Avelox I.V.

Moxifloxacin injection may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• nausea
• vomiting
• stomach pain
• diarrhea
• constipation
• heartburn
• irritation, pain, tenderness, redness, warmth, or swelling at the injection spot

If you experience any of the following symptoms, or any of the symptoms described in the IMPORTANT WARNING section, stop using moxifloxacin injection and call your doctor immediately or get emergency medical help:

• severe diarrhea (watery or bloody stools) that may occur with or without fever and stomach cramps (may occur up to 2 months or more after your treatment)
• rash
• hives
• itching
• peeling or blistering of the skin
• fever
• swelling of the eyes, face, mouth. lips, tongue, throat, hands, feet, ankles or lower legs
• hoarseness
• difficulty breathing or swallowing
• ongoing or worsening cough
• fast or fluttering heartbeat
• fainting
• loss of consciousness
• feeling shaky
• yellowing of the skin or eyes
• pale skin
• dark urine
• light colored stool
• decreased urination
• frequent urination
• unusual bruising or bleeding
• joint or muscle pain
• extreme thirst or hunger
• extreme tiredness
• sweating

Moxifloxacin injection may cause problems with bones, joints, and tissues around joints in children. Moxifloxacin injection should not be given to children younger than 18 years of age.

Moxifloxacin injection may cause other side effects. Call your doctor if you have any unusual problems while you are using this medication.

If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of moxifloxacin injection in the pediatric population. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of moxifloxacin injection in the elderly. However, elderly patients are more likely to have age-related heart problems, or develop severe tendon problems (including tendon rupture), which may require caution in patients receiving moxifloxacin injection.

Pregnancy

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are receiving this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Amifampridine
• Amisulpride
• Bepridil
• Cisapride
• Dronedarone
• Mesoridazine
• Pimozide
• Piperaquine
• Saquinavir
• Sparfloxacin
• Terfenadine
• Thioridazine
• Ziprasidone

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Acarbose
• Acetohexamide
• Alfuzosin
• Alogliptin
• Amiodarone
• Amitriptyline
• Anagrelide
• Apomorphine
• Aripiprazole
• Aripiprazole Lauroxil
• Arsenic Trioxide
• Asenapine
• Astemizole
• Atazanavir
• Azithromycin
• Bedaquiline
• Benfluorex
• Buserelin
• Canagliflozin
• Chloroquine
• Chlorpromazine
• Chlorpropamide
• Cholera Vaccine, Live
• Ciprofloxacin
• Citalopram
• Clarithromycin
• Clomipramine
• Clozapine
• Crizotinib
• Cyclobenzaprine
• Dabrafenib
• Dapagliflozin
• Dasatinib
• Degarelix
• Delamanid
• Desipramine
• Deslorelin
• Deutetrabenazine
• Disopyramide
• Dofetilide
• Dolasetron
• Domperidone
• Donepezil
• Doxepin
• Droperidol
• Ebastine
• Efavirenz
• Eribulin
• Erythromycin
• Escitalopram
• Exenatide
• Famotidine
• Felbamate
• Fingolimod
• Flecainide
• Fluconazole
• Fluoxetine
• Foscarnet
• Fosphenytoin
• Galantamine
• Gatifloxacin
• Gemifloxacin
• Gliclazide
• Glimepiride
• Glipizide
• Gliquidone
• Glyburide
• Gonadorelin
• Goserelin
• Granisetron
• Halofantrine
• Haloperidol
• Histrelin
• Hydroquinidine
• Hydroxychloroquine
• Hydroxyzine
• Ibutilide
• Iloperidone
• Imipramine
• Insulin
• Insulin Aspart, Recombinant
• Insulin Bovine
• Insulin Degludec
• Insulin Detemir
• Insulin Glargine, Recombinant
• Insulin Glulisine
• Insulin Lispro, Recombinant
• Itraconazole
• Ivabradine
• Ketoconazole
• Lapatinib
• Leuprolide
• Levofloxacin
• Linagliptin
• Liraglutide
• Lumefantrine
• Mefloquine
• Metformin
• Methadone
• Metronidazole
• Mifepristone
• Miglitol
• Mizolastine
• Nafarelin
• Nateglinide
• Nelfinavir
• Nilotinib
• Norfloxacin
• Octreotide
• Ofloxacin
• Olanzapine
• Ondansetron
• Paliperidone
• Panobinostat
• Paroxetine
• Pasireotide
• Pazopanib
• Pentamidine
• Perphenazine
• Pimavanserin
• Pioglitazone
• Pipamperone
• Pitolisant
• Posaconazole
• Pramlintide
• Probucol
• Procainamide
• Prochlorperazine
• Promethazine
• Propafenone
• Protriptyline
• Quetiapine
• Quinidine
• Quinine
• Ranolazine
• Rasagiline
• Repaglinide
• Ribociclib
• Rilpivirine
• Risperidone
• Ritonavir
• Rosiglitazone
• Saxagliptin
• Sertindole
• Sevoflurane
• Sitagliptin
• Sodium Phosphate
• Sodium Phosphate, Dibasic
• Sodium Phosphate, Monobasic
• Solifenacin
• Sorafenib
• Sotalol
• Sulpiride
• Sunitinib
• Tacrolimus
• Tamoxifen
• Telaprevir
• Telavancin
• Telithromycin
• Tetrabenazine
• Tizanidine
• Tolazamide
• Tolbutamide
• Tolterodine
• Toremifene
• Trazodone
• Trimipramine
• Triptorelin
• Vandetanib
• Vardenafil
• Vemurafenib
• Venlafaxine
• Vildagliptin
• Vinflunine
• Voriconazole
• Vorinostat
• Warfarin
• Zuclopenthixol

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Aminolevulinic Acid
• Lanthanum Carbonate
• Rifampin

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Bradycardia (slow heartbeat) or
• Diabetes or
• Diarrhea or
• Heart disease or
• Heart rhythm problems (eg, prolonged QT interval), or family history of or
• Hypoglycemia (low blood sugar) or
• Hypokalemia (low potassium in the blood) or
• Seizures (epilepsy), history of—Use with caution. May make these conditions worse.

• Brain disease (eg, hardening of the arteries) or
• Kidney disease or
• Liver disease (including cirrhosis) or
• Organ transplant (eg, heart, kidney, or lung), history of or
• Tendon disorder (eg, rheumatoid arthritis), history of—Use with caution. May cause side effects to become worse.

• Myasthenia gravis (severe muscle weakness), or history of—Should not be used in patients with this condition.

AVELOX Tablets and I.V. are indicated for the treatment of adults (>/= 18 years of age) with infections caused by susceptible strains of the designated microorganisms in the conditions listed below. (See DOSAGE AND ADMINISTRATION for specific recommendations. In addition, for I.V. use see PRECAUTIONS , Geriatric Use .)

Acute Bacterial Sinusitis caused by Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis .

Acute Bacterial Exacerbation of Chronic Bronchitis caused by Streptococcus pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Staphylococcus aureus, or Moraxella catarrhalis .

Community Acquired Pneumonia caused by Streptococcus pneumoniae (including multi-drug resistant strains * ), Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, Klebsiella pneumoniae, Mycoplasma pneumoniae, or Chlamydia pneumoniae .

Uncomplicated Skin and Skin Structure Infections caused by Staphylococcus aureus or Streptococcus pyogenes .

Complicated Skin and Skin Structure Infections caused by methicillin-susceptible Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae , or Enterobacter cloacae (See Clinical Studies ).

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

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

Single oral overdoses up to 2.8 g were not associated with any serious adverse events. In the event of acute overdose, the stomach should be emptied and adequate hydration maintained. ECG monitoring is recommended due to the possibility of QT interval prolongation. The patient should be carefully observed and given supportive treatment. The administration of activated charcoal as soon as possible after oral overdose may prevent excessive increase of systemic moxifloxacin exposure. About 3% and 9% of the dose of moxifloxacin, as well as about 2% and 4.5% of its glucuronide metabolite are removed by continuous ambulatory peritoneal dialysis and hemodialysis, respectively.

Single oral moxifloxacin doses of 2000, 500, and 1500 mg/kg were lethal to rats, mice, and Cynomolgus monkeys, respectively. The minimum lethal intravenous dose in mice and rats was 100 mg/kg. Toxic signs after administration of a single high dose of moxifloxacin to these animals included CNS and gastrointestinal effects such as decreased activity, somnolence, tremor, convulsions, vomiting and diarrhea.

Acute Bacterial Exacerbation of Chronic Bronchitis

AVELOX Tablets (400 mg once daily for five days) were evaluated for the treatment of acute bacterial exacerbation of chronic bronchitis in a large, randomized, double-blind, controlled clinical trial conducted in the US. This study compared AVELOX with clarithromycin (500 mg twice daily for 10 days) and enrolled 629 patients. The primary endpoint for this trial was clinical success at 7-17 days post-therapy. The clinical success for AVELOX was 89% (222/250) compared to 89% (224/251) for clarithromycin.

The following outcomes are the clinical success rates at the follow-up visit for the clinically evaluable patient groups by pathogen:

The microbiological eradication rates (eradication plus presumed eradication) in AVELOX treated patients were Streptococcus pneumoniae 100%, Haemophilus influenzae 89%, Haemophilus parainfluenzae 100%, Moraxella catarrhalis 85%, Staphylococcus aureus 94%, and Klebsiella pneumoniae 85%.

Community Acquired Pneumonia

A large, randomized, double-blind, controlled clinical trial was conducted in the US to compare the efficacy of AVELOX Tablets (400 mg once daily) to that of high-dose clarithromycin (500 mg twice daily) in the treatment of patients with clinically and radiologically documented community acquired pneumonia. This study enrolled 474 patients (382 of whom were valid for the primary efficacy analysis conducted at the 14-35 day follow-up visit). Clinical success for clinically evaluable patients was 95% (184/194) for AVELOX and 95% (178/188) for high dose clarithromycin.

A large, randomized, double-blind, controlled trial was conducted in the US and Canada to compare the efficacy of sequential IV/PO AVELOX 400 mg QD for 7-14 days to an IV/PO fluoroquinolone control (trovafloxacin or levofloxacin) in the treatment of patients with clinically and radiologically documented community acquired pneumonia. This study enrolled 516 patients, 362 of whom were valid for the primary efficacy analysis conducted at the 7-30 day post-therapy visit. The clinical success rate was 86% (157/182) for AVELOX therapy and 89% (161/180) for the fluoroquinolone comparators.

An open-label ex-US study that enrolled 628 patients compared AVELOX to sequential IV/PO amoxicillin/clavulanate (1.2 g IV q8h/625 mg PO q8h) with or without high-dose IV/PO clarithromycin (500 mg BID). The intravenous formulations of the comparators are not FDA approved. The clinical success rate at Day 5-7 (the primary efficacy timepoint) for AVELOX therapy was 93% (241/258) and demonstrated superiority to amoxicillin/clavulanate ± clarithromycin (85%, 239/280) [95% C.I. 2.9%, 13.2%]. The clinical success rate at the 21-28 days post-therapy visit for AVELOX was 84% (216/258), which also demonstrated superiority to the comparators (74%, 208/280) [95% C.I. 2.6%, 16.3%].

The clinical success rates by pathogen across four CAP studies are presented below:

Community Acquired Pneumonia caused by Multi-Drug Resistant Streptococcus pneumoniae (MDRSP) *

Avelox was effective in the treatment of community acquired pneumonia (CAP) caused by multi-drug resistant Streptococcus pneumoniae MDRSP * isolates. Of 37 microbiologically evaluable patients with MDRSP isolates, 35 patients (95.0%) achieved clinical and bacteriological success post-therapy. The clinical and bacteriological success rates based on the number of patients treated are shown in the table below.

Not all isolates were resistant to all antimicrobial classes tested. Success and eradication rates are summarized in the table below:

Acute Bacterial Sinusitis

In a large, controlled double-blind study conducted in the US, AVELOX Tablets (400 mg once daily for ten days) were compared with cefuroxime axetil (250 mg twice daily for ten days) for the treatment of acute bacterial sinusitis. The trial included 457 patients valid for the primary efficacy determination. Clinical success (cure plus improvement) at the 7 to 21 day post-therapy test of cure visit was 90% for AVELOX and 89% for cefuroxime.

An additional non-comparative study was conducted to gather bacteriological data and to evaluate microbiological eradication in adult patients treated with AVELOX 400 mg once daily for seven days. All patients (n = 336) underwent antral puncture in this study. Clinical success rates and eradication/presumed eradication rates at the 21 to 37 day follow-up visit were 97% (29 out of 30) for Streptococcus pneumoniae, 83% (15 out of 18) for Moraxella catarrhalis and 80% (24 out of 30) for Haemophilus influenzae .

Uncomplicated Skin and Skin Structure Infections

A randomized, double-blind, controlled clinical trial conducted in the US compared the efficacy of AVELOX 400 mg once daily for seven days with cephalexin HCl 500 mg three times daily for seven days. The percentage of patients treated for uncomplicated abscesses was 30%, furuncles 8%, cellulitis 16%, impetigo 20%, and other skin infections 26%. Adjunctive procedures (incision and drainage or debridement) were performed on 17% of the AVELOX treated patients and 14% of the comparator treated patients. Clinical success rates in evaluable patients were 89% (108/122) for AVELOX and 91% (110/121) for cephalexin HCl.

Complicated Skin and Skin Structure Infections

Two randomized, active controlled trials of cSSSI were performed. A double-blind trial was conducted primarily in North America to compare the efficacy of sequential IV/PO AVELOX 400 mg QD for 7-14 days to an IV/PO beta-lactam/beta-lactamase inhibitor control in the treatment of patients with cSSSI. This study enrolled 617 patients, 335 of which were valid for the primary efficacy analysis. A second open-label International study compared AVELOX 400 mg QD for 7-21 days to sequential IV/PO beta-lactam/beta-lactamase inhibitor control in the treatment of patients with cSSSI. This study enrolled 804 patients, 632 of which were valid for the primary efficacy analysis. Surgical incision and drainage or debridement was performed on 55% of the moxifloxacin treated and 53% of the comparator treated patients in these studies and formed an integral part of therapy for this indication. Success rates varied with the type of diagnosis ranging from 61% in patients with infected ulcers to 90% in patients with complicated erysipelas. These rates were similar to those seen with comparator drugs. The overall success rates in the evaluable patients and the clinical success by pathogen are shown below:

1. Clinical and Laboratory Standards Institute, Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically -Sixth Edition. Approved Standard CLSI, Document M7-A6, Vol. 23, No. 2, CLSI, Wayne, PA, January, 2003.
2. Clinical and Laboratory Standards Institute, Performance Standards for Antimicrobial Disk Susceptibility Tests -Eighth Edition. Approved Standard CLSI, Document M2-A8, Vol. 23, No. 1, CLSI, Wayne, PA, January, 2003.

Patient Information About:
AVELOX

(moxifloxacin hydrochloride)

400 mg Tablets

This section contains important information about AVELOX (moxifloxacin hydrochloride), and should be read completely before you begin treatment. This section does not take the place of discussions with your doctor or health care professional about your medical condition or your treatment. This section does not list all benefits and risks of AVELOX. The medicine described here can be prescribed only by a licensed health care professional. If you have any questions about AVELOX talk with your health care professional. Only your health care professional can determine if AVELOX is right for you.

What is AVELOX?

AVELOX is an antibiotic used to treat lung, sinus, or skin infections caused by certain germs called bacteria. AVELOX kills many of the types of bacteria that can infect the lungs and sinuses and has been shown in a large number of clinical trials to be safe and effective for the treatment of bacterial infections.

Sometimes viruses rather than bacteria may infect the lungs and sinuses (for example the common cold). AVELOX, like all other antibiotics, does not kill viruses.

You should contact your doctor if you think your condition is not improving while taking AVELOX.

AVELOX Tablets are red and contain 400 mg of active drug.

How and when should I take AVELOX?

AVELOX should be taken once a day for 5-21 days depending on your prescription. It should be swallowed and may be taken with or without food. Try to take the tablet at the same time each day.

You may begin to feel better quickly; however, in order to make sure that all bacteria are killed, you should complete the full course of medication. Do not take more than the prescribed dose of AVELOX even if you missed a dose by mistake. You should not take a double dose.

Who should not take AVELOX?

You should not take AVELOX if you have ever had a severe allergic reaction to any of the group of antibiotics known as "quinolones" such as ciprofloxacin or levofloxacin. If you develop hives, difficulty breathing, or other symptoms of a severe allergic reaction, seek emergency treatment right away. If you develop a skin rash, you should stop taking AVELOX and call your health care professional.

You should avoid AVELOX if you have a rare condition known as congenital prolongation of the QT interval. If you or any of your family members have this condition you should inform your health care professional. You should avoid AVELOX if you are being treated for heart rhythm disturbances with certain medicines such as quinidine, procainamide, amiodarone or sotalol. Inform your health care professional if you are taking a heart rhythm drug.

You should also avoid AVELOX if the amount of potassium in your blood is low. Low potassium can sometimes be caused by medicines called diuretics such as furosemide and hydrochlorothiazide. If you are taking a diuretic medicine you should speak with your health care professional.

If you are pregnant or planning to become pregnant while taking AVELOX, talk to your doctor before taking this medication. AVELOX is not recommended for use during pregnancy or nursing, as the effects on the unborn child or nursing infant are unknown.

AVELOX is not recommended for children.

What are the possible side effects of AVELOX?

AVELOX is generally well tolerated. The most common side effects caused by AVELOX, which are usually mild, include dizziness, nausea, and diarrhea. If diarrhea persists call your health care provider. You should be careful about driving or operating machinery until you are sure AVELOX is not causing dizziness. If you notice any side effects not mentioned in this section or you have any concerns about the side effects you are experiencing, please inform your health care professional.

In some people, AVELOX, as with some other antibiotics, may produce a small effect on the heart that is seen on an electrocardiogram test. Although this has not caused any serious problems in more than 8,600 patients who have already taken the medication in clinical studies, in theory it could result in extremely rare cases of abnormal heartbeat which may be dangerous. Contact your health care professional if you develop heart palpitations (fast beating), or have fainting spells.

Convulsions have been reported in patients receiving quinolone antibiotics. Be sure to let your physician know if you have a history of convulsions. Quinolones, including AVELOX, have been rarely associated with other central nervous system events including confusion, tremors, hallucinations, and depression.

Quinolones, including AVELOX, have been rarely associated with inflammation of tendons. If you experience pain, swelling or rupture of a tendon, you should stop taking AVELOX and call your health care professional.

What about other medicines I am taking?

Tell your doctor about all other prescription and non-prescription medicines or supplements you are taking. You should avoid taking AVELOX with certain medicines used to treat an abnormal heartbeat. These include quinidine, procainamide, amiodarone, and sotalol.

Some medicines also produce an effect on the electrocardiogram test, including cisapride, erythromycin, some antidepressants and some antipsychotic drugs. These may increase the risk of heart beat problems when taken with AVELOX.

Many antacids and multivitamins may interfere with the absorption of AVELOX and may prevent it from working properly. You should take AVELOX either 4 hours before or 8 hours after taking these products.

Remember

Take your dose of AVELOX once a day.

Complete the course of medication even if you are feeling better.

Keep this medication out of the reach of children.

This information does not take the place of discussions with your doctor or health care professional about your medical condition or your treatment.

For more complete information about AVELOX request full prescribing information from your health care professional, pharmacist, or visit our website at www.aveloxusa.com.

Manufactured by:

Bayer HealthCare

Bayer Pharmaceuticals Corporation

400 Morgan Lane

West Haven, CT 06516

Made in Germany

Distributed by:

Schering-Plough

Schering Corporation

Kenilworth, NJ 07033

AVELOX is a registered trademark of Bayer Aktiengesellschaft and is used under license by Schering Corporation.

Rx Only

08918409, R.2    7/05         12780

©2005 Bayer Pharmaceuticals Corporation

Printed in U.S.A.