Professional Information

Ciprofloxacin

Pronouncation: (SIP-roe-FLOX-a-sin)
Class: Antibiotic, Fluoroquinolone

Trade Names:
Ciloxan
- Ointment, ophthalmic 3.33 mg/g (equivalent to 3 mg base)
- Solution, ophthalmic 3.5 mg/mL (equivalent to 3 mg base)

Trade Names:
Cipro
- Tablets 250 mg
- Tablets 500 mg
- Tablets 750 mg
- Powder for oral suspension 250 mg per 5 mL (5%) (when reconstituted)
- Powder for oral suspension 500 mg per 5 mL (10%) (when reconstituted)

Trade Names:
Cipro IV
- Injection (premixed) 200 mg
- Injection (premixed) 400 mg
- Injection (concentrate) 10 mg/mL

Trade Names:
Cipro XR
- Tablets, extended-release 500 mg
- Tablets, extended-release 1,000 mg

Trade Names:
Proquin XR
- Tablets, extended-release 500 mg

Apo-Ciproflox (Canada)
Cipro XL (Canada)
CO Ciprofloxacin (Canada)
Gen-Ciprofloxacin (Canada)
PMS-Ciprofloxacin (Canada)
RAN-Ciprofloxacin (Canada)
ratio-Ciprofloxacin (Canada)
Sandoz Ciprofloxacin (Canada)
Taro-Ciprofloxacin (Canada)

Pharmacology

Inhibits microbial DNA replication, transcription, repair, and recombination.

Pharmacokinetics

Absorption

Oral

Rapidly and well absorbed. Bioavailability is about 70%. T _max is 1 to 2 h (1 to 4 h for extended-release; 6 h for Proquin XR ). C _max is 1.2 to 5.4 mcg/mL (250 to 1,000 mg for immediate-release); 1.59 to 3.11 mcg/mL (500 to 1,000 mg for extended-release); 0.82 mcg/mL ( Proquin XR ).

C _max is 2.1 to 4.6 mcg/mL.

Distribution

20% to 40% protein bound. Widely distributed. Diffuses into the CSF, but concentrations are less than 10% of peak serum concentrations. Vd for IV is 2.1 to 2.7 L/kg.

Metabolism

Oral

Four metabolites have been identified that account for about 15% of the dose (11% for Proquin XR ); they are less active than the parent compound.

Three metabolites have been identified that account for about 10% of the dose.

Elimination

Oral

About 40% to 50% is excreted unchanged in urine (30% for Proquin XR ); 20% to 35% is recovered in feces (43% for Proquin XR ). The t _½ is about 4 h (4.5 h for Proquin XR ). Cl is about 300 mL/min.

About 50% to 70% is excreted unchanged in urine; about 15% is recovered in feces. The t _½ is about 5 to 6 h. Cl is about 35 L/h.

Special Populations

Renal Function Impairment

The t _½ is prolonged.

Hepatic Function Impairment

No changes in pharmacokinetics in patients with chronic liver cirrhosis. Acute hepatic function impairment has not been fully evaluated.

Elderly

C _max increased 16% to 40%, AUC increased about 20% to 30%, and t _½ increased about 20%.

Indications and Usage

Tablets, oral suspension ( Cipro ) Adults

Treatment of acute sinusitis, acute uncomplicated cystitis in women, bone and joint infections, chronic bacterial prostatitis, complicated intra-abdominal infections, infectious diarrhea, lower respiratory tract infections, skin and skin structure infections, typhoid fever, uncomplicated cervical and urethral gonorrhea, UTIs.

Extended-release tablets Adults ( Cipro XR )

Treatment of acute cystitis, complicated UTIs, acute uncomplicated pyelonephritis.

Adults ( Proquin XR )

Treatment of uncomplicated UTIs.

IV ( Cipro IV ) Adults

Treatment of acute sinusitis, bone and joint infections, chronic bacterial prostatitis, complicated intra-abdominal infections, empirical therapy for febrile neutropenic patients, lower respiratory tract infections, nosocomial pneumonia, skin and skin structure infections, UTIs.

Children (1 to 17 yr of age)

Treatment of complicated UTIs and pyelonephritis (tablets, oral suspension, IV).

Adults and children

Treatment of inhalational anthrax (tablets, oral suspension, IV).

Ophthalmic use

Treatment of corneal ulcers (solution only) and conjunctivitis caused by susceptible organisms.

Unlabeled Uses

Multidrug-resistant tuberculosis; alternative regimen for tularemia, cutaneous and GI anthrax, plague, and disseminated gonorrhea; cystic fibrosis and gastroenteritis in children; as part of combination therapy for treating atypical mycobacterial infections.

Contraindications

Coadministration with tizanidine; standard considerations.

Dosage and Administration

Acute Sinusitis
Adults

PO 500 mg or IV 400 mg every 12 h for 10 days.

Acute Uncomplicated Pyelonephritis
Adults

PO ( Cipro XR ) 1,000 mg every 24 h for 7 to 14 days.

Bone and Joint Infections
Adults Mild/Moderate

PO 500 mg or IV 400 mg every 12 h for at least 4 to 6 wk.

Severe/Complicated

PO 750 mg every 12 h or IV 400 mg every 8 h for at least 4 to 6 wk.

Chronic Bacterial Prostatitis
Adults (mild/moderate)

PO 500 mg or IV 400 mg every 12 h for 28 days.

Empirical Therapy for Febrile Neutropenic Patients
Adults (severe)

IV ciprofloxacin 400 mg every 8 h plus piperacillin 50 mg/kg (not to exceed 24 g/day) every 4 h for 7 to 14 days.

Infectious Diarrhea
Adults

PO 500 mg every 12 h for 5 to 7 days.

Inhalational Anthrax (Postexposure)
Adults

PO 500 mg or IV 400 mg every 12 h for 60 days.

Children

PO 15 mg/kg/dose (max, 500 mg dose) or IV 10 mg/kg/dose (max, 400 mg dose) every 12 h for 60 days.

Intra-abdominal Infections
Adults (complicated)

PO 500 mg or IV 400 mg every 12 h for 7 to 14 days in combination with metronidazole.

Lower Respiratory Tract Infections
Adults Mild/Moderate

PO 500 mg or IV 400 mg every 12 h for 7 to 14 days.

Severe/Complicated

PO 750 mg every 12 h or IV 400 mg every 8 h for 7 to 14 days.

Nosocomial Pneumonia
Adults

IV 400 mg every 8 h for 10 to 14 days.

Ocular Infections
Corneal ulcers

Solution Day 1: 2 drops in affected eye every 15 min for 6 h, then 2 drops every 30 min for remainder of day 1. Day 2: 2 drops every hour. Days 3 through 14: 2 drops every 4 h. May continue treatment after 14 days if corneal re-epithelialization has not occurred.

Conjunctivitis

Ointment Apply half-inch ribbon into conjunctival sac 3 times daily for the first 2 days, then twice daily for the next 5 days. Solution 1 to 2 drops every 2 h while awake for 2 days, then 1 to 2 drops every 4 h while awake for 5 days.

Skin and Skin Structure Infections
Adults Mild/Moderate

PO 500 mg or IV 400 mg every 12 h for 7 to 14 days.

Severe/Complicated

PO 750 mg every 12 h or IV 400 mg every 8 h for 7 to 14 days.

Typhoid Fever
Adults (mild/moderate)

PO 500 mg every 12 h for 10 days.

Urethral/Cervical Gonococcal Infections
Adults (uncomplicated)

PO 250 mg as a single dose.

UTIs
Adults Acute Uncomplicated

PO 250 mg every 12 h for 3 days. For Cipro XR , PO 500 mg every 24 h for 3 days. For Proquin XR , PO 500 mg once daily for 3 days.

Mild/Moderate

PO 250 mg or IV 200 mg every 12 h for 7 to 14 days.

Severe/Complicated

PO 500 mg or IV 400 mg every 12 h for 7 to 14 days. For Cipro XR , PO 1,000 mg every 24 h for 7 to 14 days.

Complicated UTI or Pyelonephritis in Children
Children 1 to 17 yr of age

PO 10 to 20 mg/kg every 12 h (max, 750 mg/dose, even in patients weighing more than 51 kg) or IV 6 to 10 mg/kg every 8 h (max, 400 mg/dose, even in patients weighing more than 51 kg) for 10 to 21 days.

Renal Function Impairment
Adults

PO Immediate-release/oral suspension: Usual dosage with CrCl more than 50 mL/min; 250 to 500 mg every 12 h for CrCl 30 to 50 mL/min; 250 to 500 mg every 18 h for CrCl 5 to 29 mL/min; 250 to 500 mg every 24 h (after dialysis) for patients on peritoneal or hemodialysis. Cipro XR : Usual dosage when using 500 mg tablets; for CrCl less than 30 mL/min max, dose is 500 mg every 24 h. For patients on dialysis, administer dose after dialysis procedure is complete. Proquin XR : No dosage adjustment is needed for patients with mild to moderate renal function impairment. IV Usual dosage with CrCl more than 30 mL/min; 200 to 400 mg every 18 to 24 h for CrCl 5 to 29 mL/min.

General Advice

Conversion of IV to oral dosing with immediate-release tablets or suspension in adults
200 mg IV every 12 h equivalent to 250 mg orally every 12 h; 400 mg IV every 12 h equivalent to 500 mg orally every 12 h; 400 mg IV every 8 h equivalent to 750 mg orally every 12 h.

Tablets and suspension
Immediate-release tablets and suspension are interchangeable on a mg-to-mg basis.
Extended-release tablets and immediate-release tablets are not interchangeable.
Extended-release Cipro XR and extended-release Proquin XR are not interchangeable.
Extended-release tablets are for treatment of UTIs only. Safety and efficacy in treating infections other than UTIs have not been demonstrated. Proquin XR is indicated only for treating uncomplicated UTIs.
Administer tablets with a full glass of water without regard to meals. Administer with food if GI upset occurs.
Administer extended-release tablets whole. Do not split, cut, crush, or chew.
Administer Proquin XR with a main meal of the day, preferably the evening meal.
Do not administer with dairy products or calcium-fortified juices unless they are part of a meal.
Administer ciprofloxacin 2 h before or 6 h after magnesium/aluminum antacids, sucralfate, didanosine buffered tablets or pediatric powder, or other products containing calcium, iron, or zinc.
Shake suspension vigorously for 15 sec before measuring dose.
Measure and administer prescribed dose of suspension using dosing spoon, syringe, or cup. Caution patient not to chew the microcapsules in the suspension.
Suspension cannot be administered through feeding tube.

Ophthalmic Solution and Ointment
For ophthalmic use only. Not for use on the skin or for injection into eye.
Instill prescribed number of drops or ribbon of ointment into affected eye(s) as ordered.
If using other topical ophthalmic drugs, separate each medication by at least 5 min. Instill ointment last.

Injection
For IV infusion only. Not for intradermal, subcutaneous, IM, IV bolus, or intra-arterial administration.
Injection concentrate must be diluted before administration. Withdraw prescribed dose of concentrate from vial and dilute with a compatible IV solution for a final concentration of 1 to 2 mg/mL. Discard any unused portion of injection concentrate.
Ciprofloxacin in premixed flexible containers do not require further dilution.
Infuse prescribed dose over 60 min by direct infusion in a large vein or through a Y-type IV infusion set.
If other drugs are being administered through the same IV line, administer each medication separately.

Storage/Stability

Tablets and oral suspension

Store immediate-release tablets below 86°F. Store extended-release tablets at controlled room temperature (59° to 86°F). Store oral suspension below 77°F and protect from freezing. Store reconstituted suspension at room temperature below 86°F. Protect suspension from freezing. Discard any unused suspension after 14 days.

Ophthalmic solution and ointment

Store at 36° to 77°F. Keep containers tightly closed.

Injection

Store vials of injection concentrate between 41° and 86°F. Store flexible containers for IV infusion between 41° and 77°F. Protect from light, excessive heat, and freezing. Injection concentrate diluted in compatible IV infusion fluid is stable for up to 14 days in refrigerator (36° to 46°F) or at room temperature below 86°F.

Drug Interactions

Antacids, calcium, didanosine, iron salts, sucralfate, zinc salts

May decrease oral absorption of fluoroquinolones. Stagger administration times.

Anticoagulants

May increase effect of warfarin; monitor PT.

Azlocillin

Decreased Cl of ciprofloxacin.

Caffeine

Caffeine Cl is reduced.

Cyclosporine

Nephrotoxic effects of cyclosporine may be increased; monitor renal function.

Glyburide

Coadministration has resulted in severe hypoglycemia. Fatalities have been reported.

Methadone

Methadone plasma concentrations may be elevated, increasing the pharmacologic effects and adverse reactions.

Methotrexate

Renal tubular transport of methotrexate may be inhibited, increasing methotrexate plasma levels.

Metoclopramide

Rate of ciprofloxacin oral absorption may be accelerated; however, bioavailability is not affected.

NSAIDs

Risk of convulsions may be increased in patients receiving high-dose ciprofloxacin.

Omeprazole

AUC and C _max of ciprofloxacin are reduced by 20% and 23%, respectively.

Phenytoin

Plasma levels of phenytoin may be increased or decreased.

Probenecid

Decreased ciprofloxacin renal Cl.

Procainamide

Plasma levels may be elevated by ciprofloxacin.

Sevelamer

Bioavailability of ciprofloxacin may be reduced.

Theophylline

Increased plasma levels of theophylline may result in toxicity and death; monitor theophylline level.

Tizanidine

Plasma levels of tizanidine may be elevated 7-fold, increasing the risk of hypotension and sedation. Coadministration with ciprofloxacin is contraindicated.

Adverse Reactions

Cardiovascular

Arrhythmias; atrial flutter; bradycardia; cardiopulmonary arrest; cerebral thrombosis; CV collapse; MI; syncope; vasculitis; ventricular ectopy; postural hypotension, torsades de pointes, vasculitis (postmarketing).

CNS

Dizziness, headache, insomnia, nervousness, somnolence (3%); restlessness (more than 1%); abnormal dreams, abnormal gait, agitation, confusion, convulsive seizures, delirium, depersonalization, depression, hallucinations, hyperesthesia, hypertonia, incoordination, migraine, peripheral neuropathy, tonic-clonic seizures, toxic psychosis, tremor, twitching, vertigo (postmarketing).

Dermatologic

Rash (2%); erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis; fixed eruption (postmarketing).

EENT

Ocular crystalline precipitates (17%); nasopharyngitis, rhinitis (3%); conjunctival hypermia, foreign body sensation; itching, keratopathy, lid margin crusting (more than 1% to less than 10%); anosmia, blurred vision, decreased visual acuity, diplopia, dry eye, eye pain, hearing loss, lid erythema, nystagmus, tearing, (postmarketing).

GI

Diarrhea, vomiting (5%); dyspepsia, nausea (4%); abdominal pain (3%); constipation, dysphagia, flatulence, GI bleeding, intestinal pancreatitis, perforation, pseudomembranous colitis, taste loss (postmarketing).

Genitourinary

Micturition urgency, vaginal moniliasis (2%); abnormal kidney function, acute renal insufficiency or failure, candiduria, crystalluria, dysmenorrhea, hematuria, hemorrhagic cystitis, interstitial nephritis, renal calculi, urethral bleeding, vaginal candidiasis, vaginitis (postmarketing).

Hematologic-Lymphatic

Agranulocytosis, aplastic anemia, decreased or increased PT, eosinophilia, hemolytic anemia, leukopenia, methemoglobinemia, serum sickness, thrombocytopenia, thrombotic thrombocytopenia purpura (postmarketing).

Hepatic

Elevations of ALT and AST (2%); abnormal liver function tests (1%); acute hepatic necrosis or failure; hepatitis; jaundice.

Lab Tests

Elevated serum creatinine (1%); elevated cholesterol, elevated triglycerides (postmarketing).

Metabolic-Nutritional

Elevated blood glucose, hyperkalemia (postmarketing).

Musculoskeletal

Abnormal gait or joint exam in children (9%); flare-up of gout; myasthenia gravis; myoclonus; myasthenia, tendonitis, tendon rupture (postmarketing).

Respiratory

Asthma (2%); allergic pneumonitis; pleural effusion; pulmonary edema; pulmonary embolism; respiratory arrest.

Miscellaneous

Accidental injury, fungal infections (3%); fever (2%); anaphylactic reactions; moniliasis, photosensitivity (postmarketing).

Precautions

Monitor

Ensure CBC (including platelets and differential), renal function, and liver enzymes are evaluated before starting therapy and periodically thereafter during prolonged therapy. Monitor patient's response to therapy. Periodically assess organ system function with prolonged therapy.

Pregnancy

Category C .

Lactation

Excreted in breast milk.

Children

Not drug of first choice in children because of increased incidence of adverse reactions related to joints and surrounding tissue. Do not use ciprofloxacin tablets, oral suspension, or injection in children younger than 18 yr of age, except for listed indications. Do not use ophthalmic solution in children younger than 1 yr of age, ophthalmic ointment in children younger than 2 yr of age, or extended-release tablets in children younger than 18 yr of age.

Elderly

Because of risk of reduced renal function due to age, take care in dose selection, and renal function monitoring may be useful. May be more susceptible to effects on QT interval or tendons.

Hypersensitivity

Serious and potentially fatal reactions have occurred. Discontinue drug if allergic reaction occurs.

Renal Function

Adjust dose downward accordingly.

Superinfection

Use of antibiotics may result in bacterial or fungal overgrowth.

Photosensitivity

Moderate to severe reactions have occurred with some fluoroquinolones; avoid excessive sunlight and discontinue therapy if phototoxicity occurs.

CNS disorders

Seizures, increased intracranial pressure, and toxic psychosis have been reported. May also cause nervousness, agitation, insomnia, anxiety, nightmares, paranoia, dizziness, confusion, tremors, hallucinations, depression, and rarely, suicidal thoughts or acts. Discontinue therapy and institute appropriate measures if these reactions occur. Use with caution in patients with known or suspected CNS disorders or other risk factors (eg, drug therapy, renal function impairment) that may predispose to seizures or lower the seizure threshold.

Crystalline precipitate

An ocular white crystalline precipitate in superficial portion of corneal defect may occur.

Crystalluria

Has been reported rarely. Avoid alkalinity of the urine and keep patient well hydrated.

Extended-release tablets

Ensure that extended-release tablets are not used to treat infections other than UTIs.

Peripheral neuropathy

Sensory or sensorimotor axonal polyneuropathy resulting in paresthesias, hypoesthesias, dysesthesias, and weakness has been rarely reported. To prevent development of an irreversible condition, discontinue therapy if patient experiences symptoms of neuropathy.

Pseudomembranous colitis

Consider possibility in patients with diarrhea.

Syphilis

Not effective in treatment of syphilis. All patients with gonorrhea should have a serologic test for syphilis at time of diagnosis and 3 mo after treatment with ciprofloxacin.

Tendon ruptures

Achilles and other tendon ruptures requiring surgical repair and prolonged disability have been reported. Risk increased with concomitant corticosteroid therapy, especially in the elderly. Discontinue use if patient experiences pain, inflammation, or rupture of tendon.

Overdosage

Symptoms

Acute renal failure.

Patient Information

Advise patient to review the patient information leaflet carefully before starting therapy and to read and check for new information each time the medication is refilled.
Review dosing schedule and prescribed length of therapy with patient.
Reinforce to patient or caregiver the need to take exactly as prescribed and complete the entire course of therapy, even if symptoms of infection have disappeared. Caution patient or caregiver that skipping doses or not completing the full course of therapy may allow the infection to worsen, increase the possibility that the bacteria will become resistant to the antibiotic, and may cause infections that will not be treatable in the future.
Advise patient to drink fluids liberally (eg, eight 8 oz glasses of water daily) while taking this medication.
Advise patient to discontinue therapy and contact health care provider immediately if fainting, hives, itching, shortness of breath, skin rash, or palpitations occur.
Advise patient to discontinue therapy, and to rest and refrain from exercise and to notify health care provider if pain, tenderness, or rupture of tendon occurs.
Advise patient that medication may cause nerve problems and to discontinue therapy and notify health care provider immediately if burning, pain, tingling, numbness, and/or weakness develops.
Advise patient to report the following signs of superinfection to health care provider: black, furry tongue; white patches in mouth; foul-smelling stools; vaginal itching or discharge.
Warn patient that diarrhea containing blood or pus may be a sign of a serious disorder and to seek medical care if noted and not treat at home.
Caution patient that drug may cause dizziness and light-headedness and to use caution while driving or performing other tasks requiring mental alertness until tolerance is determined.
Advise patient to limit ingestion of caffeine-containing beverages/products because ciprofloxacin may cause caffeine to accumulate in the body, resulting in exaggerated caffeine effects.
Advise patient to avoid unnecessary exposure to sunlight or tanning lamps and to use sunscreen and wear protective clothing to avoid photosensitivity reactions.

Tablets and Suspension
Advise patient that medication can be taken without regard to meals, but to take with food if GI upset occurs. Proquin XR should be taken with the main meal of the day, preferably in the evening.
Advise patient to take ciprofloxacin 2 h before or 6 h after the following: magnesium/aluminum antacids, sucralfate, didanosine buffered tablets or pediatric powder, or other products containing calcium, iron, or zinc.
Caution patient not to take with dairy products or calcium-fortified juices unless they are part of a meal.
Instruct patient to take tablets with a full glass of water.
Caution patient taking extended-release tablets to swallow whole and not to chew, crush, or split the tablet.
Advise patient that if a dose is missed to take it as soon as remembered. However, if it is nearing the time for the next dose, to skip the dose and take the next dose at the regularly scheduled time. Caution patient taking extended-release tablets to never take more than 1 tablet/day, even if a dose is missed.
Instruct patient using oral suspension to shake vigorously for 15 sec before measuring dose.
Advise patient to use dosing spoon, syringe, or cup to measure and administer dose. Caution patient not to chew the microcapsules in the suspension.

Ophthalmic solution and ointment
Remind patient that eye drops and ointment are for use in the eye only.
Teach patient, family, or caregiver the following proper technique for instilling eye drops: Wash hands; do not allow dropper to touch eye; tilt head back, look up; pull lower eyelid down; instill prescribed number of drops. Close eye for 1 to 2 min and apply gentle pressure to bridge of nose for 3 to 5 min. Do not rub eye.
Teach patient, family, or caregiver the following proper technique for instilling ointment: Wash hands; do not allow tip of tube to touch eye, eyelid, fingers, or any other surface; tilt head back, look up; pull lower eyelid down to form pocket; place prescribed amount of ointment in the pocket. Look downward before closing eye. Do not rub eye.
Advise patient that if more than 1 topical ophthalmic drug is being used to administer the drugs at least 5 min apart. Administer ointment last.
Inform patient that temporary blurred vision, eye pain, or eye discomfort are the most common adverse reactions and to contact health care provider if they occur and are bothersome.
Advise patient to contact health care provider if eye or eyelid inflammation is noted or if eye symptoms do not improve or worsen.
Instruct patient not to wear contact lenses if they have signs and symptoms of bacterial conjunctivitis.