus 7% in nonquinolone-treated patients).

Multiple cases of achilles tendon rupture had been reported to the US FDA. Some ruptures have also occurred in the hand or shoulder. Other risk factors identified included age and corticosteroid use.

Musculoskeletal side effects reported in pediatric patients included arthralgia, abnormal gait, abnormal joint exam, joint sprains, leg pain, back pain, arthrosis, bone pain, pain, myalgia, arm pain, and decreased range of motion in a joint (knee, elbow, ankle, hip, wrist, shoulder).
Myalgia, tendinitis, and tendon rupture have also been reported during postmarketing experience.
Torsade de pointes was reported mainly in patients with risk factors for QT prolongation.
Vasculitis has also been reported during postmarketing experience.
Elevated serum theophylline has been reported in patients receiving theophylline concomitantly.
Gait disturbance and elevated serum potassium have also been reported during postmarketing experience.
Quinolone class antibiotics have been associated with symptomatic hypoglycemia.
Allergic interstitial nephritis resulting in nonoliguric renal failure has been described in numerous case reports. Several cases included symptoms of rash, fever, and arthralgia and were accompanied by eosinophilia and eosinophiluria. Cases of allergic interstitial nephritis often responded to short courses of corticosteroid therapy.

Quinolone class antibiotics have been associated with cataracts and multiple punctate lenticular opacities.

Allergic reactions ranged from urticaria to anaphylactic reactions, including life-threatening anaphylactic shock.



Dosage (Top)
ADULT
Intraabdominal Infection
IV: 400 mg IV q12h x7-14d
Oral: 500 mg PO  q12h x7-14d
INDICATION: In combination with metronidazole, for treatment of complicated intraabdominal infections due to Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis, Klebsiella pneumoniae, or Bacteroides fragilis
Joint & Bone Infection
IV: 400 mg IV q8-12h x4-8wks
Oral: 500 to 750 mg PO q12h x4-8wks
INDICATION: For treatment of bone and joint infections due to Enterobacter cloacae, Serratia marcescens, or P aeruginosa
Nosocomial Pneumonia
400 mg IV q8h x10-14d 
*Initial empiric treatment with broad-spectrum coverage according to the hospital's and/or ICU's antibiogram is recommended if multidrug-resistant organisms are suspected.
*INDICATION: Haemophilus influenzae or K pneumoniae
Pneumonia
IV: 400 mg IV q8-12h x7-14d
Oral: 500 to 750 mg po q12h x7-14d
INDICATION: For treatment of lower respiratory tract infections due to E coli, K pneumoniae, E cloacae, P mirabilis, P aeruginosa, H influenzae, H parainfluenzae, or S pneumoniae; for the treatment of AECB due to Moraxella catarrhalis
Skin and Structure Infection
IV: 400 mg IV q8-12h x7-14d
Oral: 500 to 750 mg PO q12h x7-14d
Duration of therapy: 7 to 14 days
INDICATION to E coli, K pneumoniae, E cloacae, P mirabilis, P vulgaris, Providencia stuartii, Morganella morganii, Citrobacter freundii, P aeruginosa, Staphylococcus aureus (methicillin-susceptible), S epidermidis (methicillin-susceptible), or S pyogenes
*animal bites = ok for Pasteurella, doesn't cover some anaerobes & MRSASurgical Site Infection
Incisional surgical site infection: IV 400mg q12h or PO 750mg q12h
Infection after animal bite:   IV 400mg q12h or PO 500-750mg q12h  

*Use with metronidazole if after intestinal/genitourinary tract surgery, surgery of axilla or perineum
*coverage for MRSA may be needed
Urinary Tract Infection
IV: 200 to 400 mg IV q8-12h x7-14d 
Oral: Immediate-release: 250 to 500 mg PO q12h x7-14d; 
Oral: Extended-release: (uncomplicated)  500 mg PO q24h x3d 
Oral: Extended-release: (complicated) 1000 mg  PO q24h x7-14d
Indication (UTIs) due to E coli, K pneumoniae, E cloacae, S marcescens, P mirabilis, P rettgeri, M morganii, C koseri, C freundii, P aeruginosa, S epidermidis (methicillin-susceptible), S saprophyticus, or Enterococcus faecalis
Pyelonephritis
Oral: 1000 mg PO q24h x7-14d
Indication: For the treatment of acute uncomplicated pyelonephritis due to E coli
Cystitis
Immediate-release: 250 mg PO q12h x3d
Extended-release: 500 mg PO q12h x3d
*drug should be saved for treatment of acute uncomplicated cystitis/uncomplicated UTI (acute cystitis) in patients with no alternative treatment options.
INDICATION: uncomplicated E coli, S saprophyticus,  K pneumoniae, P mirabilis, E faecalis
Prostatitis
IV: 400 mg IV q12h x28d
Oral: 500 mg PO q12h x28d
Indication: E coli or P mirabilis
Gonococcal Infection -- Uncomplicated
250 mg PO x1
**Not recommended for treatment of gonococcal infections in the US due to resistance; dual therapy with ceftriaxone and azithromycin is the recommended regimen for treatment of gonorrhea in the US.
Chancroid
500 mg PO BID x3d
*Sexual partner(s) should also be evaluated/treated
**There are better treatment regimens
Granuloma Inguinale
750 mg orally twice a day BID x3wks or more until lesions healed
*Sexual partner(s) should also be evaluated/treated
**There are better treatment regimens
Surgical Prophylaxis
400 mg IV once, starting within 120 minutes before surgical incision

Usual Pediatric Dose
-In patients younger than 18 years, this drug is only US FDA-approved for complicated UTIs, prevention of inhalation anthrax (postexposure), and plague.
Pyelonephritis
>1yr  
IV: 6 to 10 mg/kg IV q8h, (max dose 400mg/dose) x10-12d
PO: 10 to 20 mg/kg PO  q12h, (max dose: 750mg/dose)
*Not DOC in pediatric patients b/c side effects.
Indication: For treatment of complicated UTIs and pyelonephritis due to E coli
Urinary Tract Infection
>1yr
IV: 6 to 10 mg/kg IV q8h, (max dose 400mg/dose) x10-21d
PO: 10 to 20 mg/kg PO  q12h, (max dose: 750mg/dose)  x10-21d
*Not DOC in pediatric patients b/c side effects.  
Surgical Prophylaxis
>1yr
10 mg/kg IV x1 (max dose 400mg/dose)
*review local antibiotogram
Additional Dosage (Top)

Renal Dose Adjustments

Adults:
IV:
CrCl 5 to 29 mL/min: 200 to 400 mg IV q18-24h

PO:
Immediate-release:
CrCl 30 to 50 mL/min: 250 to 500 mg PO q12h
CrCl 5 to 29 mL/min: 250 to 500 mg PO q18h

Extended-release:
Cipro(R) XR:
CrCl 30 mL/min or less: 500 mg PO q24h

Proquin(R) XR:
Mild to moderate renal dysfunction: No adjustment recommended.
Severe renal dysfunction: Data not available

Pediatric Patients:
CrCl < 50 mL/min: Data not available

*Patients with severe infections and severe renal dysfunction may be given an oral dose of 750 mg (immediate-release) at the intervals above and should be monitored closely

Dialysis

Hemodialysis, peritoneal dialysis (ADULTS):
IV: Data not available
Oral: Immediate-release: 250 to 500 mg orally every 24 hours

Extended-release:
Cipro(R) XR: 500 mg orally every 24 hours
Proquin(R) XR: Data not available

*Dose should be administered after dialysis.

Other Comments
Infuse IV doses over at least 60 minutes
Proquin(R) XR with a main meal, preferably the evening meal; others formulas does not matter
Do not administer suspension through feeding or nasogastric tubes.
May administer oral doses with meals that include dairy products (like milk, yogurt) or calcium-fortified juices; do not administer with such products alone.
Administer oral doses at least 2 hours before or 6 hours after magnesium/aluminum antacids, polymeric phosphate binders (e.g., sevelamer, lanthanum carbonate), sucralfate, buffered didanosine, other highly buffered drugs, or other products containing calcium, iron, or zinc; administer Proquin(R) XR at least 4 hours before or 2 hours after such products.

​INTERESTING STUDIES
​Animal studies and human studies suggest an association between Ciprofloxacin and aortic pathology. (1,2,3,4)
AKI - Large study showed odds ratio of 1.48 of AKI after treatment with ciprofloxacin in patients >65yrs  compared w/ amoxicillin with. ​(5)
  1. Pasternak  B, Inghammar  M, Svanström  H.  Fluoroquinolone use and risk of aortic aneurysm and dissection: nationwide cohort study.  BMJ. 2018;360:k678. 
  2. Lee  CC, Lee  MT, Chen  YS,  et al.  Risk of aortic dissection and aortic aneurysm in patients taking oral 
  3. US Food and Drug Administration. FDA drug safety communication: FDA updates warnings for oral and injectable fluoroquinolone antibiotics due to disabling side effects. Published May 12, 2016. Accessed February 13, 2018.
  4. Daneman  N, Lu  H, Redelmeier  DA.  Fluoroquinolones and collagen associated severe adverse events: a longitudinal cohort study.  BMJ Open. 2015;5(11):e010077. 
  5. Crellin, Elizabeth, et al. "Trimethoprim use for urinary tract infection and risk of adverse outcomes in older patients: cohort study." bmj 360 (2018): k341.
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