Ciprofloxacin Extended-Release

CIPRO XR (ciprofloxacin*) extended-release tablets contain ciprofloxacin, a synthetic antimicrobial agent for oral administration. CIPRO XR tablets are coated, bilayer tablets consisting of an immediate-release layer and an erosion-matrix type controlled-release layer. The tablets contain a combination of two types of ciprofloxacin drug substance, ciprofloxacin hydrochloride and ciprofloxacin betaine (base). Ciprofloxacin hydrochloride is 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3quinolinecarboxylic acid hydrochloride. It is provided as a mixture of the monohydrate and the sesquihydrate. The empirical formula of the monohydrate is C17H18FN3O3 • HCl • H2O and its molecular weight is 385.8. The empirical formula of the sesquihydrate is C17H18FN3O3 • HCl • 1.5 H2O and its molecular weight is 394.8. The drug substance is a faintly yellowish to light yellow crystalline substance. The chemical structure of the monohydrate is as follows:

Ciprofloxacin betaine is 1-cyclopropyl-6-fluoro-1, 4-dihydro-4-oxo-7-(1-piperazinyl)-3quinolinecarboxylic acid. As a hydrate, its empirical formula is C17H18FN3O3 • 3.5 H2O and its molecular weight is 394.3. It is a pale yellowish to light yellow crystalline substance and its chemical structure is as follows:

CIPRO XR is available in 500 mg and 1000 mg (ciprofloxacin equivalent) tablet strengths. CIPRO XR tablets are nearly white to slightly yellowish, film-coated, oblong-shaped tablets. Each CIPRO XR 500 mg tablet contains 500 mg of ciprofloxacin as ciprofloxacin HCl (287.5 mg, calculated as ciprofloxacin on the dried basis) and ciprofloxacin† (212.6 mg, calculated on the dried basis). Each CIPRO XR 1000 mg tablet contains 1000 mg of ciprofloxacin as ciprofloxacin HCl (574.9 mg, calculated as ciprofloxacin on the dried basis) and ciprofloxacin† (425.2 mg, calculated on the dried basis). The inactive ingredients are crospovidone, hypromellose, magnesium stearate, polyethylene glycol, silica colloidal anhydrous, succinic acid, and titanium dioxide.

* as ciprofloxacin† and ciprofloxacin hydrochloride
† does not comply with the loss on drying test and residue on ignition test of the USP monograph.

CIPRO®
(Sip-row)
(ciprofloxacin hydrochloride) Tablets for oral use

CIPRO®
(Sip-row)
(ciprofloxacin hydrochloride) for oral suspension

CIPRO® XR
(Sip-row)
(ciprofloxacin hydrochloride) Tablets for oral use

CIPRO® IV
(Sip-row)
(ciprofloxacin) Injection for intravenous infusion

Read this Medication Guide before you start taking CIPRO and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.

What is the most important information I should know about CIPRO?

CIPRO, a fluoroquinolone antibacterial medicine, can cause serious side effects. Some of these serious side effects can happen at the same time and could result in death.

If you get any of the following serious side effects while you take CIPRO, you should stop taking CIPRO immediately and get medical help right away.

1. Tendon rupture or swelling of the tendon (tendinitis).

• Tendon problems can happen in people of all ages who take CIPRO. Tendons are tough cords of tissue that connect muscles to bones. Symptoms of tendon problems may include:
  • pain
  • swelling
  • tears and swelling of the tendons including the back of the ankle (Achilles), shoulder, hand, or other tendon sites.
• The risk of getting tendon problems while you take CIPRO is higher if you:
  • are over 60 years of age
  • are taking steroids (corticosteroids)
  • have had a kidney, heart or lung transplant
• Tendon problems can happen in people who do not have the above risk factors when they take CIPRO.
• Other reasons that can increase your risk of tendon problems can include:
  • physical activity or exercise
  • kidney failure
  • tendon problems in the past, such as in people with rheumatoid arthritis (RA)
• Stop taking CIPRO immediately and get medical help right away at the first sign of tendon pain, swelling or inflammation.
  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.
• Tendon rupture can happen while you are taking or after you have finished taking CIPRO. Tendon ruptures can happen within hours or days of taking CIPRO and have happened up to several months after people have finished taking their fluoroquinolone.
• Stop taking CIPRO immediately and 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

2. 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 CIPRO. Stop taking CIPRO immediately and talk to your healthcare provider right away if you get any of the following symptoms of peripheral neuropathy in your arms, hands, legs, or feet:

• pain
• numbness
• burning
• weakness
• tingling

CIPRO may need to be stopped to prevent permanent nerve damage.

3. Central Nervous System (CNS) effects. Seizures have been reported in people who take fluoroquinolone antibacterial medicines, including CIPRO. Tell your healthcare provider if you have a history of seizures before you start taking CIPRO. CNS side effects may happen as soon as after taking the first dose of CIPRO. Stop taking CIPRO immediately and talk to your healthcare provider right away if you get any of these side effects, or other changes in mood or behavior:

• seizures
• trouble sleeping
• hear voices, see things, or sense things that are not there (hallucinations)
• nightmares
• feel lightheaded or dizzy
• feel restless
• feel more suspicious (paranoia)
• tremors
• suicidal thoughts or acts
• feel anxious or nervous
• headaches that will not go away, with or without blurred vision
• confusion
• depression

4. Worsening of myasthenia gravis (a problem that causes muscle weakness). Fluoroquinolones like CIPRO may cause worsening of myasthenia gravis symptoms, including muscle weakness and breathing problems. Tell your healthcare provider if you have a history of myasthenia gravis before you start taking CIPRO. Call your healthcare provider right away if you have any worsening muscle weakness or breathing problems.

What is CIPRO?

CIPRO is a fluoroquinolone antibacterial medicine used in adults age 18 years and older to treat certain infections caused by certain germs called bacteria. These bacterial infections include:

• urinary tract infection
• chronic prostate infection
• lower respiratory tract infection
• sinus infection
• skin infection
• bone and joint infection
• nosocomial pneumonia
• intra-abdominal infection, complicated
• infectious diarrhea
• typhoid (enteric) fever
• cervical and urethral gonorrhea, uncomplicated
• people with a low white blood cell count and a fever
• inhalational anthrax
• plague
• Studies of CIPRO for use in the treatment of plague and anthrax were done in animals only, because plague and anthrax could not be studied in people.
• CIPRO should not be used in patients with acute exacerbation of chronic bronchitis, acute uncomplicated cystitis, and sinus infections, if there are other treatment options available.
• CIPRO should not be used as the first choice of antibacterial medicine to treat lower respiratory tract infections cause by a certain type of bacterial called Streptococcus pneumoniae.
• CIPRO is also used in children younger than 18 years of age to treat complicated urinary tract and kidney infections or who may have breathed in anthrax germs, have plague or have been exposed to plague germs.
• Children younger than 18 years of age have a higher chance of getting bone, joint, or tendon (musculoskeletal) problems such as pain or swelling while taking CIPRO. CIPRO should not be used as the first choice of antibacterial medicine in children under 18 years of age.
• CIPRO XR is only used in adults 18 years of age and older to treat urinary tract infections (complicated and uncomplicated), including kidney infections (pyelonephritis).
• It is not known if CIPRO XR is safe and effective in children under 18 years of age.

Who should not take CIPRO?

Do not take CIPRO if you:

• Have ever had a severe allergic reaction to an antibacterial medicine known as a fluoroquinolone, or are allergic to ciprofloxacin hydrochloride or any of the ingredients in CIPRO. See the end of this Medication Guide for a complete list of ingredients in CIPRO.
• Also take a medicine called tizanidine (Zanaflex®). Ask your healthcare provider if you are not sure.

What should I tell my healthcare provider before taking CIPRO?

Before you take CIPRO, tell your healthcare provider if you:

• have tendon problems; CIPRO should not be used in patients who have a history of tendon problems
• have a disease that causes muscle weakness (myasthenia gravis); CIPRO should not be used in patients who have a known history of myasthenia gravis
• have liver problems
• have central nervous system problems (such as epilepsy)
• have nerve problems; CIPRO should not be used in patients who have a history of a nerve problem called peripheral neuropathy
• have or anyone in your family has an irregular heartbeat, especially a condition called “QT prolongation”
• have or have had seizures
• have kidney problems. You may need a lower dose of CIPRO if your kidneys do not work well.
• have joint problems including rheumatoid arthritis (RA)
• have trouble swallowing pills
• have any other medical conditions
• are pregnant or plan to become pregnant. It is not known if CIPRO will harm your unborn baby.
• are breastfeeding or plan to breastfeed. CIPRO passes into breast milk. You and your healthcare provider should decide whether you will take CIPRO or breastfeed. You should not do both.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

CIPRO and other medicines can affect each other causing side effects.

Especially tell your healthcare provider if you take:

• a steroid medicine
• an anti-psychotic medicine
• a tricyclic antidepressant
• a water pill (diuretic)
• theophylline (such as Theo-24®, Elixophyllin®, Theochron®, Uniphyl®, Theolair®)
• a medicine to control your heart rate or rhythm (antiarrhythmics)
• an oral anti-diabetes medicine
• phenytoin (Fosphenytoin Sodium®, Cerebyx®, Dilantin-125®, Dilantin®, Extended Phenytoin Sodium®, Prompt Phenytoin Sodium®, Phenytek®)
• cyclosporine (Gengraf®, Neoral®, Sandimmune®, Sangcya®).
• a blood thinner (such as warfarin, Coumadin®, Jantoven®)
• methotrexate (Trexall®)
• ropinirole (Requip®)
• clozapine (Clozaril®, Fazaclo® ODT®)
• a Non-Steroidal Anti-Inflammatory Drug (NSAID). Many common medicines for pain relief are NSAIDs. Taking an NSAID while you take CIPRO or other fluoroquinolones may increase your risk of central nervous system effects and seizures.
• sildenafil (Viagra®, Revatio®)
• duloxetine
• products that contain caffeine
• probenecid (Probalan®, Col-probenecid ®)
• certain medicines may keep CIPRO Tablets, CIPRO Oral Suspension from working correctly. Take CIPRO Tablets and Oral Suspension either 2 hours before or 6 hours after taking these medicines, vitamins, or supplements:
  • an antacid, multivitamin, or other medicine or supplements that has magnesium, calcium, aluminum, iron, or zinc
  • sucralfate (Carafate®)
  • didanosine (Videx®, Videx EC®)

Ask your healthcare provider for a list of these medicines if you are not sure.

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

How should I take CIPRO?

• Take CIPRO exactly as your healthcare provider tells you to take it.
• Your healthcare provider will tell you how much CIPRO to take and when to take it.
• Take CIPRO 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 cannot swallow the tablet whole.
• Take CIPRO Oral Suspension in the morning and evening at about the same time each day. Shake the CIPRO Oral Suspension bottle well each time before use for about 15 seconds to make sure the suspension is mixed well. Close the bottle completely after use.
• Take CIPRO XR one time each day 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 cannot swallow the tablet whole.
• CIPRO IV is given to you by intravenous (IV) infusion into your vein, slowly, over 60 minutes, as prescribed by your healthcare provider.
• CIPRO can be taken with or without food.
• CIPRO 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 CIPRO.
• Do not skip any doses of CIPRO, or stop taking it, even if you begin to feel better, until you finish your prescribed treatment unless:
  • you have tendon problems. See “What is the most important information I should know about CIPRO?”
  • you have nerve problems. See “What is the most important information I should know about CIPRO?”
  • you have central nervous system problems. See “What is the most important information I should know about CIPRO?”
  • you have a serious allergic reaction. See “What are the possible side effects of CIPRO?”
  • your healthcare provider tells you to stop taking CIPRO
    Taking all of your CIPRO doses will help make sure that all of the bacteria are killed. Taking all of your CIPRO doses will help lower the chance that the bacteria will become resistant to CIPRO. If you become resistant to CIPRO, CIPRO and other antibacterial medicines may not work for you in the future.
• If you take too much CIPRO, call your healthcare provider or get medical help right away.

What should I avoid while taking CIPRO?

• CIPRO 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 CIPRO affects you.
• Avoid sunlamps, tanning beds, and try to limit your time in the sun. CIPRO can make your skin sensitive to the sun (photosensitivity) and the light from sunlamps and tanning beds. You could get a severe sunburn, blisters or swelling of your skin. If you get any of these symptoms while you take CIPRO, 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 CIPRO?

CIPRO may cause serious side effects, including:

• See, “What is the most important information I should know about CIPRO?”
• Serious allergic reactions. Serious allergic reactions, including death, can happen in people taking fluoroquinolones, including CIPRO, even after only 1 dose. Stop taking CIPRO 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
  • skin rash
    Skin rash may happen in people taking CIPRO even after only 1 dose. Stop taking CIPRO 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 CIPRO.
• Liver damage (hepatotoxicity). Hepatotoxicity can happen in people who take CIPRO. Call your healthcare provider right away if you have unexplained symptoms such as:
  • nausea or vomiting
  • stomach pain
  • fever
  • weakness
  • abdominal pain or tenderness
  • itching
  • unusual tiredness
  • loss of appetite
  • light colored bowel movements
  • dark colored urine
  • yellowing of your skin or the whites of your eyes
    Stop taking CIPRO and tell your healthcare provider right away if you have 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 CIPRO (a liver problem). Intestine infection (Pseudomembranous colitis). Pseudomembranous colitis can happen with many antibacterial medicines, including CIPRO. 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 antibacterial medicine.
• Serious heart rhythm changes (QT prolongation and torsade 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. CIPRO 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)
• Joint Problems. Increased chance of problems with joints and tissues around joints in children under 18 years old can happen. Tell your child's healthcare provider if your child has any joint problems during or after treatment with CIPRO.
• Sensitivity to sunlight (photosensitivity). See “What should I avoid while taking CIPRO?”

The most common side effects of CIPRO include:

• nausea
• diarrhea
• changes in liver function tests
• vomiting
• rash

Tell your healthcare provider about any side effect that bothers you, or that does not go away.

These are not all the possible side effects of CIPRO. For more information, ask your healthcare provider or pharmacist.

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 CIPRO?

CIPRO Tablets

• Store at room temperature between 20° to 25°C (68° to 77°F).

CIPRO Oral Suspension

• Store microcapsules and diluent below 25°C (77°F).
• Do not freeze.
• After your CIPRO treatment is finished, safely throw away any unused oral suspension.

CIPRO XR

• Store CIPRO XR between 59°F to 86°F (15°C to 30°C).

Keep CIPRO and all medicines out of the reach of children.

General Information about the safe and effective use of CIPRO.

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use CIPRO for a condition for which it is not prescribed. Do not give CIPRO 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 CIPRO. If you would like more information about CIPRO, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about CIPRO that is written for healthcare professionals.

For more information call 1-888-842-2937.

What are the ingredients in CIPRO?

CIPRO Tablets:

• Active ingredient: ciprofloxacin hydrochloride
• Inactive ingredients: cornstarch, microcrystalline cellulose, silicon dioxide, crospovidone, magnesium stearate, hypromellose, titanium dioxide, and polyethylene glycol

CIPRO Oral Suspension:

• Active ingredient: ciprofloxacin hydrochloride
• Inactive ingredients:
  • Microcapsules contains: povidone, methacrylic acid copolymer, hypromellose, magnesium stearate, and Polysorbate 20
  • Diluent contains: medium-chain triglycerides, sucrose, soy-lecithin, water, and strawberry flavor

CIPRO XR:

• Active ingredient: ciprofloxacin hydrochloride
• Inactive ingredients: crospovidone, hypromellose, magnesium stearate, polyethylene glycol, silica colloidal anhydrous, succinic acid, and titanium dioxide

CIPRO IV:

• Active ingredient: ciprofloxacin
• Inactive ingredients: lactic acid as a solubilizing agent, hydrochloric acid for pH adjustment

The following serious and otherwise important adverse drug reactions are discussed in greater detail in other sections of labeling:

• Disabling and Potentially Irreversible Serious Adverse Reactions [see WARNINGS AND PRECAUTIONS]
• Tenditits and Tendon Rupture[see WARNINGS AND PRECAUTIONS]
• Peripheral Neuropathy [see WARNINGS AND PRECAUTIONS]
• Central Nervous System Effects [see WARNINGS AND PRECAUTIONS]
• Exacerbation of Myasthenia Gravis [see WARNINGS AND PRECAUTIONS]
• Other Serious and Sometimes Fatal Adverse Reactions [see WARNINGS AND PRECAUTIONS]
• Hypersensitivity Reactions [see WARNINGS AND PRECAUTIONS]
• Hepatotoxicity [see WARNINGS AND PRECAUTIONS]
• Serious Adverse Reactions with Concomitant Theophylline [see WARNINGS AND PRECAUTIONS]
• Clostridium difficile-Associated Diarrhea [see WARNINGS AND PRECAUTIONS]
• Prolongation of the QT Interval [see WARNINGS AND PRECAUTIONS]
• Musculoskeletal Disorders in Pediatric Patients [see WARNINGS AND PRECAUTIONS]
• Photosensitivity/Phototoxicity [see WARNINGS AND PRECAUTIONS]
• Development of Drug Resistant Bacteria [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Clinical trials in patients with urinary tract infections enrolled 961 patients treated with 500 mg or 1000 mg CIPRO XR. The overall incidence, type and distribution of adverse reactions were similar in patients receiving both 500 mg and 1000 mg of CIPRO XR. The adverse reaction information from clinical studies does, however, provide a basis for identifying the adverse events that appear to be related to drug use and for approximating rates.

In the clinical trial of uncomplicated UTIs, CIPRO XR (500 mg once daily) in 444 patients was compared to ciprofloxacin immediate-release tablets (250 mg twice daily) in 447 patients for 3 days. Discontinuations due to adverse reactions thought to be drug-related occurred in 0.2% (1/444) of patients in the CIPRO XR arm and in 0% (0/447) of patients in the control arm.

In the clinical trial of cUTI and acute uncomplicated pyelonephritis (AUP) defined as infections occurring in premenopausal, non-pregnant women with no known urological abnormalities or comorbidities, CIPRO XR (1000 mg once daily) in 517 patients was compared to ciprofloxacin immediate-release tablets (500 mg twice daily) in 518 patients for 7 to 14 days. Discontinuations due to adverse reactions thought to be drug-related occurred in 3.1% (16/517) of patients in the CIPRO XR arm and in 2.3% (12/518) of patients in the control arm. The most common reasons for discontinuation in the CIPRO XR arm were nausea/vomiting (4 patients) and dizziness (3 patients). In the control arm the most common reason for discontinuation was nausea/vomiting (3 patients).

In these clinical trials, the following events occurred in ≥ 2% of all CIPRO XR patients: nausea (4%), headache (3%), dizziness (2%), diarrhea (2%), vomiting (2%) and vaginal moniliasis (2%).

Adverse reactions, judged by investigators to be at least possibly drug-related, occurring in greater than or equal to 1% of all CIPRO XR treated patients were: nausea (3%), diarrhea (2%), headache (1%), dyspepsia (1%), dizziness (1%), and vaginal moniliasis (1%). Vomiting (1%) occurred in the 1000 mg group.

Table 2: Medically Important Adverse Reactions That Occurred In < 1% of CIPRO XR Patients

Postmarketing Experience

The following adverse reactions have been reported from worldwide marketing experience with fluoroquinolones, including CIPRO XR. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure (Table 3).

Table 3: Postmarketing Reports of Adverse Drug Reactions

Adverse Laboratory Changes

Changes in laboratory parameters while on CIPRO are listed below:

Hepatic�?"Elevations of ALT (SGPT), AST (SGOT), alkaline phosphatase, LDH, serum bilirubin.

Hematologic�?"Eosinophilia, leukopenia, decreased blood platelets, elevated blood platelets, pancytopenia.

Renal�?"Elevations of serum creatinine, BUN, crystalluria, cylindruria, and hematuria have been reported.

Other changes occurring 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, and leukocytosis.

Read the entire FDA prescribing information for Cipro XR (Ciprofloxacin Extended-Release)