Ciprofloxacin

PD-Rx Pharmaceuticals, Inc.
PD-Rx Pharmaceuticals, Inc.

Ciprofloxacin Tablets, USP03/11

FULL PRESCRIBING INFORMATION: CONTENTS*

• WARNING
• CIPROFLOXACIN DESCRIPTION
• CLINICAL PHARMACOLOGY
  • Absorption
  • Distribution
  • Metabolism
  • Excretion
  • Drug-drug Interactions
  • Special Populations
  • MICROBIOLOGY
  • Susceptibility Tests
• CIPROFLOXACIN INDICATIONS AND USAGE
  • Adult Patients
  • Pediatric patients (1 to 17 years of age)
  • Adult and Pediatric Patients
• CIPROFLOXACIN CONTRAINDICATIONS
• WARNINGS
  • Tendinopathy and Tendon Rupture
  • Exacerbation of Myasthenia Gravis
  • Pregnant Women
  • Pediatrics
  • Cytochrome P450 (CYP450)
  • Central Nervous System Disorders
  • Theophylline
  • Hypersensitivity Reactions
  • Pseudomembranous Colitis
  • Peripheral Neuropathy
  • Syphilis
• PRECAUTIONS
  • General
  • Information for Patients
  • Drug Interactions
  • Carcinogenesis, Mutagenesis, Impairment of Fertility
  • Pregnancy
  • Nursing Mothers
  • Pediatric Use
  • Geriatric Use
• CIPROFLOXACIN ADVERSE REACTIONS
  • Adverse Reactions in Adult Patients
  • Adverse Reactions in Pediatric Patients
  • Post-Marketing Adverse Event Reports
  • Adverse Laboratory Changes
• OVERDOSAGE
• CIPROFLOXACIN DOSAGE AND ADMINISTRATION
  • CIPROFLOXACIN DOSAGE AND ADMINISTRATION - ADULTS
  • CIPROFLOXACIN DOSAGE AND ADMINISTRATION - PEDIATRICS
• HOW SUPPLIED
• ANIMAL PHARMACOLOGY
• CLINICAL STUDIES
  • Complicated Urinary Tract Infection and Pyelonephritis – Efficacy in Pediatric Patients
  • INHALATIONAL ANTHRAX IN ADULTS AND PEDIATRICS – ADDITIONAL INFORMATION
• REFERENCES
• MEDICATION GUIDE
  • What is the most important information I should know about Ciprofloxacin Tablets?
  • What are Ciprofloxacin Tablets?
  • Who should not take Ciprofloxacin Tablets?
  • What should I tell my healthcare provider before taking Ciprofloxacin Tablets?
  • How should I take Ciprofloxacin Tablets?
  • What should I avoid while taking Ciprofloxacin Tablets?
  • What are the possible side effects of Ciprofloxacin Tablets?
  • How should I store Ciprofloxacin Tablets?
  • General Information about Ciprofloxacin Tablets
  • What are the ingredients in Ciprofloxacin Tablets?
• PRINCIPAL DISPLAY PANEL

FULL PRESCRIBING INFORMATION

CIPROFLOXACIN DESCRIPTION

CLINICAL PHARMACOLOGY

Absorption

Distribution

Metabolism

Excretion

Drug-drug Interactions

Special Populations

MICROBIOLOGY

Aerobic gram-positive microorganisms

Aerobic gram-negative microorganisms

Aerobic gram-positive microorganisms

Aerobic gram-negative microorganisms

Susceptibility Tests

Dilution Techniques

Diffusion Techniques

CIPROFLOXACIN INDICATIONS AND USAGE

Adult Patients

Pediatric patients (1 to 17 years of age)

Adult and Pediatric Patients

CIPROFLOXACIN CONTRAINDICATIONS

WARNINGS

Tendinopathy and Tendon Rupture

Fluoroquinolones, including Ciprofloxacin Tablets, are associated with an increased risk of tendinitis and tendon rupture in all ages. This adverse reaction most frequently involves the Achilles tendon, and rupture of the Achilles tendon may require surgical repair. Tendinitis and tendon rupture in the rotater cuff (the shoulder), the hand, the biceps, the thumb, and other tendon sites have also been reported. The risk of developing fluoroquinolone-associated tendinitis and tendon rupture is further increased in older patients usually over 60 years of age, in patients taking corticosteroid drugs, and in patients with kidney, heart or lung transplants. Factors, in addition to age and corticosteroid use, that may independently increase the risk of tendon rupture include strenuous physical activity, renal failure, and previous tendon disorders such as rheumatoid arthritis. Tendinitis and tendon rupture have also occurred in patients taking fluoroquinolones who do not have the above risk factors. Tendon rupture can occur during or after completion of therapy; cases occurring up to several months after completion of therapy have been reported. Ciprofloxacin Tablets should be discontinued if the patient experiences pain, swelling, inflammation or rupture of a tendon. Patients should be advised to rest at the first sign of tendinitis or tendon rupture, and to contact their healthcare provider regarding changing to a non-quinolone antimicrobial drug.

Exacerbation of Myasthenia Gravis

Fluoroquinolones, including ciprofloxacin, have neuromuscular blocking activity and may exacerbate muscle weakness in persons with myasthenia gravis. Postmarketing serious adverse events, including deaths and requirement for ventilatory support, have been associated with fluoroquinolone use in persons with myasthenia gravis. Avoid ciprofloxacin in patients with known history of myasthenia gravis. (See PRECAUTIONS/Information for Patients and ADVERSE REACTIONS/Post-Marketing Adverse Event Reports).

Pregnant Women

Pediatrics

Cytochrome P450 (CYP450)

Central Nervous System Disorders

Theophylline

Hypersensitivity Reactions

• fever, rash, or severe dermatologic reactions (e.g., toxic epidermal necrolysis, Stevens-Johnson syndrome);
• 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.

The drug should be discontinued immediately at the first appearance of a skin rash, jaundice, or any other sign of hypersensitivity and supportive measures instituted (See PRECAUTIONS: Information for Patients and ADVERSE REACTIONS ).

Pseudomembranous Colitis

Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Ciprofloxacin Tablets, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile .

C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

Peripheral Neuropathy

Syphilis

PRECAUTIONS

General

Information for 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 Tablets 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.
• that fluoroquinolones like ciprofloxacin may cause worsening of myasthenia gravis symptoms, including muscle weakness and breathing problems. Patients should call their healthcare provider right away if they have any worsening muscle weakness or breathing problems.
• that antibacterial drugs including Ciprofloxacin Tablets should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Ciprofloxacin Tablets are 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 Tablets or other antibacterial drugs in the future.
• that ciprofloxacin may be taken with or without meals and to drink fluids liberally. As with other quinolones, concurrent administration of ciprofloxacin with magnesium/aluminum antacids, or sucralfate, Videx^® (didanosine) chewable/buffered tablets or pediatric powder, other highly buffered drugs, or with other products containing calcium, iron or zinc should be avoided. Ciprofloxacin may be taken two hours before or six hours after taking these products. 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.
• that ciprofloxacin may be associated with hypersensitivity reactions, even following a single dose, and to discontinue the drug at the first sign of a skin rash or other allergic reaction.
• that photosensitivity/phototoxicity has been reported in patients receiving quinolones. Patients should 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, they should 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, patients should contact their physician.
• that peripheral neuropathies have been associated with ciprofloxacin use. If symptoms of peripheral neuropathy including pain, burning, tingling, numbness and/or weakness develop, they should discontinue treatment and contact their physicians.                       
• that ciprofloxacin may cause dizziness and lightheadedness; therefore, patients should know how they react to this drug before they operate an automobile or machinery or engage in activities requiring mental alertness or coordination.
• that ciprofloxacin increases the effects of tizanidine (Zanaflex^®). Patients should not use ciprofloxacin if they are already taking tizanidine.
• that ciprofloxacin may increase the effects of theophylline and caffeine. There is a possibility of caffeine accumulation when products containing caffeine are consumed while taking quinolones.
• that convulsions have been reported in patients receiving quinolones, including ciprofloxacin, and to notify their physician before taking this drug if there is a history of this condition.
• that ciprofloxacin has been associated with an increased rate of adverse events involving joints and surrounding tissue structures (like tendons) in pediatric patients (less than 18 years of age). Parents should inform their child’s physician if the child has a history of joint-related problems before taking this drug. Parents of pediatric patients should also notify their child’s physician of any joint-related problems that occur during or following ciprofloxacin therapy. (See WARNINGS, PRECAUTIONS, Pediatric Use and ADVERSE REACTIONS .)
• that 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, patients should contact their physician as soon as possible.

Drug Interactions

Carcinogenesis, Mutagenesis, Impairment of Fertility

Pregnancy

Teratogenic effects

Nursing Mothers

Pediatric Use

Ciprofloxacin, like other quinolones, causes arthropathy and histological changes in weight-bearing joints of juvenile animals resulting in lameness. (See ANIMAL PHARMACOLOGY .)

Inhalational Anthrax (Post-Exposure)

Complicated Urinary Tract Infection and Pyelonephritis

Ciprofloxacin is indicated for the treatment of complicated urinary tract infections and pyelonephritis due to Escherichia coli. Although effective in clinical trials, ciprofloxacin is not a drug of first choice in the pediatric population due to an increased incidence of adverse events compared to the controls, including events related to joints and/or surrounding tissues. The rates of these events in pediatric patients with complicated urinary tract infection and pyelonephritis within six weeks of follow-up were 9.3% (31/335) versus 6% (21/349) for control agents. The rates of these events occurring at any time up to the one year follow-up were 13.7% (46/335) and 9.5% (33/349), respectively. The rate of all adverse events regardless of drug relationship at six weeks was 41% (138/335) in the ciprofloxacin arm compared to 31% (109/349) in the control arm. (See ADVERSE REACTIONS.)

Cystic Fibrosis

Short-term safety data from a single trial in pediatric cystic fibrosis patients are available. In a randomized, double-blind clinical trial for the treatment of acute pulmonary exacerbations in cystic fibrosis patients (ages 5 - 17 years), 67 patients received ciprofloxacin I.V. 10 mg/kg/dose q8h for one week followed by ciprofloxacin tablets 20 mg/kg/dose q12h to complete 10 - 21 days treatment and 62 patients received the combination of ceftazidime I.V. 50 mg/kg/dose q8h and tobramycin I.V. 3 mg/kg/dose q8h for a total of 10 - 21 days. Patients less than 5 years of age were not studied. Safety monitoring in the study included periodic range of motion examinations and gait assessments by treatment-blinded examiners. Patients were followed for an average of 23 days after completing treatment (range 0 - 93 days). This study was not designed to determine long term effects and the safety of repeated exposure to ciprofloxacin. 

Musculoskeletal adverse events in patients with cystic fibrosis were reported in 22% of the patients in the ciprofloxacin group and 21% in the comparison group. Decreased range of motion was reported in 12% of the subjects in the ciprofloxacin group and 16% in the comparison group. Arthralgia was reported in 10% of the patients in the ciprofloxacin group and 11% in the comparison group. Other adverse events were similar in nature and frequency between treatment arms. One of sixty-seven patients developed arthritis of the knee nine days after a ten-day course of treatment with ciprofloxacin. Clinical symptoms resolved, but an MRI showed knee effusion without other abnormalities eight months after treatment. However, the relationship of this event to the patient’s course of ciprofloxacin can not be definitively determined, particularly since patients with cystic fibrosis may develop arthralgias/arthritis as part of their underlying disease process.

Geriatric Use

CIPROFLOXACIN ADVERSE REACTIONS

Side Effects in Adult Patients

Side Effects in Pediatric Patients

Ciprofloxacin, administered I.V. and/or orally, was compared to a cephalosporin for treatment of complicated urinary tract infections (cUTI) or pyelonephritis in pediatric patients 1 to 17 years of age (mean age of 6 ± 4 years). The trial was conducted in the U.S., Canada, Argentina, Peru, Costa Rica, Mexico, South Africa, and Germany. The duration of therapy was 10 to 21 days (mean duration of treatment was 11 days with a range of 1 to 88 days). The primary objective of the study was to assess musculoskeletal and neurological safety within 6 weeks of therapy and through one year of follow-up in the 335 ciprofloxacin- and 349 comparator-treated patients enrolled.
 
An Independent Pediatric Safety Committee (IPSC) reviewed all cases of musculoskeletal adverse events as well as all patients with an abnormal gait or abnormal joint exam (baseline or treatment-emergent). These events were evaluated in a comprehensive fashion and included such conditions as 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.

The affected joints included: knee, elbow, ankle, hip, wrist, and shoulder. Within 6 weeks of treatment initiation, the rates of these events were 9.3% (31/335) in the ciprofloxacin-treated group versus 6% (21/349) in comparator-treated patients. The majority of these events were mild or moderate in intensity. All musculoskeletal events occurring by 6 weeks resolved (clinical resolution of signs and symptoms), usually within 30 days of end of treatment.

Radiological evaluations were not routinely used to confirm resolution of the events. The events occurred more frequently in ciprofloxacin-treated patients than control patients, regardless of whether they received I.V. or oral therapy. Ciprofloxacin-treated patients were more likely to report more than one event and on more than one occasion compared to control patients. These events occurred in all age groups and the rates were consistently higher in the ciprofloxacin group compared to the control group. At the end of 1 year, the rate of these events reported at any time during that period was 13.7% (46/335) in the ciprofloxacin-treated group versus 9.5% (33/349) comparator-treated patients.

An adolescent female discontinued ciprofloxacin for wrist pain that developed during treatment. An MRI performed 4 weeks later showed a tear in the right ulnar fibrocartilage. A diagnosis of overuse syndrome secondary to sports activity was made, but a contribution from ciprofloxacin cannot be excluded. The patient recovered by 4 months without surgical intervention.
 

Post-Marketing Adverse Event Reports

Adverse Laboratory Changes

Changes in laboratory parameters listed as adverse events without regard to drug relationship are listed below:
 
Hepatic         –   Elevations of ALT (SGPT) (1.9%), AST (SGOT) (1.7%), alkaline phosphatase (0.8%), LDH (0.4%), serum bilirubin (0.3%).
 
Hematologic  –   Eosinophilia (0.6%), leukopenia (0.4%), decreased blood platelets (0.1%), elevated blood platelets (0.1%), pancytopenia (0.1%). 
 
Renal             –   Elevations of serum creatinine (1.1%), BUN (0.9%), CRYSTALLURIA, CYLINDRURIA, AND HEMATURIA HAVE BEEN REPORTED.
 
Other changes occurring in less than 0.1% of courses were: elevation of serum gammaglutamyl transferase, elevation of serum amylase, reduction in blood glucose, elevated uric acid, decrease in hemoglobin, anemia, bleeding diathesis, increase in blood monocytes, leukocytosis.

To report SUSPECTED ADVERSE EVENTS, contact West-ward Pharmaceutical Corp. at 1-877-233-2001 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

OVERDOSAGE

CIPROFLOXACIN DOSAGE AND ADMINISTRATION

DOSAGE AND ADMINISTRATION - ADULTS

  ^*   used in conjunction with metronidazole
  ^† Generally ciprofloxacin should be continued for at least 2 days after the signs and symptoms of infection
     have disappeared, except for inhalational anthrax (post-exposure).
^**  Drug administration should begin as soon as possible after suspected or confirmed exposure.
     This indication is based on a surrogate endpoint, ciprofloxacin serum concentrations achieved in humans,
     reasonably likely to predict clinical benefit.⁴ For a discussion of ciprofloxacin serum concentrations in various
     human populations, see INHALATIONAL ANTHRAX – ADDITIONAL INFORMATION .

Conversion of I.V. to Oral Dosing in Adults

Patients whose therapy is started with ciprofloxacin I.V. may be switched to Ciprofloxacin Tablets when clinically indicated at the discretion of the physician (See CLINICAL PHARMACOLOGY and table below for the equivalent dosing regimens).  

DOSAGE AND ADMINISTRATION - PEDIATRICS

HOW SUPPLIED

Ciprofloxacin Tablets USP, are available as white, round, film-coated tablets containing 250 mg ciprofloxacin. The 250 mg tablet is coded with "WW927" on one side.

Ciprofloxacin Tablets, USP area also available as white, capsule shaped, film-coated tablets containing 500 mg or 750 mg ciprofloxacin. The 500 mg tablet is coded with "WW928" on one side. The 750 mg tablet is coded with "WW929" on one side. Ciprofloxacin Tablets, USP 250 mg and 500 mg are available in bottles of 30's, 100's and 500's.

Ciprofloxacin Tablets, USP 750 mg are available in bottles of 50's and 100's and Unit Dose Boxes of 100 tablets.

                                                        Strength                Tablet Identification

Bottles of 30's:                                    250 mg                        WW927
                                                            500 mg                        WW928
Bottles of 50's:                                    750 mg                        WW929
Bottles of 100's:                                  250 mg                        WW927
                                                            500 mg                        WW928
                                                            750 mg                        WW929
Bottles of 500's:                                  250 mg                        WW927
                                                            500 mg                        WW928
Unit Dose Boxes of 100                      250 mg                        WW927
                                                            500 mg                        WW928
                                                            750 mg                        WW929

   

Store at 20-25°C (68-77°F) [See USP Controlled Room Temperature]. Dispense in a well-closed container as defined in the USP using a child-resistant closure.

ANIMAL PHARMACOLOGY

CLINICAL STUDIES

Complicated Urinary Tract Infection and Pyelonephritis – Efficacy in Pediatric Patients

INHALATIONAL ANTHRAX IN ADULTS AND PEDIATRICS – ADDITIONAL INFORMATION

The mean serum concentrations of ciprofloxacin associated with a statistically significant improvement in survival in the rhesus monkey model of inhalational anthrax are reached or exceeded in adult and pediatric patients receiving oral and intravenous regimens. (See DOSAGE AND ADMINISTRATION .) Ciprofloxacin pharmacokinetics have been evaluated in various human populations. The mean peak serum concentration achieved at steady-state in human adults receiving 500 mg orally every 12 hours is 2.97 μg/mL, and 4.56 μg/mL following 400 mg intravenously every 12 hours. The mean trough serum concentration at steady-state for both of these regimens is 0.2 μg/mL.

In a study of 10 pediatric patients between 6 and 16 years of age, the mean peak plasma concentration achieved is 8.3 μg/mL and trough concentrations range from 0.09 to 0.26 μg/mL, following two 30-minute intravenous infusions of 10 mg/kg administered 12 hours apart. After the second intravenous infusion patients switched to 15 mg/kg orally every 12 hours achieve a mean peak concentration of 3.6 μg/mL after the initial oral dose. Long-term safety data, including effects on cartilage, following the administration of ciprofloxacin to pediatric patients are limited. (For additional information, see PRECAUTIONS, Pediatric Use .) Ciprofloxacin serum concentrations achieved in humans serve as a surrogate endpoint reasonably likely to predict clinical benefit and provide the basis for this indication.⁵

A placebo-controlled animal study in rhesus monkeys exposed to an inhaled mean dose of 11 LD₅₀ (~5.5 x 10⁵ spores (range 5 to 30 LD₅₀) of B. anthracis was conducted. The minimal inhibitory concentration (MIC) of ciprofloxacin for the anthrax strain used in this study was 0.08 μg/mL. In the animals studied, mean serum concentrations of ciprofloxacin achieved at expected T_max (1 hour post-dose) following oral dosing to steady-state ranged from 0.98 to 1.69 μg/mL. Mean steady-state trough concentrations at 12 hours post-dose ranged from 0.12 to 0.19 μg/mL.⁶ Mortality due to anthrax for animals that received a 30-day regimen of oral ciprofloxacin beginning 24 hours post-exposure was significantly lower (1/9), compared to the placebo group (9/10) [p=0.001]. The one ciprofloxacin-treated animal that died of anthrax did so following the 30-day drug administration period.⁷

More than 9300 persons were recommended to complete a minimum of 60 days of antibiotic prophylaxis against possible inhalational exposure to B. anthracis during 2001. Ciprofloxacin was recommended to most of those individuals for all or part of the prophylaxis regimen. Some persons were also given anthrax vaccine or were switched to alternative antibiotics. No one who received ciprofloxacin or other therapies as prophylactic treatment subsequently developed inhalational anthrax. The number of persons who received ciprofloxacin as all or part of their post-exposure prophylaxis regimen is unknown.
 
Among the persons surveyed by the Centers for Disease Control and Prevention, over 1000 reported receiving ciprofloxacin as sole post-exposure prophylaxis for inhalational anthrax. Gastrointestinal adverse events (nausea, vomiting, diarrhea, or stomach pain), neurological adverse events (problems sleeping, nightmares, headache, dizziness or lightheadedness) and musculoskeletal adverse events (muscle or tendon pain and joint swelling or pain) were more frequent than had been previously reported in controlled clinical trials. This higher incidence, in the absence of a control group, could be explained by a reporting bias, concurrent medical conditions, other concomitant medications, emotional stress or other confounding factors, and/or a longer treatment period with ciprofloxacin. Because of these factors and limitations in the data collection, it is difficult to evaluate whether the reported symptoms were drug-related.

REFERENCES

• National Committee for Clinical Laboratory Standards, Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically-Fifth Edition. Approved Standard NCCLS Document M7-A5, Vol. 20, No. 2, NCCLS, Wayne, PA, January, 2000.
• Clinical and Laboratory Standards Institute, Methods for Antimicrobial Dilution and Disk Susceptibility Testing of Infrequently Isolated or Fastidious Bacteria; Approved Guideline., CLSI Document M45-A, Vol. 26, No. 19, CLSI, Wayne, PA, 2006.
• National Committee for Clinical Laboratory Standards, Performance Standards for Antimicrobial Disk Susceptibility Tests-Seventh Edition. Approved Standard NCCLS Document M2-A7, Vol. 20, No. 1, NCCLS, Wayne, PA, January, 2000.
• Report presented at the FDA’s Anti-Infective Drug and Dermatological Drug Product’s Advisory Committee meeting, March 31, 1993, Silver Spring, MD. Report available from FDA, CDER, Advisors and Consultants Staff, HFD-21, 1901 Chapman Avenue, Room 200, Rockville, MD20852, USA.
• 21 CFR 314.510 (Subpart H – Accelerated Approval of New Drugs for Life-Threatening Illnesses).
• Kelly DJ, et al. Serum concentrations of penicillin, doxycycline, and ciprofloxacin during prolonged therapy in rhesus monkeys. J Infect Dis 1992; 166:1184-7.
• Friedlander AM, et al. Postexposure prophylaxis against experimental inhalational anthrax. J Infect Dis 1993; 167:1239-42.
• Friedman J, Polifka J. Teratogenic effects of drugs: a resource for clinicians (TERIS). Baltimore, Maryland: Johns Hopkins University Press, 2000:149-195.
• Loebstein R, Addis A, Ho E, et al. Pregnancy outcome following gestational exposure to fluoroquinolones: a multicenter prospective controlled study. Antimicrob Agents Chemother. 1998;42(6):1336-1339.
• Schaefer C, Amoura-Elefant E, Vial T, et al. Pregnancy outcome after prenatal quinolone exposure. Evaluation of a case registry of the European network of teratology information services (ENTIS). Eur J Obstet Gynecol Reprod Biol. 1996;69:83-89.

MEDICATION GUIDE

What is the most important information I should know about Ciprofloxacin Tablets?

• Tendons are tough cords of tissue that connect muscles to bones.
• Pain, swelling, tears, and inflammation of tendons including the back of the ankle (Achilles), shoulder, hand, or other tendon sites can happen in people of all ages who take fluoroquinolone antibiotics, including Ciprofloxacin Tablets. The risk of getting tendon problems is higher if you:
  • are over 60 years of age
  • are taking steroids (corticosteroids)
  • have had a kidney, heart, or lung transplant.
    Swelling of the tendon (tendinitis) and tendon rupture (breakage) have also happened in patients who take fluoroquinolones who do not have the above risk factors.
• Other reasons for tendon ruptures can include:
  • physical activity or exercise
  • kidney failure
  • tendon problems in the past, such as in people with rheumatoid arthritis (RA)
• Call your healthcare provider right away at the first sign of tendon pain, swelling or inflammation. Stop taking Ciprofloxacin Tablets until tendinitis or tendon rupture has been ruled out by your healthcare provider. Avoid exercise and using the affected area. The most common area of pain and swelling is the Achilles tendon at the back of your ankle. This can also happen with other tendons. Talk to your healthcare provider about the risk of tendon rupture with continued use of Ciprofloxacin Tablets. You may need a different antibiotic that is not a fluoroquinolone to treat your infection.
• Tendon rupture can happen while you are taking or after you have finished taking Ciprofloxacin Tablets. Tendon ruptures have happened up to several months after patients have finished taking their fluoroquinolone.
• Get medical help right away if you get any of the following signs or symptoms of a tendon rupture:
  • hear or feel a snap or pop in a tendon area
  • bruising right after an injury in a tendon area
  • unable to move the affected area or bear weight
• Worsening of myasthenia gravis (a disease which causes muscle weakness). Fluoroquinolones like Ciprofloxacin Tablets may cause worsening of myasthenia gravis symptoms, including muscle weakness and breathing problems. Call your heallthcare provider right away if you have any worsening muscle weakness or breathing problems.
• See the section   “What are the possible side effects of Ciprofloxacin Tablets?” for more information about side effects.

What are Ciprofloxacin Tablets?

Call your healthcare provider if you think your condition is not getting better while you are taking Ciprofloxacin Tablets.

Who should not take Ciprofloxacin Tablets?

Do not take Ciprofloxacin Tablets if you:

• have ever had a severe allergic reaction to an antibiotic known as a fluoroquinolone, or are allergic to any of the ingredients in Ciprofloxacin Tablets. Ask  your healthcare provider if you are not sure. See the list of ingredients in Ciprofloxacin Tablets at the end of this Medication Guide.
• also take a medicine called tizanidine (Zanaflex^®). Serious side effects from tizanidine are likely to happen.

What should I tell my healthcare provider before taking Ciprofloxacin Tablets?

See “What is the most important information I should know about Ciprofloxacin Tablets?”

Tell your healthcare provider about all your medical conditions, including if you:

• have tendon problems
• have a disease that causes muscle weakness (myasthenia gravis)
• have central nervous system problems (such as epilepsy)
• have nerve problems
• have or anyone in your family has an irregular heartbeat, especially a condition called “QT prolongation”
• have a history of seizures
• have kidney problems. You may need a lower dose of Ciprofloxacin Tablets if your kidneys do not work well.
• have rheumatoid arthritis (RA) or other history of joint problems
• have trouble swallowing pills
• are pregnant or planning to become pregnant. It is not known if ciprofloxacin tablets will harm your unborn child.
• are breast-feeding or planning to breast-feed. Ciprofloxacin passes into breast milk. You and your healthcare provider should decide whether you will take Ciprofloxacin Tablets or breast-feed.

Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins and herbal and dietary supplements. Ciprofloxacin Tablets and other medicines can affect each other causing side effects. Especially tell your healthcare provider if you take:

• an NSAID (Non-Steroidal Anti-Inflammatory Drug). Many common medicines for pain relief are NSAIDs. Taking an NSAID while you take Ciprofloxacin Tablets or other fluoroquinolones may increase your risk of central nervous system effects and seizures. See “What are the possible side effects of Ciprofloxacin Tablets?”  
• a blood thinner (Warfarin, Coumadin^®, Jantoven^®) 
• tizanidine (Zanaflex^®). You should not take Ciprofloxacin Tablets if you are already taking tizanidine. See “Who should not take Ciprofloxacin Tablets?”   
• theophylline (Theo-24^®, Elixophyllin^®, Theochron^®, Uniphyl^®, Theolair^®)
• glyburide (Micronase^®, Glynase^®, Diabeta^®, Glucovance^®). See “What are the possible side effects of Ciprofloxacin Tablets?”  
• phenytoin (Fosphenytoin Sodium^®, Cerebyx^®, Dilantin-125^®, Dilantin^®, Extended Phenytoin Sodium^®, Prompt Penytoin Sodium^®, Phenytek^®)
• products that contain caffeine
• a medicine to control your heart rate or rhythm (antiarrhythmics) See “What are the possible side effects of Ciprofloxacin Tablets?”
• an anti-psychotic medicine
• a tricyclic antidepressant
• a water pill (diuretic)
• a steroid medicine. Corticosteroids taken by mouth or by injection may increase the chance of tendon injury. See “What is the most important information I should know about ciprofloxacin tablets?”
• methotrexate (Trexall^®)
• Probenecid (Probalan^®, Col-probenacid^®)
• Metoclopromide (Reglan^®, Reglan ODT^®)
• Certain medicines may keep Ciprofloxacin Tablets from working correctly. Take Ciprofloxacin Tablets either 2 hours before or 6 hours after taking these products:
  • an antacid, multivitamin, or other product that has magnesium, calcium, aluminum, iron, or zinc
  • sucralfate
  • didanosine (Videx^®, Videx^® EC).

Ask your healthcare provider if you are not sure if any of your medicines are listed above.

Know the medicines you take. Keep a list of your medicines and show it to your healthcare provider and pharmacist when you get a new medicine.

How should I take Ciprofloxacin Tablets?

• Take Ciprofloxacin Tablets exactly as prescribed by your healthcare provider.
• Take Ciprofloxacin Tablets in the morning and evening at about the same time each day. Swallow the tablet whole. Do not split, crush or chew the tablet. Tell your healthcare provider if you can not swallow the tablet whole.
• Ciprofloxacin Tablets can be taken with or without food.
• Ciprofloxacin Tablets should not be taken with dairy products (like milk or yogurt) or calcium-fortified juices alone, but may be taken with a meal that contains these products.
• Drink plenty of fluids while taking Ciprofloxacin Tablets.
• Do not skip any doses, or stop taking Ciprofloxacin Tablets even if you begin to feel better, until you finish your prescribed treatment, unless:
  • you have tendon effects (see “What is the most important information I should know about Ciprofloxacin Tablets?” ),
  • you have a serious allergic reaction (see “What are the possible side effects of Ciprofloxacin Tablets?” ), or
  •  your healthcare provider tells you to stop.

• If you miss a dose of Ciprofloxacin Tablets, take it as soon as you remember. Do not take two doses at the same time, and do not take more than two doses in one day.
• If you take too much, call your healthcare provider or get medical help immediately.

If you have been prescribed Ciprofloxacin Tablets after being exposed to anthrax:

• Ciprofloxacin Tablets have been approved to lessen the chance of getting anthrax disease or worsening of the disease after you are exposed to the anthrax bacteria germ.
• Take Ciprofloxacin Tablets exactly as prescribed by your healthcare provider. Do not stop taking Ciprofloxacin Tablets without talking with your healthcare provider. If you stop taking ciprofloxacin tablets too soon, it may not keep you from getting the anthrax disease.
• Side effects may happen while you are taking Ciprofloxacin Tablets. When taking your Ciprofloxacin Tablets to prevent anthrax infection, you and your healthcare provider should talk about whether the risks of stopping Ciprofloxacin Tablets too soon are more important than the risks of side effects with Ciprofloxacin Tablets.
• If you are pregnant, or plan to become pregnant while taking Ciprofloxacin Tablets, you and your healthcare provider should decide whether the benefits of taking Ciprofloxacin Tablets for anthrax are more important than the risks.

What should I avoid while taking Ciprofloxacin Tablets?

• Ciprofloxacin Tablets can make you feel dizzy and lightheaded. Do not drive, operate machinery, or do other activities that require mental alertness or coordination until you know how Ciprofloxacin Tablets affect you.
• Avoid sunlamps, tanning beds, and try to limit your time in the sun. Ciprofloxacin Tablets can make your skin sensitive to the sun (photosensitivity) and the light from sunlamps and tanning beds. You could get severe sunburn, blisters or swelling of your skin. If you get any of these symptoms while taking Ciprofloxacin Tablets, call your healthcare provider right away. You should use a sunscreen and wear a hat and clothes that cover your skin if you have to be in sunlight.

What are the possible side effects of Ciprofloxacin Tablets?

• Ciprofloxacin Tablets can cause side effects that may be serious or even cause death. See “What is the most important information I should know about Ciprofloxacin Tablets?”

Other serious side effects of Ciprofloxacin Tablets include:

• Central Nervous System Effects

Seizures have been reported in people who take fluoroquinolone antibiotics including Ciprofloxacin Tablets. Tell your healthcare provider if you have a history of seizures. Ask your healthcare provider whether taking Ciprofloxacin Tablets will change your risk of having a seizure.

Central Nervous System (CNS) side effects may happen as soon as after taking the first dose of Ciprofloxacin Tablets. Talk to your healthcare provider right away if you get any of these side effects, or other changes in mood or behavior:

• feel dizzy
• seizures
• hear voices, see things, or sense things that are not there (hallucinations)
• feel restless
• tremors
• feel anxious or nervous
• confusion
• depression
• trouble sleeping
• nightmares
• feel more suspicious (paranoia)
• suicidal thoughts or acts

• Serious allergic reactions
  Allergic reactions can happen in people taking fluoroquinolones, including Ciprofloxacin Tablets, even after only one dose. Stop taking Ciprofloxacin Tablets and get emergency medical help right away if you get any of the following symptoms of a severe allergic reaction:

• hives
• trouble breathing or swallowing
• swelling of the lips, tongue, face
• throat tightness, hoarseness
• rapid heartbeat
• faint
• yellowing of the skin or eyes. Stop taking Ciprofloxacin Tablets and tell your healthcare provider right away if you get yellowing of your skin or white part of your eyes, or if you have dark urine. These can be signs of a serious reaction to Ciprofloxacin Tablets (a liver problem).

• Skin rash

Skin rash may happen in people taking ciprofloxacin tablets even after only one dose. Stop taking ciprofloxacin tablets at the first sign of a skin rash and call your healthcare provider. Skin rash may be a sign of a more serious reaction to ciprofloxacin tablets.

• Serious heart rhythm changes (QT prolongation and torsades de pointes)

Tell your healthcare provider right away if you have a change in your heart beat (a fast or irregular heartbeat), or if you faint. Ciprofloxacin Tablets may cause a rare heart problem known as prolongation of the QT interval. This condition can cause an abnormal heartbeat and can be very dangerous. The chances of this event are higher in people:

• who are elderly
• with a family history of prolonged QT interval
• with low blood potassium (hypokalemia)
• who take certain medicines to control heart rhythm (antiarrhythmics)

• Intestine infection (Pseudomembranous colitis)

Pseudomembranous colitis can happen with most antibiotics, including Ciprofloxacin Tablets. Call your healthcare provider right away if you get watery diarrhea, diarrhea that does not go away, or bloody stools. You may have stomach cramps and a fever. Pseudomembranous colitis can happen 2 or more months after you have finished your antibiotic.

• Changes in sensation and possible nerve damage (Peripheral Neuropathy)

Damage to the nerves in arms, hands, legs, or feet can happen in people who take fluoroquinolones, including Ciprofloxacin Tablets. Talk with your healthcare provider right away if you get any of the following symptoms of peripheral neuropathy in your arms, hands, legs, or feet:

• pain
• burning
• tingling
• numbness
• weakness

Ciprofloxacin Tablets may need to be stopped to prevent permanent nerve damage.

• Low blood sugar (hypoglycemia)

People who take Ciprofloxacin Tablets and other fluoroquinolone medicines with the oral anti-diabetes medicine glyburide (Micronase, Glynase, Diabeta, Glucovance)can get low blood sugar (hypoglycemia) which can sometimes be severe. Tell your healthcare provider if you get low blood sugar with Ciprofloxacin Tablets. Your antibiotic medicine may need to be changed.

• Sensitivity to sunlight (photosensitivity)

See “What should I avoid while taking Ciprofloxacin Tablets?”  

• Joint Problems

Increased chance of problems with joints and tissues around joints in children under 18 years old. Tell your child’s healthcare provider if your child has any joint problems during or after treatment with Ciprofloxacin Tablets.

The most common side effects of Ciprofloxacin Tablets include:

• nausea
• headache
• diarrhea
• vomiting
• vaginal yeast infection
• changes in liver function tests
• pain or discomfort in the abdomen

These are not all the possible side effects of Ciprofloxacin Tablets. Tell your healthcare provider about any side effect that bothers you, or that does not go away.

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

How should I store Ciprofloxacin Tablets?

General Information about Ciprofloxacin Tablets

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Ciprofloxacin Tablets for a condition for which it is not prescribed. Do not give Ciprofloxacin Tablets to other people, even if they have the same symptoms that you have. It may harm them.

This Medication Guide summarizes the most important information about Ciprofloxacin Tablets. If you would like more information about Ciprofloxacin Tablets, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about Ciprofloxacin Tablets that is written for healthcare professionals.

What are the ingredients in Ciprofloxacin Tablets?

Active ingredient: ciprofloxacin

Inactive ingredients: colloidal silicon dioxide, corn starch, hydrogenated vegetable oil, hypromellose, magnesium stearate, microcrystalline  cellulose, polyacrylate dispersion (methylacrylate and ethylacrylate copolymer), polyethylene glycol, purified water, simethicone emulsion, sodium starch glycolate, talc, and titanium dioxide.

Revised March 2011

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Distributed by: 
West-ward Pharmaceutical Corp.
Eatontown, NJ 07724

Manufactured by:
Hikma Pharmaceuticals
P.O. Box 182400
Amman 11118 - Jordan  
 
 

PRINCIPAL DISPLAY PANEL

Ciprofloxacin Tablets, USP
250 mg/100 Tablets
NDC # 0143-9927-01