Cipro

Cipro and Cipro XR as well as other antibiotics in the fluoroquinolone class of antibiotics has been associated with tendonitis and even tendon rupture, particularly the Achilles tendon. Some doctors and other medical professionals recommend that their patients discontinue vigorous exercise while they are taking fluoroquinolone antibiotics.

Fluoroquinolones have neuromuscular blocking activity and can worsen muscle weakness in individuals with myasthenia gravis.

Mechanism Of Action

Ciprofloxacin is a member of the fluoroquinolone class of antibacterial agents [see Microbiology].

Pharmacokinetics

CIPRO XR tablets are formulated to release drug at a slower rate compared to immediate-release tablets. Approximately 35% of the dose is contained within an immediate-release component, while the remaining 65% is contained in a slow-release matrix.

Maximum plasma ciprofloxacin concentrations are attained between 1 and 4 hours after dosing with CIPRO XR. In comparison to the 250 mg and 500 mg ciprofloxacin immediate-release twice a day (BID) treatment, the Cmax of CIPRO XR 500 mg and 1000 mg once daily are higher than the corresponding BID doses, while the AUCs over 24 hours are equivalent.

The following table compares the pharmacokinetic parameters obtained at steady state for these four treatment regimens (500 mg once a day (QD) CIPRO XR versus 250 mg BID ciprofloxacin immediate-release tablets and 1000 mg QD CIPRO XR versus 500 mg BID ciprofloxacin immediate-release).

Table 5: Ciprofloxacin Pharmacokinetics (Mean ± SD) Following CIPRO and CIPRO XR Administration

Results of the pharmacokinetic studies demonstrate that CIPRO XR may be administered with or without food (for example, high-fat and low-fat meals or under fasted conditions).

The volume of distribution calculated for intravenous ciprofloxacin is approximately 2.1.2.7 L/kg. Studies with the oral and intravenous forms of ciprofloxacin have demonstrated penetration of ciprofloxacin into a variety of tissues. The binding of ciprofloxacin to serum proteins is 20% to 40%, which is not likely to be high enough to cause significant protein binding interactions with other drugs. Following administration of a single dose of CIPRO XR, ciprofloxacin concentrations in urine collected up to 4 hours after dosing averaged over 300 mg/L for both the 500 mg and 1000 mg tablets; in urine excreted from 12 to 24 hours after dosing, ciprofloxacin concentration averaged 27 mg/L for the 500 mg tablet, and 58 mg/L for the 1000 mg tablet.

Four metabolites of ciprofloxacin were identified in human urine. The metabolites have antimicrobial activity, but are less active than unchanged ciprofloxacin. The primary metabolites are oxociprofloxacin (M3) and sulfociprofloxacin (M2), each accounting for roughly 3% to 8% of the total dose. Other minor metabolites are desethylene ciprofloxacin (M1), and formylciprofloxacin (M4). The relative proportion of drug and metabolite in serum corresponds to the composition found in urine. Excretion of these metabolites was essentially complete by 24 hours after dosing. Ciprofloxacin is an inhibitor of CYP1A2 mediated metabolism. Co-administration of ciprofloxacin with other drugs primarily metabolized by CYP1A2 results in increased plasma concentrations of these drugs and could lead to clinically significant adverse events of the co-administered drug [see CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS and DRUG INTERACTIONS].

The elimination kinetics of ciprofloxacin are similar for the immediate-release and the CIPRO XR tablet. In studies comparing the CIPRO XR and immediate-release ciprofloxacin, approximately 35% of an orally administered dose was excreted in the urine as unchanged drug for both formulations. The urinary excretion of ciprofloxacin is virtually complete within 24 hours after dosing. The renal clearance of ciprofloxacin, which is approximately 300 mL/minute, exceeds the normal glomerular filtration rate of 120 mL/minute. Thus, active tubular secretion would seem to play a significant role in its elimination. Co-administration of probenecid with immediate-release ciprofloxacin results in about a 50% reduction in the ciprofloxacin renal clearance and a 50% increase in its concentration in the systemic circulation. Although bile concentrations of ciprofloxacin are several fold higher than serum concentrations after oral dosing with the immediate-release tablet, only a small amount of the dose administered is recovered from the bile as unchanged drug. An additional 1 to 2% of the dose is recovered from the bile in the form of metabolites. Approximately 20 to 35% of an oral dose of immediate-release ciprofloxacin is recovered from the feces within 5 days after dosing. This may arise from either biliary clearance or transintestinal elimination.

Specific Populations

Elderly Pharmacokinetic studies of the immediate-release oral tablet (single dose) and intravenous (single and multiple dose) forms of ciprofloxacin indicate that plasma concentrations of ciprofloxacin are higher in elderly subjects (> 65 years) as compared to young adults. Cmax is increased 16 to 40%,and mean AUC isincreasedapproximately 30%,which canbeatleastpartiallyattributed to decreased renal clearance in the elderly. Elimination half-life is only slightly (~20%) prolonged in the elderly. These differences are not considered clinically significant [see Use In Specific Populations].

In patients with reduced renal function, the half-life of ciprofloxacin is slightly prolonged. No dose adjustment is required for patients with uncomplicated UTIs receiving 500 mg CIPRO XR. For cUTI and AUP, where 1000 mg is the appropriate dose, the dosage of CIPRO XR should be reduced to CIPRO XR 500 mg q24h in patients with creatinine clearance equal to or below 30 mL/min [see DOSAGE AND ADMINISTRATION].

In preliminary studies in patients with stable chronic cirrhosis, no significant changes in ciprofloxacin pharmacokinetics have been observed. The kinetics of ciprofloxacin in patients with acute hepatic insufficiency, however, have not been fully elucidated [see Use In Specific Populations].

Drug-Drug Interactions

Concurrent administration of antacids containing magnesium hydroxide or aluminum hydroxide may reduce the bioavailability of CIPRO by as much as 90% [see DOSAGE AND ADMINISTRATION and DRUG INTERACTIONS].

Histamine H2-receptor antagonists appear to have no significant effect on the bioavailability of CIPRO.

The serum concentrations of CIPRO and metronidazole were not altered when these two drugs were given concomitantly.

In a pharmacokinetic study, systemic exposure of tizanidine (4 mg single dose) was significantly increased (Cmax 7-fold, AUC 10-fold) when the drug was given concomitantly with CIPRO (500 mg twice a day for 3 days). Concomitant administration of tizanidine and CIPRO XR is contraindicated due to the potentiation of hypotensive and sedative effects of tizanidine [see CONTRAINDICATIONS].

In a study conducted in 12 patients with Parkinsonfs disease who were administered 6 mg ropinirole once daily with 500 mg CIPRO twice-daily, the mean Cmax and mean AUC of ropinirole were increased by 60% and 84%, respectively. Monitoring for ropinirole-related adverse reactions and appropriate dose adjustment of ropinirole is recommended during and shortly after co-administration with CIPRO XR [see WARNINGS AND PRECAUTIONS].

Following concomitant administration of 250 mg CIPRO with 304 mg clozapine for 7 days, serum concentrations of clozapine and N-desmethylclozapine were increased by 29% and 31%, respectively. Careful monitoring of clozapine associated adverse reactions and appropriate adjustment of clozapine dosage during and shortly after co-administration with CIPRO XR are advised.

Following concomitant administration of a single oral dose of 50 mg sildenafil with 500 mg CIPRO to healthy subjects, the mean Cmax and mean AUC of sildenafil were both increased approximately two-fold. Use sildenafil with caution when co-administered with CIPRO XR due to the expected two-fold increase in the exposure of sildenafil upon co-administration of CIPRO [see DRUG INTERACTIONS].

In clinical studies it was demonstrated that concomitant use of duloxetine with strong inhibitors of the CYP450 1A2 isozyme such as fluvoxamine, may result in a 5-fold increase in mean AUC and a 2.5-fold increase in mean Cmax of duloxetine.

In a study conducted in 9 healthy volunteers, concomitant use of 1.5 mg/kg IV lidocaine with 500 mg ciprofloxacin twice daily resulted in an increase of lidocaine Cmax and AUC by 12% and 26%, respectively. Although lidocaine treatment was well tolerated at this elevated exposure, a possible interaction with CIPRO XR and an increase in adverse reactions related to lidocaine may occur upon concomitant administration.

Metoclopramide significantly accelerates the absorption of oral ciprofloxacin resulting in a shorter time to reach maximum plasma concentrations. No significant effect was observed on the bioavailability of ciprofloxacin.

When CIPRO XR was administered as a single 1000 mg dose concomitantly with omeprazole (40 mg once daily for three days) to 18 healthy volunteers, the mean AUC and Cmax of ciprofloxacin were reduced by 20% and 23%, respectively.

The clinical significance of this interaction has not been determined.

Microbiology

The bactericidal action of ciprofloxacin results from inhibition of the enzymes topoisomerase II (DNA gyrase) and topoisomerase IV (both Type II topoisomerases), which are required for bacterial DNA replication, transcription, repair, and recombination.

The mechanism of action of fluoroquinolones, including ciprofloxacin, is different from that of other antimicrobial agents such as beta-lactams, macrolides, tetracyclines, or aminoglycosides; therefore, microorganisms resistant to these classes of drugs may be susceptible to ciprofloxacin. Resistance to fluoroquinolones occurs primarily by either mutations in the DNA gyrases, decreased outer membrane permeability, or drug efflux. In vitro resistance to ciprofloxacin develops slowly by multiple step mutations. Resistance to ciprofloxacin due to spontaneous mutations occurs at a general frequency of between < 10-9 to 1x10-6 .

There is no known cross-resistance between ciprofloxacin and other classes of antimicrobials.

Ciprofloxacin has been shown to be active against most isolates of the following bacteria, both in vitro and in clinical infections ciprofloxacin [see INDICATIONS].

Enterococcus faecalis
Staphylococcus saprophyticus

Escherichia coli
Klebsiella pneumoniae
Proteus mirabilis
Pseudomonas aeruginosa

The following in vitro data are available, but their clinical significance is unknown. At least 90 percent of the following bacteria exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for ciprofloxacin (≤1 mcg/mL). However, the efficacy of ciprofloxacin in treating clinical infections due to these bacteria has not been established in adequate and well-controlled clinical trials.

Citrobacter koseri
Citrobacter freundii
Edwardsiella tarda
Enterobacter aerogenes
Enterobacter cloacae
Klebsiella oxytoca
Morganella morganii
Proteus vulgaris
Providencia rettgeri
Providencia stuartii
Serratia marcescens

Susceptibility Test Methods

When available, the clinical microbiology laboratory should provide the results of in vitro susceptibility test results for antimicrobial drug products used in resident hospitals to the physician as periodic reports that describe the susceptibility profile of nosocomial and community-acquired pathogens. These reports should aid the physician in selecting an antibacterial drug product for treatment.

Quantitative methods are used to determine antimicrobial minimum inhibitory concentrations (MICs). These MICs provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs should be determined using a standardized test method (broth and/or agar).1,3 The MIC values should be interpreted according to criteria provided in Table 5.

Quantitative methods that require measurement of zone diameters can also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. The zone size provides an estimate of the susceptibility of bacteria to antimicrobial compounds. The zone size should be determined using a standardized test method.2,3 This procedure uses paper disks impregnated with 5 mcg ciprofloxacin to test the susceptibility of bacteria to ciprofloxacin. The disc diffusion interpretive criteria are provided in Table 6.

Table 6: Susceptibility Test Interpretive Criteria for Ciprofloxacin

A report of “Susceptible” indicates that the antimicrobial is likely to inhibit growth of the pathogen if the antimicrobial compound reaches the concentrations at the site of infection necessary to inhibit growth of the pathogen. A report of “Intermediate” indicates that the result should be considered equivocal, and, if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where high dosage of drug can be used. This category also provides a buffer zone that prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of “Resistant” indicates that the antimicrobial is not likely to inhibit growth of the pathogen if the antimicrobial compound reaches the concentrations usually achievable at the infection site; other therapy should be selected.

Standardized susceptibility test procedures require the use of laboratory controls to monitor the accuracy and precision of supplies and reagents used in the assay, and the techniques of the individuals performing the test.1, 2 Standard ciprofloxacin powder should provide the following range of MIC values noted in Table 7. For the diffusion technique using the ciprofloxacin 5 mcg disk the criteria in Table 7 should be achieved.

Table 7: Acceptable Quality Control Ranges for Ciprofloxacin

Animal Toxicology And/Or Pharmacology

Ciprofloxacin and other quinolones have been shown to cause arthropathy in immature animals of most species tested [see WARNINGS AND PRECAUTIONS]. Damage of weight bearing joints was observed in juvenile dogs and rats. In young beagles, 100 mg/kg ciprofloxacin, given daily for 4 weeks, caused degenerative articular changes of the knee joint. At 30 mg/kg, the effect on the joint was minimal. In a subsequent study in young beagle dogs, oral ciprofloxacin doses of 30 mg/kg and 90 mg/kg given daily for 2 weeks caused articular changes which were still observed by histopathology after a treatment-free period of 5 months. At 10 mg/kg no effects on joints were observed. This dose was also not associated with arthrotoxicity after an additional treatment-free period of 5 months. In another study, removal of weight bearing from the joint reduced the lesions but did not totally prevent them.

Crystalluria, sometimes associated with secondary nephropathy, occurs in laboratory animals dosed with ciprofloxacin. This is primarily related to the reduced solubility of ciprofloxacin under alkaline conditions, which predominate in the urine of test animals; in man, crystalluria is rare since human urine is typically acidic. In rhesus monkeys, crystalluria without nephropathy has been noted after single oral doses as low as 5 mg/kg (approximately 0.1-times the highest recommended therapeutic dose based upon body surface area. After 6 months of intravenous dosing at 10 mg/kg/day, no nephropathological changes were noted; however, nephropathy was observed after dosing at 20 mg/kg/day for the same duration (approximately 0.4 times the highest recommended therapeutic dose based upon body surface area).

In dogs, ciprof1oxacin administered at 3 and 10 mg/kg by rapid infusion injection (15 sec.) produces hypotensive effects. These effects are considered to be related to histamine release because they are partially antagonized by pyrilamine, an antihistamine. In rhesus monkeys, rapid infusion injection also produces hypotension. but the effect in this species is inconsistent and less pronounced.

In mice, concomitant administration of nonsteroidal anti-inflammatory drugs such as phenylbutazone and indomethacin with quinolones has been reported to enhance the CNS stimulatory effect of quinolones.

Ocular toxicity seen with some related drugs has not been observed in ciprofloxacin-treated animals.

Clinical Studies

Uncomplicated Urinary Tract Infections (Acute Cystitis)

CIPRO XR was evaluated for the treatment of uncomplicated UTIs (acute cystitis) in a randomized, double-blind, controlled clinical trial conducted in the US. This study compared CIPRO XR (500 mg once daily for three days) with ciprofloxacin immediate-release tablets (CIPRO® 250 mg two times a day (BID) for three days). Of the 905 patients enrolled, 452 were randomly assigned to the CIPRO XR treatment group and 453 were randomly assigned to the control group. The primary efficacy variable was bacteriologic eradication of the baseline organism(s) with no new infection or superinfection at test-ofcure (Day 4.11 Post-therapy).

The bacteriologic eradication and clinical success rates were similar between CIPRO XR and the control group. The eradication and clinical success rates and their corresponding 95% confidence intervals for the differences between rates (CIPRO XR minus control group) are given in Table 8:

Table 8: Bacteriological Eradication and Clinical Cure Rates at the Test-of-Cure (TOC) Visit

Complicated Urinary Tract Infections And Acute Uncomplicated Pyelonephritis

CIPRO XR was evaluated for the treatment of cUTI and acute uncomplicated pyelonephritis (AUP) in a randomized, double-blind, controlled clinical trial conducted in the US and Canada. The study enrolled 1,042 patients (521 patients per treatment arm) and compared CIPRO XR (1000 mg once daily for 7 to 14 days) with immediate-release ciprofloxacin (500 mg BID for 7 to 14 days). The primary efficacy endpoint for this trial was bacteriologic eradication of the baseline organism(s) with no new infection or superinfection at 5 to 11 days post-therapy (test-of-cure or TOC) for the Per Protocol and Modified Intent-To-Treat (MITT) populations.

The Per Protocol population was defined as patients with a diagnosis of cUTI or AUP, a causative organism(s) at baseline present at ≥105 CFU/mL, no inclusion criteria violation, a valid test-of-cure urine culture within the TOC window, an organism susceptible to study drug, no premature discontinuation or loss to follow-up, and compliance with the dosage regimen (among other criteria). More patients in the CIPRO XR arm than in the control arm were excluded from the Per Protocol population and this should be considered in the interpretation of the study results. Reasons for exclusion with the greatest discrepancy between the two arms were no valid test-of-cure urine culture, an organism resistant to the study drug, and premature discontinuation due to adverse events.

An analysis of all patients with a causative organism(s) isolated at baseline and who received study medication, defined as the MITT population, included 342 patients in the CIPRO XR arm and 324 patients in the control arm. Patients with missing responses were counted as failures in this analysis. In the MITT analysis of cUTI patients, bacteriologic eradication was 160/271 (59%) versus 156/248 (62.9%) in CIPRO XR and control arm, respectively [97.5% CI* (-13.5%, 5.7%)]. Clinical cure was 184/271 (67.9%) for CIPRO XR and 182/248 (73.4%) for control arm, respectively [97.5% CI* (-14.4%, 3.5%)]. Bacterial eradication in the MITT analysis of patients with AUP at TOC was 47/71 (66.2%) and 58/76 (76.3%) for CIPRO XR and control arm, respectively [97.5% CI* (-26.8%, 6.5%)]. Clinical cure at TOC was 50/71 (70.4%) for CIPRO XR and 58/76 (76.3%) for the control arm [97.5% CI* (-22.0%, 10.4%)].

* confidence interval of the difference in rates (CIPRO XR minus control).

In the Per Protocol population, the differences between CIPRO XR and the control arm in bacteriologic eradication rates at the TOC visit were not consistent between AUP and cUTI patients. The bacteriologic eradication rate for cUTI patients was higher in the CIPRO XR arm than in the control arm. For AUP patients, the bacteriologic eradication rate was lower in the CIPRO XR arm than in the control arm. This inconsistency was not observed between the two treatment groups for clinical cure rates. Clinical cure rates were 96.1% (198/206) and 92.1% (211/229) for CIPRO XR and the control arm, respectively [difference: 4.0% with a two-sided 97.5% CI (-1.3%, 9.4%)].

The bacterial eradication and clinical cure rates by infection type for CIPRO XR and the control arm at the TOC visit and their corresponding 97.5% confidence intervals for the differences between rates (CIPRO XR minus control arm) are given in Table 9 for the Per Protocol population analysis.

Table 9: Bacteriological Eradication and Clinical Cure Rates at the Test-of-Cure (TOC) Visit

Of the 166 cUTI patients treated with CIPRO XR, 148 (89%) had the causative organism(s) eradicated, 8 (5%) had persistence, 5 (3%) patients developed superinfections and 5 (3%) developed new infections. Of the 177 cUTI patients treated in the control arm, 144 (81%) had the causative organism(s) eradicated, 16 (9%) patients had persistence, 3 (2%) developed superinfections and 14 (8%) developed new infections. Of the 40 patients with AUP treated with CIPRO XR, 35 (87.5%) had the causative organism(s) eradicated, 2 (5%) patients had persistence and 3 (7.5%) developed new infections. Of the 5 CIPRO XR AUP patients without eradication at TOC, 4 were considered clinical cures and did not receive alternative antibiotic therapy. Of the 52 patients with AUP treated in the control arm, 51 (98%) had the causative organism(s) eradicated. One patient (2%) had persistence.

REFERENCES

1. Clinical and Laboratory Standards Institute, Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard.Tenth Edition. CLSI Document M7-A10 [2015]. Clinical and Laboratory Standards Institute , 950 West Valley Rd., Suite 2500, Wayne, PA. PA. 19087-1898

2. Clinical and Laboratory Standards Institute (CLSI), Performance Standards for Antimicrobial Disk Susceptibility Tests; Approved Standard.Twelfth Edition. CLSI Document M2-A12 [2015]. Clinical and Laboratory Standards Institute, 950 West Valley Rd., Suite 2500, Wayne, PA. 19087-1898.

3. Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Susceptibility Testing; Twenty-seventh Informational Supplement. CLSI Document M100 S27 [2017]. Clinical and Laboratory Standards Institute, 950 West Valley Rd., Suite 2500, Wayne, PA. 19087-1898.

Cipro is part of the drug class:

• Fluoroquinolones

Medications can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods.

While taking Cipro you should limit your caffeine intake as this medication may lead to the accumulation of caffeine by interfering with the body's ability to remove it. Caffeine-containing products include coffee, tea, energy drinks, soft drinks (colas), chocolate, and other foods and beverages.

Cipro should not be taken with dairy products (like milk or yogurt) or calcium-fortified juices alone since Cipro absorption may be significantly reduced; however, Cipro may be taken with a meal that contains these products.

In the U.S.

• Cipro

Available Dosage Forms:

• Powder for Suspension
• Tablet

Therapeutic Class: Antibiotic

Chemical Class: Fluoroquinolone

It is very important that your doctor check your or your child's progress while you are using this medicine. This will allow your doctor to see if the medicine is working properly and to decide if you should continue to use it. Blood and urine tests may be needed to check for unwanted effects.

If your or your child's symptoms do not improve within a few days, or if they become worse, check with your doctor.

Do not use this medicine if you are also taking tizanidine (Zanaflex®). Tell your doctor if you or your child are also using theophylline (Theo-Dur®) or other products that contain caffeine (eg, coffee, soda, chocolate). Using these medicines together may increase risks for more serious side effects.

Ciprofloxacin may rarely cause inflammation (tendinitis) or tearing of a tendon (the cord that attaches muscles to bones). This can occur while you are taking the medicine or after you finish taking it. The risk of having tendon problems may be increased if you are over 60 years of age, are using steroid medicines (eg, dexamethasone, prednisolone, prednisone, Medrol®), have severe kidney problems, have a history of tendon problems (eg, rheumatoid arthritis), or if you have received an organ transplant (eg, heart, kidney, or lung). Check with your doctor right away if you have sudden pain or swelling in a tendon after exercise (eg, ankle, back of the knee or leg, shoulder, elbow, or wrist), bruise more easily after an injury, or are unable to bear weight or move the affected area. Refrain from exercise until your doctor says otherwise.

Tell your doctor right away if you have any of the following symptoms while using this medicine: convulsions, feeling anxious, confused, or depressed, seeing, hearing, or feeling things that are not there, severe headache, trouble sleeping, or unusual thoughts or behaviors.

This medicine may cause serious allergic reactions, including anaphylaxis, which can be life-threatening and require immediate medical attention. Call your doctor right away if you or your child have a rash, itching, hives, hoarseness, trouble breathing, trouble swallowing, or any swelling of your hands, face, mouth, or throat after you take this medicine.

Serious side effects can occur during treatment with this medicine. Sometimes serious side effects can occur without warning. However, possible warning signs are including black, tarry stools, blistering, peeling, or loosening of the skin, bloody or cloudy urine, chills, decreased urination, diarrhea, fever, joint or muscle pain, red skin lesions, often with a purple center, sores, ulcers, or white spots in the mouth or on the lips, severe stomach pain, skin rash, swelling of the face, fingers, feet, and/or lower legs, unusual bleeding or bruising, unusual weight gain, or yellow skin or eyes. Stop taking this medicine and check with your doctor immediately if you or your child notice any of these warning signs.

Check with your doctor right away if you have dark urine, clay-colored stools, abdominal or stomach pain, or yellow eyes or skin. These maybe symptoms of a serious liver problem.

Ciprofloxacin may cause diarrhea, and in some cases it can be severe. It may occur 2 months or more after you or your child stop taking this medicine. Do not take any medicine to treat diarrhea without first checking with your doctor. Diarrhea medicines may make the diarrhea worse or make it last longer. If you have any questions about this or if mild diarrhea continues or gets worse, check with your doctor.

Check with your doctor right away if you or your child start having numbness, tingling, or burning pain in your hands, arms, legs, or feet. These may be symptoms of a condition called peripheral neuropathy.

Some people who take ciprofloxacin may become more sensitive to sunlight than they are normally. Exposure to sunlight, even for brief periods of time, may cause severe sunburn, skin rash, redness, itching, or discoloration. When you begin using this medicine:

• Stay out of direct sunlight, especially between the hours of 10:00 AM and 3:00 PM, if possible.
• Wear protective clothing, including a hat and sunglasses.
• Apply a sun block product that has a sun protection factor (SPF) of at least 15. Some people may require a product with a higher SPF number, especially if they have a fair complexion. If you have any questions about this, check with your doctor.
• Do not use a sun lamp or tanning bed or booth.

If you have a severe reaction from the sun, check with your doctor.

Ciprofloxacin may cause some people to become dizzy, lightheaded, drowsy, or less alert than they are normally. Make sure you know how you react to this medicine before you drive, use machines, or do anything else that could be dangerous if you are dizzy or not alert. If these reactions are especially bothersome, check with your doctor.

If you are a diabetic patient taking diabetes medicine by mouth: Ciprofloxacin may cause hypoglycemia (low blood sugar) in some patients. Symptoms of low blood sugar must be treated before they lead to unconsciousness (passing out). Different people may feel different symptoms of low blood sugar. If you experience symptoms of low blood sugar, stop taking ciprofloxacin and check with your doctor right away:

• Symptoms of low blood sugar can include: Anxious feeling, behavior change similar to being drunk, blurred vision, cold sweats, confusion, cool pale skin, difficulty with concentrating, drowsiness, excessive hunger, headache, nausea, nervousness, rapid heartbeat, shakiness, or unusual tiredness or weakness.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Cipro (ciprofloxacin) is a fluoroquinolone (flor-o-KWIN-o-lone) antibiotic that fights bacteria in the body.

Cipro is used to treat different types of bacterial infections. It is also used to treat people who have been exposed to anthrax or certain types of plague.

Fluoroquinolone antibiotics can cause serious or disabling side effects. Cipro should be used only for infections that cannot be treated with a safer antibiotic.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

• Cipro is a brand (trade) name for ciprofloxacin. Ciprofloxacin is an antibiotic used to treat a wide range of infections.
• Cipro belongs to a group of medicines known as fluoroquinolones (also called quinolones).

• Take exactly as directed and for the duration intended.
• Only use when prescribed by a doctor to treat infections caused by susceptible bacteria as improper use increases the chance of resistant bacteria developing.
• Do not take Cipro within two hours of magnesium/aluminum-containing antacids or other products containing calcium, iron or zinc. Other products may also affect absorption (check product information).
• Avoid administration of Cipro with dairy products (eg, milk or yogurt) or calcium-fortified juices alone; however, Cipro may be taken with meals that contain calcium.
• Protect yourself from sunlight and avoid excessive exposure to the sun when taking Cipro.
• Keep well hydrated when taking Cipro to avoid the formation of highly concentrated urine.
• Discontinue if pain, swelling, inflammation or tendon rupture occurs and seek immediate medical advice.
• Discontinue immediately if a skin rash, yellowing of the skin, dark urine, itchiness, or allergy symptoms develop.
• Seek medical advice if chronic diarrhea develops during or following Cipro.

You should not use ciprofloxacin if you are also taking tizanidine.

Ciprofloxacin may cause swelling or tearing of a tendon (the fiber that connects bones to muscles in the body), especially in the Achilles' tendon of the heel. This effect may be more likely to occur if you are over 60, if you use steroid medication, or if you have had a kidney, heart, or lung transplant.

Call your doctor at once if you have sudden pain, swelling, bruising, tenderness, stiffness, or movement problems in any of your joints. Rest the joint until you receive medical care or instructions.

Do not take ciprofloxacin with dairy products such as milk or yogurt, or with calcium-fortified juice. You may eat or drink these products as part of a regular meal, but do not use them alone when taking ciprofloxacin. They could make the medication less effective.

Avoid caffeine while you are taking ciprofloxacin, because the medication can make the effects of caffeine stronger.

Antibiotic medicines can cause diarrhea, which may be a sign of a new infection. If you have diarrhea that is watery or bloody, call your doctor. Do not use anti-diarrhea medicine unless your doctor tells you to.

Avoid exposure to sunlight or tanning beds. Ciprofloxacin can make you sunburn more easily. Wear protective clothing and use sunscreen (SPF 30 or higher) when you are outdoors. Call your doctor if you have severe burning, redness, itching, rash, or swelling after being in the sun.

Ciprofloxacin may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.