Ciprofloxacin

• Ciprofloxacin administered together with theophylline (Respbid, Slo-Bid, Theo-24, Theolair) can lead to elevated, toxic blood levels of theophylline. Theophylline is used to open airways in the treatment of asthma. Toxic levels of theophylline can lead to seizures, and disturbances in heart rhythm. If concurrent use of ciprofloxacin and theophylline cannot be avoided, frequent blood tests to monitor theophylline blood levels are recommended.
• Ciprofloxacin increases the effect of tizanidine (Zanaflex) that is used to treat muscle spasticity. Therefore, the two drugs should not be combined.
• Iron salts (for example, ferrous sulfate) may reduce the absorption of ciprofloxacin because of formation of a ciprofloxacin-iron complex that is not absorbable. Antacids also may reduce the absorption of ciprofloxacin. If patients are receiving iron salts or antacids and ciprofloxacin, the ciprofloxacin should be given two hours before or six hours after the iron salt or antacid.
• Ciprofloxacin may increase the blood thinning effect of warfarin (Coumadin, Jantoven). The reason for this is unknown. Anticoagulant activity should be monitored after starting or stopping ciprofloxacin.
• Sevelamer (Renagel) may reduce the absorption of ciprofloxacin and possibly reduce the effectiveness of ciprofloxacin. Milk and orange juice also may reduce the absorption of ciprofloxacin. Ciprofloxacin, as with iron and antacids, should be given two hours before or six hours after milk or orange juice.
• Administration of ciprofloxacin with diabetic medications (for example glyburide [Micronase, Diabeta, Glynase, Prestab]) may lead to severe low blood glucose.
• Ciprofloxacin may increase blood concentrations of sildenafil (Viagra) that is used for treating erectile dysfunction. This combination should be avoided if possible.
• Patients taking Cipro, Cipro XR can develop sensitivity of the skin to direct sunlight (photosensitivity) and should avoid exposure to sunlight or use sunblock.
• Fluoroquinolones worsen low blood glucose levels when combined with sulfonylureas, for example, glyburide (Micronase, Diabeta, Glynase, Prestab).

CIPRO XR is indicated for the treatment of infections caused by susceptible isolates of the designated microorganisms in the conditions and patient populations listed below.

Uncomplicated Urinary Tract Infections (Acute Cystitis)

CIPRO XR is indicated for the treatment of uncomplicated urinary tract infections (UTIs) caused by Escherichia coli, Proteus mirabilis, Enterococcus faecalis, or Staphylococcus saprophyticus.

Because fluoroquinolones, including CIPRO XR, have been associated with serious adverse reactions [see WARNINGS AND PRECAUTIONS] and for some patients uncomplicated UTI (acute cystitis) is self-limiting, reserve CIPRO XR for treatment of uncomplicated UTIs (acute cystitis) in patients who have no alternative treatment options.

Complicated Urinary Tract Infections, And Acute Uncomplicated Pyelonephritis

CIPRO XR is indicated for the treatment of complicated urinary tract infections (cUTI) caused by Escherichia coli, Klebsiella pneumoniae, Enterococcus faecalis, Proteus mirabilis, or Pseudomonas aeruginosa and acute uncomplicated pyelonephritis (AUP) caused by Escherichia coli.

Limitations Of Use

• The safety and efficacy of CIPRO XR in treating infections other than urinary tract infections has not been demonstrated.
• CIPRO XR is not indicated for pediatric patients.

Usage

To reduce the development of drug-resistant bacteria and maintain the effectiveness of CIPRO XR and other antibacterial drugs, CIPRO XR should be used only to treat infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Appropriate culture and susceptibility tests should be performed before treatment in order to isolate and identify organisms causing infection and to determine their susceptibility to ciprofloxacin. Therapy with CIPRO XR may be initiated before results of these tests are known; once results become available appropriate therapy should be continued.

As with other drugs, some isolates of Pseudomonas aeruginosa may develop resistance fairly rapidly during treatment with ciprofloxacin. Culture and susceptibility testing performed periodically during therapy will provide information not only on the therapeutic effect of the antimicrobial agent but also on the possible emergence of bacterial resistance.

Ciprofloxacin may be found in some form under the following brand names:

• Cetraxal

• Ciloxan

• Cipro

• Cipro HC

• Cipro XR

• Ciprodex

• Proquin

Ciprofloxacin is part of the drug class:

• Fluoroquinolones

If you take too much ciprofloxacin, call your healthcare provider or get medical help immediately.

You should not use ciprofloxacin if:

• you are also taking tizanidine (Zanaflex);
• you have a history of myasthenia gravis; or
• you are allergic to ciprofloxacin or similar medications such as gemifloxacin (Factive), levofloxacin (Levaquin), moxifloxacin (Avelox), ofloxacin (Floxin), norfloxacin (Noroxin), and others.

To make sure you can safely take ciprofloxacin, tell your doctor if you have any of these other conditions:

• heart rhythm disorder, especially if you take quinidine (Quin-G), disopyramide (Norpace), bretylium (Bretylol), procainamide (Pronestyl, Procan SR), amiodarone (Cordarone, Pacerone), or sotalol (Betapace);
• a history of head injury or brain tumor;
• a condition called pseudotumor cerebri (high pressure inside the skull that may cause headaches, vision loss, or other symptoms);
• a history of allergic reaction to an antibiotic;
• joint problems;
• kidney or liver disease;
• epilepsy or seizures;
• diabetes;
• muscle weakness or trouble breathing;
• low levels of potassium in your blood (hypokalemia); or
• a personal or family history of Long QT syndrome.

FDA pregnancy category C. It is not known whether ciprofloxacin will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication.

Ciprofloxacin passes into breast milk and may harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

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. These effects may be more likely to occur if you are over 60, if you take steroid medication, or if you have had a kidney, heart, or lung transplant. Stop taking ciprofloxacin and call your doctor at once if you have sudden pain, swelling, tenderness, stiffness, or movement problems in any of your joints. Rest the joint until you receive medical care or instructions.

Do not share this medication with another person (especially a child), even if they have the same symptoms you have.

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

• Advise patients to read manufacturer’s patient information (medication guide) prior to initiating ciprofloxacin therapy and each time prescription refilled.1

• Advise patients that antibacterials (including ciprofloxacin) should only be used to treat bacterial infections and not used to treat viral infections (e.g., the common cold).1 579 778 856

• Importance of completing full course of therapy, even if feeling better after a few days.1 579 778 856

• Advise patients that skipping doses or not completing the full course of therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with ciprofloxacin or other antibacterials in the future.1 579 778 856

• May be taken without regard to meals, but do not take with dairy products (e.g., milk, yogurt) or calcium-fortified juices alone (without a meal) since absorption of the drug may be decreased.1 856

• Importance of taking ciprofloxacin at least 2 hours before or 6 hours after multivitamins containing calcium, magnesium, or zinc; aluminum- or magnesium-containing antacids; or buffered didanosine (pediatric oral suspension admixed with antacids).1 856

• Importance of drinking fluids liberally during therapy to avoid formation of highly concentrated urine and crystal formation in urine.1 579 778 856

• Advise patients that regular consumption of large quantities of coffee, tea, or caffeine-containing soft drinks or drugs during treatment may result in exaggerated or prolonged caffeine effects.1 513 579 856

• Inform patients that systemic fluoroquinolones, including ciprofloxacin, have been associated with disabling and potentially irreversible serious adverse reactions (e.g., tendinitis and tendon rupture, peripheral neuropathy, CNS effects) that may occur together in same patient.1 140 145 579 856 Advise patients to immediately discontinue ciprofloxacin and contact a clinician if they experience any signs or symptoms of serious adverse effects (e.g., unusual joint or tendon pain, muscle weakness, a “pins and needles” tingling or pricking sensation, numbness of the arms or legs, confusion, hallucinations) while taking the drug.1 140 145 579 Advise patients to talk with clinician if they have any questions or concerns.1 140 145 579 856

• Inform patients that systemic fluoroquinolones, including ciprofloxacin, are associated with an increased risk of tendinitis and tendon rupture in all age groups and this risk is increased risk in adults >60 years of age, individuals receiving corticosteroids, and kidney, heart, or lung transplant recipients.1 579 851 852 778 856 Symptoms may be irreversible.1 579 778 856 Importance of resting and refraining from exercise at the first sign of tendinitis or tendon rupture (e.g., pain, swelling, or inflammation of a tendon or weakness or inability to use a joint) and importance of immediately discontinuing the drug and contacting a clinician.1 579 778 856 (See Tendinitis and Tendon Rupture under Cautions.)

• Inform patients that peripheral neuropathies have been reported with systemic fluoroquinolones, including ciprofloxacin, and that symptoms may occur soon after initiation of the drug and may be irreversible.1 130 579 778 856 Importance of immediately discontinuing ciprofloxacin and contacting a clinician if symptoms of peripheral neuropathy (e.g., pain, burning, tingling, numbness, and/or weakness) occur.1 130 579 778 856

• Inform patients that systemic fluoroquinolones, including ciprofloxacin, have been associated with CNS effects (e.g., convulsions, dizziness, lightheadedness, increased intracranial pressure).1 579 778 856 Importance of informing clinician about any history of convulsions before initiating therapy with the drug.1 579 778 856 Importance of contacting a clinician if persistent headache with or without blurred vision occurs.1 579 856

• Advise patients that ciprofloxacin may cause dizziness and lightheadedness;1 579 778 856 caution patients not to engage in activities requiring mental alertness and motor coordination (e.g., driving a vehicle, operating machinery) until effects of the drug on the individual are known.1 579 778 856

• Advise patients that systemic fluoroquinolones, including ciprofloxacin, may worsen myasthenia gravis symptoms;1 579 778 856 importance of informing clinician of any history of myasthenia gravis.1 579 778 856 Importance of immediately contacting a clinician if any symptoms of muscle weakness, including respiratory difficulties, occur.1 579 778 856

• Inform patients that ciprofloxacin may be associated with hypersensitivity reactions (including anaphylactic reactions), even after first dose.1 579 778 856 Importance of immediately discontinuing ciprofloxacin and informing a clinician at first sign of rash, hives, other skin reaction, jaundice, rapid heartbeat, difficulty swallowing or breathing, any swelling suggesting angioedema (e.g., swelling of lips, tongue, or face; tightness of throat; hoarseness), or any other sign of hypersensitivity.1 579 778 856

• Inform patients that photosensitivity/phototoxicity reactions reported following exposure to sun or UV light in patients receiving fluoroquinolones.1 579 778 856 Importance of avoiding or minimizing exposure to sunlight or artificial UV light (e.g., sunlamps, tanning beds, UVA/UVB treatment) and using protective measures (e.g., sunscreen, wearing a hat and clothing that covers the skin) if in sunlight during ciprofloxacin therapy.1 579 778 856 Importance of discontinuing ciprofloxacin and contacting a clinician if a sunburn-like reaction or skin eruption occurs.1 579 778 856

• Inform patients that severe hepatotoxicity, including acute hepatitis and some fatalities, reported.1 579 778 856 Importance of immediately discontinuing ciprofloxacin and contacting a clinician if any signs or symptoms of hepatotoxicity (e.g., loss of appetite, nausea, vomiting, fever, weakness, tiredness, right upper quadrant tenderness, itching, yellowing of skin or eyes, light colored bowel movements, dark colored urine) occur.1 579 778 856

• Importance of informing clinician of personal or family history of QT interval prolongation or proarrhythmic conditions (e.g., hypokalemia, bradycardia, recent myocardial ischemia) or current therapy with any class IA (e.g., quinidine, procainamide) or class III (amiodarone, sotalol) antiarrhythmic agents.1 579 778 856 Importance of contacting clinician if any symptoms of prolongation of QT interval (e.g., prolonged heart palpitations, loss of consciousness) occur.1 579 778 856

• Advise patients that hypoglycemia has been reported in patients receiving ciprofloxacin and oral antidiabetic agents.1 579 778 856 If low blood glucose occurs, importance of contacting clinician to determine whether the anti-infective should be changed.1 579 778 856

• Advise patients that diarrhea is a common problem caused by anti-infectives and usually ends when the drug is discontinued.1 579 778 856 Importance of contacting a clinician if watery and bloody stools (with or without stomach cramps and fever) occur during or as late as 2 months or longer after the last dose.1 579 778 856

• If considering ciprofloxacin for a pediatric patient (see Pediatric Use under Cautions), importance of parent informing clinician if the child has a history of joint-related problems.1 579 778 856 Importance of parent contacting a clinician if the child develops any joint-related problems during or following ciprofloxacin therapy.1 579 778 856

• Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs (e.g., drugs that may affect QT interval, tizanidine, theophylline, antidiabetic agent, warfarin), as well as any concomitant illnesses.1 579 778 856

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 579 778 856

• Importance of advising patients of other important precautionary information.1 579 778 856 (See Cautions.)

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

More common

• Diarrhea

Rare

• Bloody or black, tarry stools
• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
• changes in skin color
• changes in urination
• chest pain or discomfort
• chest tightness or heaviness
• chills or fever
• clumsiness or unsteadiness
• confusion
• continuing ringing or buzzing or other unexplained noise in the ears
• coughing or spitting up blood
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• fast, irregular, pounding, or racing heartbeat or pulse
• headache, severe and throbbing
• hearing loss
• hives or welts or skin rash
• joint stiffness
• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
• light-colored stools
• muscle pain or stiffness
• nausea and vomiting
• nightmares
• numbness of the hands
• pain in the joints
• pain or discomfort in the arms, jaw, back, or neck
• painful, red lumps under the skin, mostly on the legs
• pounding in the ears
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• redness of the face, neck, arms, and occasionally, upper chest
• seizures
• severe abdominal or stomach pain, cramping, or burning
• shakiness in the legs, arms, hands, or feet
• swelling of the face, feet, or lower legs
• swollen, painful, or tender lymph glands in the neck, armpit, or groin
• thick, white vaginal discharge with no odor or with a mild odor
• unsteadiness, trembling, or other problems with muscle control or coordination
• unusual drowsiness, dullness, tiredness, weakness, or feeling of sluggishness
• white patches in the mouth and/or on the tongue
• yellow eyes or skin

Incidence not known

• Acid or sour stomach
• blistering, peeling, or loosening of the skin
• bluish-colored lips, fingernails, or palms
• bone pain
• diarrhea, watery and severe, which may also be bloody
• difficulty with breathing, chewing, or talking
• double vision
• excessive muscle tone
• feeling of discomfort
• feeling, seeing, or hearing things that are not there
• increased sensitivity to pain
• increased sensitivity to touch
• irregular or slow heart rate
• mood changes
• nosebleeds
• rapid heart rate
• red skin lesions, often with a purple center
• seeing, hearing, or feeling things that are not there
• sores, ulcers, or white spots on the lips or in the mouth
• unusual bleeding or bruising
• unusual excitement, nervousness, or restlessness
• vaginal yeast infection

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

Less common

• Runny nose
• sneezing
• stuffy nose

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Eight in vitro mutagenicity tests have been conducted with Ciprofloxacin, and the test results are listed below:

• Salmonella/Microsome Test (Negative) • E. coli DNA Repair Assay (Negative) • Mouse Lymphoma Cell Forward Mutation Assay (Positive) • Chinese Hamster V79 Cell HGPRT Test (Negative) • Syrian Hamster Embryo Cell Transformation Assay (Negative) • Saccharomyces cerevisiae Point Mutation Assay (Negative) • Saccharomyces cerevisiae Mitotic Crossover and Gene Conversion Assay (Negative) • Rat Hepatocyte DNA Repair Assay (Positive)

Thus, 2 of the 8 tests were positive, but results of the following 3 in vivo test systems gave negative results:

• Rat Hepatocyte DNA Repair Assay • Micronucleus Test (Mice) • Dominant Lethal Test (Mice)

Long-term carcinogenicity studies in rats and mice resulted in no carcinogenic or tumorigenic effects due to Ciprofloxacin at daily oral dose levels up to 250 mg/kg and 750 mg/kg to rats and mice, respectively (approximately 1.7-and 2.5-times the highest recommended therapeutic dose based upon body surface area, respectively).

Results from photo co-carcinogenicity testing indicate that Ciprofloxacin does not reduce the time to appearance of UV-induced skin tumors as compared to vehicle control. Hairless (Skh-1) mice were exposed to UVA light for 3.5 hours five times every two weeks for up to 78 weeks while concurrently being administered Ciprofloxacin tablets. The time to development of the first skin tumors was 50 weeks in mice treated concomitantly with UVA and Ciprofloxacin tablets (mouse dose approximately equal to the maximum recommended human dose based upon body surface area), as opposed to 34 weeks when animals were treated with both UVA and vehicle. The times to development of skin tumors ranged from 16 weeks to 32 weeks in mice treated concomitantly with UVA and other quinolones.9

In this model, mice treated with Ciprofloxacin alone did not develop skin or systemic tumors. There are no data from similar models using pigmented mice and/or fully haired mice. The clinical significance of these findings to humans is unknown.

Fertility studies performed in rats at oral doses of Ciprofloxacin up to 100 mg/kg (approximately 0.7-times the highest recommended therapeutic dose based upon body surface area) revealed no evidence of impairment.

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 (5.11)]. 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 Ciprofloxacin (approximately 1.3-times and 3.5-times the pediatric dose based upon comparative plasma AUCs) 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 (approximately 0.6-times the pediatric dose based upon comparative plasma AUCs), 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 was noted after single oral doses as low as 5 mg/kg. (approximately 0.07-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 0.2-times the highest recommended therapeutic dose based upon body surface area).

In dogs, Ciprofloxacin at 3 mg/kg and 10 mg/kg by rapid intravenous injection (15 sec.) produces pronounced hypotensive effects. These effects are considered to be related to histamine release, since they are partially antagonized by pyrilamine, an antihistamine. In rhesus monkeys, rapid intravenous 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

Advise the patient to read the FDA-approved patient labeling (Medication Guide)

Antibacterial Resistance
Inform patients that antibacterial drugs including Ciprofloxacin should only be used to treat bacterial infections. They do not treat viral infections (for example, the common cold). When Ciprofloxacin is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by Ciprofloxacin, or other antibacterial drugs in the future.

Administration with Food, Fluids, and Concomitant Medications
Inform patients that Ciprofloxacin may be taken with or without food.

Inform patients to drink fluids liberally while taking Ciprofloxacin to avoid formation of highly concentrated urine and crystal formation in the urine.

Inform patients that antacids containing magnesium, or aluminum, as well as sucralfate, metal cations such as iron, and multivitamin preparations with zinc or didanosine should be taken at least two hours before or six hours after Ciprofloxacin administration. Ciprofloxacin should not be taken with dairy products (like milk or yogurt) or calcium-fortified juices alone since absorption of Ciprofloxacin may be significantly reduced; however, Ciprofloxacin may be taken with a meal that contains these products.

Serious and Potentially Serious Adverse Reactions
Inform patients of the following serious adverse reactions that have been associated with Ciprofloxacin or other fluoroquinolone use:

• Tendon Disorders: Instruct patients to contact their healthcare provider if they experience pain, swelling, or inflammation of a tendon, or weakness or inability to use one of their joints; rest and refrain from exercise; and discontinue Ciprofloxacin treatment. The risk of severe tendon disorder with fluoroquinolones is higher in older patients usually over 60 years of age, in patients taking corticosteroid drugs, and in patients with kidney, heart or lung transplants. • Exacerbation of Myasthenia Gravis: Instruct patients to inform their physician of any history of myasthenia gravis. Instruct patients to notify their physician if they experience any symptoms of muscle weakness, including respiratory difficulties. • Hypersensitivity Reactions: Inform patients that Ciprofloxacin can cause hypersensitivity reactions, even following a single dose, and to discontinue the drug at the first sign of a skin rash, hives or other skin reactions, a rapid heartbeat, difficulty in swallowing or breathing, any swelling suggesting angioedema (for example, swelling of the lips, tongue, face, tightness of the throat, hoarseness), or other symptoms of an allergic reaction. • Hepatotoxicity: Inform patients that severe hepatotoxicity (including acute hepatitis and fatal events) has been reported in patients taking Ciprofloxacin. Instruct patients to inform their physician if they experience any signs or symptoms of liver injury including: loss of appetite, nausea, vomiting, fever, weakness, tiredness, right upper quadrant tenderness, itching, yellowing of the skin and eyes, light colored bowel movements or dark colored urine. • Convulsions: Inform patients that convulsions have been reported in patients receiving fluoroquinolones, including Ciprofloxacin. Instruct patients to notify their physician before taking this drug if they have a history of convulsions. • Neurologic Adverse Effects (for example, dizziness, lightheadedness, increased intracranial pressure): Inform patients that they should know how they react to Ciprofloxacin before they operate an automobile or machinery or engage in other activities requiring mental alertness and coordination. Instruct patients to notify their physician if persistent headache with or without blurred vision occurs. • Diarrhea: Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibiotic. If this occurs, instruct patients to contact their physician as soon as possible. • Peripheral Neuropathies: Inform patients that peripheral neuropathies have been associated with Ciprofloxacin use, symptoms may occur soon after initiation of therapy and may be irreversible. If symptoms of peripheral neuropathy including pain, burning, tingling, numbness and/or weakness develop, immediately discontinue Ciprofloxacin and contact their physician. • Prolongation of the QT Interval: Instruct patients to inform their physician of any personal or family history of QT prolongation or proarrhythmic conditions such as hypokalemia, bradycardia, or recent myocardial ischemia; if they are taking any Class IA (quinidine, procainamide), or Class III (amiodarone, sotalol) antiarrhythmic agents. Instruct patients to notify their physician if they have any symptoms of prolongation of the QT interval, including prolonged heart palpitations or a loss of consciousness. • Musculoskeletal Disorders in Pediatric Patients: Instruct parents to inform their child’s physician if the child has a history of joint-related problems before taking this drug. Inform parents of pediatric patients to notify their child’s physician of any joint-related problems that occur during or following Ciprofloxacin therapy [see Warnings and Precautions (5.10) and Use in Specific Populations (8.4)]. • Tizanidine: Instruct patients not to use Ciprofloxacin if they are already taking tizanidine. Ciprofloxacin increases the effects of tizanidine (Zanaflex®). • Theophylline: Inform patients that Ciprofloxacin may increase the effects of theophylline. Life-threatening CNS effects and arrhythmias can occur. Advise the patients to immediately seek medical help if they experience seizures, palpitations, or difficulty breathing. • Caffeine: Inform patients that Ciprofloxacin tablets may increase the effects of caffeine. There is a possibility of caffeine accumulation when products containing caffeine are consumed while taking quinolones. • Photosensitivity/Phototoxicity: Inform patients that photosensitivity/phototoxicity has been reported in patients receiving fluoroquinolones. Inform patients to minimize or avoid exposure to natural or artificial sunlight (tanning beds or UVA/B treatment) while taking quinolones. If patients need to be outdoors while using quinolones, instruct them to wear loose-fitting clothes that protect skin from sun exposure and discuss other sun protection measures with their physician. If a sunburn-like reaction or skin eruption occurs, instruct patients to contact their physician.

Drug Interactions Oral Antidiabetic Agents
Inform patients that hypoglycemia has been reported when Ciprofloxacin and oral antidiabetic agents were co-administered; if low blood sugar occurs with Ciprofloxacin, instruct them to consult their physician and that their antibacterial medicine may need to be changed.

Anthrax and Plague Studies
Inform patients given Ciprofloxacin for these conditions that efficacy studies could not be conducted in humans for feasibility reasons. Therefore, approval for these conditions was based on efficacy studies conducted in animals.