FACTIVE- gemifloxacin mesylate tablet

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

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Active ingredient:
GEMIFLOXACIN MESYLATE (UNII: X4S9F8RL01) (GEMIFLOXACIN - UNII:OKR68Y0E4T)
Available from:
Merus Labs International Inc.
INN (International Name):
GEMIFLOXACIN MESYLATE
Composition:
GEMIFLOXACIN 320 mg
Administration route:
ORAL
Prescription type:
PRESCRIPTION DRUG
Therapeutic indications:
FACTIVE is indicated for the treatment of infections caused by susceptible strains of the designated microorganisms in the conditions listed below. (See DOSAGE AND ADMINISTRATION and CLINICAL STUDIES. ) Acute bacterial exacerbation of chronic bronchitis (ABECB) caused by Streptococcus pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, or Moraxella catarrhalis . Because fluoroquinolones, including FACTIVE, have been associated with serious adverse reactions (see WARNINGS ) and for some patients ABECB is self-limiting, reserve FACTIVE for treatment of ABECB in patients who have no alternative treatment options. Community-acquired pneumonia (of mild to moderate severity) caused by Streptococcus pneumoniae (including multi-drug resistant strains [MDRSP])*, Haemophilus influenzae, Moraxella catarrhalis, Mycoplasma pneumoniae, Chlamydia pneumoniae, or Klebsiella pneumoniae . *MDRSP: multi-drug resistant Streptococcus pneumoniae , includes isolates previously known as PRSP (penicillin-resista
Product summary:
FACTIVE (gemifloxacin mesylate) is available as white to off-white, oval, film-coated tablets with breaklines and GE 320 debossed on both faces. Each tablet contains gemifloxacin mesylate equivalent to 320 mg of gemifloxacin. 320 mg Unit of Use (CR*) 5's             NDC 44001-321-05 320 mg Unit of Use (CR*) 7's             NDC 44001-321-07 *Child Resistant Store at 25ºC (77ºF); excursions permitted to 15º-30ºC (59º-86ºF) [see USP Controlled Room Temperature]. Protect from light.
Authorization status:
New Drug Application
Authorization number:
44001-321-05, 44001-321-07

FACTIVE- gemifloxacin mesylate tablet

Merus Labs International Inc.

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MEDICATION GUIDE

FACTIVE® [FAC-tiv]

(gemifloxacin)

320mg Tablets

Read the Medication Guide that comes with FACTIVE before you start taking it and each time you get a

refill. There may be new information. This Medication Guide 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

FACTIVE?

FACTIVE, 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 are taking FACTIVE, you should stop

taking FACTIVE 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 FACTIVE.

Tendons are tough cords of tissue that connect muscles to bones.

Symptoms of tendon problems may include: Pain, swelling, tears, and inflammation of

tendons including the back of the ankle (Achilles), shoulder, hand, or other tendon sites.

The risk of getting tendon problems while you take FACTIVE 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

FACTIVE.

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 FACTIVE immediately and get medical help right away at the first sign of tendon

pain, swelling or inflammation. Stop taking FACTIVE until tendinitis or tendon rupture has been

ruled out by your healthcare provider. Avoid exercise and using the affected area. The most

common area of pain and swelling is the Achilles tendon at the back of your ankle. This can also

happen with other tendons.

Talk to your healthcare provider about the risk of tendon rupture with continued use of FACTIVE.

You may need a different antibiotic that is not a fluoroquinolone to treat your infection.

Tendon rupture can happen while you are taking or after you have finished taking

FACTIVE. Tendon ruptures can happen within hours or days of taking FACTIVE, and have

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

Get medical help right away if you get any of the following signs or symptoms of a tendon

rupture:

hear or feel a snap or pop in a tendon area

bruising right after an injury in a tendon area

unable to move the affected area or bear weight

2. Changes in sensation and possible nerve damage (Peripheral Neuropathy). Damage to the nerves in

arms, hands, legs, or feet can happen in people taking fluoroquinolones, including FACTIVE. Stop

FACTIVE and talk with your healthcare provider right away if you get any of the following symptoms of

peripheral neuropathy in your arms, hands, legs, or feet:

pain

burning

tingling

numbness

weakness

The nerve damage may be permanent.

3. Central Nervous System (CNS) Effects. Seizures have been reported in people who take

fluoroquinolone antibiotics, including FACTIVE. Tell your healthcare provider if you have a history of

seizures. Ask your healthcare provider whether taking FACTIVE will change your risk of having a

seizure. Central Nervous System (CNS) side effects may happen as soon as after taking the first dose of

FACTIVE. Talk to your healthcare provider right away if you get any of these side effects, or other

changes in mood or behavior:

feel dizzy

seizures

hear voices, see things, or sense things that are not there (hallucinations)

feel restless

tremors

feel anxious or nervous

confusion

depression

trouble sleeping

feel more suspicious (paranoia)

suicidal thoughts or acts

nightmares

4. Worsening of myasthenia gravis (a disease which causes muscle weakness). Fluoroquinolones like

FACTIVE 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 FACTIVE. Call your healthcare provider right away if you have any worsening muscle

weakness or breathing problems.

See the section “ What are the possible side effects of FACTIVE?” for more information about side

effects.

What is FACTIVE?

FACTIVE is a fluoroquinolone antibiotic medicine used to treat certain infections caused by certain

germs called bacteria in adults 18 years or older. It is not known if FACTIVE is safe and works in

children under 18 years of age. Children have a higher chance of getting bone, joint, or tendon

(musculoskeletal) problems such as pain or swelling while taking fluoroquinolone antibiotic medicines.

Sometimes infections are caused by viruses rather than by bacteria. Examples include viral infections in

the sinuses and lungs, such as the common cold or flu. Antibiotics including FACTIVE do not kill

viruses.

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

FACTIVE.

Who should not take FACTIVE?

Do not take FACTIVE if you have ever had a severe allergic reaction to an antibiotic known as a

fluoroquinolone, or are allergic to any of the ingredients in FACTIVE. Ask your healthcare provider if

you are not sure. See the list of ingredients in FACTIVE at the end of this Medication Guide.

What should I tell my healthcare provider before taking

FACTIVE?

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

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

have tendon problems. FACTIVE should not be used in patients who have a history of tendon

problems.

have a disease that causes muscle weakness (myasthenia gravis). FACTIVE should not be used in

patients who have a known history of myasthenia gravis.

have central nervous system problems (such as epilepsy)

have nerve problems. FACTIVE should not be used in patients who have a history of nerve

problems called peripheral neuropathy.

have or anyone in your family has an irregular heartbeat, especially a condition called “QT

prolongation”

have low blood potassium (hypokalemia) or magnesium (hypomagnesemia)

have a slow heartbeat (bradycardia)

have a history of seizures

have kidney problems. You may need a lower dose of FACTIVE if your kidneys do not work

well.

have rheumatoid arthritis (RA) or other history of joint problems

are pregnant or planning to become pregnant. It is not known if FACTIVE will harm your unborn

child.

are breast-feeding or planning to breast-feed. It is not known if FACTIVE passes into breast milk.

You and your healthcare provider should decide whether you will take FACTIVE or breast-feed.

Tell your healthcare provider about all the medicines you take, including prescription and non-

prescription medicines, vitamins, and herbal and dietary supplements. FACTIVE and other medicines can

affect each other causing side effects. Especially tell your healthcare provider if you take:

an NSAID (Non-Steroidal Anti-Inflammatory Drug). Many common medicines for pain relief are

NSAIDs. Taking an NSAID while you take FACTIVE or other fluoroquinolones may increase

your risk of central nervous system effects and seizures. See “ What are the possible side effects of

FACTIVE?”

a blood thinner (warfarin, Coumadin®, Jantoven®)

a medicine to control your heart rate or rhythm (antiarrhythmics). See “ What are the possible side

effects of FACTIVE? ”

an anti-psychotic medicine

a tricyclic antidepressant

a water pill (diuretic)

probenecid (Probalan, Col-Probenecid)

a steroid medicine. Corticosteroids taken by mouth or by injection may increase the chance of

tendon injury. See “ What is the most important information I should know about FACTIVE? ”

Certain medicines may keep FACTIVE from working correctly. Take FACTIVE either 3 hours

before or 2 hours after taking these products:

an antacid, multivitamin, or other product that contains magnesium, aluminum, iron, or

zinc.

sucralfate (Carafate®).

didanosine (Videx®, Videx EC®).

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

Know the medicines you take. Keep a list of your medicines and show it to your healthcare provider and

pharmacist when you get a new medicine.

How should I take FACTIVE?

Take FACTIVE exactly as prescribed by your healthcare provider.

Take FACTIVE at about the same time each day.

FACTIVE tablets should be swallowed.

FACTIVE can be taken with or without food.

FACTIVE 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 FACTIVE.

Do not skip any doses, or stop taking FACTIVE even if you begin to feel better, until you finish

your prescribed treatment, unless:

you have tendon effects (see “ What is the most important information I should know

about FACTIVE? ”),

you have nerve problems (see " What is the most important information I should know

about FACTIVE? ”),

you have central nervous system problems (see “ What is the most important information I

should know about FACTIVE? ”),

you have a serious allergic reaction (see “ What are the possible side effects of FACTIVE?

”), or your healthcare provider tells you to stop.

This will help make sure that all of the bacteria are killed and lower the chance that the bacteria

will become resistant to FACTIVE. If this happens, FACTIVE and other antibiotic medicines may

not work in the future.

If you miss a dose of FACTIVE, take it as soon as you remember. Do not take more than 1 dose of

FACTIVE in one day.

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

What should I avoid while taking FACTIVE?

FACTIVE 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 FACTIVE affects you.

Avoid sunlamps, tanning beds, and try to limit your time in the sun. FACTIVE can make your

skin sensitive to the sun (photosensitivity) and the light from sunlamps and tanning beds. You

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

taking FACTIVE, call your healthcare provider right away. You should use 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 FACTIVE?

FACTIVE can cause side effects that may be serious or even cause death. See “ What is the most

important information I should know about FACTIVE? ”

Other serious side effects of FACTIVE include:

Serious allergic reactions

Allergic reactions can happen in people taking fluoroquinolones, including FACTIVE, even after only

one dose. Stop taking FACTIVE and get emergency medical help right away if you get any of the

following symptoms of a severe allergic reaction:

hives

trouble breathing or swallowing

swelling of the lips, tongue, face

throat tightness, hoarseness

rapid heartbeat

faint

Yellowing of the skin or eyes

Stop taking FACTIVE and call your healthcare provider right away if you get yellowing of your skin or

white part of your eyes, or if you have dark urine. These can be signs of a serious reaction to FACTIVE (a

liver problem).

Skin rash

Skin rash may happen in people taking FACTIVE. Stop taking FACTIVE 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 FACTIVE. Rash

happens more often with FACTIVE in:

women, especially women who take hormone replacement therapy

people under 40 years of age

people who take FACTIVE for longer than 5 days.

Serious heart rhythm changes (QTc prolongation and torsades de pointes)

Tell your healthcare provider right away if you have a change in your heartbeat (a fast or irregular

heartbeat), or if you faint. FACTIVE 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 happening are higher in people:

who are elderly

with a family history of prolonged QT interval

with low blood potassium (hypokalemia)

who take certain medicines to control heart rhythm (antiarrhythmics).

Intestine infection (Pseudomembranous colitis)

Pseudomembranous colitis can happen with most antibiotics, including FACTIVE. Call your healthcare

provider right away if you get watery diarrhea, diarrhea that does not go away, or bloody stools. You may

have stomach cramps and a fever. Pseudomembranous colitis can happen 2 or more months after you

have finished your antibiotic.

Sensitivity to sunlight (photosensitivity)

See “What should I avoid while taking FACTIVE?”

Joint problems

The most common side effects of FACTIVE include:

diarrhea

rash

nausea

headache

stomach pain

vomiting

dizziness

These are not all the possible side effects of FACTIVE. Tell your healthcare provider about any side

effect that bothers you or that does not go away.

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

FDA-1088.

How should I store FACTIVE?

Store FACTIVE at room temperature between 59º - 86ºF (15º to 30ºC).

Keep FACTIVE away from light.

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

General Information about FACTIVE

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not

use FACTIVE for a condition for which it is not prescribed. Do not give FACTIVE 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 FACTIVE. If you would like

more information about FACTIVE, talk with your healthcare provider. You can ask your healthcare

provider or pharmacist for information about FACTIVE that is written for healthcare professionals. For

more information go to www.FACTIVE.com or call 1-888-431-4276.

What are the ingredients in Factive?

Active ingredient: gemifloxacin

Inactive ingredients: crospovidone, hydroxypropyl methycellulose, magnesium stearate,

microcrystalline cellulose, polyethylene glycol, povidone, titanium dioxide.

© Merus Labs International Inc.

FACTIVE is a registered trademark of LG Life Sciences.

Manufactured for:

Toronto, ON M5K 1H1 Canada

Licensed from LG Life Sciences, Ltd. Seoul, Korea

MRS-001-0313-03

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

Revised 07/2016

Revised: 8/2016

Document Id: f5157025-9ab5-4697-81bc-1adb13ea1dfc

Set id: 63f60426-e27f-4258-9bfc-b4a15ebdca83

Version: 3

Effective Time: 20160801

Merus Labs International Inc.

FACTIVE- gemifloxacin mesylate tablet

Merus Labs International Inc.

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FACTIVE

(gemifloxacin mesylate) Tablets

WARNING: SERIOUS ADVERSE REACTIONS INCLUDING TENDINITIS, TENDON

RUPTURE, PERIPHERAL NEUROPATHY, CENTRAL NERVOUS SYSTEM EFFECTS

AND EXACERBATION OF MYASTHENIA GRAVIS

Fluoroquinolones, including FACTIVE

, have been associated with with disabling and

potentially irreversible serious adverse reactions that have occurred together (See

WARNINGS) including:

Tendinitis and tendon rupture

Peripheral neuropathy

Central nervous system effects

Discontinue FACTIVE immediately and avoid the use of fluoroquinolones, including

FACTIVE, in patients who experience any of these serious adverse reactions (See

WARNINGS).

Fluoroquinolones, including FACTIVE, may exacerbate muscle weakness in persons

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

gravis (See WARNINGS ).

Because fluoroquinolones, including FACTIVE, have been associated with serious

adverse reactions (See WARNINGS), reserve FACTIVE for use in patients who have

no alternative treatment options for acute bacterial exacerbation of chronic bronchitis

(See INDICATIONS AND USAGE).

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

other antibacterial drugs, FACTIVE should be used only to treat infections that are proven or strongly

suspected to be caused by bacteria.

DESCRIPTION

FACTIVE (gemifloxacin mesylate) is a synthetic broad-spectrum antibacterial agent for oral

administration. Gemifloxacin, a compound related to the fluoroquinolone class of antibiotics, is

available as the mesylate salt in the sesquihydrate form. Chemically, gemifloxacin is (R,S)-7-[(4Z)-3-

(aminomethyl)-4-(methoxyimino)-1-pyrrolidinyl]-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-

naphthyridine-3-carboxylic acid.

The mesylate salt is a white to light brown solid with a molecular weight of 485.49. Gemifloxacin is

considered freely soluble at neutral pH (350 μg/mL at 37ºC, pH 7.0). Its empirical formula is

H FN O CH O S and its chemical structure is:

Each white to off-white, oval, film-coated FACTIVE tablet has breaklines and GE 320 debossed on

both faces and contains gemifloxacin mesylate equivalent to 320 mg gemifloxacin. The inactive

ingredients are crospovidone, hydroxypropyl methylcellulose, magnesium stearate, microcrystalline

cellulose, polyethylene glycol, povidone, and titanium dioxide.

®

®

CLINICAL PHARMACOLOGY

Pharmacokinetics

The pharmacokinetics of gemifloxacin are approximately linear over the dose range from 40 mg to 640

mg. There was minimal accumulation of gemifloxacin following multiple oral doses up to 640 mg a day

for 7 days (mean accumulation <20%). Following repeat oral administration of 320 mg gemifloxacin

once daily, steady-state is achieved by the third day of dosing.

Absorption and Bioavailability

Gemifloxacin, given as an oral tablet, is rapidly absorbed from the gastrointestinal tract. Peak plasma

concentrations of gemifloxacin were observed between 0.5 and 2 hours following oral tablet

administration and the absolute bioavailability of the 320 mg tablet averaged approximately 71% (95%

CI 60%-84%). Following repeat oral doses of 320 mg to healthy subjects, the mean ± SD maximal

gemifloxacin plasma concentrations (Cmax) and systemic drug exposure (AUC (0-24)) were 1.61 ± 0.51

μg/mL (range 0.70-2.62 μg/mL) and 9.93 ± 3.07 μghr/mL (range 4.71-20.1 μghr/mL), respectively. In

patients with respiratory and urinary tract infections (n=1423), similar estimates of systemic drug

exposure were determined using a population pharmacokinetics analysis (geometric mean AUC (0-24),

8.36 μghr/mL; range 3.2 – 47.7 μghr/mL).

The pharmacokinetics of gemifloxacin were not significantly altered when a 320 mg dose was

administered with a high-fat meal. Therefore FACTIVE tablets may be administered without regard to

meals.

Distribution

In vitro binding of gemifloxacin to plasma proteins in healthy subjects is approximately 60 to 70% and is

concentration independent. After repeated doses, the in vivo plasma protein binding in healthy elderly

and young subjects ranged from 55% to 73% and was unaffected by age. Renal impairment does not

significantly affect the protein binding of gemifloxacin. The blood-to-plasma concentration ratio of

gemifloxacin was 1.2:1. The geometric mean for Vdss/F is 4.18 L/kg (range, 1.66 – 12.12 L/kg).

Gemifloxacin is widely distributed throughout the body after oral administration. Concentrations of

gemifloxacin in bronchoalveolar lavage fluid exceed those in the plasma. Gemifloxacin penetrates well

into lung tissue and fluids. After five daily doses of 320 mg gemifloxacin, concentrations in plasma,

bronchoalveolar macrophages, epithelial lining fluid and bronchial mucosa at approximately 2 hours

were as in Table 1.

Table 1. Gemifloxacin Concentrations in Plasma and Tissues (320 mg Oral Dosing)

Tis s ue

Concentration

(mean ± SD)

Ratio compared with plasma

(mean ± SD)

Plasma

1.40 (0.442) μg/mL

Bronchoalveolar Macrophages

107 (77) μg/g

90.5 (106.3)

Epithelial Lining Fluid

2.69 (1.96) μg/mL

1.99 (1.32)

Bronchial Mucosa

9.52 (5.15) μg/g

7.21 (4.03)

Metabolism

Gemifloxacin is metabolized to a limited extent by the liver. The unchanged compound is the

predominant drug-related component detected in plasma (approximately 65%) up to 4 hours after dosing.

All metabolites formed are minor (<10% of the administered oral dose); the principal ones are N-acetyl

gemifloxacin, the E-isomer of gemifloxacin and the carbamyl glucuronide of gemifloxacin.

Cytochrome P450 enzymes do not play an important role in gemifloxacin metabolism, and the metabolic

activity of these enzymes is not significantly inhibited by gemifloxacin.

Excretion

Gemifloxacin and its metabolites are excreted via dual routes of excretion. Following oral

administration of gemifloxacin to healthy subjects, a mean (± SD) of 61 ± 9.5% of the dose was

excreted in the feces and 36 ± 9.3% in the urine as unchanged drug and metabolites. The mean (± SD)

renal clearance following repeat doses of 320 mg was approximately 11.6 ± 3.9 L/hr (range 4.6-17.6

L/hr), which indicates active secretion is involved in the renal excretion of gemifloxacin. The mean (±

SD) plasma elimination half-life at steady state following 320 mg to healthy subjects was approximately

7 ± 2 hours (range 4-12 hours).

Special Populations

Pediatric: The pharmacokinetics of gemifloxacin in pediatric subjects have not been studied.

Geriatric: In adult subjects, the pharmacokinetics of gemifloxacin are not affected by age.

Gender: There are no significant differences between gemifloxacin pharmacokinetics in males and

females when differences in body weight are taken into account. Population pharmacokinetic studies

indicated that following administration of 320 mg gemifloxacin, AUC values were approximately 10%

higher in healthy female patients compared to males. Males and females had mean AUC values of 7.98

μghr/mL (range, 3.21 – 42.71 μghr/mL) and 8.80 μghr/mL (range, 3.33 – 47.73 μghr/mL),

respectively. No gemifloxacin dosage adjustment based on gender is necessary.

Hepatic Insufficiency: The pharmacokinetics following a single 320 mg dose of gemifloxacin were

studied in patients with mild (Child-Pugh Class A) to moderate (Child-Pugh Class B) liver disease.

There was a mean increase in AUC (0-inf) of 34% and a mean increase in Cmax of 25% in these patients

with hepatic impairment compared to healthy volunteers.

The pharmacokinetics of a single 320 mg dose of gemifloxacin were also studied in patients with

severe hepatic impairment (Child-Pugh Class C). There was a mean increase in AUC (0-inf) of 45% and

a mean increase in Cmax of 41% in these subjects with hepatic impairment compared to healthy

volunteers.

These average pharmacokinetic increases are not considered to be clinically significant. There was no

significant change in plasma elimination half-life in the mild, moderate or severe hepatic impairment

patients. No dosage adjustment is recommended in patients with mild (Child-Pugh Class A), moderate

(Child-Pugh Class B) or severe (Child-Pugh Class C) hepatic impairment. (See DOSAGE AND

ADMINISTRATION .)

Renal Insufficiency: Results from population pharmacokinetic and clinical pharmacology studies with

repeated 320 mg doses indicate the clearance of gemifloxacin is reduced and the plasma elimination is

prolonged, leading to an average increase in AUC values of approximately 70% in patients with renal

insufficiency. In the pharmacokinetic studies, gemifloxacin Cmax was not significantly altered in

subjects with renal insufficiency. Dose adjustment in patients with creatinine clearance >40 mL/min is

not required. Modification of the dosage is recommended for patients with creatinine clearance ≤40

mL/min. (See DOSAGE AND ADMINISTRATION .)

Hemodialysis removes approximately 20 to 30% of an oral dose of gemifloxacin from plasma.

Photosensitivity Potential

In a study of the skin response to ultraviolet and visible radiation conducted in 40 healthy volunteers, the

minimum erythematous dose (MED) was assessed following administration of either gemifloxacin 160

mg once daily, gemifloxacin 320 mg once daily, ciprofloxacin 500 mg BID, or placebo for 7 days. At 5

of the 6 wavelengths tested (295-430 nm), the photosensitivity potential of gemifloxacin was not

statistically different from placebo. At 365 nm (UVA region), gemifloxacin showed a photosensitivity

potential similar to that of ciprofloxacin 500 mg BID and the photosensitivity potential for both drugs

were statistically greater than that of placebo. Photosensitivity reactions were reported rarely in

clinical trials with gemifloxacin (0.039%). (See ADVERSE REACTIONS.)

It is difficult to ascribe relative photosensitivity/phototoxicity among various fluoroquinolones during

actual patient use because other factors play a role in determining a subject’s susceptibility to this

adverse event such as: a patient’s skin pigmentation, frequency and duration of sun and artificial

ultraviolet light (UV) exposure, wearing of sun screen and protective clothing, the use of other

concomitant drugs and the dosage and duration of fluoroquinolone therapy. (See ADVERSE

REACTIONS and ADVERSE REACTIONS: Post-Marketing Adverse Reactions. )

Drug-Drug Interactions

Antacids/Di- and Trivalent Cations: The systemic availability of gemifloxacin is significantly reduced

when an aluminum- and magnesium- containing antacid is concomitantly administered (AUC decreased

85%; Cmax decreased 87%). Administration of an aluminum- and magnesium- containing antacid or

ferrous sulfate (325 mg) at 3 hours before or at 2 hours after gemifloxacin did not significantly alter the

systemic availability of gemifloxacin. Therefore, aluminum- and/or magnesium- containing antacids,

ferrous sulfate (iron), multivitamin preparations containing zinc or other metal cations, or Videx

(didanosine) chewable/buffered tablets or the pediatric powder for oral solution should not be taken

within 3 hours before or 2 hours after taking FACTIVE tablets.

Calcium carbonate (1000 mg) given either 2 hr before or 2 hr after gemifloxacin administration showed

no notable reduction in gemifloxacin systemic availability. Calcium carbonate administered

simultaneously with gemifloxacin resulted in a small, not clinically significant, decrease in

gemifloxacin exposure [AUC (0-inf) decreased 21% and Cmax decreased].

Sucralfate: When sucralfate (2 g) was administered 3 hours prior to gemifloxacin, the oral

bioavailability of gemifloxacin was significantly reduced (53% decrease in AUC; 69% decrease in

Cmax). When sucralfate (2 g) was administered 2 hours after gemifloxacin, the oral bioavailability of

gemifloxacin was not significantly affected; therefore FACTIVE should be taken at least 2 hours

before sucralfate. (See PRECAUTIONS.)

In Vitro Metabolism: Results of in vitro inhibition studies indicate that hepatic cytochrome P450

(CYP450) enzymes do not play an important role in gemifloxacin metabolism. Therefore gemifloxacin

should not cause significant in vivo pharmacokinetic interactions with other drugs that are metabolized

by CYP450 enzymes.

Theophylline: Gemifloxacin 320 mg at steady-state did not affect the repeat dose pharmacokinetics of

theophylline (300 to 400 mg BID to healthy male subjects).

Digoxin: Gemifloxacin 320 mg at steady-state did not affect the repeat dose pharmacokinetics of

digoxin (0.25 mg once daily to healthy elderly subjects).

Oral Contraceptives: The effect of an oral estrogen/progesterone contraceptive product (once daily for

21 days) on the pharmacokinetics of gemifloxacin (320 mg once daily for 6 days) in healthy female

subjects indicates that concomitant administration caused an average reduction in gemifloxacin AUC and

Cmax of 19% and 12%. These changes are not considered clinically significant. Gemifloxacin 320 mg

at steady-state did not affect the repeat dose pharmacokinetics of an ethinylestradiol/levonorgestrol oral

contraceptive product (30 μg/150 μg once daily for 21 days to healthy female subjects).

Cimetidine: Co-administration of a single dose of 320 mg gemifloxacin with cimetidine 400 mg four

times daily for 7 days resulted in slight average increases in gemifloxacin AUC(0-inf) and Cmax of

10% and 6%, respectively. These increases are not considered clinically significant.

Omeprazole: Co-administration of a single dose of 320 mg gemifloxacin with omeprazole 40 mg once

daily for 4 days resulted in slight average increases in gemifloxacin AUC(0-inf) and Cmax of 10% and

11%, respectively. These increases are not considered clinically significant.

Warfarin: Administration of repeated doses of gemifloxacin (320 mg once daily for 7 days) to healthy

subjects on stable warfarin therapy had no significant effect on warfarin-induced anticoagulant activity

(i.e., International Normalized Ratios for Prothrombin Time). (See PRECAUTIONS: Drug

Interactions. )

Probenecid: Administration of a single dose of 320 mg gemifloxacin to healthy subjects who also

received repeat doses of probenecid (total dose = 4.5 g) reduced the mean renal clearance of

gemifloxacin by approximately 50%, resulting in a mean increase of 45% in gemifloxacin AUC (0-inf)

and a prolongation of mean half-life by 1.6 hours. Mean gemifloxacin Cmax increased 8%.

MICROBIOLOGY

Gemifloxacin has in vitro activity against a wide range of Gram-negative and Gram-positive

microorganisms. Gemifloxacin is bactericidal with minimum bactericidal concentrations (MBCs)

generally within one dilution of the minimum inhibitory concentrations (MICs). Gemifloxacin acts by

inhibiting DNA synthesis through the inhibition of both DNA gyrase and topoisomerase IV (TOPO IV),

which are essential for bacterial growth. Streptococcus pneumoniae showing mutations in both DNA

gyrase and TOPO IV (double mutants) are resistant to most fluoroquinolones. Gemifloxacin has the

ability to inhibit both enzyme systems at therapeutically relevant drug levels in S. pneumoniae (dual

targeting), and has MIC values that are still in the susceptible range for some of these double mutants.

However, the presence of double mutants was not evaluated in clinical trials; therefore, the clinical

significance of these in vitro data are unknown.

The mechanism of action of quinolones, including gemifloxacin, is different from that of macrolides,

beta-lactams, aminoglycosides, or tetracyclines; therefore, microorganisms resistant to these classes of

drugs may be susceptible to gemifloxacin and other quinolones. There is no known cross-resistance

between gemifloxacin and the above mentioned classes of antimicrobials.

The main mechanism of fluoroquinolone resistance is due to mutations in DNA gyrase and/or TOPO IV.

Resistance to gemifloxacin develops slowly via multistep mutations and efflux in a manner similar to

other fluoroquinolones. The frequency of spontaneous mutation is low (10

to <10

). Although

cross-resistance has been observed between gemifloxacin and other fluoroquinolones, some

microorganisms resistant to other fluoroquinolones may be susceptible to gemifloxacin.

Gemifloxacin has been shown to be active against most strains of the following microorganisms, both in

vitro and in clinical infections as described in the INDICATIONS AND USAGE section.

Aerobic Gram-positive microorganisms

Streptococcus pneumoniae (including multi-drug resistant strains [MDRSP])

MDRSP: multi-drug resistant Streptococcus pneumoniae, includes isolates previously known as PRSP

(penicillin-resistant Streptococcus pneumoniae), and are strains resistant to two or more of the following

antibiotics: penicillin (MIC ≥2 μg/mL), 2nd generation cephalosporins (e.g., cefuroxime), macrolides,

tetracyclines and trimethoprim/sulfamethoxazole.

Aerobic Gram-negative microorganisms

Haemophilus influenzae

Haemophilus parainfluenzae

Klebsiella pneumoniae (many strains are only moderately susceptible)

Moraxella catarrhalis

Other microorganisms

Chlamydia pneumoniae

Mycoplasma pneumoniae

The following data are available, but their clinical significance is unknown.

Gemifloxacin exhibits in vitro minimal inhibitory concentrations (MICs) of 0.25 μg/mL or less against

most (≥90%) strains of the following microorganisms; however, the safety and effectiveness of

gemifloxacin in treating clinical infections due to these microorganisms has not been established in

adequate and well-controlled clinical trials:

Aerobic Gram-positive microorganisms

Staphylococcus aureus (methicillin-susceptible strains only)

Streptococcus pyogenes

Aerobic Gram-negative microorganisms

Acinetobacter lwoffii

Klebsiella oxytoca

Legionella pneumophila

Proteus vulgaris

Susceptibility Tests

Dilution techniques: Quantitative methods are used to determine antimicrobial minimum inhibitory

concentrations (MICs). These MICs provide estimates of the susceptibility of bacteria to antimicrobial

compounds. The MICs should be determined using a standardized procedure. Standardized procedures

are based on a dilution method (broth or agar) or equivalent with standardized inoculum concentrations

and standardized concentrations of gemifloxacin powder. The MICs should be interpreted according to

the following criteria:

For testing Klebsiella pneumoniae:

MIC (µg/mL)

Interpretation

0.25

Susceptible (S)

Intermediate (I)

Resistant (R)

For testing Haemophilus influenzae and Haemophilus parainfluenzae :

MIC (µg/mL)

Interpretation

0.12

Susceptible (S)

This interpretive standard is applicable only to broth microdilution susceptibility testing with

Haemophilus influenzae and Haemophilus parainfluenzae using Haemophilus Test Medium (HTM) .

The current absence of data on resistant strains precludes defining any results other than Susceptible.

Strains yielding MIC results suggestive of a nonsusceptible category should be submitted to a

reference laboratory for further testing.

For testing Streptococcus pneumoniae :

MIC (µg/mL)

Interpretation

0.12

Susceptible (S)

0.25

Intermediate (I)

Resistant (R)

These interpretive standards are applicable only to broth microdilution susceptibility tests using

cation-adjusted Mueller-Hinton broth with 2-5% lysed horse blood.

A report of Susceptible indicates that the pathogen is likely to be inhibited if the antimicrobial

compound in the blood reaches the concentration usually achievable. A report of Intermediate indicates

that the result should be considered equivocal, and if the microorganism is not fully susceptible to

alternative, clinically feasible drugs, the test should be repeated. This category implies possible

clinical applicability in body sites where the drug is physiologically concentrated or in situations

where high dosage of drug can be used. This category also provides a buffer zone, which prevents

small uncontrolled technical factors from causing major discrepancies in interpretation. A report of

Resistant indicates that the pathogen is not likely to be inhibited if the antimicrobial compound in the

blood reaches the concentration usually achievable; other therapy should be selected.

Standardized susceptibility test procedures require the use of laboratory control microorganisms to

control the technical aspects of the laboratory procedures. Standard gemifloxacin powder should

provide the following MIC values:

Microorganism

MIC Range (µg/mL)

Escherichia coli

ATCC 25922

0.004-0.016

Haemophilus influenzae

ATCC 49247

0.002-0.008c

Streptococcus pneumoniae

ATCC 49619

0.008-0.03d

This quality control range is applicable to only H. influenzae ATCC 49247 tested by a broth

microdilution procedure using Haemophilus Test Medium (HTM) .

This quality control range is applicable to only S. pneumoniae ATCC 49619 tested by a broth

microdilution procedure using cation-adjusted Mueller-Hinton broth with 2-5% lysed horse blood.

Diffusion Techniques: Quantitative methods that require measurement of zone diameters also provide

reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. One such

standardized procedure requires the use of standardized inoculum concentrations. This procedure uses

paper disks impregnated with 5 g gemifloxacin to test the susceptibility of microorganisms to

gemifloxacin.

Reports from the laboratory providing results of the standard single-disk susceptibility test with a 5 g

gemifloxacin disk should be interpreted according to the following criteria:

For testing Klebsiella pneumoniae:

Zone Diameter (mm)

Interpretation

Susceptible (S)

16-19

Intermediate (I)

Resistant (R)

For testing Haemophilus influenzae and Haemophilus parainfluenzae :

Zone Diameter (mm)

Interpretation

Susceptible (S)

This interpretive standard is applicable only to disk diffusion susceptibility testing with Haemophilus

influenzae and Haemophilus parainfluenzae using Haemophilus Test Medium (HTM).

The current absence of data on resistant strains precludes defining any results other than Susceptible.

Strains yielding zone diameter results suggestive of a nonsusceptible category should be submitted to a

reference laboratory for further testing.

For testing Streptococcus pneumoniae :

Zone Diameter (mm)

Interpretation

Susceptible (S)

20-22

Intermediate (I)

Resistant (R)

These zone diameter standards apply only to tests performed using Mueller-Hinton agar supplemented

with 5% defibrinated sheep blood incubated in 5% CO .

Interpretation should be as stated above for results using dilution techniques. Interpretation involves

correlation of the diameter obtained in the disk test with the MIC for gemifloxacin.

As with standardized dilution techniques, diffusion methods require the use of laboratory control

microorganisms that are used to control the technical aspects of the laboratory procedures. For the

diffusion technique, the 5 g gemifloxacin disk should provide the following zone diameters in these

laboratory quality control strains:

Microorganism

Zone Diameter (mm)

Escherichia coli

ATCC 25922

29-36

Haemophilus influenzae

ATCC 49247

30-37g

Streptococcus pneumoniae

ATCC 49619

28-34h

This quality control range is applicable to only H. influenzae ATCC 49247 tested by a disk diffusion

procedure using Haemophilus Test Medium (HTM) .

This quality control range is applicable to only S. pneumoniae ATCC 49619 tested by a disk diffusion

procedure using Mueller-Hinton agar supplemented with 5% defibrinated sheep blood and incubated in

5% CO .

INDICATIONS AND USAGE

FACTIVE is indicated for the treatment of infections caused by susceptible strains of the designated

microorganisms in the conditions listed below. (See DOSAGE AND ADMINISTRATION and

CLINICAL STUDIES. )

Acute bacterial exacerbation of chronic bronchitis (ABECB) caused by Streptococcus pneumoniae,

Haemophilus influenzae, Haemophilus parainfluenzae, or Moraxella catarrhalis.

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

(see WARNINGS) and for some patients ABECB is self-limiting, reserve FACTIVE for treatment of

ABECB in patients who have no alternative treatment options.

Community-acquired pneumonia (of mild to moderate severity) caused by Streptococcus pneumoniae

(including multi-drug resistant strains [MDRSP])*, Haemophilus influenzae, Moraxella catarrhalis,

Mycoplasma pneumoniae, Chlamydia pneumoniae, or Klebsiella pneumoniae.

*MDRSP: multi-drug resistant Streptococcus pneumoniae, includes isolates previously known as PRSP

(penicillin-resistant Streptococcus pneumoniae), and are strains resistant to two or more of the following

antibiotics: penicillin (MIC ≥2 μg/mL), 2nd generation cephalosporins (e.g., cefuroxime), macrolides,

tetracyclines and trimethoprim/sulfamethoxazole.

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

other antibacterial drugs, FACTIVE should be used only to treat infections that are proven or strongly

suspected to be caused by susceptible bacteria. When culture and susceptibility information are

available, they should be considered in selecting or modifying antibacterial therapy. In the absence of

such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of

therapy.

CONTRAINDICATIONS

FACTIVE is contraindicated in patients with a history of hypersensitivity to gemifloxacin,

fluoroquinolone antibiotic agents, or any of the product components.

WARNINGS

Disabling and Potentially Irreversible Serious Adverse Reactions Including Tendinitis and Tendon

Rupture, Peripheral Neuropathy, and Central Nervous System Effects:

Fluoroquinolones, including FACTIVE 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 FACTIVE.

Patients of any age or without pre-existing risk factors have experienced these adverse reactions (See

WARNINGS, Tendinitis and Tendon Rupture, Peripheral Neuropathy and Central Nervous

System Effects ).

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

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

of these serious adverse reactions associated with fluoroquinolones.

Tendinitis and Tendon Rupture: Fluoroquinolones, including FACTIVE, have been associated with an

increased risk of tendinitis and tendon rupture in all ages. 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

after starting FACTIVE, or as long as several months after completion of 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, in addition to age and corticosteroid use, that may independently increase the

risk of tendon rupture include strenuous physical activity, renal failure, and previous tendon disorders

such as rheumatoid arthritis. Tendinitis and tendon rupture have also occurred in patients taking

fluoroquinolones who do not have the above risk factors. Discontinue FACTIVE if the patient

experiences pain, swelling, inflammation or rupture of a tendon. Avoid fluoroquinolones, including

FACTIVE, in patients who have a history of tendon disorders or have experienced tendinitis or tendon

rupture. Patients should be advised to rest at the first sign of tendinitis or tendon rupture, and to contact

their healthcare provider regarding changing to a non-quinolone antimicrobial drug.

Peripheral Neuropathy: Fluoroquinolones, including FACTIVE, 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 FACTIVE. Symptoms may occur soon after

initiation of FACTIVE and may be irreversible in some patients. Discontinue FACTIVE 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.

CNS Effects: Fluoroquinolones, including FACTIVE, have been associated with an increased risk of

central nervous system (CNS) effects, including convulsions, increased intracranial pressure (including

pseudotumor cerebri), and toxic psychosis. In clinical studies with FACTIVE, central nervous system

(CNS) effects have been reported infrequently. As with other fluoroquinolones, FACTIVE should be

used with caution in patients with CNS diseases such as epilepsy or patients predisposed to

convulsions. CNS stimulation which may lead to tremors, restlessness, anxiety, lightheadedness,

confusion, hallucinations, paranoia, depression, insomnia, and rarely suicidal thoughts or acts may also

be caused by other fluoroquinolones. If these reactions occur in patients receiving FACTIVE,

discontinue FACTIVE immediately and institute appropriate measures.

Exacerbation of Myasthenia Gravis: Fluoroquinolones, including FACTIVE, 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 FACTIVE in patients

with known history of myasthenia gravis. (See PRECAUTIONS/Information for Patients and

Adverse Reactions/Post-Marketing Adverse Reactions. )

THE SAFETY AND EFFECTIVENESS OF FACTIVE IN CHILDREN, ADOLESCENTS (LESS

THAN 18 YEARS OF AGE), PREGNANT WOMEN, AND LACTATING WOMEN HAVE NOT

BEEN ESTABLISHED. (See PRECAUTIONS: Pediatric Use, Pregnancy and Nursing Mothers

s ubs ections .)

QT Effects: Fluoroquinolones may prolong the QT interval in some patients. FACTIVE should be

avoided in patients with a history of prolongation of the QTc interval, patients with uncorrected

electrolyte disorders (hypokalemia or hypomagnesemia), and patients receiving Class IA (e.g.,

quinidine, procainamide) or Class III (e.g., amiodarone, sotalol) antiarrhythmic agents.

Pharmacokinetic studies between gemifloxacin and drugs that prolong the QTc interval such as

erythromycin, antipsychotics, and tricyclic antidepressants have not been performed. FACTIVE should

be used with caution when given concurrently with these drugs, as well as in patients with ongoing

proarrhythmic conditions, such as clinically significant bradycardia or acute myocardial ischemia. No

cardiovascular morbidity or mortality attributable to QTc prolongation occurred with FACTIVE

treatment in over 8119 patients, including 707 patients concurrently receiving drugs known to prolong

the QTc interval and 7 patients with hypokalemia.

The likelihood of QTc prolongation may increase with increasing dose of the drug; therefore, the

recommended dose should not be exceeded especially in patients with renal or hepatic impairment

where the Cmax and AUC are slightly higher. QTc prolongation may lead to an increased risk for

ventricular arrhythmias including torsades de pointes. The maximal change in the QTc interval occurs

approximately 5-10 hours following oral administration of gemifloxacin.

Hypersensitivity Reactions: Serious hypersensitivity and/or anaphylactic reactions have been reported in

patients receiving fluoroquinolone therapy, including FACTIVE. Hypersensitivity reactions reported in

patients receiving fluoroquinolone therapy have occasionally been fatal. These reactions may occur

following the first dose. Some reactions have been accompanied by cardiovascular collapse,

hypotension/shock, seizure, loss of consciousness, tingling, angioedema (including tongue, laryngeal,

throat or facial edema/swelling), airway obstruction (including bronchospasm, shortness of breath and

acute respiratory distress), dyspnea, urticaria, itching and other serious skin reactions.

FACTIVE should be discontinued immediately at the appearance of any sign of an immediate type I

hypersensitivity skin rash or any other manifestation of a hypersensitivity reaction; the need for

continued fluoroquinolone therapy should be evaluated. As with other drugs, serious acute

hypersensitivity reactions may require treatment with epinephrine and other resuscitative measures,

including oxygen, intravenous fluids, antihistamines, corticosteroids, pressor amines and airway

management as clinically indicated. (See PRECAUTIONS and ADVERSE REACTIONS.)

Other serious and sometimes fatal reqactions, some due to hypersensitivity and some due to uncertain

etiology, have been reported rarely in patients receiving therapy with quinolones, including FACTIVE.

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 (e.g., toxic epidermal necrolysis, Stevens-Johnson

Syndrome);

vasculitis; arthralgia; myalgia; serum sickness;

allergic pneumonitis;

interstitial nephritis; acute renal insufficiency or failure;

hepatitis; jaundice; acute hepatic necrosis or failure;

anemia, including hemolytic and aplastic;

thrombocytopenia, including thrombotic thrombocytopenic purpura; leukopenia agranulocytosis;

pancytopenia; and/or other hematologic abnormalities.

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

hypersensitivity and institute supportive measures instituted (See PRECAUTIONS: Information for

Patients and ADVERSE REACTIONS ).

Clostridium difficile Associated Diarrhea: Clostridium difficile associated diarrhea (CDAD) has been

reported with use of nearly all antibacterial agents, including FACTIVE, and may range in severity from

mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon

leading to overgrowth of C. difficile.

C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin

producing strains of C. difficile cause increased morbidity and mortality, as these infections can be

refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients

who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD

has been reported to occur over two months after the administration of antibacterial agents.

If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to

be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic

treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

PRECAUTIONS

General: Prescribing FACTIVE in the absence of a proven or strongly suspected bacterial infection is

unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant

bacteria.

Rash: In clinical studies, rash occurred more often with FACTIVE than with therapy with comparator

agents (2.7% vs. 0.6%). Increasing incidence of rash was associated with younger age (especially

below 40), female gender, use of hormone replacement therapy and longer durations of therapy (see

Table 2). Urticarial reactions, some of which were not classified as rash, were more common in

FACTIVE patients than in comparator patients (0.6% vs. 0.2%). FACTIVE should be discontinued in

patients developing a rash or urticaria while on treatment. (See ADVERSE REACTIONS and

CLINICAL STUDIES .)

Table 2. Rash Incidence in FACTIVE Treated Patients from the Clinical Studies Population* by

Gender, Age, and Duration of Therapy

Gender & Age

(yr) Category

Duration of FACTIVE Therapy

5 days

7 days

10 days**

14 days**

Female < 40

10/399 (2.5%)

49/407 (12.0%)

20/131 (15.3%)

7/31 (22.6%)

Female ≥ 40

30/1438 (2.1%)

34/887 (3.8%)

19/308 (6.2%)

10/126 (7.9%)

Male < 40

6/356 (1.7%)

26/453 (5.7%)

7/74 (9.5%)

3/39 (7.7%)

Male ≥ 40

10/1503 (0.7%)

26/984 (2.6%)

9/345 (2.6%)

3/116 (2.6%)

Totals

56/3696 (1.5%)

135/2732 (4.9%)

55/858 (6.4%)

23/312 (7.4%)

*includes patients from studies of community-acquired pneumonia, acute bacterial exacerbation of

chronic bronchitis, and other indications

**exceeds the recommended duration of therapy (see DOSAGE AND ADMINISTRATION)

The most common form of rash associated with FACTIVE was described as maculopapular and mild to

moderate in severity. Eighty percent of rashes resolved within 14 days. Approximately 10% of the

rashes (0.5% of all patients) were described as of severe intensity and approximately 10% of those with

rash were treated with systemic steroids. There were no documented cases in the clinical trials of more

serious skin reactions known to be associated with significant morbidity or mortality.

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

exaggerated sunburn reactions (e.g., 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 use of quinolones after sun or UV light exposure.

Therefore excessive exposure to these sources of light should be avoided. Drug therapy should be

discontinued if phototoxicity occurs. (See ADVERSE REACTIONS and ADVERSE REACTIONS/

Post-Marketing Adverse Reactions.)

Hepatic Effects: Liver enzyme elevations (increased ALT and/or AST) occurred at similar rates in

patients receiving FACTIVE 320 mg daily relative to comparator antimicrobial agents (ciprofloxacin,

levofloxacin, clarithromycin/cefuroxime axetil, amoxicillin/clavulanate potassium, and ofloxacin). In

patients who received gemifloxacin at doses of 480 mg per day or greater there was an increased

incidence of elevations in liver enzymes. (See ADVERSE REACTIONS.)

There were no clinical symptoms associated with these liver enzyme elevations. The liver enzyme

elevations resolved following cessation of therapy. The recommended dose of FACTIVE 320 mg daily

should not be exceeded and the recommended length of therapy should not be exceeded. (See

DOSAGE AND ADMINISTRATION.)

Renal Effects: Alteration of the dosage regimen is necessary for patients with impairment of renal

function (creatinine clearance ≤40 mL/min). (See DOSAGE AND ADMINISTRATION.)

Adequate hydration of patients receiving FACTIVE should be maintained to prevent the formation of a

highly concentrated urine.

Information for Patients

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

Serious Adverse Reactions

Advise patients to stop taking FACTIVE 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 FACTIVE or

other fluoroquinolone use:

Disabling and potentially irreversible serious adverse reactions that may occur together, including

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

associated with use of FACTIVE and may occur together in the same patient. Inform patients to stop

taking FACTIVE 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 FACTIVE treatment. The risk of severe tendon disorders

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 the

use of FACTIVE, that 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, patients should immediately discontinue FACTIVE and 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 FACTIVE. Patients should notify their physician before taking

FACTIVE if they have a history of convulsions, seizures, or epilepsy; Inform patients that other

central nervous system problems such as tremors, restlessness, lightheadedness, confusion and

hallucinations may occur rarely;

Exacerbation of Myasthenia Gravis: Inform patients that fluoroquinolones like FACTIVE may cause

worsening of myasthenia gravis symptoms, including muscle weakness and breathing problems.

Patients should call their healthcare provider right away if they have any worsening muscle

weakness or breathing problems;

Hypersensitivity Reactions: Inform patients that FACTIVEmay be associated with hypersensitivity

reactions, including anaphylactic reactions, even following a single dose; patients should

immediately discontinue the drug at the sign of a rash or other allergic reaction and seek medical

care; Inform patients that FACTIVE has been associated with rash and hives. Rash occurs more

commonly in those under 40, especially women and in women on hormone replacement therapy. The

incidence of rash increases with duration more than 5 days and particularly longer than 7 days.

Patients should discontinue FACTIVE and call their healthcare provider if they develop a rash;

Diarrhea: Inform patients that diarrhea is a common problem caused by antibiotics which usually

ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients

can develop watery and bloody stools (with or without stomach cramps and fever) even as late as

two or more months after having taken the last dose of the antibiotic. If this occurs, patients should

contact their physician as soon as possible;

Prolongation of the QT interval: inform patients of the following:that FACTIVE may cause changes

in the electrocardiogram (QTc interval prolongation);

that FACTIVE may cause changes in the electrocardiogram (QTc interval prolongation);

that FACTIVE should be avoided in patients receiving Class IA (e.g., quinidine, procainamide)

or Class III (e.g., amiodarone, sotalol) antiarrhythmic agents;

that FACTIVE should be used with caution in patients receiving drugs that affect the QTc

interval such as cisapride, erythromycin, antipsychotics, and tricyclic antidepressants;

to inform their physician of any personal or family history of QTc prolongation or

proarrhythmic conditions such as hypokalemia, bradycardia, or recent myocardial ischemia;

to contact their physician if they experience palpitations or fainting spells while taking

FACTIVE;

that FACTIVE may cause dizziness; if this occurs, patients should not operate an automobile or

machinery or engage in activities requiring mental alertness or coordination;

Photosensitivity/Phototoxicity: Inform patients that photosensitivity/phototoxicity has been reported

in patients receiving quinolones. Patients should minimize or avoid exposure to natural or artificial

sunlight (tanning beds or UVA/B treatment) while taking quinolones. If patients need to be outdoors

while using quinolones, they should wear loose-fitting clothes that protect skin from sun exposure

and discuss other sun protection measures with their physician. If a sunburn-like reaction or skin

eruption occurs, patients should contact their physician; (See CLINICAL PHARMACOLOGY:

Photosensitivity Potential ).

Other Information

Advise Patients:

that increases of the International Normalized Ratio (INR), or prothrombin time (PT), and/or clinical

episodes of bleeding have been noted with concurrent administration of warfarin or its derivatives,

and FACTIVE. Patients should notify their physicians if they are taking warfarin or its derivatives;

to inform their physician of any other medications when taken concurrently with FACTIVE,

including over-the-counter medications and dietary supplements;

that FACTIVE may be taken with or without meals;

to drink fluids liberally;

not to take antacids containing magnesium and/or aluminum or products containing ferrous sulfate

(iron), multivitamin preparations containing zinc or other metal cations, or Videx (didanosine)

chewable/buffered tablets or the pediatric powder for oral solution within 3 hours before or 2

hours after taking FACTIVE tablets;

that FACTIVE should be taken at least 2 hours before sucralfate;

that antibacterial drugs including FACTIVE should only be used to treat bacterial infections. They

do not treat viral infections (e.g., the common cold). When FACTIVE is prescribed to treat a

bacterial infection, patients should be told that although it is common to feel better early in the

course of therapy, the medication should be taken exactly as directed. Skipping doses or not

completing the full course of therapy may (1) decrease effectiveness of the immediate treatment and

(2) increase the likelihood that bacteria will develop resistance and will not be treatable by

FACTIVE or other antibacterial drugs in the future.

Drug Interactions: Administration of repeat doses of FACTIVE had no effect on the repeat dose

pharmacokinetics of theophylline, digoxin or an ethinylestradiol/levonorgestrol oral contraceptive

product in healthy subjects. (See CLINICAL PHARMACOLOGY: Drug-Drug Interactions.)

product in healthy subjects. (See CLINICAL PHARMACOLOGY: Drug-Drug Interactions.)

Concomitant administration of FACTIVE and calcium carbonate, cimetidine, omeprazole, or an

estrogen/progesterone oral contraceptive produced minor changes in the pharmacokinetics of

gemifloxacin, which were considered to be without clinical significance. (See CLINICAL

PHARMACOLOGY.)

Concomitant administration of FACTIVE with probenecid resulted in a 45% increase in systemic

exposure to gemifloxacin. (See CLINICAL PHARMACOLOGY .)

FACTIVE had no significant effect on the anticoagulant effect of warfarin in healthy subjects on stable

warfarin therapy. However, post-marketing reports of increases in the INR, or PT, and/or clinical

episodes of bleeding in patients have been noted with the use of quinolones, including FACTIVE, and

warfarin, or its derivatives. In addition, infectious disease and its accompanying inflammatory process,

age and general status of the patient are risk factors for increased anticoagulation activity. Therefore,

the PT, INR or other suitable coagulation test should be closely monitored if a quinolone antimicrobial,

including FACTIVE, is administered concomitantly with warfarin or its derivatives.

Quinolones form chelates with alkaline earth and transition metals. The absorption of oral gemifloxacin

is significantly reduced by the concomitant administration of an antacid containing aluminum and

magnesium. Magnesium- and/or aluminum-containing antacids, products containing ferrous sulfate (iron),

multivitamin preparations containing zinc or other metal cations, or Videx

(didanosine)

chewable/buffered tablets or the pediatric powder for oral solution should not be taken within 3 hours

before or 2 hours after FACTIVE. Sucralfate should not be taken within 2 hours of FACTIVE. (See

CLINICAL PHARMACOLOGY.)

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis: Long term studies in animals to determine the carcinogenic potential of gemifloxacin

have not been conducted.

Photocarcinogenesis: Gemifloxacin did not shorten the time to development of UVR-induced skin tumors

in hairless albino (Skh-1) mice; thus, it was not photocarcinogenic in this model. These mice received

oral gemifloxacin and concurrent irradiation with simulated sunlight 5 days per week for 40 weeks

followed by a 12-week treatment-free observation period. The daily dose of UV radiation used in this

study was approximately 1/3 of the minimal dose of UV radiation that would induce erythema in

Caucasian humans. The median time to the development of skin tumors in the hairless mice was similar

in the vehicle control group (36 weeks) and those given up to 100 mg/kg gemifloxacin daily (39 weeks).

Following repeat doses of 100 mg/kg gemifloxacin per day, the mice had skin gemifloxacin

concentrations of approximately 7.4 μg/g. Plasma levels following this dose were approximately 1.4

μg/mL in the mice around the time of irradiation. There are no data on gemifloxacin skin levels in

humans, but the mouse plasma gemifloxacin levels are in the expected range of human plasma Cmax

levels (0.7-2.6 μg/mL, with an overall mean of about 1.6 μg/mL) following multiple 320 mg oral doses.

Mutagenesis: Gemifloxacin was not mutagenic in 4 bacterial strains (TA 98, TA 100, TA 1535, TA

1537) used in an Ames Salmonella reversion assay. It did not induce micronuclei in the bone marrow of

mice following intraperitoneal doses of up to 40 mg/kg and it did not induce unscheduled DNA

synthesis in hepatocytes from rats which received oral doses of up to 1600 mg/kg. Gemifloxacin was

clastogenic in vitro in the mouse lymphoma and human lymphocyte chromosome aberration assays. It was

clastogenic in vivo in the rat micronucleus assay at oral and intravenous dose levels (≥800 mg/kg and

≥40 mg/kg, respectively) that produced bone marrow toxicity. Fluoroquinolone clastogenicity is

apparently due to inhibition of mammalian topoisomerase activity which has threshold implications.

Impairment of Fertility: Gemifloxacin did not affect the fertility of male or female rats at AUC levels

following oral administration (216 and 600 mg/kg/day) that were approximately 3- to 4-fold higher than

the AUC levels at the clinically recommended dose.

Pregnancy: Teratogenic Effects. Pregnancy Category C. Gemifloxacin treatment during

organogenesis caused fetal growth retardation in mice (oral dosing at 450 mg/kg/day), rats (oral dosing

at 600 mg/kg/day) and rabbits (IV dosing at 40 mg/kg/day) at AUC levels which were 2-, 4- and 3-fold

those in women given oral doses of 320 mg. In rats, this growth retardation appeared to be reversible in

a pre- and postnatal development study (mice and rabbits were not studied for the reversibility of this

effect). Treatment of pregnant rats at 8-fold clinical exposure (based upon AUC comparisons) caused

fetal brain and ocular malformations in the presence of maternal toxicity. The overall no-effect

exposure level in pregnant animals was approximately 0.8 to 3-fold clinical exposure.

The safety of FACTIVE in pregnant women has not been established. FACTIVE should not be used in

pregnant women unless the potential benefit to the mother outweighs the risk to the fetus. There are no

adequate and well-controlled studies in pregnant women.

Nursing Mothers: Gemifloxacin is excreted in the breast milk of rats. There is no information on

excretion of gemifloxacin into human milk. Therefore, FACTIVE should not be used in lactating women

unless the potential benefit to the mother outweighs the risk.

Pediatric Use: Safety and effectiveness in children and adolescents less than 18 years of age have not

been established. Fluoroquinolones, including gemifloxacin, cause arthropathy and osteochondrosis in

immature animals. (See WARNINGS.)

Geriatric Use: Geriatric patients are at increased risk for developing severe tendon disorders

including tendon rupture when being treated with a fluoroquinolone such as FACTIVE. 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 FACTIVE to elderly patients especially those on

corticosteroids. Patients should be informed of this potential side effect and advised to discontinue

FACTIVE and contact their healthcare provider if any symptoms of tendinitis or tendon rupture occur

(See Boxed Warning, WARNINGS, and ADVERSE REACTIONS/Post-Marketing Adverse Event

Reports. )

Of the total number of subjects in clinical studies of FACTIVE, 29% (2314) were 65 and over, while

11% (865) were 75 and over. No overall difference in effectiveness was observed between these

subjects and younger subjects; the adverse event rate for this group was similar to or lower than that for

younger subjects with the exception that the incidence of rash was lower in geriatric patients compared

to patients less than 40 years of age.

Elderly patients may be more susceptible to drug-associated effects on the QT interval. Therefore,

FACTIVE should be avoided in patients taking drugs that can result in prolongation of the QT interval

(e.g., Class IA or Class III antiarrhythmics) or in patients with risk factors for torsades de pointes (e.g.,

known QT prolongation, uncorrected hypokalemia).

ADVERSE REACTIONS

In clinical studies, 8119 patients received daily oral doses of 320 mg FACTIVE. In addition, 1797

healthy volunteers and 81 patients with renal or hepatic impairment received single or repeat doses of

gemifloxacin in clinical pharmacology studies. The majority of adverse reactions experienced by

patients in clinical trials were considered to be of mild to moderate severity.

FACTIVE was discontinued because of an adverse event (determined by the investigator to be possibly

or probably related to drug) in 2.0% of patients, primarily due to rash (0.8%), nausea (0.3%), diarrhea

(0.3%), urticaria (0.2%) and vomiting (0.2%). Comparator antibiotics were discontinued because of an

adverse event at an overall comparable rate of 2.1%, primarily due to diarrhea (0.5%), nausea (0.4%),

vomiting (0.3%), rash (0.3%), abdominal pain (0.2%) and vertigo (0.2%).

The most commonly reported adverse events with a frequency of ≥2% for patients receiving 320 mg

FACTIVE versus comparator drug (beta-lactam antibiotics, macrolides or other fluoroquinolones) are

as follows: diarrhea 5.0% vs. 6.2%; rash 3.5% vs. 1.1%; nausea 3.7% vs. 4.5%; headache 4.2% vs.

5.2%; abdominal pain 2.2% vs. 2.2%; vomiting 1.6% vs. 2.0%; and dizziness 1.7% vs. 2.6%.

Adverse Events with a Frequency of Less than 1%

Additional drug-related adverse events (possibly or probably related) in the 8119 patients, with a

frequency of >0.1% to ≤1% included: abdominal pain, anorexia, constipation, dermatitis, dizziness, dry

mouth, dyspepsia, fatigue, flatulence, fungal infection, gastritis, genital moniliasis, genital pruritus,

hyperglycemia, increased alkaline phosphatase, increased ALT, increased AST, increased creatine

phosphokinase, insomnia, leukopenia, pruritus, somnolence, taste perversion, thrombocythemia,

urticaria, vaginitis, and vomiting.

Other adverse events reported from clinical trials which have potential clinical significance and which

were considered to have a suspected relationship to the drug, that occurred in ≤0.1% of patients were:

abnormal urine, abnormal vision, anemia, arthralgia, asthenia, back pain, bilirubinemia, dyspnea, eczema,

eosinophilia, facial edema, flushing, gastroenteritis, granulocytopenia, hot flashes, increased GGT,

increased non-protein nitrogen, leg cramps, moniliasis, myalgia, nervousness, non-specified

gastrointestinal disorder, pain, pharyngitis, photosensitivity/phototoxicity reactions, pneumonia,

thrombocytopenia, tremor, vertigo. (See PRECAUTIONS.)

In clinical trials of acute bacterial exacerbation of chronic bronchitis (ABECB) and community acquired

pneumonia (CAP), the incidences of rash were as follows (Table 3):

Table 3. Incidence of Rash by Clinical Indication in Patients Treated with FACTIVE

ABECB (5 days)

N = 2284

CAP (5 days)

N = 256

CAP (7 days)

N = 643

Totals

27/2284

1/256

26/643

Females, < 40 years

1/37

8/88

Females, ≥ 40 years

16/1040

0/73

5/214

Males, < 40 years

0/65

5/101

Males, ≥ 40 years

11/1203

0/81

8/240

* insufficient number of patients in this category for a meaningful analysis

(See PRECAUTIONS).

Laboratory Changes: The percentages of patients who received multiple doses of FACTIVE and had

a laboratory abnormality are listed below. It is not known whether these abnormalities were related to

FACTIVE or an underlying condition.

Clinical Chemistry: increased ALT (1.7%), increased AST (1.3%), increased creatine phosphokinase

(0.7%), increased alkaline phosphatase (0.4%), increased total bilirubin (0.4%), increased potassium

(0.3%), decreased sodium (0.2%), increased blood urea nitrogen (0.3%), decreased albumin (0.3%),

increased serum creatinine (0.2%), decreased calcium (0.1%), decreased total protein (0.1%),

decreased potassium (0.1%), increased sodium (0.1%), increased lactate dehydrogenase (<0.1%) and

increased calcium (<0.1%).

CPK elevations were noted infrequently: 0.7% in FACTIVE patients vs. 0.7% in the comparator patients.

Hematology: increased platelets (1.0%), decreased neutrophils (0.5%), increased neutrophils (0.5%),

decreased hematocrit (0.3%), decreased hemoglobin (0.2%), decreased platelets (0.2%), decreased red

blood cells (0.1%), increased hematocrit (0.1%), increased hemoglobin (0.1%), and increased red blood

cells (0.1%).

In clinical studies, approximately 7% of the FACTIVE treated patients had elevated ALT values

immediately prior to entry into the study. Of these patients, approximately 15% showed a further

elevation of their ALT at the on-therapy visit and 9% showed a further elevation at the end of therapy

visit. None of these patients demonstrated evidence of hepatocellular jaundice. For the pooled

comparators, approximately 6% of patients had elevated ALT values immediately prior to entry into the

study. Of these patients, approximately 7% showed a further elevation of their ALT at the on-therapy

visit and 4% showed a further elevation at the end of therapy visit.

In a clinical trial where 638 patients received either a single 640 mg dose of gemifloxacin or 250 mg

BID of ciprofloxacin for 3 days, there was an increased incidence of ALT elevations in the

gemifloxacin arm (3.9%) vs. the comparator arm (1.0%). In this study, two patients experienced ALT

elevations of 8 to 10 times the upper limit of normal. These elevations were asymptomatic and

reversible.

Post-Marketing Adverse Reactions: The majority of the post-marketing adverse events reported

were cutaneous and most of these were rash. Some of these cutaneous adverse events were considered

serious. The majority of the rashes occurred in women and in patients under 40 years of age.

The following are additional adverse reactions reported during the post-marketing use of FACTIVE.

Since these reactions are reported voluntarily from a population of uncertain size, it is impossible to

reliably estimate their frequency or establish a causal relationship to FACTIVE exposure:

peripheral neuropathy that may be irreversible;

anaphylactic reaction, erythema multiforme, skin exfoliation, facial swelling;

exacerbation of myasthenia gravis;

hemorrhage, increased international normalized ratio (INR), retinal hemorrhage;

peripheral edema;

renal failure;

prolonged QT, supraventricular tachycardia, syncope, transient ischemic attack;

photosensitivity/phototoxicity reaction (See PRECAUTIONS.);

antibiotic-associated colitis;

tendon rupture.

OVERDOSAGE

Any signs or symptoms of overdosage should be treated symptomatically. No specific antidote is

known. In the event of acute oral overdosage, the stomach should be emptied by inducing vomiting or by

gastric lavage; the patient should be carefully observed and treated symptomatically with appropriate

hydration maintained. Hemodialysis removes approximately 20 to 30% of an oral dose of gemifloxacin

from plasma.

Mortality occurred at oral gemifloxacin doses of 1600 mg/kg in rats and 320 mg/kg in mice. The

minimum lethal intravenous doses in these species were 160 and 80 mg/kg, respectively. Toxic signs

after administration of a single high oral dose (400 mg/kg) of gemifloxacin to rodents included ataxia,

lethargy, piloerection, tremor, and clonic convulsions.

DOSAGE AND ADMINISTRATION

FACTIVE can be taken with or without food and should be swallowed whole with a liberal amount of

liquid. The recommended dose of FACTIVE is 320 mg daily, according to the following table (Table

Table 4. Recommended Dosage Regimen of FACTIVE

The clinical decision regarding the use of a 5 or 7 day regimen should be guided by results of the

initial sputum culture.

INDICATION

DOSE / DURATION

Acute bacterial exacerbation of chronic bronchitis

One 320 mg tablet daily for

5 days

Community-acquired pneumonia (of mild to moderate severity)

due to known or suspected S. pneumoniae, H. influenzae, M. pneumoniae, or C.

pneumoniae infection

One 320 mg tablet daily for

5 days

due to known or suspected MDRSP*, K. pneumoniae, or M. catarrhalis infection

One 320 mg tablet daily for

7 days

*MDRSP: multi-drug resistant Streptococcus pneumoniae, includes isolates previously known as PRSP

(penicillin-resistant Streptococcus pneumoniae), and are strains resistant to two or more of the

following antibiotics: penicillin (MIC 2 µg/mL), 2nd generation cephalosporins (e.g., cefuroxime),

macrolides, tetracyclines and trimethoprim/sulfamethoxazole.

The recommended dose and duration of FACTIVE should not be exceeded (see Table 2).

Use in Renally Impaired Patients: Dose adjustment in patients with creatinine clearance >40 mL/min is

not required. Modification of the dosage is recommended for patients with creatinine clearance 40

mL/min. Table 5 provides dosage guidelines for use in patients with renal impairment.

Table 5. Recommended Doses for Patients with Renal Impairment

Creatinine Clearance

(mL/min)

Dos e

>40

See Usual Dosage

160 mg every 24 hours

Patients requiring routine hemodialysis or continuous ambulatory peritoneal dialysis (CAPD) should

receive 160 mg every 24 hours.

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

creatinine clearance.

Creatinine Clearance Formula

Women: 0.85 x the value calculated for men

Use in Hepatically Impaired Patients: No dosage adjustment is recommended in patients with mild

(Child-Pugh Class A), moderate (Child-Pugh Class B) or severe (Child-Pugh Class C) hepatic

impairment.

Use in Elderly: No dosage adjustment is recommended.

HOW SUPPLIED

FACTIVE (gemifloxacin mesylate) is available as white to off-white, oval, film-coated tablets with

breaklines and GE 320 debossed on both faces. Each tablet contains gemifloxacin mesylate equivalent to

320 mg of gemifloxacin.

320 mg Unit of Use (CR*) 5's NDC 44001-321-05

320 mg Unit of Use (CR*) 7's NDC 44001-321-07

*Child Resistant

Storage

Store at 25ºC (77ºF); excursions permitted to 15º-30ºC (59º-86ºF) [see USP Controlled Room

Temperature]. Protect from light.

ANIMAL PHARMACOLOGY

Quinolones have been shown to cause arthropathy in immature animals. Degeneration of articular

cartilage occurred in juvenile dogs given at least 192 mg/kg/day gemifloxacin in a 28-day study

(producing about 6 times the systemic exposure at the clinical dose), but not in mature dogs. There was

no damage to the articular surfaces of joints in immature rats given repeated doses of up to 800

mg/kg/day.

Some quinolones have been reported to have proconvulsant properties that are potentiated by the

concomitant administration of non-steroidal anti-inflammatory drugs (NSAIDs). Gemifloxacin alone had

effects in tests of behavior or CNS interaction typically at doses of at least 160 mg/kg. No convulsions

occurred in mice given the active metabolite of the NSAID, fenbufen, followed by 80 mg/kg

gemifloxacin.

Dogs given 192 mg/kg/day (about 6 times the systemic exposure at the clinical dose) for 28 days, or 24

mg/kg/day (approximately equivalent to the systemic exposure at the clinical dose) for 13 weeks

showed reversible increases in plasma ALT activities and local periportal liver changes associated

with blockage of small bile ducts by crystals containing gemifloxacin.

Quinolones have been associated with prolongation of the electrocardiographic QT interval in dogs.

Gemifloxacin produced no effect on the QT interval in dogs dosed orally to provide about 4 times

human therapeutic plasma concentrations at Cmax, and transient prolongation after intravenous

administration at more than 4 times human plasma levels at Cmax. Gemifloxacin exhibited weak activity

in the cardiac I

(hERG) channel inhibition assay, having an IC

of approximately 270 μM.

Gemifloxacin, like many other quinolones, tends to crystallize at the alkaline pH of rodent urine,

resulting in a nephropathy in rats that is reversible on drug withdrawal (oral no-effect dose 24

mg/kg/day).

Gemifloxacin was weakly phototoxic to hairless mice given a single 200 mg/kg oral dose and exposed

to UVA radiation. However, no evidence of phototoxicity was observed at 100 mg/kg/day dosed orally

for 13 weeks in a standard hairless mouse model, using simulated sunlight.

CLINICAL STUDIES

Acute Bacterial Exacerbation of Chronic Bronchitis (ABECB)

FACTIVE (320 mg once daily for 5 days) was evaluated for the treatment of acute bacterial

exacerbation of chronic bronchitis in three pivotal double-blind, randomized, actively-controlled

clinical trials (studies 068, 070, and 212). The primary efficacy parameter in these studies was the

clinical response at follow-up (day 13 to 24). The results of the clinical response at follow-up for the

principal ABECB studies demonstrate that FACTIVE 320 mg PO once daily for 5 days was at least as

good as the comparators given for 7 days. The results are shown in Table 6 below.

Table 6. Clinical Response at Follow-Up (Test of Cure): Pivotal ABECB Studies

Drug Regimen

Success Rate

% (n/N)

Treatment Difference

(95% CI)

Study 068

FACTIVE 320 mg x 5 days

86.0 (239/278)

1.2 (-4.7, 7.0)

Clarithromycin 500 mg BID x 7 days

84.8 (240/283)

Study 070

FACTIVE 320 mg x 5 days

93.6 (247/264)

0.4 (-3.9, 4.6)

Amoxicillin/clavulanate

500 mg/125 mg TID x 7 days

93.2 (248/266)

Study 212

FACTIVE 320 mg x 5 days

88.2 (134/152)

3.1 (-4.7, 10.7)

Levofloxacin 500 mg x 7 days

85.1 (126/148)

Community Acquired Pneumonia (CAP)

5 Day Treatment Regimen

To evaluate the safety and efficacy of a 5-day course of FACTIVE, 510 outpatient and hospitalized

adults with clinically and radiologically determined mild to moderate community-acquired pneumonia

were clinically evaluated in a double-blind, randomized, prospective, multicenter study comparing

FACTIVE 320 mg for five days to FACTIVE 320 mg for seven days (Study OP-634-001).

Clinical success rates in the clinically evaluable population were 95.0% in the 5 day group and 92.1%

in the 7 day group.

Table 7. Clinical Response at Follow-Up (Test of Cure): Study OP-634-001

Drug Regimen

Success Rate

% (n/N)

Treatment Difference

(95% CI)

Study OP-634-001

FACTIVE 320 mg x 5 days

95.0 (230/242)

3.0 (-1.5, 7.4)

FACTIVE 320 mg x 7 days

92.1 (209/227)

The microbiological efficacy of the 5-day regimen was documented for pathogens listed in Table 8

below.

Table 8. Bacterial Eradication by Pathogen for Patients Treated with FACTIVE in Study OP-

634-001

5-day

7-day

Pathogen

n/N

%

n/N

%

Streptococcus pneumoniae

26/26

34/40

85.0

Mycoplasma pneumoniae

22/25

88.0

19/20

95.0

Haemophilus influenzae

21/22

95.5

18/18

Chlamydia pneumoniae

17/18

94.4

30/31

96.8

7 Day Treatment Regimen

Previous clinical studies evaluated the efficacy of FACTIVE in a 7-day treatment of CAP in adults.

This clinical program consisted of three double-blind, randomized, actively-controlled clinical studies

(studies 011, 012, and 049) and one open-label, actively-controlled study (study 185). In addition, two

uncontrolled studies (studies 061 and 287) were conducted. Three of the studies, controlled study 011

and the uncontrolled studies, had a fixed 7-day duration of treatment for FACTIVE. Controlled study

011 compared a 7-day course of FACTIVE with a 10-day treatment course of amoxicillin/clavulanate

(1g/125 mg TID) and clinical success rates were similar between treatment arms. The results of

comparative studies 049, 185, and 012 were supportive although treatment duration could have been 7

to 14 days. The results of the clinical studies with a fixed 7-day duration of FACTIVE are shown in

Table 9.

Table 9. Clinical Response at Follow-Up (Test of Cure): CAP Studies with a Fixed 7-day

Duration of Treatment

Drug Regimen

Success Rate

% (n/N)

Treatment Difference

(95% CI)*

Study 011

FACTIVE 320 mg x 7 days

88.7 (102/115)

1.1 (-7.3, 9.5)

Amoxicillin/clavulanate

1 g/125 mg TID x 10 days

87.6 (99/113)

Study 061

FACTIVE 320 mg x 7 days

91.7 (154/168)

(86.1, 95.2)

Study 287

FACTIVE 320 mg x 7 days

89.8 (132/147)

(84.9, 94.7)

*For uncontrolled studies, the 95% CI around the success rate is shown

The combined bacterial eradication rates for patients treated with a fixed 7-day treatment regimen of

FACTIVE are shown in Table 10.

Table 10. Bacterial Eradication by Pathogen for Patients Treated with FACTIVE in Studies with

a Fixed 7-day Duration of Treatment

Pathogen

n/N

%

S. pneumoniae

102/117

87.2

M. pneumoniae

40/42

95.2

H. influenzae

48/53

90.6

C. pneumoniae

43/45

95.6

K. pneumoniae

18/20

90.0

M. catarrhalis

11/12

91.7

7 Day Treatment Regimen of Community-Acquired Pneumonia Due to Multi-Drug Resistant

Streptococcus pneumoniae (MDRSP)

FACTIVE was also effective in the treatment of CAP due to multi-drug resistant Streptococcus

pneumoniae (MDRSP*). Of 35 patients with MDRSP treated for 7 days, 29 (82.9%) achieved clinical

and bacteriological success at follow-up. The clinical and bacteriological success for the 35 patients

with MDRSP isolates are shown in Table 11.

*MDRSP: multi-drug resistant Streptococcus pneumoniae, includes isolates previously known as PRSP

(penicillin-resistant Streptococcus pneumoniae), and are strains resistant to two or more of the following

antibiotics: penicillin (MIC ≥2 μg/mL), 2nd generation cephalosporins (e.g., cefuroxime), macrolides,

tetracyclines and trimethoprim/sulfamethoxazole.

Table 11. Clinical and Bacteriological Success for 35 Patients Treated with FACTIVE in CAP

Studies with a 7-day Duration of Treatment for MDRSP

Screening Susceptibility

Clinical

Succes s

Bacteriological

Succes s

n/N

%

n/N

%

Penicillin-resistant

15/16

93.8

15/16

93.8

generation cephalosporin-resistant

20/22

90.9

20/22

90.9

Macrolide-resistant

24/28

85.7

23/28

82.1

Trimethoprim/sulfamethoxazole-resistant

23/26

88.5

23/26

88.5

Tetracycline-resistant

21/27

77.8

20/27

74.1

n = the number of patients successfully treated; N = number of patients with MDRSP

n = the number of bacteriological isolates successfully treated; N = number of isolates studied

Macrolide antibiotics tested include clarithromycin and erythromycin

Not all isolates were resistant to all antimicrobial classes tested. Success and eradication rates are

summarized in Table 12 below.

Table 12. Resistant Streptococcus pneumoniae Clinical Success and Bacteriological Eradication

Rates

S. pneumoniae with MDRSP

Clinical

Cure Rate

Bacteriological

Eradication Rate

n/N

%

n/N

%

Resistant to 2 antimicrobials

8/11

72.7

7/11

63.6

Resistant to 3 antimicrobials

71.4

71.4

Resistant to 4 antimicrobials

88.9

88.9

Resistant to 5 antimicrobials

Bacteremia with MDRSP

Clinical Safety Study of Rash

To further characterize gemifloxacin-associated rash, which in early clinical studies appeared to be

associated with age less than 40 and female gender, a clinical pharmacology study was conducted. The

study enrolled 1,011 healthy female volunteers less than 40 years of age. Subjects were randomized in a

5:1 ratio to receive either FACTIVE 320 mg PO daily (819 subjects) or ciprofloxacin 500 mg PO twice

daily for 10 days (164 subjects). This study was designed to enroll subjects at a high risk for rash

(women <40 years of age and dosing beyond the recommended duration of therapy for FACTIVE [10

days]) and over estimates the risk to patients taking FACTIVE as prescribed. Subjects who received

FACTIVE were 7 times more likely to develop rash than those who received ciprofloxacin. Of the 260

rashes in subjects receiving FACTIVE, the majority of rashes were maculopapular and of mild to

moderate severity; 7% of the rashes were reported as severe, and severity appeared to correlate with

the extent of the rash. In 68% of the subjects reporting a severe rash and approximately 25% of all those

reporting rash, >60% of the body surface area was involved; the characteristics of the rash were

otherwise indistinguishable from those subjects reporting a mild rash. The histopathology was

consistent with the clinical observation of uncomplicated exanthematous morbilliform eruption.

Approximately 11% of the rashes were described as being “urticaria-like”. There were no documented

cases of hypersensitivity syndrome or findings suggestive of angioedema or other serious cutaneous

reactions.

The majority of rashes (81.9%) occurred on days 8 through 10 of the planned 10 day course of

FACTIVE; 2.7% of rash events occurred within one day of the start of dosing. The median duration of

rash was 6 days. The rash resolved without treatment in the majority of subjects. Approximately 19%

received antihistamines and 5% received steroids, although the therapeutic benefit of these therapies is

uncertain.

In the second part of this study after a 4 to 6 week wash out period, subjects developing a rash on

FACTIVE were treated with ciprofloxacin (n=136) or placebo (n=50); 5.9% developed rash when

treated with ciprofloxacin and 2.0% developed rash when treated with placebo. The cross sensitization

rate to other fluoroquinolones was not evaluated in this clinical study. There was no evidence of sub-

clinical sensitization to FACTIVE on a second exposure (i.e., subjects who had not developed a rash to

FACTIVE in the first part of the study were not at higher risk of developing a rash to FACTIVE with a

second exposure).

a

b

There was no relationship between the incidence of rash and systemic exposure (Cmax and AUC) to

either gemifloxacin or its major metabolite, N-acetyl gemifloxacin.

REFERENCES

1. Clinical and Laboratory Standards Institute. Methods for Dilution Antimicrobial Susceptibility Tests

for Bacteria that Grow Aerobically-Seventh Edition. Clinical and Laboratory Standards Institute

document M7-A7, Vol. 26, No. 2, CLSI, Wayne, PA, January 2006.

2. Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Disk

Susceptibility Tests-Ninth Edition. Clinical and Laboratory Standards Institute document M2-A9, Vol.

26, No. 1, CLSI, Wayne, PA, January 2006.

DATE OF REVISION May 2016

© Merus Labs International Inc.

FACTIVE is a registered trademark of LG Life Sciences.

Rx only

Manufactured for:

Toronto, ON M5K 1H1 Canada

Licensed from LG Life Sciences, Ltd. Seoul, Korea

MRS-001-0313-03

MEDICATION GUIDE

FACTIVE [FAC-tiv]

(gemifloxacin)

320mg Tablets

Read the Medication Guide that comes with FACTIVE before you start taking it and each time you get a

refill. There may be new information. This Medication Guide 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 FACTIVE?

FACTIVE, 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 are taking FACTIVE, you should stop

taking FACTIVE 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 FACTIVE.

Tendons are tough cords of tissue that connect muscles to bones.

Symptoms of tendon problems may include: Pain, swelling, tears, and inflammation of tendons

including the back of the ankle (Achilles), shoulder, hand, or other tendon sites.

The risk of getting tendon problems while you take FACTIVE 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 FACTIVE.

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 FACTIVE immediately and get medical help right away at the first sign of tendon

pain, swelling or inflammation. Stop taking FACTIVE until tendinitis or tendon rupture has been

ruled out by your healthcare provider. Avoid exercise and using the affected area. The most

common area of pain and swelling is the Achilles tendon at the back of your ankle. This can also

happen with other tendons.

Talk to your healthcare provider about the risk of tendon rupture with continued use of

FACTIVE. You may need a different antibiotic that is not a fluoroquinolone to treat your infection.

Tendon rupture can happen while you are taking or after you have finished taking

FACTIVE. Tendon ruptures can happen within hours or days of taking FACTIVE, and have

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

Get medical help right away if you get any of the following signs or symptoms of a tendon

rupture:

hear or feel a snap or pop in a tendon area

bruising right after an injury in a tendon area

unable to move the affected area or bear weight

2. Changes in sensation and possible nerve damage (Peripheral Neuropathy). Damage to the

nerves in arms, hands, legs, or feet can happen in people taking fluoroquinolones, including FACTIVE.

Stop FACTIVE and talk with your healthcare provider right away if you get any of the following

symptoms of peripheral neuropathy in your arms, hands, legs, or feet:

pain

burning

tingling

numbness

weakness

The nerve damage may be permanent.

3. Central Nervous System (CNS) Effects. Seizures have been reported in people who take

fluoroquinolone antibiotics, including FACTIVE. Tell your healthcare provider if you have a history

of seizures. Ask your healthcare provider whether taking FACTIVE will change your risk of having a

seizure. Central Nervous System (CNS) side effects may happen as soon as after taking the first dose of

FACTIVE. Talk to your healthcare provider right away if you get any of these side effects, or other

changes in mood or behavior:

feel dizzy

seizures

hear voices, see things, or sense things that are not there (hallucinations)

feel restless

tremors

feel anxious or nervous

confusion

depression

trouble sleeping

feel more suspicious (paranoia)

suicidal thoughts or acts

nightmares

4. Worsening of myasthenia gravis (a disease which causes muscle weakness). Fluoroquinolones

like FACTIVE 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 FACTIVE. Call your healthcare provider right away if you have any worsening muscle

weakness or breathing problems.

See the section “ What are the possible side effects of FACTIVE?” for more information about

side effects.

What is FACTIVE?

FACTIVE is a fluoroquinolone antibiotic medicine used to treat certain infections caused by certain

germs called bacteria in adults 18 years or older. It is not known if FACTIVE is safe and works in

children under 18 years of age. Children have a higher chance of getting bone, joint, or tendon

(musculoskeletal) problems such as pain or swelling while taking fluoroquinolone antibiotic medicines.

Sometimes infections are caused by viruses rather than by bacteria. Examples include viral infections in

the sinuses and lungs, such as the common cold or flu. Antibiotics including FACTIVE do not kill

viruses.

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

FACTIVE.

Who should not take FACTIVE?

Do not take FACTIVE if you have ever had a severe allergic reaction to an antibiotic known as a

fluoroquinolone, or are allergic to any of the ingredients in FACTIVE. Ask your healthcare provider if

you are not sure. See the list of ingredients in FACTIVE at the end of this Medication Guide.

What should I tell my healthcare provider before taking FACTIVE?

See “What is the most important information I should know about FACTIVE?

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

have tendon problems. FACTIVE should not be used in patients who have a history of tendon

problems.

have a disease that causes muscle weakness (myasthenia gravis). FACTIVE should not be used in

patients who have a known history of myasthenia gravis.

have central nervous system problems (such as epilepsy)

have nerve problems. FACTIVE should not be used in patients who have a history of nerve

problems called peripheral neuropathy.

have or anyone in your family has an irregular heartbeat, especially a condition called “QT

prolongation”

have low blood potassium (hypokalemia) or magnesium (hypomagnesemia)

have a slow heartbeat (bradycardia)

have a history of seizures

have kidney problems. You may need a lower dose of FACTIVE if your kidneys do not work well.

have rheumatoid arthritis (RA) or other history of joint problems

are pregnant or planning to become pregnant. It is not known if FACTIVE will harm your unborn

child.

are breast-feeding or planning to breast-feed. It is not known if FACTIVE passes into breast milk.

You and your healthcare provider should decide whether you will take FACTIVE or breast-feed.

Tell your healthcare provider about all the medicines you take, including prescription and non-

prescription medicines, vitamins, and herbal and dietary supplements. FACTIVE and other medicines can

affect each other causing side effects. Especially tell your healthcare provider if you take:

an NSAID (Non-Steroidal Anti-Inflammatory Drug). Many common medicines for pain relief are

NSAIDs. Taking an NSAID while you take FACTIVE or other fluoroquinolones may increase your

risk of central nervous system effects and seizures. See “ What are the possible side effects of

FACTIVE?

a blood thinner (warfarin, Coumadin , Jantoven )

a medicine to control your heart rate or rhythm (antiarrhythmics). See “ What are the possible side

effects of FACTIVE?

an anti-psychotic medicine

a tricyclic antidepressant

a water pill (diuretic)

probenecid (Probalan, Col-Probenecid)

a steroid medicine. Corticosteroids taken by mouth or by injection may increase the chance of tendon

injury. See “ What is the most important information I should know about FACTIVE?

Certain medicines may keep FACTIVE from working correctly. Take FACTIVE either 3 hours

before or 2 hours after taking these products:

an antacid, multivitamin, or other product that contains magnesium, aluminum, iron, or zinc.

sucralfate (Carafate

sucralfate (Carafate

didanosine (Videx

, Videx EC ).

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

Know the medicines you take. Keep a list of your medicines and show it to your healthcare provider and

pharmacist when you get a new medicine.

How should I take FACTIVE?

Take FACTIVE exactly as prescribed by your healthcare provider.

Take FACTIVE at about the same time each day.

FACTIVE tablets should be swallowed.

FACTIVE can be taken with or without food.

FACTIVE 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 FACTIVE.

Do not skip any doses, or stop taking FACTIVE even if you begin to feel better, until you finish

your prescribed treatment, unless:

you have tendon effects (see “ What is the most important information I should know about

FACTIVE? ”),

you have nerve problems (see " What is the most important information I should know

about FACTIVE? ”),

you have central nervous system problems (see “ What is the most important information I

should know about FACTIVE? ”),

you have a serious allergic reaction (see “ What are the possible side effects of FACTIVE?

”), or your healthcare provider tells you to stop.

This will help make sure that all of the bacteria are killed and lower the chance that the bacteria will

become resistant to FACTIVE. If this happens, FACTIVE and other antibiotic medicines may not

work in the future.

If you miss a dose of FACTIVE, take it as soon as you remember. Do not take more than 1 dose of

FACTIVE in one day.

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

What should I avoid while taking FACTIVE?

FACTIVE 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 FACTIVE affects you.

Avoid sunlamps, tanning beds, and try to limit your time in the sun. FACTIVE can make your skin

sensitive to the sun (photosensitivity) and the light from sunlamps and tanning beds. You could get

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

FACTIVE, call your healthcare provider right away. You should use 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 FACTIVE?

FACTIVE can cause side effects that may be serious or even cause death. See “ What is the most

important information I should know about FACTIVE?

Other serious side effects of FACTIVE include:

Serious allergic reactions

Allergic reactions can happen in people taking fluoroquinolones, including FACTIVE, even after only

one dose. Stop taking FACTIVE and get emergency medical help right away if you get any of the

following symptoms of a severe allergic reaction:

hives

trouble breathing or swallowing

swelling of the lips, tongue, face

throat tightness, hoarseness

rapid heartbeat

faint

Yellowing of the skin or eyes

Stop taking FACTIVE and call your healthcare provider right away if you get yellowing of your skin or

white part of your eyes, or if you have dark urine. These can be signs of a serious reaction to

FACTIVE (a liver problem).

Skin rash

Skin rash may happen in people taking FACTIVE. Stop taking FACTIVE 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 FACTIVE.

Rash happens more often with FACTIVE in:

women, especially women who take hormone replacement therapy

people under 40 years of age

people who take FACTIVE for longer than 5 days.

Serious heart rhythm changes (QTc prolongation and torsades de pointes)

Tell your healthcare provider right away if you have a change in your heartbeat (a fast or irregular

heartbeat), or if you faint. FACTIVE 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 happening are higher in people:

who are elderly

with a family history of prolonged QT interval

with low blood potassium (hypokalemia)

who take certain medicines to control heart rhythm (antiarrhythmics).

Intestine infection (Pseudomembranous colitis)

Pseudomembranous colitis can happen with most antibiotics, including FACTIVE. Call your healthcare

provider right away if you get watery diarrhea, diarrhea that does not go away, or bloody stools. You

may have stomach cramps and a fever. Pseudomembranous colitis can happen 2 or more months after

you have finished your antibiotic.

Sensitivity to sunlight (photosensitivity)

See “What should I avoid while taking FACTIVE?

Joint problems

The most common side effects of FACTIVE include:

diarrhea

rash

nausea

headache

stomach pain

vomiting

dizziness

These are not all the possible side effects of FACTIVE. Tell your healthcare provider about any side

effect that bothers you or that does not go away.

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

FDA-1088.

How should I store FACTIVE?

Store FACTIVE at room temperature between 59º - 86ºF (15º to 30ºC).

Keep FACTIVE away from light.

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

General Information about FACTIVE

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not

use FACTIVE for a condition for which it is not prescribed. Do not give FACTIVE 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 FACTIVE. If you would like

more information about FACTIVE, talk with your healthcare provider. You can ask your healthcare

provider or pharmacist for information about FACTIVE that is written for healthcare professionals. For

more information go to www.FACTIVE.com or call 1-888-431-4276.

What are the ingredients in Factive?

Active ingredient: gemifloxacin

Inactive ingredients: crospovidone, hydroxypropyl methycellulose, magnesium stearate,

microcrystalline cellulose, polyethylene glycol, povidone, titanium dioxide.

© Merus Labs International Inc.

FACTIVE is a registered trademark of LG Life Sciences.

Manufactured for:

Toronto, ON M5K 1H1 Canada

Licensed from LG Life Sciences, Ltd. Seoul, Korea

MRS-001-0313-03

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

Revised 07/2016

Factive 5 Tablets

Factive 7 Tablets

FACTIVE

gemifloxacin mesylate tablet

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:440 0 1-321

Route of Administration

ORAL

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

GEMIFLO XACIN MESYLATE (UNII: X4S9 F8 RL0 1) (GEMIFLOXACIN - UNII:OKR6 8 Y0 E4T)

GEMIFLOXACIN

320 mg

Inactive Ingredients

Ingredient Name

Stre ng th

CRO SPO VIDO NE (UNII: 2S78 30 E56 1)

Merus Labs International Inc.

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

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

PO VIDO NE (UNII: FZ9 8 9 GH9 4E)

TITANIUM DIO XIDE (UNII: 15FIX9 V2JP)

HYPRO MELLO SE 2 9 10 ( 15 MPA.S) (UNII: 36 SFW2JZ0 W)

HYPRO MELLO SE 2 9 10 ( 5 MPA.S) (UNII: R75537T0 T4)

PO LYETHYLENE GLYCO L 4 0 0 0 (UNII: 4R4HFI6 D9 5)

PO LYETHYLENE GLYCO L 6 0 0 0 (UNII: 30 IQX730 WE)

Product Characteristics

Color

WHITE (white to o ff-white)

S core

2 pieces

S hap e

OVAL

S iz e

16 mm

Flavor

Imprint Code

GE;320

Contains

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:440 0 1-321-0 5

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

0 4/0 4/20 0 3

2

NDC:440 0 1-321-0 7

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

0 4/0 4/20 0 3

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

NDA0 21158

0 4/0 4/20 0 3

Labeler -

Merus Labs International Inc. (244172404)

Establishment

Name

Ad d re s s

ID/FEI

Busine ss Ope rations

Patheo n Inc.

0 0 528 6 8 22

ma nufa c ture (440 0 1-321)

Revised: 8/2016

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