CIPROFLOXACIN- ciprofloxacin tablets tablet, coated

United States - English - NLM (National Library of Medicine)

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Active ingredient:
CIPROFLOXACIN HYDROCHLORIDE (UNII: 4BA73M5E37) (CIPROFLOXACIN - UNII:5E8K9I0O4U)
Available from:
REMEDYREPACK INC.
Administration route:
ORAL
Prescription type:
PRESCRIPTION DRUG
Therapeutic indications:
Ciprofloxacin tablets are indicated in adult patients for treatment of skin and skin structure infections caused by Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Proteus mirabilis, Proteus vulgaris, Providencia stuartii, Morganella morganii, Citrobacter freundii, Pseudomonas aeruginosa, methicillin-susceptible Staphylococcus aureus, methicillin-susceptible Staphylococcus epidermidis, or Streptococcus pyogenes. Ciprofloxacin tablets are indicated in adult patients for treatment of bone and joint infections caused by Enterobacter cloacae, Serratia marcescens, or Pseudomonas aeruginosa. Ciprofloxacin tablets are indicated in adult patients for treatment of complicated intra-abdominal infections (used in combination with metronidazole) caused by Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis, Klebsiella pneumoniae, or Bacteroides fragilis . Ciprofloxacin tablet
Product summary:
Ciprofloxacin Tablets, USP 250 mg are available as round, white film-coated tablets debossed with “Y101” on one side.   Ciprofloxacin tablets, USP 500 mg are available as oval shaped, white film-coated tablets, debossed with “Y102” on one side. Ciprofloxacin Tablets, USP 250 mg and 500 mg are available in bottles of 100 and 500. Strength NDC Code Tablet Identification Bottles of 100 250 mg NDC 69117-0008-1 500 mg NDC 69117-0009-2 500 mg NDC 69117-0009-1 Y102 Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Preserve in well-closed container.
Authorization status:
Abbreviated New Drug Application
Authorization number:
70518-2286-0, 70518-2286-1, 70518-2286-2

CIPROFLOXACIN- ciprofloxacin tablets tablet, coated

REMEDYREPACK INC.

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Medication Guide

Ciprofloxacin (sip

roe flox

a sin) Tablets, USP

for oral use

Read this Medication Guide before you start taking ciprofloxacin tabletsand 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 ciprofloxacin tablets?

Ciprofloxacin tablets, 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 ciprofloxacin tablets, you should stop

taking ciprofloxacin tablets 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 ciprofloxacin tablets. Tendons are tough cords

of tissue that connect muscles to bones. Symptoms of tendon problems may include:

Pain, swelling, tears and swelling of tendons including the back of the ankle (Achilles), shoulder, hand,

or other tendon sites.

The risk of getting tendon problems while you take ciprofloxacin tablets 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

ciprofloxacin tablets.

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 ciprofloxacin tablets 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 ciprofloxacin tablets.

Tendon ruptures can happen within hours or days of taking ciprofloxacin tablets and have happened up to

several months after people have finished taking their fluoroquinolone.

Stop taking ciprofloxacin tablets 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 ciprofloxacin. Stop taking

ciprofloxacin tablets 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

burning

tingling

numbness

weakness

Ciprofloxacin tablets 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 ciprofloxacin tablets. Tell your healthcare provider if you have a history of

seizures before you start taking ciprofloxacin tablets. CNS side effects may happen as soon as after taking the

first dose of ciprofloxacin tablets. Stop taking ciprofloxacin tablets 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

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 lightheaded or dizzy

feel more suspicious (paranoia)

suicidal thoughts or acts

headaches that will not go away, with or without

blurred vision

4. Worsening of myasthenia gravis (a problem that causes muscle weakness).

Fluoroquinolones like ciprofloxacin 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 ciprofloxacin tablets. Call your healthcare provider right away if you have any

worsening muscle weakness or breathing problems.

What are ciprofloxacin tablets?

Ciprofloxacin tablets are 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 ciprofloxacin tablets for use in the treatment of plague and anthrax were done in animals only,

because plague and anthrax could not be studied in people.

Ciprofloxacin tablets 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.

Ciprofloxacin tablets 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.

C iprofloxacin tablets are 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 ciprofloxacin tablets. Ciprofloxacin tablets

should not be used as the first choice of antibacterial medicine in children under 18 years of age.

Who should not take ciprofloxacin tablets?

Do not take ciprofloxacin tablets 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 ciprofloxacin tablets. See the end of this

Medication Guide for a complete list of ingredients in ciprofloxacin tablets.

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 ciprofloxacin tablets?

Before you take ciprofloxacin tablets, tell your healthcare provider if you:

have tendon problems; ciprofloxacin tablets should not be used in patients who have a history of tendon

problems

have a disease that causes muscle weakness (myasthenia gravis); ciprofloxacin tablets 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; ciprofloxacin tablets should not be used in patients who have a history of a nerve

problem called peripheral neuropathy

have or 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 ciprofloxacin tablets 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 ciprofloxacin tablets will harm your unborn

baby.

are breastfeeding or plan to breastfeed. Ciprofloxacin passes into breast milk. You and your healthcare

provider should decide whether you will take ciprofloxacin tablets 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.

Ciprofloxacin tablets 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 ciprofloxacin tablets 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 ciprofloxacin tablets from working correctly.

Take ciprofloxacin tablets 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 ciprofloxacin tablets?

Take ciprofloxacin tablets exactly as your healthcare provider tells you to take it.

Your healthcare provider will tell you how much ciprofloxacin tablets to take and when to take it.

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 cannot 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 of ciprofloxacin tablets, 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

ciprofloxacin tablets?”

you have nerve problems. See “What is the most important information I should know about

ciprofloxacin tablets?”

you have central nervous system problems. 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?”

your healthcare provider tells you to stop taking ciprofloxacin tablets

Taking all of your ciprofloxacin tablets doses will help make sure that all of the bacteria are killed.

Taking all of your ciprofloxacin tablets doses will help lower the chance that the bacteria will become

resistant to ciprofloxacin tablets. If you become resistant to ciprofloxacin tablets, ciprofloxacin tablets and

other antibacterial medicines may not work for you in the future.

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

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 affects

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 a

severe sunburn, blisters or swelling of your skin. If you get any of these symptoms while you take

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 may cause serious side effects, including:

See, “What is the most important information I should know about ciprofloxacin tablets?”

Serious allergic reactions. Serious allergic reactions, including death, can happen in people taking

fluoroquinolones, including ciprofloxacin tablets, even after only 1 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

skin rash

Skin rash may happen in people taking ciprofloxacin tablets even after only 1 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.

Liver damage (hepatotoxicity). Hepatotoxicity can happen in people who take ciprofloxacin tablets. 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 ciprofloxacin tablets 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

ciprofloxacin tablets (a liver problem).

Aortic aneurysm and dissection. Tell your healthcare provider if you have ever been told that you have an

aortic aneurysm, a swelling of the large artery that carries blood from the heart to the body. Get emergency

medical help right away if you have sudden chest, stomach, or back pain.

Intestine infection (Pseudomembranous colitis). Pseudomembranous colitis can happen with many

antibacterial medicines, 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 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 irregularheartbeat), 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)

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 ciprofloxacin tablets.

Sensitivity to sunlight (photosensitivity). See “What should I avoid while taking ciprofloxacin tablets?”

Changes in blood sugar

People who take ciprofloxacin tablets and other fluoroquinolone medicines with oral anti-diabetes

medicines or with insulin can get low blood sugar (hypoglycemia) and high blood sugar (hyperglycemia).

Follow your healthcare provider's instructions for how often to check your blood sugar. If you have diabetes

and you get low blood sugar while taking ciprofloxacin tablets, stop taking ciprofloxacin tablets and call your

healthcare provider right away. Your antibiotic medicine may need to be changed.

The most common side effects of ciprofloxacin tablets 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 ciprofloxacin tablets. 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 ciprofloxacin tablets?

Store at 20° to 25°C (68° to 77°F). Preserve in well -closed container.

Keep ciprofloxacin tablets and all medicines out of the reach of children.

General Information about the safe and effective use of 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.

For more information call 1-877-736-5697.

What are the ingredients in ciprofloxacin tablets?

Active ingredient: ciprofloxacin hydrochloride

Inactive ingredients: colloidal silicon dioxide, corn starch, partially pregelatinised maize starch,

magnesium stearate, microcrystalline cellulose, sodium starch Glycolate (starch from potato), hypromellose,

titanium dioxide and PEG.

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

Manufacturer:

Yiling Pharmaceutical Ltd

No. 36 Zhujiang Road, Shijiazhuang, 050035, China.

Distributor:

Yiling Pharmaceutical, Inc.

5348 Vegas Dr., Las Vegas, NV 89108, USA

Rx Only

Revised

07/2019

Revised: 2/2020

Document Id: 9e590ce0-b399-824d-e053-2995a90ac97d

34391-3

Set id: d8b99e06-fc99-4751-88cf-25bf510035f3

Version: 3

Effective Time: 20200211

REMEDYREPACK INC.

CIPROFLOXACIN- ciprofloxacin tablets tablet, coated

REMEDYREPACK INC.

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HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use CIPROFLOXACIN TABLETS safely and

effectively. See full prescribing information for CIPROFLOXACIN TABLETS.

CIPROFLOXACIN TABLETS, for oral use

Initial U.S. Approval: 1987

WARNING: SERIOUS ADVERSE REACTIONS INCLUDING TENDINITIS, TENDON RUPTURE,

PERIPHERAL NEUROPATHY, CENTRAL NERVOUS SYSTEM EFFECTS AND EXACERBATION OF

MYASTHENIA GRAVIS

See full prescribing information for complete boxed warning.

Fluoroquinolones,including ciprofloxacin, have been associated with disabling and potentially

irreversible serious adverse reactions that have occurred together ( 5.1), including:

Tendinitis and tendon rupture ( 5.2)

Peripheral neuropathy ( 5.3)

Central nervous system effects ( 5.4)

Discontinue ciprofloxacin immediately and avoid the use of fluoroquinolones, including ciprofloxacin,

in patients who experience any of these serious adverse reactions ( 5.1)

Fluoroquinolones,including ciprofloxacin, may exacerbate muscle weakness in patients with

myasthenia gravis. Avoid ciprofloxacin in patients with known history of myasthenia gravis. ( 5.5)

Because fluoroquinolones, including ciprofloxacin, have been associated with serious adverse reactions

(5.1-5.16), reserve ciprofloxacin for use in patients who have no alternative treatment options for the

following indications:

Acute exacerbation of chronic bronchitis ( 1.10)

Acute uncomplicated cystitis ( 1.11)

Acute sinusitis (1.12)

RECENT MAJOR CHANGES

Warnings and Precautions, Central Nervous System Effects ( 5.4) 03/2019

Warnings and Precautions, Risk of Aortic Aneurysm Dissection ( 5.9) 07/2019

Warnings and Precautions, Blood Glucose Disturbances ( 5.19) 03/2019

INDICATIONS AND USAGE

Ciprofloxacin is a fluoroquinolone antibacterial indicated in adults (18 years of age and older) with the following infections

caused by designated, susceptible bacteria and in pediatric patients where indicated:

Skin and Skin Structure Infections ( 1.1)

Bone and Joint Infections ( 1.2)

Complicated Intra-Abdominal Infections ( 1.3)

Infectious Diarrhea ( 1.4)

Typhoid Fever (Enteric Fever) ( 1.5)

Uncomplicated Cervical and Urethral Gonorrhea ( 1.6)

Inhalational Anthrax post-exposure in adult and pediatric patients ( 1.7)

Plague in adult and pediatric patients ( 1.8)

Chronic Bacterial Prostatitis ( 1.9)

Lower Respiratory Tract Infections ( 1.10)

Acute Exacerbation of Chronic Bronchitis

Urinary Tract Infections ( 1.11)

Urinary Tract Infections (UTI)

Acute Uncomplicated Cystitis

Complicated UTI and Pyelonephritis in Pediatric Patients

Acute Sinusitis ( 1.12)

Usage

To reduce the development of drug-resistant bacteria and maintain the effectiveness of ciprofloxacin and other

antibacterial drugs, ciprofloxacin should be used only to treat or prevent infections that are proven or strongly suspected to

be caused by bacteria. ( 1.13)

DOSAGE AND ADMINISTRATION

Adult Dosage Guidelines

Infe c tio n

Do se

Frequency

Duratio n

Skin and Skin Structure

500 -750 mg

every 12 hours

7 to 14 days

Bone and Joint

500-750 mg

every 12 hours

4 to 8 weeks

Complicated Intra-Abdominal

500 mg

every 12 hours

7 to 14 days

Infectious Diarrhea

500 mg

every 12 hours

5 to 7 days

Typhoid Fever

500 mg

every 12 hours

10 days

Uncomplicated Gonorrhea

250 mg

single dose

single dose

Inhalational anthrax (post-exposure)

500 mg

every 12 hours

60 days

Plague

500–750 mg

every 12 hours

14 days

Chronic Bacterial Prostatitis

500 mg

every 12 hours

28 days

Lower Respiratory Tract

500 -750 mg

every 12 hours

7 to 14 days

Urinary Tract

250-500 mg

every 12 hours

7 to 14 days

Acute Uncomplicated Cystitis

250 mg

every 12 hours

3 days

Acute Sinusitis

500 mg

every 12 hours

10 days

Adults with creatinine clearance 30–50 mL/min 250–500 mg q 12 h (2.3)

Adults with creatinine clearance 5–29 mL/min 250–500 mg q 18 h ( 2.3)

Patients on hemodialysis or peritoneal dialysis 250–500 mg q 24 h (after dialysis) ( 2.3)

Pediatric Oral Dosage Guidelines

Infe c tio n

Do se

Frequency

Duratio n

Complicated UTI and Pyelonephritis

(1 to 17 years of age)

10–20 mg/kg

(maximum 750 mg per dose)

Every 12 hours

10–21 days

Inhalational Anthrax

(Post-Exposure )

15 mg/kg

(maximum

500 mg per dose)

Every 12 hours

60 days

Plague

15mg/kg

(maximum 500 mg per dose)

Every 8 to 12 hours

10–21 days

DOSAGE FORMS AND STRENGTHS

Tablets: 250 mg, 500 mg (3)

CONTRAINDICATIONS

Known hypersensitivity to ciprofloxacin or other quinolones ( 4.1, 5.6, 5.7)

Concomitant administration with tizanidine ( 4.2)

WARNINGS AND PRECAUTIONS

Hypersensitivity and other serious reactions: Serious and sometimes fatal reactions (for example, anaphylactic reactions)

may occur after the first or subsequent doses of ciprofloxacin. Discontinue ciprofloxacin at the first sign of skin rash,

jaundice or any sign of hypersensitivity. ( 4.1, 5.6, 5.7)

Hepatotoxicity: Discontinue immediately if signs and symptoms of hepatitis occur. ( 5.8)

Clostridium difficile-associated diarrhea: Evaluate if colitis occurs. ( 5.11)

QT Prolongation: Prolongation of the QT interval and isolated cases of torsade de pointes have been reported. Avoid use

in patients with known prolongation, those with hypokalemia, and with other drugs that prolong the QT interval. ( 5.12, 7,

8.5)

ADVERSE REACTIONS

The most common adverse reactions ≥1% were nausea, diarrhea, liver function tests abnormal, vomiting, and rash. ( 6)

To report SUSPECTED ADVERSE REACTIONS, contact Yiling Pharmaceutical, Inc. at 1-877-736-5697 or FDA

at 1-800-FDA-1088 or www.fda.gov/medwatch.

DRUG INTERACTIONS

Interacting Drug

Inte rac tio n

The ophylline

Serious and fatal reactions. Avoid concomitant use. Monitor serum

level ( 7)

Warfarin

Anticoagulant effect enhanced. Monitor prothrombin time, INR,

and bleeding ( 7)

Antidiabetic agents

Hypoglycemia including fatal outcomes have been reported.

Monitor blood glucose ( 7)

Phe nytoin

Monitor phenytoin level ( 7)

Me thotre xate

Monitor for methotrexate toxicity ( 7)

Cyclosporine

May increase serum creatinine. Monitor serum creatinine ( 7)

Multivalent cation-containing products

including antacids, metal cations or didanosine

Decreased ciprofloxacin absorption. Take 2 hours before or 6

hours after ciprofloxacin ( 7)

USE IN SPECIFIC POPULATIONS

See Full Prescribing Information for use in pediatric and geriatric patients ( 8.4, 8.5)

See 17 for PATIENT COUNSELING INFORMATION and Medication Guide.

Revised: 2/2020

FULL PRESCRIBING INFORMATION: CONTENTS*

WARNING: SERIOUS ADVERSE REACTIONS INCLUDING TENDINITIS, TENDON

RUPTURE, PERIPHERAL NEUROPATHY, CENTRAL NERVOUS SYSTEM EFFECTS

AND EXACERBATION OF MYASTHENIA GRAVIS

1 INDICATIONS AND USAGE

1.1 Skin and Skin Structure Infections

1.2 Bone and Joint Infections

1.3 Complicated Intra-Abdominal Infections

1.4 Infectious Diarrhea

1.5 Typhoid Fever (Enteric Fever)

1.6 Uncomplicated Cervical and Urethral Gonorrhea

1.7 Inhalational Anthrax (Post-Exposure)

1.8 Plague

1.9 Chronic Bacterial Prostatitis

1.10 Lower Respiratory Tract Infections

1.11 Urinary Tract Infections

1.12 Acute Sinusitis

1.13 Usage

2 DOSAGE AND ADMINISTRATION

2.1 Dosage in Adults

2.2 Dosage in Pediatric Patients

2.3 Dosage Modifications in Patients with Renal Impairment

2.4 Important Administration Instructions

3 DOSAGE FORMS AND STRENGTHS

4 CONTRAINDICATIONS

4.1 Hypersensitivity

4.2 Tizanidine

5 WARNINGS AND PRECAUTIONS

5.1 Disabling and Potentially Irreversible Serious Adverse Reactions Including Tendinitis and

Tendon Rupture, Peripheral Neuropathy, and Central Nervous System Effects

5.2 Tendinitis and Tendon Rupture

5.3 Peripheral Neuropathy

5.4 Central Nervous System Effects

5.5 Exacerbation of Myasthenia Gravis

5.6 Other Serious and Sometimes Fatal Adverse Reactions

5.7 Hypersensitivity Reactions

5.8 Hepatotoxicity

5.9 Risk of Aortic Aneurysm and Dissection

5.10 Serious Adverse Reactions with Concomitant Theophylline

5.11 Clostridium difficile-Associated Diarrhea

5.12 Prolongation of the QT Interval

5.13 Musculoskeletal Disorders in Pediatric Patients and Arthropathic Effects in Animals

5.14 Photosensitivity/Phototoxicity

5.15 Development of Drug Resistant Bacteria

5.16 Potential Risks with Concomitant Use of Drugs Metabolized by Cytochrome P450 1A2

Enzymes

5.17 Interference with Timely Diagnosis of Syphilis

5.18 Crystalluria

5.19 Blood Glucose Disturbances

6 ADVERSE REACTIONS

6.1 Clinical Trials Experience

6.2 Postmarketing Experience

6.3 Adverse Laboratory Changes

7 DRUG INTERACTIONS

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

8.3 Nursing Mothers

8.4 Pediatric Use

8.5 Geriatric Use

8.6 Renal Impairment

8.7 Hepatic Impairment

10 OVERDOSAGE

11 DESCRIPTION

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

12.3 Pharmacokinetics

12.4 Microbiology

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

13.2 Animal Toxicology and/or Pharmacology

14 CLINICAL STUDIES

14.1 Complicated Urinary Tract Infection and Pyelonephritis–Efficacy in Pediatric Patients

14.2 Inhalational Anthrax in Adults and Pediatrics

14.3 Plague

15 REFERENCES

16 HOW SUPPLIED/STORAGE AND HANDLING

17 PATIENT COUNSELING INFORMATION

Sections or subsections omitted from the full prescribing information are not listed.

FULL PRESCRIBING INFORMATION

WARNING: SERIOUS ADVERSE REACTIONS INCLUDING TENDINITIS, TENDON

RUPTURE, PERIPHERAL NEUROPATHY, CENTRAL NERVOUS SYSTEM EFFECTS

AND EXACERBATION OF MYASTHENIA GRAVIS

Fluoroquinolones, including ciprofloxacin, have been associated with disabling and

potentially irreversible serious adverse reactions that have occurred together [see Warnings

and Precautions ( 5.1)], including:

Tendinitis and tendon rupture [see Warnings and Precautions ( 5.2)].

Peripheral neuropathy [see Warnings and Precautions ( 5.3)].

Central nervous system effects [see Warnings and Precautions ( 5.4)].

Discontinue ciprofloxacin immediately and avoid the use of fluoroquinolones, including

ciprofloxacin, in patients who experience any of these serious adverse reactions [see

Warnings and Precautions ( 5.1)] . Fluoroquinolones, including ciprofloxacin, may exacerbate

muscle weakness in patients with myasthenia gravis. Avoid ciprofloxacin in patients with

known history of myasthenia gravis [see Warnings and Precautions ( 5.5)].

Because fluoroquinolones, including ciprofloxacin, have been associated with serious

adverse reactions[see Warnings and Precautions (5.1-5.16)], reserve ciprofloxacin for use in

patients who have no alternative treatment options for the following indications:

Acute exacerbation of chronic bronchitis [see Indications and Usage ( 1.10)].

Acute uncomplicated cystitis [see Indications and Usage ( 1.11)].

Acute sinusitis [see Indications and Usage ( 1.12)].

1 INDICATIONS AND USAGE

1.1 Skin and Skin Structure Infections

Ciprofloxacin tablets are indicated in adult patients for treatment of skin and skin structure infections

caused by Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Proteus mirabilis, Proteus

vulgaris, Providencia stuartii, Morganella morganii, Citrobacter freundii, Pseudomonas aeruginosa,

methicillin-susceptible Staphylococcus aureus, methicillin-susceptible Staphylococcus epidermidis, or

Streptococcus pyogenes.

1.2 Bone and Joint Infections

Ciprofloxacin tablets are indicated in adult patients for treatment of bone and joint infections caused by

Enterobacter cloacae, Serratia marcescens, or Pseudomonas aeruginosa.

1.3 Complicated Intra-Abdominal Infections

Ciprofloxacin tablets are indicated in adult patients for treatment of complicated intra-abdominal

infections (used in combination with metronidazole) caused by Escherichia coli, Pseudomonas

aeruginosa, Proteus mirabilis, Klebsiella pneumoniae, or Bacteroides fragilis.

1.4 Infectious Diarrhea

Ciprofloxacin tablets are indicated in adult patients for treatment of infectious diarrhea caused by

Escherichia coli (enterotoxigenic isolates), Campylobacter jejuni, Shigella boydii

, Shigella dysenteriae,

Shigella flexneri or Shigella sonnei

when antibacterial therapy is indicated.

Although treatment of infections due to this organism in this organ system demonstrated a clinically

significant outcome, efficacy was studied in fewer than 10 patients.

1.5 Typhoid Fever (Enteric Fever)

Ciprofloxacin tablets are indicated in adult patients for treatment of typhoid fever (enteric fever) caused

by Salmonella typhi. The efficacy of ciprofloxacin in the eradication of the chronic typhoid carrier state

has not been demonstrated.

1.6 Uncomplicated Cervical and Urethral Gonorrhea

Ciprofloxacin tablets are indicated in adult patients for treatment of uncomplicated cervical and urethral

gonorrhea due to Neisseria gonorrhoeae [see Warnings and Precautions ( 5.17)].

1.7 Inhalational Anthrax (Post-Exposure)

Ciprofloxacin tablets are indicated in adults and pediatric patients from birth to 17 years of age for

inhalational anthrax (post-exposure) to reduce the incidence or progression of disease following

exposure to aerosolized Bacillus anthracis.

Ciprofloxacin serum concentrations achieved in humans served as a surrogate endpoint reasonably

likely to predict clinical benefit and provided the initial basis for approval of this indication.

Supportive clinical information for ciprofloxacin for anthrax post-exposure prophylaxis was obtained

during the anthrax bioterror attacks of October 2001 [see Clinical Studies ( 14.2)].

1.8 Plague

Ciprofloxacin tablets are indicated for treatment of plague, including pneumonic and septicemic plague,

due to Yersinia pestis (Y. pestis) and prophylaxis for plague in adults and pediatric patients from birth to

17 years of age. Efficacy studies of ciprofloxacin could not be conducted in humans with plague for

feasibility reasons. Therefore this indication is based on an efficacy study conducted in animals only

[see Clinical Studies ( 14.3)] .

1.9 Chronic Bacterial Prostatitis

Ciprofloxacin tablets are indicated in adult patients for treatment of chronic bacterial prostatitis caused

by Escherichia coli or Proteus mirabilis.

1.10 Lower Respiratory Tract Infections

Ciprofloxacin tablets are indicated in adult patients for treatment of lower respiratory tract infections

caused by Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Proteus mirabilis, Pseudomonas

aeruginosa, Haemophilus influenzae, Haemophilus parainfluenzae, or Streptococcus pneumoniae.

Ciprofloxacin tablets are not a drug of first choice in the treatment of presumed or confirmed

pneumonia secondary to Streptococcus pneumoniae.

Ciprofloxacin tablets are indicated for the treatment of acute exacerbations of chronic bronchitis

(AECB) caused by Moraxella catarrhalis.

Because fluoroquinolones, including ciprofloxacin, have been associated with serious adverse

reactions [see Warnings and Precautions (5.1–5.16)]and for some patients AECB is self-limiting,

reserve ciprofloxacin tablets for treatment of AECB in patients who have no alternative treatment

options .

1.11 Urinary Tract Infections

Urinary Tract Infections in Adults

Ciprofloxacin tablets are indicated in adult patients for treatment of urinary tract infections caused by

Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Serratia marcescens, Proteus mirabilis,

Providencia rettgeri, Morganella morganii, Citrobacter koseri, Citrobacter freundii, Pseudomonas

aeruginosa, methicillin-susceptible Staphylococcus epidermidis, Staphylococcus saprophyticus, or

Enterococcus faecalis.

Acute Uncomplicated Cystitis

Ciprofloxacin tablets are indicated in adult female patients for treatment of acute uncomplicated cystitis

caused by Escherichia coli or Staphylococcus saprophyticus.

Because fluoroquinolones, including ciprofloxacin, have been associated with serious adverse

reactions [see Warnings and Precautions ( 5.1-5.16)] and for some patients acute uncomplicated cystitis

is self-limiting, reserve ciprofloxacin tablets for treatment of acute uncomplicated cystitis in patients

who have no alternative treatment options.

Complicated Urinary Tract Infection and Pyelonephritis in Pediatric Patients

Ciprofloxacin tablets are indicated in pediatric patients aged one to 17 years of age for treatment of

complicated urinary tract infections (cUTI) and pyelonephritis due to Escherichia coli [see Use in Specific

Populations ( 8.4)] .

Although effective in clinical trials, ciprofloxacin tablets are not a drug of first choice in the pediatric

population due to an increased incidence of adverse reactions compared to controls, including reactions

related to joints and/or surrounding tissues . Ciprofloxacin tablets, like other fluoroquinolones, are

associated with arthropathy and histopathological changes in weight-bearing joints of juvenile animals

[see Warnings and Precautions (5.13), Adverse Reactions ( 6.1), Use in Specific Populations ( 8.4) and

Nonclinical Toxicology ( 13.2)].

1.12 Acute Sinusitis

Ciprofloxacin tablets are indicated in adult patients for treatment of acute sinusitis caused by

Haemophilus influenzae, Streptococcus pneumoniae, or Moraxella catarrhalis.

Because fluoroquinolones, including ciprofloxacin, have been associated with serious adverse

reactions [see Warnings and Precautions ( 5.1-5.15)] and for some patients acute sinusitis is self-

limiting, reserve ciprofloxacin tablets for treatment of acute sinusitis in patients who have no alternative

treatment options .

1.13 Usage

To reduce the development of drug-resistant bacteria and maintain the effectiveness of ciprofloxacin

tablets and other antibacterial drugs, ciprofloxacin tablets should be used only to treat or prevent

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.

If anaerobic organisms are suspected of contributing to the infection, appropriate therapy should be

administered. 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 ciprofloxacin tablets 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.

2 DOSAGE AND ADMINISTRATION

Ciprofloxacin tablets should be administered orally as described in the appropriate Dosage Guidelines

tables.

2.1 Dosage in Adults

The determination of dosage and duration for any particular patient must take into consideration the

severity and nature of the infection, the susceptibility of the causative microorganism, the integrity of

the patient’s host-defense mechanisms, and the status of renal and hepatic function.

Ciprofloxacin Tablets may be administered to adult patients when clinically indicted at the discretions

of the physician.

Table 1: Adult Dosage Guidelines

Infection

Dos e

Frequency

Usual Durations

Skin and Skin Structure

500–750 mg

every 12 hours

7 to 14 days

Bone and Joint

500–750 mg

every 12 hours

4 to 8 weeks

Complicated Intra–Abdominal 500 mg

every 12 hours

7 to 14 days

Infectious Diarrhea

500 mg

every 12 hours

5 to 7 days

Typhoid Fever

500 mg

every 12 hours

10 days

Uncomplicated Urethral and

Cervical Gonococcal

Infections

250 mg

single dose

single dose

Inhalational anthrax (post-

exposure)

500 mg

every 12 hours

60 days

Plague

500–750 mg

every 12 hours

14 days

Chronic Bacterial Prostatitis

500 mg

every 12 hours

28 days

Lower Respiratory Tract

Infections

500–750 mg

every 12 hours

7 to 14 days

Urinary Tract Infections

250–500 mg

every 12 hours

7 to 14 days

Acute Uncomplicated Cystitis 250 mg

every 12 hours

3 days

Acute Sinusitis

500 mg

every 12 hours

10 days

Conversion of IV to Oral Dosing in Adults

Patients whose therapy is started with CIPRO IV (product of Bayer HealthCare Pharmaceuticals Inc.)

may be switched to ciprofloxacin tablets when clinically indicated at the discretion of the physician

(Table 2) [see Clinical Pharmacology (12.3)].

Table 2: Equivalent AUC Dosing Regimens

Ciprofloxacin Oral Dosage

Equivalent CIPRO IV Dosage

250 mg Tablet every 12 hours

200 mg intravenous every 12 hours

500 mg Tablet every 12 hours

400 mg intravenous every 12 hours

750 mg Tablet every 12 hours

400 mg intravenous every 8 hours

2.2 Dosage in Pediatric Patients

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).

Used in conjunction with metronidazole.

Begin drug administration as soon as possible after suspected or confirmed exposure.

Dosing and initial route of therapy (that is, IV or oral) for cUTI or pyelonephritis should be determined

by the severity of the infection. Ciprofloxacin tablets should be administered as described in Table 3.

Table 3: Pediatric Dosage Guidelines

Infection

Dos e

Frequency

Total Duration

Complicated Urinary Tract or

Pyelonephritis

(patients from 1 to 17 years of

age)

10 mg/kg to 20 mg/kg

(maximum 750 mg per dose; not to be

exceeded even in patients weighing

more than 51 kg)

Every 12 hours

10–21 days

Inhalational Anthrax (Post-

Exposure)

15 mg/kg

(maximum 500 mg per dose)

Every 12 hours

60 days

Plague

15 mg/kg

(maximum 500 mg per dose)

Every 8 to 12

hours

10–21 days

The total duration of therapy for cUTI and pyelonephritis in the clinical trial was determined by the

physician. The mean duration of treatment was 11 days (range 10 to 21 days).

Begin drug administration as soon as possible after suspected or confirmed exposure.

Begin drug administration as soon as possible after suspected or confirmed exposure to Y. pestis.

2.3 Dosage Modifications in Patients with Renal Impairment

Ciprofloxacin is eliminated primarily by renal excretion; however, the drug is also metabolized and

partially cleared through the biliary system of the liver and through the intestine. These alternative

pathways of drug elimination appear to compensate for the reduced renal excretion in patients with renal

impairment. Nonetheless, some modification of dosage is recommended, particularly for patients with

severe renal dysfunction. Dosage guidelines for use in patients with renal impairment are shown in

Table 4.

Table 4: Recommended Starting and Maintenance Doses for Adult Patients with Impaired Renal

Function

Creatinine Clearance (mL/min)

Dos e

> 50

See Usual Dosage.

30–50

250–500 mg every12 hours

5–29

250–500 mg every 18 hours

Patients on hemodialysis or Peritoneal dialysis

250–500 mg every 24 hours (after dialysis)

When only the serum creatinine concentration is known, the following formulas may be used to estimate

creatinine clearance:

Men - Creatinine clearance (mL/min) = Weight (kg) x (140–age)

72 x serum creatinine (mg/dL)

Women - 0.85 x the value calculated for men.

The serum creatinine should represent a steady state of renal function.

In patients with severe infections and severe renal impairment, a unit dose of 750 mg may be

administered at the intervals noted above. Patients should be carefully monitored.

Pediatric patients with moderate to severe renal insufficiency were excluded from the clinical trial of

cUTI and pyelonephritis. No information is available on dosing adjustments necessary for pediatric

patients with moderate to severe renal insufficiency (that is, creatinine clearance of < 50 mL/min/1.73m

2.4 Important Administration Instructions

With Multivalent Cations

Administer ciprofloxacin tablets at least 2 hours before or 6 hours after magnesium/aluminum antacids;

polymeric phosphate binders (for example, sevelamer, lanthanum carbonate) or sucralfate; Videx®

(didanosine) chewable/buffered tablets or pediatric powder for oral solution; other highly buffered

drugs; or other products containing calcium, iron or zinc.

With Dairy Products

Concomitant administration of ciprofloxacin tablets with dairy products (like milk or yogurt) or calcium-

fortified juices alone should be avoided since decreased absorption is possible; however, ciprofloxacin

tablets may be taken with a meal that contains these products.

Hydration of Patients Receiving Ciprofloxacin Tablets

Assure adequate hydration of patients receiving ciprofloxacin tablets to prevent the formation of highly

concentrated urine. Crystalluria has been reported with quinolones.

Instruct the patient of the appropriate ciprofloxacin tablets administration [see Patient Counseling

Information (17)].

3 DOSAGE FORMS AND STRENGTHS

Ciprofloxacin Tablets, USP 250 mg, white, round shaped tablets, plain on one side, and “Y101” with

no breakline on the other side.

Ciprofloxacin Tablets, USP 500 mg, white, oval shaped tablets, plain on one side, and “Y102” with

no breakline on the other side.

4 CONTRAINDICATIONS

4.1 Hypersensitivity

Ciprofloxacin tablets are contraindicated in persons with a history of hypersensitivity to ciprofloxacin,

any member of the quinolone class of antibacterials, or any of the product components [see Warnings

and Precautions ( 5.7)].

4.2 Tizanidine

Concomitant administration with tizanidine is contraindicated [see Drug Interactions ( 7)].

5 WARNINGS AND PRECAUTIONS

5.1 Disabling and Potentially Irreversible Serious Adverse Reactions Including Tendinitis and

Tendon Rupture, Peripheral Neuropathy, and Central Nervous System Effects

Fluoroquinolones, including ciprofloxacin, have been associated with disabling and potentially

irreversible serious adverse reactions from different body systems that can occur together in the same

patient. Commonly seen adverse reactions include tendinitis, tendon rupture, arthralgia, myalgia,

peripheral neuropathy, and central nervous system effects (hallucinations, anxiety, depression, insomnia,

severe headaches, and confusion). These reactions can occur within hours to weeks after starting

ciprofloxacin. Patients of any age or without pre-existing risk factors have experienced these adverse

reactions [see Warnings and Precautions ( 5.2, 5.3, 5.4)] .

Discontinue ciprofloxacin immediately at the first signs or symptoms of any serious adverse reaction. In

addition, avoid the use of fluoroquinolones, including ciprofloxacin, in patients who have experienced

any of these serious adverse reactions associated with fluoroquinolones.

5.2 Tendinitis and Tendon Rupture

Fluoroquinolones, including ciprofloxacin, have been associated with an increased risk of tendinitis and

tendon rupture in all ages [see Warnings and Precautions ( 5.1) and Adverse Reactions ( 6.2)] . This

adverse reaction most frequently involves the Achilles tendon, and has also been reported with the

rotator cuff (the shoulder), the hand, the biceps, the thumb, and other tendons. Tendinitis or tendon

rupture can occur, within hours or days of starting ciprofloxacin, or as long as several months after

completion of fluoroquinolone therapy. Tendinitis and tendon rupture can occur bilaterally.

The risk of developing fluoroquinolone-associated tendinitis and tendon rupture is increased in patients

over 60 years of age, in patients taking corticosteroid drugs, and in patients with kidney, heart or lung

transplants. Other factors 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. Discontinue ciprofloxacin immediately if the patient experiences pain, swelling,

inflammation or rupture of a tendon. Avoid fluoroquinolones, including ciprofloxacin, in patients who

have a history of tendon disorders or have experienced tendinitis or tendon rupture [see Adverse

Reactions ( 6.2)].

5.3 Peripheral Neuropathy

Fluoroquinolones, including ciprofloxacin, have been associated with an increased risk of peripheral

neuropathy. Cases of sensory or sensorimotor axonal polyneuropathy affecting small and/or large axons

resulting in paresthesias, hypoesthesias, dysesthesias and weakness have been reported in patients

receiving fluoroquinolones, including ciprofloxacin. Symptoms may occur soon after initiation of

ciprofloxacin and may be irreversible in some patients [see Warnings and Precautions ( 5.1) and Adverse

Reactions ( 6.1, 6.2)] .

Discontinue ciprofloxacin immediately if the patient experiences symptoms of peripheral neuropathy

including pain, burning, tingling, numbness, and/or weakness, or other alterations in sensations including

light touch, pain, temperature, position sense and vibratory sensation, and/or motor strength in order to

minimize the development of an irreversible condition. Avoid fluoroquinolones, including

ciprofloxacin, in patients who have previously experienced peripheral neuropathy [see Adverse

Reactions ( 6.1, 6.2)].

5.4 Central Nervous System Effects

Psychiatric Adverse Reactions

Fluoroquinolones, including ciprofloxacin, have been associated with an increased risk of psychiatric

adverse reactions, including: toxic psychosis, psychotic reactions progressing to suicidal

ideations/thoughts, hallucinations, or paranoia; depression, or self-injurious behavior such as attempted

or completed suicide; anxiety, agitation, or nervousness; confusion, delirium, disorientation, or

disturbances in attention; insomnia or nightmares; memory impairment. These reactions may occur

following the first dose. Advise patients receiving ciprofloxacin to inform their healthcare provider

immediately if these reactions occur, discontinue the drug, and institute appropriate care.

Central Nervous System Adverse Reactions

Fluoroquinolones, including ciprofloxacin, have been associated with an increased risk of

seizures (convulsions), increased intracranial pressure (pscudotumor cerebri), dizziness, and tremors.

Ciprofloxacin, like other fluoroquinolones, is known to trigger seizures or lower the seizure threshold.

Cases of status epilepticus have been reported. As with all fluoroquinolones, use ciprofloxacin with

caution in epileptic patients and patients with known or suspected CNS disorders that may predispose to

seizures or lower the seizure threshold (for example, severe cerebral arteriosclerosis, previous

history of convulsion, reduced cerebral blood flow, altered brain structure, or stroke), or in the

presence of other risk factors that may predispose to seizures or lower the seizure threshold (for

example, certain drug therapy, renal dysfunction). If seizures occur, discontinue ciprofloxacin and

institute appropriate care [see Adverse Reactions ( 6.1) and Drug Interactions ( 7)].

5.5 Exacerbation of Myasthenia Gravis

Fluoroquinolones, including ciprofloxacin, have neuromuscular blocking activity and may exacerbate

muscle weakness in patients with myasthenia gravis. Postmarketing serious adverse reactions, including

deaths and requirement for ventilatory support, have been associated with fluoroquinolone use in

patients with myasthenia gravis. Avoid ciprofloxacin in patients with known history of myasthenia gravis

[see Adverse Reactions ( 6.2)].

5.6 Other Serious and Sometimes Fatal Adverse Reactions

Other serious and sometimes fatal adverse reactions, some due to hypersensitivity, and some due to

uncertain etiology, have been reported in patients receiving therapy with quinolones, including

ciprofloxacin. These events may be severe and generally occur following the administration of multiple

doses. Clinical manifestations may include one or more of the following:

Fever, rash, or severe dermatologic reactions (for example, 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.

Discontinue ciprofloxacin immediately at the first appearance of a skin rash, jaundice, or any other sign

of hypersensitivity and supportive measures instituted [see Adverse Reactions ( 6.1, 6.2)].

5.7 Hypersensitivity Reactions

Serious and occasionally fatal hypersensitivity (anaphylactic) reactions, some following the first dose,

have been reported in patients receiving fluoroquinolone therapy, including ciprofloxacin. Some

reactions were accompanied by cardiovascular collapse, loss of consciousness, tingling, pharyngeal or

facial edema, dyspnea, urticaria, and itching. Only a few patients had a history of hypersensitivity

reactions. Serious anaphylactic reactions require immediate emergency treatment with epinephrine and

other resuscitation measures, including oxygen, intravenous fluids, intravenous antihistamines,

corticosteroids, pressor amines, and airway management, including intubation, as indicated [see Adverse

Reactions ( 6.1)].

5.8 Hepatotoxicity

Cases of severe hepatotoxicity, including hepatic necrosis, life-threatening hepatic failure, and fatal

events, have been reported with ciprofloxacin. Acute liver injury is rapid in onset (range 1–39 days),

and is often associated with hypersensitivity. The pattern of injury can be hepatocellular, cholestatic, or

mixed. Most patients with fatal outcomes were older than 55 years old. In the event of any signs and

symptoms of hepatitis (such as anorexia, jaundice, dark urine, pruritus, or tender abdomen), discontinue

treatment immediately.

There can be a temporary increase in transaminases, alkaline phosphatase, or cholestatic jaundice,

especially in patients with previous liver damage, who are treated with ciprofloxacin [see Adverse

Reactions ( 6.2, 6.3)].

5.9 Risk of Aortic Aneurysm and Dissection

Epidemiologic studies report an increased rate of aortic aneurysm and dissection within two months

following use of fluoroquinolones, particularly in elderly patients. The cause for the increased risk has

not been identified. In patients with a known aortic aneurysm or patients who are at greater risk for aortic

aneurysms, reserve ciprofloxacin for use only when there are no alternative antibacterial treatments

available.

5.10 Serious Adverse Reactions with Concomitant Theophylline

Serious and fatal reactions have been reported in patients receiving concurrent administration of

ciprofloxacin and theophylline. These reactions have included cardiac arrest, seizure, status

epilepticus, and respiratory failure. Instances of nausea, vomiting, tremor, irritability, or palpitation have

also occurred.

Although similar serious adverse reactions have been reported in patients receiving theophylline alone,

the possibility that these reactions may be potentiated by ciprofloxacin cannot be eliminated. If

concomitant use cannot be avoided, monitor serum levels of theophylline and adjust dosage as

appropriate [see Drug Interactions ( 7)].

5.11 Clostridium difficile-Associated Diarrhea

Clostridium difficile (C. difficile)-associated diarrhea (CDAD) has been reported with use of nearly all

antibacterial agents, including ciprofloxacin, 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 isolates 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 antibacterial 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 antibacterial use not directed against C. difficile may need

to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial

treatment of C. difficile, and institute surgical evaluation as clinically indicated [see Adverse Reactions

(6.1)].

5.12 Prolongation of the QT Interval

Some fluoroquinolones, including ciprofloxacin, have been associated with prolongation of the QT

interval on the electrocardiogram and cases of arrhythmia. Cases of torsade de pointes have been

reported during postmarketing surveillance in patients receiving fluoroquinolones, including

ciprofloxacin.

Avoid ciprofloxacin in patients with known prolongation of the QT interval, risk factors for QT

prolongation or torsade de pointes (for example, congenital long QT syndrome, uncorrected electrolyte

imbalance, such as hypokalemia or hypomagnesemia and cardiac disease, such as heart failure,

myocardial infarction, or bradycardia), and patients receiving Class IA antiarrhythmic agents (quinidine,

procainamide), or Class III antiarrhythmic agents (amiodarone, sotalol), tricyclic antidepressants,

macrolides, and antipsychotics. Elderly patients may also be more susceptible to drug-associated

effects on the QT interval [see Adverse Reactions ( 6.2), Use in Specific Populations ( 8.5)].

5.13 Musculoskeletal Disorders in Pediatric Patients and Arthropathic Effects in Animals

Ciprofloxacin is indicated in pediatric patients (less than 18 years of age) only for cUTI, prevention of

inhalational anthrax (post exposure), and plague [see Indications and Usage ( 1.7, 1.8, 1.11)] . An

increased incidence of adverse reactions compared to controls, including reactions related to joints

and/or surrounding tissues, has been observed [see Adverse Reactions ( 6.1)] .

In pre-clinical studies, oral administration of ciprofloxacin caused lameness in immature dogs.

Histopathological examination of the weight-bearing joints of these dogs revealed permanent lesions of

the cartilage. Related quinolone-class drugs also produce erosions of cartilage of weight-bearing

joints and other signs of arthropathy in immature animals of various species [see Use in Specific

Populations ( 8.4) and Nonclinical Toxicology ( 13.2)].

5.14 Photosensitivity/Phototoxicity

Moderate to severe photosensitivity/phototoxicity reactions, the latter of which may manifest

as exaggerated sunburn reactions (for example, burning, erythema, exudation, vesicles, blistering,

edema) involving areas exposed to light (typically the face, “V” area of the neck, extensor surfaces of

the forearms, dorsa of the hands), can be associated with the use of quinolones including ciprofloxacin

after sun or UV light exposure. Therefore, avoid excessive exposure to these sources of light.

Discontinue ciprofloxacin if phototoxicity occurs [see Adverse Reactions (6.1)].

5.15 Development of Drug Resistant Bacteria

Prescribing ciprofloxacin tablets in the absence of a proven or strongly suspected bacterial infection or

a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the

development of drug-resistant bacteria.

5.16 Potential Risks with Concomitant Use of Drugs Metabolized by Cytochrome P450 1A2

Enzymes

Ciprofloxacin is an inhibitor of the hepatic CYP1A2 enzyme pathway. Co-administration of

ciprofloxacin and other drugs primarily metabolized by CYP1A2 (for example, theophylline,

methylxanthines, caffeine, tizanidine, ropinirole, clozapine, olanzapine and zolpidem), results in

increased plasma concentrations of the co-administered drug and could lead to clinically significant

pharmacodynamic adverse reactions of the co-administered drug [see Drug Interactions ( 7) and Clinical

Pharmacology ( 12.3)].

5.17 Interference with Timely Diagnosis of Syphilis

Ciprofloxacin has not been shown to be effective in the treatment of syphilis. Antimicrobial agents used

in high dose for short periods of time to treat gonorrhea may mask or delay the symptoms of incubating

syphilis. Perform a serologic test for syphilis in all patients with gonorrhea at the time of diagnosis.

Perform follow-up serologic test for syphilis three months after ciprofloxacin treatment.

5.18 Crystalluria

Crystals of ciprofloxacin have been observed rarely in the urine of human subjects but more frequently

in the urine of laboratory animals, which is usually alkaline [see Nonclinical Toxicology ( 13.2)].

Crystalluria related to ciprofloxacin has been reported only rarely in humans because human urine is

usually acidic. Avoid alkalinity of the urine in patients receiving ciprofloxacin. Hydrate patients well to

prevent the formation of highly concentrated urine [see Dosage and Administration ( 2.4)] .

5.19 Blood Glucose Disturbances

Fluoroquinolones, including ciprofloxacin, have been associated with disturbances of blood glucose,

including symptomatic hyperglycemia and hypoglycemia, usually in diabetic patients receiving

concomitant treatment with an oral hypoglycemic agent (for example, glyburide) or with insulin. In these

patients, careful monitoring of blood glucose is recommended. Severe cases of hypoglycemia resulting

in coma or death have been reported. If a hypoglycemic reaction occurs in a patient being treated with

ciprofloxacin, discontinue ciprofloxacin and initiate appropriate therapy immediately [see Adverse

Reactions ( 6.1), Drug Interactions ( 7)].

6 ADVERSE REACTIONS

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 (

5.1)]

Tendinitis and Tendon Rupture [see Warnings and Precautions ( 5.2)]

Peripheral Neuropathy [see Warnings and Precautions ( 5.3)]

Central Nervous System Effects [see Warnings and Precautions ( 5.4)] Exacerbation of Myasthenia

Gravis [see Warnings and Precautions ( 5.5)]

Other Serious and Sometimes Fatal Adverse Reactions [see Warnings and Precautions ( 5.6)]

Hypersensitivity Reactions [see Warnings and Precautions ( 5.7)]

Hepatotoxicity [see Warnings and Precautions ( 5.8)]

Risk of Aortic Aneurysm and Dissection [see Warnings and Precautions ( 5.9)]

Serious Adverse Reactions with Concomitant Theophylline [see Warnings and Precautions (5.10)]

Clostridium difficile-Associated Diarrhea [see Warnings and Precautions (5.11)]

Prolongation of the QT Interval [see Warnings and Precautions (5.12)]

Musculoskeletal Disorders in Pediatric Patients [see Warnings and Precautions (5.13)]

Photosensitivity/Phototoxicity [see Warnings and Precautions (5.14)]

Development of Drug Resistant Bacteria [see Warnings and Precautions (5.15)]

6.1 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.

Adult Patients

During clinical investigations with oral and parenteral ciprofloxacin, 49,038 patients received courses

of the drug.

The most frequently reported adverse reactions, from clinical trials of all formulations, all dosages, all

drug-therapy durations, and for all indications of ciprofloxacin therapy were nausea (2.5%), diarrhea

(1.6%), liver function tests abnormal (1.3%), vomiting (1%), and rash (1%).

Table 5: Medically Important Adverse Reactions That Occurred In less than 1% of Ciprofloxacin

Patients

System Organ Class

Adverse Reactions

Body as a Whole

Headache

Abdominal Pain/Discomfort

Pain

Cardiovas cular

Syncope

Angina Pectoris

Myocardial Infarction

Cardiopulmonary Arrest

Tachycardia

Hypotension

Central Nervous System

Restlessness

Dizziness

Insomnia

Nightmares

Hallucinations

Paranoia

Psychosis (toxic)

Manic Reaction

Irritability

Tremor

Ataxia

Seizures (including Status Epilepticus)

Malaise

Anorexia

Phobia

Depersonalization

Depression (potentially culminating in self-

injurious behavior

(such as suicidal ideations/thoughts and attempted

or completed suicide)

Paresthesia

Abnormal Gait

Migraine

Gas trointes tinal

Intestinal Perforation

Gastrointestinal Bleeding

Cholestatic Jaundice

Hepatitis

Pancreatitis

Hemic/Lymphatic

Petechia

Metabolic/Nutritional

Hyperglycemia

Hypoglycemia

Mus culos keletal

Arthralgia

Joint Stiffness

Muscle Weakness

Renal/Urogenital

Interstitial Nephritis

Renal Failure

Res piratory

Dyspnea

Laryngeal Edema

Hemoptysis

Bronchospasm

Skin/Hypers ens itivity

Anaphylactic Reactions including life-

threatening anaphylactic shock

Erythema Multiforme/Stevens-Johnson Syndrome

Exfoliative Dermatitis

Toxic Epidermal Necrolysis

Pruritus

Urticaria

Photosensitivity/Phototoxicity reaction

Flushing

Fever

Angioedema

Erythema Nodosum

Sweating

Special Senses

Blurred Vision

Disturbed Vision (chromatopsia and photopsia)

Decreased Visual Acuity

Diplopia

Tinnitus

Hearing Loss

Bad Taste

In randomized, double-blind controlled clinical trials comparing ciprofloxacin tablets [500 mg two

times daily (BID)] to cefuroxime axetil (250 mg–500 mg BID) and to clarithromycin (500 mg BID) in

patients with respiratory tract infections, ciprofloxacin demonstrated a CNS adverse reaction profile

comparable to the control drugs.

Pediatric Patients

Short (6 weeks) and long term (1 year) musculoskeletal and neurological safety of oral/intravenous

ciprofloxacin, was compared to a cephalosporin for treatment of cUTI or pyelonephritis in pediatric

patients 1 to 17 years of age (mean age of 6 ± 4 years) in an international multicenter trial. The duration

of therapy was 10 to 21 days (mean duration of treatment was 11 days with a range of 1 to 88 days). A

total of 335 ciprofloxacin- and 349 comparator-treated patients were enrolled.

An Independent Pediatric Safety Committee (IPSC) reviewed all cases of musculoskeletal adverse

reactions including abnormal gait or abnormal joint exam (baseline or treatment-emergent). Within 6

weeks of treatment initiation, the rates of musculoskeletal adverse reactions were 9.3% (31/335) in the

ciprofloxacin-treated group versus 6% (21/349) in comparator-treated patients. All musculoskeletal

adverse reactions 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 adverse reactions. Ciprofloxacin-treated patients were more likely to report more than

one adverse reaction and on more than one occasion compared to control patients. The rate of

musculoskeletal adverse reactions was consistently higher in the ciprofloxacin group compared to the

control group across all age subgroups. At the end of 1 year, the rate of these adverse reactions

reported at any time during that period was 13.7% (46/335) in the ciprofloxacin-treated group versus

9.5% (33/349) in the comparator-treated patients (Table 6).

Table 6: Musculoskeletal Adverse Reactions

as Assessed by the IPSC

Ciprofloxacin Tablets

Comparator

All Patients (within 6 weeks)

31/335 (9.3%)

21/349 (6%)

95% Confidence Interval

(-0.8%, +7.2%)

Age Group

12 months < 24 months

1/36 (2.8%)

0/41

2 years < 6 years

5/124 (4%)

3/118 (2.5%)

6 years < 12 years

18/143 (12.6%)

12/153 (7.8%)

12 years to 17 years

7/32 (21.9%)

6/37 (16.2 %)

All Patients (within 1 year)

46/335 (13.7%)

33/349 (9.5%)

95% Confidence Interval

(-0.6%, + 9.1%)

Included: 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 (knee, elbow, ankle, hip,

wrist, and shoulder)

The study was designed to demonstrate that the arthropathy rate for the ciprofloxacin group did not

exceed that of the control group by more than + 6%. At both the 6 week and 1 year evaluations, the 95%

confidence interval indicated that it could not be concluded that the ciprofloxacin group had findings

comparable to the control group.

1

The incidence rates of neurological adverse reactions within 6 weeks of treatment initiation were 3%

(9/335) in the ciprofloxacin group versus 2% (7/349) in the comparator group and included dizziness,

nervousness, insomnia, and somnolence.

In this trial, the overall incidence rates of adverse reactions within 6 weeks of treatment initiation were

41% (138/335) in the ciprofloxacin group versus 31% (109/349) in the comparator group. The most

frequent adverse reactions were gastrointestinal: 15% (50/335) of ciprofloxacin patients compared to

9% (31/349) of comparator patients. Serious adverse reactions were seen in 7.5% (25/335) of

ciprofloxacin-treated patients compared to 5.7% (20/349) of control patients. Discontinuation of drug

due to an adverse reaction was observed in 3% (10/335) of ciprofloxacin -treated patients versus 1.4%

(5/349) of comparator patients. Other adverse reactions that occurred in at least 1% of ciprofloxacin

patients were diarrhea 4.8%, vomiting 4.8%, abdominal pain 3.3%, dyspepsia 2.7%, nausea 2.7%, fever

2.1%, asthma 1.8% and rash 1.8%.

Short-term safety data for ciprofloxacin was also collected in a randomized, double-blind clinical trial

for the treatment of acute pulmonary exacerbations in cystic fibrosis patients (ages 5–17 years). Sixty

seven patients received CIPRO IV 10 mg/kg/dose every 8 hours for one week followed by

ciprofloxacin tablets 20 mg/kg/dose every 12 hours to complete 10–21 days treatment and 62 patients

received the combination of ceftazidime intravenous 50 mg/kg/dose every 8 hours and tobramycin

intravenous 3 mg/kg/dose every 8 hours for a total of 10–21 days. Periodic musculoskeletal

assessments were conducted by treatment-blinded examiners. Patients were followed for an average of

23 days after completing treatment (range 0–93 days). Musculoskeletal adverse reactions 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 reactions were similar in nature and frequency between treatment

arms. The efficacy of ciprofloxacin for the treatment of acute pulmonary exacerbations in pediatric

cystic fibrosis patients has not been established.

In addition to the adverse reactions reported in pediatric patients in clinical trials, it should be expected

that adverse reactions reported in adults during clinical trials or postmarketing experience may also

occur in pediatric patients.

6.2 Postmarketing Experience

The following adverse reactions have been reported from worldwide marketing experience with

fluoroquinolones, including ciprofloxacin. 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 7).

Table 7: Postmarketing Reports of Adverse Drug Reactions

System Organ Class

Adverse Reactions

Cardiovas cular

QT prolongation

Torsade de Pointes

Vasculitis and ventricular arrhythmia

Central Nervous System

Hypertonia

Myasthenia

Exacerbation of myasthenia gravis

Peripheral neuropathy

Polyneuropathy

Twitching

Eye Disorders

Nystagmus

Gas trointes tinal

Pseudomembranous colitis

Hemic/Lymphatic

Pancytopenia (life threatening or fatal outcome)

Methemoglobinemia

Hepatobiliary

Hepatic failure (including fatal cases)

Infections and Infestations

Candidiasis (oral, gastrointestinal, vaginal)

Inves tigations

Prothrombin time prolongation or decrease

Cholesterol elevation (serum)

Potassium elevation (serum)

Mus culos keletal

Myalgia

Myoclonus

T endinitis

Tendon rupture

Psychiatric Disorders

Agitation

Confusion

Delirium

Skin/Hypers ens itivity

Acute generalize exanthematous pustulosis (AGEP)

Fixed eruption

Serum sickness-like reaction

Special Senses

Anosmia

Hyperesthesia

Hypesthesia

Taste loss

6.3 Adverse Laboratory Changes

Changes in laboratory parameters while on ciprofloxacin tablets 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.

7 DRUG INTERACTIONS

Ciprofloxacin is an inhibitor of human cytochrome P450 1A2 (CYP1A2) mediated metabolism. Co-

administration of ciprofloxacin with other drugs primarily metabolized by CYP1A2 results in increased

plasma concentrations of these drugs and could lead to clinically significant adverse events of the co-

administered drug.

Table 8: Drugs That are Affected by and Affecting Ciprofloxacin

Drugs That are Affected by Ciprofloxacin

Drug(s )

Recommendation

Comments

Tizanidine

Contraindicated

Concomitant administration of tizanidine and

ciprofloxacin is contraindicated due to the

potentiation of hypotensive and sedative effects

of tizanidine [ see Contraindications ( 4.2) ]

Theophylline

Avoid Use

(Plasma Exposure Likely to be

Increased and Prolonged)

Concurrent administration of ciprofloxacin with

theophylline may result in increased risk of a

patient developing central nervous system

(CNS) or other adverse reactions. If

concomitant use cannot be avoided, monitor

serum levels of theophylline and adjust dosage

as appropriate [see Warnings and Precautions

(5.10)].

Drugs Known to

Prolong QT Interval

Avoid Use

Ciprofloxacin may further prolong the QT

interval in patients receiving drugs known to

prolong the QT interval (for example, class IA

or III antiarrhythmics, tricyclic antidepressants,

macrolides, antipsychotics) [see Warnings and

Precautions (5.12) and Use in Specific

Populations ( 8.5)].

Oral antidiabetic drugs

Use with caution

Glucose-lowering effect

potentiated

Hypoglycemia sometimes severe has been

reported when ciprofloxacin and oral

antidiabetic agents, mainly sulfonylureas (for

example, glyburide, glimepiride), were co-

administered, presumably by intensifying the

action of the oral antidiabetic agent. Fatalities

have been reported. Monitor blood glucose

when ciprofloxacin is co-administered with oral

antidiabetic drugs [see Adverse Reactions ( 6.1)].

Phenytoin

Use with caution

Altered serum levels of

phenytoin (increased and

decreased)

To avoid the loss of seizure control associated

with decreased phenytoin levels and to prevent

phenytoin overdose-related adverse reactions

upon ciprofloxacin discontinuation in patients

receiving both agents, monitor phenytoin

therapy, including phenytoin serum

concentration during and shortly after co-

administration of ciprofloxacin with phenytoin.

Cyclosporine

Use with caution

(transient elevations in serum

creatinine)

Monitor renal function (in particular serum

creatinine) when ciprofloxacin is co-

administered with cyclosporine.

Anti-coagulant drugs

Use with caution

(Increase in anticoagulant

effect)

The risk may vary with the underlying infection,

age and general status of the patient so that the

contribution of ciprofloxacin to the increase in

INR (international normalized ratio) is difficult

to assess. Monitor prothrombin time and INR

frequently during and shortly after co-

administration of ciprofloxacin with an oral anti-

coagulant (for example, warfarin).

Methotrexate

Use with caution

Inhibition of methotrexate

renal tubular transport

potentially leading to

increased methotrexate plasma

levels

Potential increase in the risk of methotrexate

associated toxic reactions. Therefore, carefully

monitor patients under methotrexate therapy

when concomitant ciprofloxacin therapy is

indicated.

Ropinirole

Use with caution

Monitoring for ropinirole-related adverse

reactions and appropriate dose adjustment of

ropinirole is recommended during and shortly

after co-administration with ciprofloxacin [see

Warnings and Precautions ( 5.16)].

Clozapine

Use with caution

Careful monitoring of clozapine associated

adverse reactions and appropriate adjustment of

clozapine dosage during and shortly after co-

administration with ciprofloxacin are advised.

NSAIDs

Use with caution

Non-steroidal anti-inflammatory drugs (but not

acetyl salicylic acid) in combination of very

high doses of quinolones have been shown to

provoke convulsions in pre-clinical studies and

in postmarketing.

Sildenafil

Use with caution

Two-fold increase in

exposure

Monitor for sildenafil toxicity [see Clinical

Pharmacology ( 12.3) ].

Duloxetine

Avoid Use

Five-fold increase in

duloxetine exposure

If unavoidable, monitor for duloxetine toxicity

Caffeine/Xanthine

Derivatives

Use with caution

Reduced clearance resulting in

elevated levels and

prolongation of serum half-

life

Ciprofloxacin inhibits the formation of

paraxanthine after caffeine administration (or

pentoxifylline containing products). Monitor for

xanthine toxicity and adjust dose as necessary.

Zolpidem

Avoid Use

Co-administration with ciprofloxacin may

increase blood levels of zolpidem, concurrent

use is not recommended

Drug(s) Affecting Pharmacokinetics of Ciprofloxacin

Antacids, Sucralfate,

Multivitamins and

Other Products

Containing Multivalent

Cations

(magnesium/aluminum

antacids; polymeric

phosphate binders (for

example, sevelamer,

lanthanum carbonate);

sucralfate; Videx

(didanosine)

chewable/buffered

tablets or pediatric

powder; other highly

buffered drugs; or

products containing

calcium, iron, or zinc

and dairy products)

Ciprofloxacin should be taken

at least two hours before or

six hours after Multivalent

cation-containing products

administration [see Dosage

and Administration ( 2.4)].

Decrease ciprofloxacin absorption, resulting in

lower serum and urine levels

Probenecid

Use with caution

(interferes with renal tubular

secretion of ciprofloxacin and

increases ciprofloxacin serum

levels)

Potentiation of ciprofloxacin toxicity may

occur.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category C

There are no adequate and well-controlled studies in pregnant women. Ciprofloxacin should not be used

during pregnancy unless the potential benefit justifies the potential risk to both fetus and mother. An

expert review of published data on experiences with ciprofloxacin use during pregnancy by TERIS–the

Teratogen Information System–concluded that therapeutic doses during pregnancy are unlikely to pose a

substantial teratogenic risk (quantity and quality of data=fair), but the data are insufficient to state that

there is no risk.

A controlled prospective observational study followed 200 women exposed to

fluoroquinolones (52.5% exposed to ciprofloxacin and 68% first trimester exposures) during gestation.

In utero exposure to fluoroquinolones during embryogenesis was not associated with increased risk of

major malformations. The reported rates of major congenital malformations were 2.2% for the

fluoroquinolone group and 2.6% for the control group (background incidence of major malformations is

1–5%). Rates of spontaneous abortions, prematurity and low birth weight did not differ between the

groups and there were no clinically significant musculoskeletal dysfunctions up to one year of age in

the ciprofloxacin exposed children.

Another prospective follow-up study reported on 549 pregnancies with fluoroquinolone

exposure (93% first trimester exposures).

There were 70 ciprofloxacin exposures, all within the first

trimester. The malformation rates among live-born babies exposed to ciprofloxacin and to

fluoroquinolones overall were both within background incidence ranges. No specific patterns of

congenital abnormalities were found. The study did not reveal any clear adverse reactions due to in

utero exposure to ciprofloxacin.

No differences in the rates of prematurity, spontaneous abortions, or birth weight were seen in women

exposed to ciprofloxacin during pregnancy.

However, these small postmarketing epidemiology

studies, of which most experience is from short term, first trimester exposure, are insufficient to

evaluate the risk for less common defects or to permit reliable and definitive conclusions regarding the

safety of ciprofloxacin in pregnant women and their developing fetuses.

Reproduction studies have been performed in rats and mice using oral doses up to 100 mg/kg (0.6 and

0.3 times the maximum daily human dose based upon body surface area, respectively) and have revealed

no evidence of harm to the fetus due to ciprofloxacin. In rabbits, oral ciprofloxacin dose levels of 30

and 100 mg/kg (approximately 0.4- and 1.3 times the highest recommended therapeutic dose based upon

body surface area) produced gastrointestinal toxicity resulting in maternal weight loss and an increased

incidence of abortion, but no teratogenicity was observed at either dose level. After intravenous

administration of doses up to 20 mg/kg (approximately 0.3-times the highest recommended therapeutic

dose based upon body surface area), no maternal toxicity was produced and no embryotoxicity or

teratogenicity was observed.

8.3 Nursing Mothers

Ciprofloxacin is excreted in human milk. The amount of Ciprofloxacin absorbed by the nursing infant is

unknown. Because of the potential risk of serious adverse reactions (including articular damage) in

infants nursing from mothers taking ciprofloxacin, a decision should be made whether to discontinue

nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

8.4 Pediatric Use

Although effective in clinical trials, ciprofloxacin is not a drug of first choice in the pediatric

population due to an increased incidence of adverse reactions compared to controls. Quinolones,

including ciprofloxacin, cause arthropathy (arthralgia, arthritis), in juvenile animals [see Warnings and

Precautions (5.13) and Nonclinical Toxicology ( 13.2)] .

Complicated Urinary Tract Infection and Pyelonephritis

Ciprofloxacin tablets are indicated for the treatment of cUTI and pyelonephritis due to Escherichia coli

2, 3

in pediatric patients 1 to 17 years of age. Although effective in clinical trials, ciprofloxacin is not a

drug of first choice in the pediatric population due to an increased incidence of adverse reactions

compared to the controls, including events related to joints and/or surrounding tissues [see Adverse

Reactions ( 6.1) and Clinical Studies ( 14.1)].

Inhalational Anthrax (Post-Exposure)

Ciprofloxacin is indicated in pediatric patients from birth to 17 years of age, for inhalational anthrax

(post-exposure). The risk-benefit assessment indicates that administration of ciprofloxacin to pediatric

patients is appropriate [see Dosage and Administration ( 2.2) and Clinical Studies ( 14.2)].

Plague

Ciprofloxacin is indicated in pediatric patients from birth to 17 years of age, for treatment of plague,

including pneumonic and septicemic plague due to Yersinia pestis ( Y. pestis) and prophylaxis for plague.

Efficacy studies of ciprofloxacin could not be conducted in humans with pneumonic plague for

feasibility reasons. Therefore, approval of this indication was based on an efficacy study conducted in

animals. The risk-benefit assessment indicates that administration of ciprofloxacin to pediatric patients

is appropriate [see Indications and Usage ( 1.8), Dosage and Administration ( 2.2) and Clinical Studies (

14.3)].

8.5 Geriatric Use

Geriatric patients are at increased risk for developing severe tendon disorders including tendon rupture

when being treated with a fluoroquinolone such as ciprofloxacin. This risk is further increased in

patients receiving concomitant corticosteroid therapy. Tendinitis or tendon rupture can involve the

Achilles, hand, shoulder, or other tendon sites and can occur during or after completion of therapy;

cases occurring up to several months after fluoroquinolone treatment have been reported. Caution

should be used when prescribing ciprofloxacin to elderly patients especially those on corticosteroids.

Patients should be informed of this potential adverse reaction and advised to discontinue ciprofloxacin

and contact their healthcare provider if any symptoms of tendinitis or tendon rupture occur . [see Boxed

Warning, Warnings and Precautions ( 5.2), and Adverse Reactions ( 6.2)].

Epidemiologic studies report an increased rate of aortic aneurysm and dissection within two months

following use of fluoroquinolones, particularly in elderly patients [see Warnings and Precautions ( 5.9)].

In a retrospective analysis of 23 multiple-dose controlled clinical trials of ciprofloxacin encompassing

over 3500 ciprofloxacin-treated patients, 25% of patients were greater than or equal to 65 years of age

and 10% were greater than or equal to 75 years of age. No overall differences in safety or

effectiveness were observed between these subjects and younger subjects, and other reported clinical

experience has not identified differences in responses between the elderly and younger patients, but

greater sensitivity of some older individuals on any drug therapy cannot be ruled out. Ciprofloxacin is

known to be substantially excreted by the kidney, and the risk of adverse reactions may be greater in

patients with impaired renal function. No alteration of dosage is necessary for patients greater than 65

years of age with normal renal function. However, since some older individuals experience reduced

renal function by virtue of their advanced age, care should be taken in dose selection for elderly

patients, and renal function monitoring may be useful in these patients [see Dosage and Administration (

2.3) and Clinical Pharmacology ( 12.3)].

In general, elderly patients may be more susceptible to drug-associated effects on the QT interval.

Therefore, precaution should be taken when using ciprofloxacin with concomitant drugs that can result

in prolongation of the QT interval (for example, class IA or class III antiarrhythmics) or in patients with

risk factors for torsade de pointes (for example, known QT prolongation, uncorrected hypokalemia)

[see Warnings and Precautions (5.12)].

8.6 Renal Impairment

Ciprofloxacin is eliminated primarily by renal excretion; however, the drug is also metabolized and

partially cleared through the biliary system of the liver and through the intestine. These alternative

pathways of drug elimination appear to compensate for the reduced renal excretion in patients with renal

impairment. Nonetheless, some modification of dosage is recommended, particularly for patients with

severe renal dysfunction [see Dosage and Administration ( 2.3) and Clinical Pharmacology ( 12.3)].

8.7 Hepatic Impairment

In preliminary studies in patients with stable chronic liver cirrhosis, no significant changes in

ciprofloxacin pharmacokinetics have been observed. The pharmacokinetics of ciprofloxacin in patients

with acute hepatic insufficiency, have not been studied.

10 OVERDOSAGE

In the event of acute overdosage, reversible renal toxicity has been reported in some cases. Empty the

stomach by inducing vomiting or by gastric lavage. Observe the patient carefully and give supportive

treatment, including monitoring of renal function, urinary pH and acidify, if required, to prevent

crystalluria and administration of magnesium, aluminum, or calcium containing antacids which can

reduce the absorption of ciprofloxacin. Adequate hydration must be maintained. Only a small amount of

ciprofloxacin (less than 10%) is removed from the body after hemodialysis or peritoneal dialysis.

11 DESCRIPTION

Ciprofloxacin Tablets, USP are synthetic antimicrobial agents for oral administration. Ciprofloxacin

hydrochloride, USP, a fluoroquinolone, is the monohydrochloride monohydrate salt of 1-cyclopropyl-

6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)- 3-quinolinecarboxylic acid. It is a faintly yellowish to

light yellow crystalline substance with a molecular weight of 385.8. Its empirical formula is C

HClH

O and its chemical structure is as follows:

Ciprofloxacin is 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic

acid. Its empirical formula is C

and its molecular weight is 331.4. It is a faintly

yellowish to light yellow crystalline substance and its chemical structure is as follows:

Ciprofloxacin film-coated tablets are available in 250 mg and 500 mg (ciprofloxacin equivalent)

strengths. Ciprofloxacin Tablets, USP are white. The inactive ingredients are colloidal silicon dioxide,

corn starch, partially pregelatinized maize starch, magnesium stearate, microcrystalline cellulose,

sodium starch glycolate (starch from non-GMO potatoes), hypromellose, titanium dioxide and PEG.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

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

12.4)].

12.3 Pharmacokinetics

Absorption

The absolute bioavailability of Ciprofloxacin when given as an oral tablet is approximately 70% with

no substantial loss by first pass metabolism. Ciprofloxacin maximum serum concentrations

Cmax and

area under the curve (AUC) are shown in the chart for the 250 mg to 1000 mg dose range (Table 9).

Table 9: Ciprofloxacin Cmax and AUC Following Adminstration of Single Doses of Ciprofloxacin

Tablets to Healthy Subjects

Dose (mg)

Cmax

(mcg/mL)

(mcghr/mL)

11.6

20.2

1000

30.8

Maximum serum concentrations are attained 1 to 2 hours after oral dosing. Mean concentrations 12 hours

after dosing with 250, 500, or 750 mg are 0.1, 0.2, and 0.4 mcg/mL, respectively. The serum elimination

half-life in subjects with normal renal function is approximately 4 hours. Serum concentrations increase

proportionately with doses up to 1000 mg.

A 500 mg oral dose given every 12 hours has been shown to produce an AUC equivalent to that

produced by an intravenous infusion of 400 mg ciprofloxacin given over 60 minutes every 12 hours. A

750 mg oral dose given every 12 hours has been shown to produce an AUC at steady-state equivalent to

that produced by an intravenous infusion of 400 mg given over 60 minutes every 8 hours. A 750 mg

oral dose results in a Cmax similar to that observed with a 400 mg intravenous dose. A 250 mg oral

dose given every 12 hours produces an AUC equivalent to that produced by an infusion of 200 mg

ciprofloxacin given every 12 hours (Table 10).

Table 10: Steady-state Cmax and AUC of Ciprofloxacin Following Administration of Multiple

Oral and IV Ciprofloxacin Doses to Healthy Subjects

Parameters

500 mg

400 mg

750 mg

400 mg

every 12 hours,

orally

every 12 hours,

intravenous

every 12 hours,

orally

every 8 hours,

intravenous

AUC (mcghr/mL)

13.7

12.71

31.62

32.93

Cmax (mcg/mL)

2.97

4.56

3.59

4.07

= AUC

= AUC

Food

When ciprofloxacin tablets are given concomitantly with food, there is a delay in the absorption of the

drug, resulting in peak concentrations that occur closer to 2 hours after dosing rather than 1 hour. The

overall absorption of ciprofloxacin tablets, however, is not substantially affected. Avoid concomitant

administration of ciprofloxacin with dairy products (like milk or yogurt) or calcium-fortified juices

alone since decreased absorption is possible; however, ciprofloxacin may be taken with a meal that

contains these products.

0–12h

0–12h

0–8h

Distribution

The binding of ciprofloxacin to serum proteins is 20% to 40% which is not likely to be high enough to

cause significant protein binding interactions with other drugs.

After oral administration, ciprofloxacin is widely distributed throughout the body. Tissue

concentrations often exceed serum concentrations in both men and women, particularly in genital tissue

including the prostate. Ciprofloxacin is present in active form in the saliva, nasal and bronchial

secretions, mucosa of the sinuses, sputum, skin blister fluid, lymph, peritoneal fluid, bile, and prostatic

secretions. Ciprofloxacin has also been detected in lung, skin, fat, muscle, cartilage, and bone. The drug

diffuses into the cerebrospinal fluid (CSF); however, CSF concentrations are generally less than 10%

of peak serum concentrations. Low levels of the drug have been detected in the aqueous and vitreous

humors of the eye.

Metabolism

Four metabolites have been identified in human urine which together account for approximately 15% of

an oral dose. The metabolites have antimicrobial activity, but are less active than unchanged

ciprofloxacin. Ciprofloxacin is an inhibitor of human cytochrome P450 1A2 (CYP1A2) mediated

metabolism. Co-administration of ciprofloxacin with other drugs primarily metabolized by CYP1A2

results in increased plasma concentrations of these drugs and could lead to clinically significant

adverse events of the co-administered drug [see Contraindications ( 4.2), Warnings and Precautions (

5.10, 5.16), and Drug Interactions ( 7)].

Excretion

The serum elimination half-life in subjects with normal renal function is approximately 4 hours.

Approximately 40 to 50% of an orally administered dose is excreted in the urine as unchanged drug.

After a 250 mg oral dose, urine concentrations of ciprofloxacin usually exceed 200 mcg/mL during the

first two hours and are approximately 30 mcg/mL at 8 to 12 hours after dosing. The urinary excretion of

ciprofloxacin is virtually complete within 24 hours after dosing. The renal clearance of ciprofloxacin,

which is approximately 300 mL/minute, exceeds the normal glomerular filtration rate of 120 mL/minute.

Thus, active tubular secretion would seem to play a significant role in its elimination. Co-administration

of probenecid with ciprofloxacin results in about a 50% reduction in the ciprofloxacin renal clearance

and a 50% increase in its concentration in the systemic circulation.

Although bile concentrations of ciprofloxacin are several fold higher than serum concentrations after

oral dosing, only a small amount of the dose administered is recovered from the bile as unchanged drug.

An additional 1% to 2% of the dose is recovered from the bile in the form of metabolites.

Approximately 20% to 35% of an oral dose is recovered from the feces within 5 days after dosing.

This may arise from either biliary clearance or transintestinal elimination.

Specific Populations

Elderly

Pharmacokinetic studies of the oral (single dose) and intravenous (single and multiple dose) forms of

ciprofloxacin indicate that plasma concentrations of ciprofloxacin are higher in elderly subjects (older

than 65 years) as compared to young adults. Although the C

is increased 16% to 40%, the increase

in mean AUC is approximately 30%, and can be at least partially attributed to decreased renal clearance

in the elderly. Elimination half-life is only slightly (~20%) prolonged in the elderly. These differences

are not considered clinically significant [see Use in Specific Populations ( 8.5)].

Renal Impairment

In patients with reduced renal function, the half-life of ciprofloxacin is slightly prolonged. Dosage

adjustments may be required [see Use in Specific Populations ( 8.6) and Dosage and Administration ( 2.3)].

Hepatic Impairment

In preliminary studies in patients with stable chronic liver cirrhosis, no significant changes in

ciprofloxacin pharmacokinetics have been observed. The kinetics of ciprofloxacin in patients with

acute hepatic insufficiency, have not been fully studied.

Drug-Drug Interactions

Antacids

Concurrent administration of antacids containing magnesium hydroxide or aluminum hydroxide may

reduce the bioavailability of ciprofloxacin by as much as 90% [see Dosage and Administration ( 2.4) and

Drug Interactions ( 7)].

Histamine H2-receptor antagonists

Histamine H

-receptor antagonists appear to have no significant effect on the bioavailability of

ciprofloxacin.

Metronidazole

The serum concentrations of ciprofloxacin and metronidazole were not altered when these two drugs

were given concomitantly.

Tizanidine

In a pharmacokinetic study, systemic exposure of tizanidine (4 mg single dose) was significantly

increased (Cmax 7-fold, AUC 10-fold) when the drug was given concomitantly with ciprofloxacin (500

mg twice a day for 3 days). Concomitant administration of tizanidine and ciprofloxacin is contraindicated

due to the potentiation of hypotensive and sedative effects of tizanidine [see Contraindications ( 4.2)].

Ropinirole

In a study conducted in 12 patients with Parkinson’s disease who were administered 6 mg ropinirole

once daily with 500 mg ciprofloxacin twice-daily, the mean Cmax and mean AUC of ropinirole were

increased by 60% and 84%, respectively. Monitoring for ropinirole-related adverse reactions and

appropriate dose adjustment of ropinirole is recommended during and shortly after co-administration

with ciprofloxacin [see Warnings and Precautions (5.10)].

Clozapine

Following concomitant administration of 250 mg ciprofloxacin with 304 mg clozapine for 7 days, serum

concentrations of clozapine and N-desmethylclozapine were increased by 29% and 31%, respectively.

Careful monitoring of clozapine associated adverse reactions and appropriate adjustment of clozapine

dosage during and shortly after co-administration with ciprofloxacin are advised.

Sildenafil

Following concomitant administration of a single oral dose of 50 mg sildenafil with 500 mg

ciprofloxacin to healthy subjects, the mean Cmax and mean AUC of sildenafil were both increased

approximately two-fold. Use sildenafil with caution when co-administered with ciprofloxacin due to the

expected two-fold increase in the exposure of sildenafil upon co-administration of ciprofloxacin.

Duloxetine

In clinical studies it was demonstrated that concomitant use of duloxetine with strong inhibitors of the

CYP450 1A2 isozyme such as fluvoxamine, may result in a 5-fold increase in mean AUC and a 2.5-fold

increase in mean Cmax of duloxetine.

Lidocaine

In a study conducted in 9 healthy volunteers, concomitant use of 1.5 mg/kg IV lidocaine with

ciprofloxacin 500 mg twice daily resulted in an increase of lidocaine Cmax and AUC by 12% and 26%,

respectively. Although lidocaine treatment was well tolerated at this elevated exposure, a possible

interaction with ciprofloxacin and an increase in adverse reactions related to lidocaine may occur upon

concomitant administration.

Metoclopramide

Metoclopramide significantly accelerates the absorption of oral ciprofloxacin resulting in a shorter

time to reach maximum plasma concentrations. No significant effect was observed on the bioavailability

of ciprofloxacin.

Omeprazole

When ciprofloxacin was administered as a single 1000 mg dose concomitantly with omeprazole (40 mg

once daily for three days) to 18 healthy volunteers, the mean AUC and Cmax of ciprofloxacin were

reduced by 20% and 23%, respectively. The clinical significance of this interaction has not been

determined.

12.4 Microbiology

Mechanism of Action

The bactericidal action of ciprofloxacin results from inhibition of the enzymes topoisomerase II (DNA

gyrase) and topoisomerase IV (both Type II topoisomerases), which are required for bacterial DNA

replication, transcription, repair, and recombination.

Mechanism of Resistance

The mechanism of action of fluoroquinolones, including ciprofloxacin, is different from that of

penicillins, cephalosporins, aminoglycosides, macrolides, and tetracyclines; therefore, microorganisms

resistant to these classes of drugs may be susceptible to ciprofloxacin. Resistance to fluoroquinolones

occurs primarily by either mutations in the DNA gyrases, decreased outer membrane permeability, or

drug efflux. In vitro resistance to ciprofloxacin develops slowly by multiple step mutations. Resistance

to ciprofloxacin due to spontaneous mutations occurs at a general frequency of between <10

to 1x10

Cross Resistance

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

Ciprofloxacin has been shown to be active against most isolates of the following bacteria, both in vitro

and in clinical infections [see Indications and Usage ( 1)].

Gram-positive bacteria

Bacillus anthracis

Enterococcus faecalis

Staphylococcus aureus (methicillin-susceptible isolates only)

Staphylococcus epidermidis (methicillin-susceptible isolates only)

Staphylococcus saprophyticus

Streptococcus pneumoniae

Streptococcus pyogenes

Gram-negative bacteria

Campylobacter jejuni

Citrobacter koseri

Citrobacter freundii

Enterobacter cloacae

Escherichia coli

Haemophilus influenzae

Haemophilus parainfluenzae

Klebsiella pneumoniae

Moraxella catarrhalis

Morganella morganii

Neisseria gonorrhoeae

Proteus mirabilis

Proteus vulgaris

Providencia rettgeri

Providencia stuartii

Pseudomonas aeruginosa

Salmonella typhi

Serratia marcescens

Shigella boydii

Shigella dysenteriae

Shigella flexneri

Shigella sonnei

Yersinia pestis

The following in vitro data are available, but their clinical significance is unknown. At least 90 percent

of the following bacteria exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal

to the susceptible breakpoint for ciprofloxacin (≤1 mcg/mL). However, the efficacy of ciprofloxacin in

treating clinical infections due to these bacteria has not been established in adequate and well-

controlled clinical trials.

Gram-positive bacteria

Staphylococcus haemolyticus (methicillin-susceptible isolates only)

Staphylococcus hominis (methicillin-susceptible isolates only)

Gram-negative bacteria

Acinetobacter lwoffi

Aeromonas hydrophila

Edwardsiella tarda

Enterobacter aerogenes

Klebsiella oxytoca

Legionella pneumophila

Pasteurella multocida

Salmonella enteritidis

Vibrio cholerae

Vibrio parahaemolyticus

Vibrio vulnificus

Yersinia enterocolitica

Susceptibility Testing

For specific information regarding susceptibility test interpretive criteria and associated test methods

and quality control standards recognized by FDA for this drug, please see: https://www.fda.gov/STIC.

13 NONCLINICAL TOXICOLOGY

13.1 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 V

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. The time to development of the first skin tumors was 50 weeks in

mice treated concomitantly with UVA and ciprofloxacin (mouse dose approximately equal to 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.

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.

13.2 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 (5.13)]. 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.

14 CLINICAL STUDIES

14.1 Complicated Urinary Tract Infection and Pyelonephritis–Efficacy in Pediatric Patients

Ciprofloxacin administered intravenously and/or orally was compared to a cephalosporin for treatment

of cUTI and pyelonephritis in pediatric patients 1 to 17 years of age (mean age of 6 ± 4 years). The trial

was conducted in the US, 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.

Patients were evaluated for clinical success and bacteriological eradication of the baseline organism(s)

with no new infection or superinfection at 5 to 9 days post-therapy (Test of Cure or TOC). The Per

Protocol population had a causative organism(s) with protocol specified colony count(s) at baseline, no

protocol violation, and no premature discontinuation or loss to follow-up (among other criteria).

The clinical success and bacteriologic eradication rates in the Per Protocol population were similar

between ciprofloxacin and the comparator group as shown below.

Table 11: Clinical Success and Bacteriologic Eradication at Test of Cure (5 to 9 Days Post-

Therapy)

Ciprofloxacin

Comparator

Randomized Patients

Per Protocol Patients

Clinical Response at 5 to 9 Days

Post-Treatment

95.7% (202/211)

92.6% (214/231)

95% CI [-1.3%, 7.3%]

Bacteriologic Eradication by Patient

at 5 to 9 Days

Post-Treatment

84.4% (178/211)

78.3% (181/231)

95% CI [-1.3%, 13.1%]

Bacteriologic Eradication of the

Baseline Pathogen at 5 to 9 Days

Post-Treatment

Escherichia coli

156/178 (88%)

161/179 (90%)

14.2 Inhalational Anthrax in Adults and Pediatrics

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. 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 mcg/mL, and 4.56 mcg/mL following 400

mg intravenously every 12 hours. The mean trough serum concentration at steady-state for both of these

regimens is 0.2 mcg/mL. In a study of 10 pediatric patients between 6 and 16 years of age, the mean peak

plasma concentration achieved is 8.3 mcg/mL and trough concentrations range from 0.09 mcg/mL to

0.26 mcg/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 mcg/mL after the initial oral dose. Long-term safety data, including

effects on cartilage, following the administration of ciprofloxacin to pediatric patients are limited.

Ciprofloxacin serum concentrations achieved in humans serve as a surrogate endpoint reasonably likely

to predict clinical benefit and provide the basis for this indication.

A placebo-controlled animal study in rhesus monkeys exposed to an inhaled mean dose of 11 LD

5.5x 10

spores (range 5–30 LD

) of B. anthracis was conducted. The minimal inhibitory

concentration (MIC) of ciprofloxacin for the anthrax strain used in this study was 0.08 mcg/mL. In the

animals studied, mean serum concentrations of ciprofloxacin achieved at expected T

(1 hour post-

dose) following oral dosing to steady-state ranged from 0.98 mcg/mL to 1.69 mcg/mL. Mean steady-

state trough concentrations at 12 hours post-dose ranged from 0.12 mcg/mL to 0.19 mcg/mL.

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.

More than 9300 persons were recommended to complete a minimum of 60 days of antibacterial

Patients with baseline pathogen(s) eradicated and no new infections or superinfections/total number of patients.

There were 5.5% (6/211) ciprofloxacin and 9.5% (22/231) comparator patients with superinfections or new

infections.

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 antibacterial drugs. 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.

14.3 Plague

A placebo-controlled animal study in African green monkeys exposed to an inhaled mean dose of 110

(range 92 to 127 LD

) of Yersinia pestis (CO92 strain) was conducted. The minimal inhibitory

concentration (MIC) of ciprofloxacin for the Y. pestis strain used in this study was 0.015 mcg/mL. Mean

peak serum concentrations of ciprofloxacin achieved at the end of a single 60 minute infusion were

3.49 ± mcg/mL 0.55 mcg/mL, 3.91 mcg/mL ± 0.58 mcg/mL and 4.03 mcg/mL ± 1.22 mcg/mL on Day 2,

Day 6 and Day 10 of treatment in African green monkeys, respectively All trough concentrations (Day 2,

Day 6 and Day 10) were <0.5 mcg /mL. Animals were randomized to receive either a 10-day regimen of

intravenous ciprofloxacin 15 mg/kg, or placebo beginning when animals were found to be febrile (a

body temperature greater than 1.5°C over baseline for two hours), or at 76 hours post-challenge,

whichever occurred sooner. Mortality in the ciprofloxacin group was significantly lower (1/10)

compared to the placebo group (2/2) [difference: -90.0%, 95% exact confidence interval: -99.8% to -

5.8%]. The one ciprofloxacin-treated animal that died did not receive the proposed dose of

ciprofloxacin due to a failure of the administration catheter. Circulating ciprofloxacin concentration

was below 0.5 mcg/mL at all time points tested in this animal. It became culture negative on Day 2 of

treatment, but had a resurgence of low grade bacteremia on Day 6 after treatment initiation. Terminal

blood culture in this animal was negative.

15 REFERENCES

1. 21 CFR 314.510 (Subpart H–Accelerated Approval of New Drugs for Life-Threatening Illnesses).

2. Friedman J, Polifka J. Teratogenic effects of drugs: a resource for clinicians (TERIS). Baltimore,

Maryland: Johns Hopkins University Press, 2000:149-195.

3. 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.

4. 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.

5. CReport 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, MD 20852,

USA.

6. Kelly DJ, et al. Serum concentrations of penicillin, doxycycline, and ciprofloxacin during prolonged

therapy in rhesus monkeys. J Infect Dis 1992; 166:1184-7.

7. Friedlander AM, et al. Postexposure prophylaxis against experimental inhalational anthrax. J Infect

Dis 1993; 167:1239-42.

8. Anti-infective Drugs Advisory Committee Meeting, April 3, 2012 - The efficacy of Ciprofloxacin

for treatment of Pneumonic Plague.

16 HOW SUPPLIED/STORAGE AND HANDLING

Ciprofloxacin Tablets, USP 250 mg are available as round, white film-coated tablets debossed with

“Y101” on one side.

Ciprofloxacin tablets, USP 500 mg are available as oval shaped, white film-coated tablets, debossed

with “Y102” on one side.

Ciprofloxacin Tablets, USP 250 mg and 500 mg are available in bottles of 100 and 500.

Strength

NDC Code

Tablet Identification

Bottles of 100

250 mg

NDC 69117-0008-1

Y101

500 mg

NDC 69117-0009-2

Y102

Bottles of 500

250 mg

NDC 69117-0008-2

Y101

500 mg

NDC 69117-0009-1

Y102

Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Preserve in well-closed

container.

17 PATIENT COUNSELING INFORMATION

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

Serious Adverse Reactions

Advise patients to stop taking ciprofloxacin tablets if they experience an adverse reaction and to call

their healthcare provider for advice on completing the full course of treatment with another

antibacterial drug.

Inform patients of the following serious adverse reactions that have been associated with ciprofloxacin

or other fluoroquinolone use:

Disabling and potentially irreversible serious adverse reactions that may occur

together: Inform patients that disabling and potentially irreversible serious adverse reactions, including

tendinitis and tendon rupture, peripheral neuropathies, and central nervous system effects, have been

associated with use of ciprofloxacin tablets and may occur together in the same patient. Inform patients

to stop taking ciprofloxacin tablets immediately if they experience an adverse reaction and to call their

healthcare provider.

Tendinitis and tendon rupture: 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 tablets treatment. Symptoms may be

irreversible. 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.

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 tablets and tell them to contact their physician.

Central nervous system effects (for example, convulsions, dizziness, lightheadedness, increased

intracranial pressure): 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. Inform patients that they should know how they react to

ciprofloxacin tablets 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.

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 tablets. 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.

Aortic aneurysm and dissection: Inform patients to seek emergency medical care if they

experience sudden chest, stomach, or back pain.

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.

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 (5.13) 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.

Blood Glucose Disturbances:Inform the patients that if they are diabetic and are being treated with

insulin or and oral hypoglycemic agent and a hypoglycemic reaction occurs, they should discontinue

ciprofloxacin and consult a physician.

Antibacterial Resistance

Inform patients that antibacterial drugs including ciprofloxacin tablets should only be used to treat

bacterial infections. They do not treat viral infections (for example, 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.

Administration with Food, Fluids, and Concomitant Medications

Inform patients that ciprofloxacin tablets may be taken with or without food.

Inform patients to drink fluids liberally while taking ciprofloxacin tablets 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 tablets administration. Ciprofloxacin tablets 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 tablets may be taken with a meal

that contains these products.

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 tablets, instruct them to consult

their physician and that their antibacterial medicine may need to be changed.

Anthrax and Plague Studies

Inform patients given ciprofloxacin tablets 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.

Manufacturer:

Yiling Pharmaceutical Ltd

No. 36 Zhujiang Road, Shijiazhuang, 050035, China.

Distributor:

Yiling Pharmaceutical, Inc.

5348 Vegas Dr., Las Vegas, NV 89108, USA

Medication Guide

Ciprofloxacin (sip roe flox a sin) Tablets, USP

for oral use

Read this Medication Guide before you start taking ciprofloxacin tabletsand 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 ciprofloxacin tablets?

Ciprofloxacin tablets, 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 ciprofloxacin tablets, you should

stop taking ciprofloxacin tablets 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 ciprofloxacin tablets. Tendons are

tough cords of tissue that connect muscles to bones. Symptoms of tendon problems may include:

Pain, swelling, tears and swelling of tendons including the back of the ankle (Achilles), shoulder,

hand, or other tendon sites.

The risk of getting tendon problems while you take ciprofloxacin tablets 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

ciprofloxacin tablets.

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 ciprofloxacin tablets 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 ciprofloxacin

tablets. Tendon ruptures can happen within hours or days of taking ciprofloxacin tablets and have

happened up to several months after people have finished taking their fluoroquinolone.

Stop taking ciprofloxacin tablets 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

ciprofloxacin. Stop taking ciprofloxacin tablets 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

burning

tingling

numbness

weakness

Ciprofloxacin tablets 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 ciprofloxacin tablets. Tell your healthcare provider

if you have a history of seizures before you start taking ciprofloxacin tablets. CNS side effects may

happen as soon as after taking the first dose of ciprofloxacin tablets. Stop taking ciprofloxacin tablets

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

hear voices, see things, or sense things that are

trouble sleeping

nightmares

not there (hallucinations)

feel restless

tremors

feel anxious or nervous

confusion

depression

feel lightheaded or dizzy

feel more suspicious (paranoia)

suicidal thoughts or acts

headaches that will not go away, with or without

blurred vision

4. Worsening of myasthenia gravis (a problem that causes muscle weakness).

Fluoroquinolones like ciprofloxacin 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 ciprofloxacin tablets. Call your healthcare provider right

away if you have any worsening muscle weakness or breathing problems.

What are ciprofloxacin tablets?

Ciprofloxacin tablets are 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 ciprofloxacin tablets for use in the treatment of plague and anthrax were done in animals

only, because plague and anthrax could not be studied in people.

Ciprofloxacin tablets 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.

Ciprofloxacin tablets 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.

C iprofloxacin tablets are 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 ciprofloxacin tablets. Ciprofloxacin

tablets should not be used as the first choice of antibacterial medicine in children under 18 years of age.

Who should not take ciprofloxacin tablets?

Do not take ciprofloxacin tablets 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 ciprofloxacin tablets. See the

end of this Medication Guide for a complete list of ingredients in ciprofloxacin tablets.

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 ciprofloxacin tablets?

Before you take ciprofloxacin tablets, tell your healthcare provider if you:

have tendon problems; ciprofloxacin tablets should not be used in patients who have a history of

tendon problems

have a disease that causes muscle weakness (myasthenia gravis); ciprofloxacin tablets 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; ciprofloxacin tablets should not be used in patients who have a history of a

nerve problem called peripheral neuropathy

have or 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 ciprofloxacin tablets 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 ciprofloxacin tablets will harm your unborn

baby.

are breastfeeding or plan to breastfeed. Ciprofloxacin passes into breast milk. You and your

healthcare provider should decide whether you will take ciprofloxacin tablets 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.

Ciprofloxacin tablets 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

a Non-Steroidal Anti-Inflammatory Drug (NSAID). 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.

sildenafil (Viagra

, Revatio

duloxetine

products that contain caffeine

probenecid (Probalan

, Col-probenecid

Certain medicines may keep ciprofloxacin tablets from working correctly.

Take ciprofloxacin tablets 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 ciprofloxacin tablets?

Take ciprofloxacin tablets exactly as your healthcare provider tells you to take it.

Your healthcare provider will tell you how much ciprofloxacin tablets to take and when to take it.

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 cannot

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 of ciprofloxacin tablets, 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

ciprofloxacin tablets?”

you have nerve problems. See “What is the most important information I should know about

ciprofloxacin tablets?”

you have central nervous system problems. 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 ?”

your healthcare provider tells you to stop taking ciprofloxacin tablets

Taking all of your ciprofloxacin tablets doses will help make sure that all of the bacteria are killed.

Taking all of your ciprofloxacin tablets doses will help lower the chance that the bacteria will become

resistant to ciprofloxacin tablets. If you become resistant to ciprofloxacin tablets, ciprofloxacin tablets

and other antibacterial medicines may not work for you in the future.

If you take too much ciprofloxacin tablets, call your healthcare provider or get medical help right

away.

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

affects 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 a

severe sunburn, blisters or swelling of your skin. If you get any of these symptoms while you take

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 may cause serious side effects, including:

See, “What is the most important information I should know about ciprofloxacin tablets?”

Serious allergic reactions. Serious allergic reactions, including death, can happen in people taking

fluoroquinolones, including ciprofloxacin tablets, even after only 1 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

skin rash

Skin rash may happen in people taking ciprofloxacin tablets even after only 1 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.

Liver damage (hepatotoxicity). Hepatotoxicity can happen in people who take ciprofloxacin tablets.

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 ciprofloxacin tablets 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 ciprofloxacin tablets (a liver problem).

Aortic aneurysm and dissection. Tell your healthcare provider if you have ever been told that you

have an aortic aneurysm, a swelling of the large artery that carries blood from the heart to the body. Get

emergency medical help right away if you have sudden chest, stomach, or back pain.

Intestine infection (Pseudomembranous colitis). Pseudomembranous colitis can happen with many

antibacterial medicines, 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

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 irregularheartbeat), 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)

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 ciprofloxacin tablets.

Sensitivity to sunlight (photosensitivity). See “What should I avoid while taking ciprofloxacin

tablets ?

Changes in blood sugar

People who take ciprofloxacin tablets and other fluoroquinolone medicines with oral anti-diabetes

medicines or with insulin can get low blood sugar (hypoglycemia) and high blood sugar

(hyperglycemia). Follow your healthcare provider's instructions for how often to check your blood

sugar. If you have diabetes and you get low blood sugar while taking ciprofloxacin tablets, stop taking

ciprofloxacin tablets and call your healthcare provider right away. Your antibiotic medicine may need to

be changed.

The most common side effects of ciprofloxacin tablets 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 ciprofloxacin tablets. 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 ciprofloxacin tablets?

Store at 20° to 25°C (68° to 77°F). Preserve in well -closed container.

Keep ciprofloxacin tablets and all medicines out of the reach of children.

General Information about the safe and effective use of 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.

For more information call 1-877-736-5697.

What are the ingredients in ciprofloxacin tablets?

Active ingredient: ciprofloxacin hydrochloride

Inactive ingredients: colloidal silicon dioxide, corn starch, partially pregelatinised maize starch,

magnesium stearate, microcrystalline cellulose, sodium starch Glycolate (starch from potato),

hypromellose, titanium dioxide and PEG.

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

Manufacturer:

Yiling Pharmaceutical Ltd

No. 36 Zhujiang Road, Shijiazhuang, 050035, China.

Distributor:

Yiling Pharmaceutical, Inc.

5348 Vegas Dr., Las Vegas, NV 89108, USA

Rx Only

Revised 07/2019

DRUG: Ciprofloxacin

GENERIC: Ciprofloxacin Tablets

DOSAGE: TABLET, COATED

ADMINSTRATION: ORAL

NDC: 70518-2286-0

NDC: 70518-2286-1

NDC: 70518-2286-2

COLOR: white

SHAPE: OVAL

SCORE: No score

SIZE: 16 mm

IMPRINT: Y102

PACKAGING: 20 in 1 BOTTLE, PLASTIC

PACKAGING: 14 in 1 BLISTER PACK

PACKAGING: 20 in 1 BLISTER PACK

ACTIVE INGREDIENT(S):

CIPROFLOXACIN HYDROCHLORIDE 500mg in 1

INACTIVE INGREDIENT(S):

CELLULOSE, MICROCRYSTALLINE

HYPROMELLOSE, UNSPECIFIED

SODIUM STARCH GLYCOLATE TYPE A CORN

TITANIUM DIOXIDE

POLYETHYLENE GLYCOL, UNSPECIFIED

MAGNESIUM STEARATE

STARCH, CORN

MODIFIED CORN STARCH (1-OCTENYL SUCCINIC ANHYDRIDE)

SILICON DIOXIDE

CIPROFLOXACIN

ciprofloxacin tablets tablet, coated

Product Information

Product T ype

HUMAN PRESCRIPTION

DRUG

Ite m Code

(S ource )

NDC:70 518 -228 6 (NDC:6 9 117-

0 0 0 9 )

Route of Administration

ORAL

Active Ingredient/Active Moiety

Ingredient Name

Basis of

Stre ng th

Stre ng th

CIPRO FLO XACIN HYDRO CHLO RIDE (UNII: 4BA73M5E37) (CIPROFLOXACIN -

UNII:5E8 K9 I0 O4U)

CIPROFLOXACIN

50 0 mg

Inactive Ingredients

Ingredient Name

Stre ng th

SILICO N DIO XIDE (UNII: ETJ7Z6 XBU4)

STARCH, CO RN (UNII: O8 232NY3SJ)

MO DIFIED CO RN STARCH ( 1-O CTENYL SUCCINIC ANHYDRIDE) (UNII: 46 1P5CJN6 T)

MAGNESIUM STEARATE (UNII: 70 0 9 7M6 I30 )

CELLULO SE, MICRO CRYSTALLINE (UNII: OP1R32D6 1U)

SO DIUM STARCH GLYCO LATE TYPE A CO RN (UNII: AG9 B6 5PV6 B)

HYPRO MELLO SE, UNSPECIFIED (UNII: 3NXW29 V3WO)

TITANIUM DIO XIDE (UNII: 15FIX9 V2JP)

PO LYETHYLENE GLYCO L, UNSPECIFIED (UNII: 3WJQ0 SDW1A)

Product Characteristics

Color

white

S core

no sco re

S hap e

OVAL (OVAL)

S iz e

16 mm

Flavor

Imprint Code

Y10 2

Contains

Packag ing

#

Item Code

Package Description

Marketing Start

Date

Marketing End

Date

1

NDC:70 518 -228 6 -

20 in 1 BOTTLE, PLASTIC; Type 0 : No t a Co mbinatio n

Pro duc t

0 8 /27/20 19

2

NDC:70 518 -228 6 -

14 in 1 BLISTER PACK; Type 0 : No t a Co mbinatio n Pro duct

0 1/10 /20 20

3

NDC:70 518 -228 6 -

20 in 1 BLISTER PACK; Type 0 : No t a Co mbinatio n Pro duct

0 2/11/20 20

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

REMEDYREPACK INC.

ANDA

ANDA20 8 9 21

0 8 /27/20 19

Labeler -

REMEDYREPACK INC. (829572556)

Revised: 2/2020

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