Rifaximin

Class: Rifamycins
VA Class: AM900
Chemical Name: [2S - (2R*,16Z,18E,20R*,21R*,22S*,23S*,24S*,25R*,26S*,27R*,22E)] - 25 - acetyloxy) - 5,6,21,23 - tetrahydroxy - 27 - methoxy - 2,4,11,16,20,22,24,26 - octamethyl - 2,7 - (epoxypentadeca[1,11,13]trienimino)benzofuro[4,5 - e]pyrido[1,2 - a]benzimidazole - 1,15(2H) - dione
Molecular Formula: C₄₃H₅₁N₃O₁₁
CAS Number: 80621-81-4
Brands: Xifaxan

Introduction

Rifamycin antibiotic;^{11 12} structural analog of rifampin.^{1 11 12}

Uses for Rifaximin

Travelers’ Diarrhea

Treatment of travelers’ diarrhea caused by noninvasive strains of Escherichia coli in adults and adolescents ≥12 years of age.^{1 3 4 12 13 14 15 16}

May be ineffective in and should not be used for treatment of diarrhea complicated by fever or bloody stools.¹

May be ineffective in and should not be used for treatment of diarrhea known or suspected to be caused by pathogens other than E. coli (e.g., Campylobacter jejuni, Shigella, Salmonella).¹

Has been used for prevention of travelers’ diarrhea†, but safety and efficacy for such prophylaxis not established.²

Hepatic Encephalopathy

Has been used for adjunctive treatment of hepatic encephalopathy† to reduce blood ammonia concentrations and decrease severity of neurologic manifestations.^{6 7 8 9 10 11 17} Designated an orphan drug by the FDA for use in this condition.⁵

Rifaximin Dosage and Administration

Administration

Oral Administration

Administer orally without regard to meals.¹

Dosage

Pediatric Patients

Travelers’ Diarrhea Caused by Noninvasive Strains of E. coli

Treatment

Oral

Adolescents ≥12 years of age: 200 mg 3 times daily for 3 days.¹

Adults

Travelers’ Diarrhea Caused by Noninvasive Strains of E. coli

Treatment

Oral

200 mg 3 times daily for 3 days.¹

Hepatic Encephalopathy†

Treatment

Oral

600–1200 mg daily (usually in 3 divided doses) for 7–21 days has been used.^{2 6 7 8 9 10 17}

Special Populations

Hepatic Impairment

No specific dosage adjustments recommended.¹

Renal Impairment

Not specifically studied in renal impairment, but clinically important differences in elimination not expected.^{1 2 11 12}

Geriatric Patients

Not specifically studied in patients ≥65 years of age.¹

Cautions for Rifaximin

Contraindications

• 
  

  Known hypersensitivity to rifaximin, other rifamycin anti-infectives, or any ingredient in the formulation.¹

  
  

Warnings/Precautions

Warnings

Treatment of Travelers’ Diarrhea

Do not use for treatment of diarrhea complicated by fever or bloody stools.¹

Do not use for treatment of travelers’ diarrhea known or suspected to be caused by C. jejuni, Shigella, or Salmonella.¹

If diarrhea worsens or persists >24–48 hours after initiating rifaximin, discontinue and consider use of another anti-infective.¹

Superinfection/Clostridium difficile-associated Colitis

Overgrowth of nonsusceptible organisms may occur.¹ If superinfection occurs, appropriate therapy should be instituted.¹

Treatment with anti-infectives may permit overgrowth of clostridia.¹ Consider Clostridium difficile-associated diarrhea and colitis (antibiotic-associated pseudomembranous colitis) if diarrhea develops and manage accordingly.¹

Some mild cases of C. difficile-associated diarrhea and colitis may respond to discontinuance alone.¹ Manage moderate to severe cases with fluid, electrolyte, and protein supplementation; appropriate anti-infective therapy (e.g., oral metronidazole or vancomycin) recommended if colitis is severe.¹

Systemic Infections

Do not use for treatment of systemic bacterial infections since <0.4% of an oral dose is absorbed systemically.^{1 11 12}

Specific Populations

Pregnancy

Category C.¹

Lactation

Not known whether distributed into milk; discontinue nursing or the drug.¹

Pediatric Use

Safety and efficacy not established in children <12 years of age.^{1 2}

Geriatric Use

Experience in those ≥65 years of age insufficient to determine whether they respond differently than younger adults.¹

Renal Impairment

Not specifically studied in renal impairment, but clinically important changes in elimination not expected since the drug is poorly absorbed from GI tract and almost entirely excreted in feces.^{1 2 11 12}

Common Adverse Effects

GI effects (flatulence, abdominal pain, rectal tenesmus, defecation urgency, nausea, constipation, vomiting), headache, fever.¹

Interactions for Rifaximin

Does not inhibit or induce CYP1A2, 2A6, 2B6, 2C9, 2C19, 2D6, and 2E1.¹ Has induced CYP3A4 in vitro, but clinically important effects on intestinal or hepatic CYP3A4 unlikely; does not inhibit CYP3A4.^{1 2}

Drugs Metabolized by Hepatic Microsomal Enzymes

Pharmacokinetic interactions with drugs metabolized by CYP1A2, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1, and 3A4 unlikely.¹

Specific Drugs

Drug	Interaction	Comments
Hormonal contraceptives (ethinyl estradiol and norgestimate)	No substantial changes in pharmacokinetics of ethinyl estradiol and norgestimate1	Dosage adjustment not necessary2
Midazolam	No substantial changes in pharmacokinetics of midolazam or its major metabolite (1′-hydroxymidazolam) 1 2	Dosage adjustment not necessary2

Rifaximin Pharmacokinetics

Absorption

Bioavailability

Poorly absorbed from GI tract;^{1 11 12} <0.4% of an oral dose absorbed systemically.^{1 11 12}

No evidence of accumulation following multiple doses.¹

Food

Oral absorption not appreciably affected by food; systemic absorption remains low in the fasting state and when given within 30 minutes of a high-fat breakfast.¹

Distribution

Extent

Animal studies indicate 80–90% of oral dose concentrated in the gut, <0.2% distributed into liver and kidney, and <0.01% into other tissues.¹

Minimal or no hepatic distribution in patients receiving oral rifaximin (400 mg 4 times daily) for 2 days prior to cholescystectomy.¹¹

Elimination

Metabolism

Does not appear to be metabolized.¹

Elimination Route

Approximately 97% of an oral dose excreted in feces as unchanged drug;^{1 11 12} <0.4% eliminated in urine.^{1 11 12}

Half-life

Approximately 6 hours.¹

Special Populations

Pharmacokinetics not studied in pediatric patients or adults ≥65 years of age.¹

Pharmacokinetics not studied in renal impairment.¹

Stability

Storage

Oral

Tablets

20–25°C (may be exposed to 15–30°C).¹

Actions and SpectrumActions

• 
  

  Like other rifamycins, rifaximin inhibits RNA synthesis in susceptible bacteria by binding to the β subunit of bacterial DNA-dependent RNA polymerase.^{1 11}

  
  


• 
  

  Escherichia coli: Active in vitro and in clinical infections (i.e., infectious diarrhea) against enterotoxigenic and enteroaggregative strains of E. coli.^{1 11} Also active in vitro against other E. coli strains, including enterohemorrhagic, enteroinvasive, enteropathogenic, and Hep-2 adherent strains.^{2 11}

  
  


• 
  

  Other bacteria: Has in vitro activity against Acinetobacter, Aeromonas, Bacillus, Bacteroides, Bifidobacterium, Campylobacter jejuni, Clostridium difficile, Enterobacter cloacae, Fusobacterium, Helicobacter, Klebsiella pneumoniae, Plesiomonas shigelloides, Peptostreptococcus, Prevotella, Proteus, Pseudomonas aeruginosa, Salmonella (groups C1 and C2), Shigella (including S. dysenteriae, S. flexneri, S. sonnei), Serratia, Staphylococcus, Streptococcus, Vibrio, and Yersinia enterocolitica.^{2 11} Also active in vitro against Cryptosporidium and Giardia.²

  
  


• 
  

  Although clinical importance unclear, resistance to rifaximin has developed in E. coli in vitro.¹ Further study needed to determine the resistance profile of rifaximin.²

  
  


• 
  

  Organisms with high rifaximin MICs also have elevated rifampin MICs;¹ however, since rifaximin is not appreciably absorbed following oral administration and is present in high concentrations in the bowel lumen, a comparison of rifaximin MICs and MICs for well-absorbed drugs (e.g., rifampin) should be interpreted with caution.^{11 12 14 15}

  
  


• 
  

  Cross-resistance between rifaximin and other classes of anti-infectives not evaluated.¹

  
  

Advice to Patients

• 
  

  Advise patients and/or their caregivers that rifaximin may be taken with or without food.¹

  
  


• 
  

  Importance of taking rifaximin exactly as prescribed and continuing therapy for entire treatment course.¹

  
  


• 
  

  Importance of discontinuing rifaximin and seeking medical care if diarrhea persists for >24–48 hours or worsens or if fever and/or bloody diarrhea develop.¹

  
  


• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, and any concomitant illnesses.¹

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹

  
  


• 
  

  Importance of informing patients of other important precautionary information.¹ (See Cautions.)

  
  

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Rifaximin

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets	200 mg	Xifaxan	Salix

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 03/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Xifaxan 200MG Tablets (SALIX PHARMACEUTICALS INC.): 30/$353.98 or 90/$1019.9

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions July 2005. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Salix Pharmaceuticals, Inc. Xifaxan tablets prescribing information. Raleigh, NC; 2004 Jun.

2. Salix Pharmaceuticals, Inc., Raleigh, NC: Personal communication.

3. Steffen R, Sack DA, Riopel L, et al. Therapy of traveler’s diarrhea with rifaximin on various continents. Am J Gastroenterol. 2003; 98:1073-8. [IDIS 502876] [PubMed 12809830]

4. Infante RM, Ericsson CD, Jiang Z, et al. Enteroaggregative Escherichia coli diarrhea in travelers: response to rifaximin therapy. Clin Gastroenterol Hepatol. 2003; 2:136-8.

5. Food and Drug Administration. Orphan designation pursuant to Section 526 of the Federal Food and Cosmetic Act as amended by the Orphan Drug Act. (P.L. 97-414). Rockville, MD; From FDA website (http: / / www.fda.gov / ForIndustry / DevelopingProductsforRareDiseasesConditions / HowtoapplyforOrphanProductDesignation / default.htm). Accessed 2004 Aug 19.

6. Riordan SM, Williams R. Treatment of hepatic encephalopathy. N Engl J Med. 1997;337:473-9.

7. Williams R, James OF, Warnes TW et al. Evaluation of the efficacy and safety of rifaximin in the treatment of hepatic encephalopathy: a double-blind, randomized, dose-finding multi-centre study. Eur J Gastroenterol Hepatol. 2000;12:203-8.

8. Puxeddu A, Quartini M, Massimetti A et al. Rifaximin in the treatment of chronic hepatic encephalopathy. Curr Med Res Opin. 1995;13:274-81.

9. Pedretti G, Calzetti C, Missale G et al. Rifaximin versus neomycin on hyperammoniemia in chronic portal systemic encephalopathy of cirrhotics. A double-blind, randomized trial. Ital J Gastroenterol. 1991;23:175-8.

10. Bucci L, Palmieri GC. Double-blind, double-dummy comparison between treatment with rifaximin and lactulose in patients with medium to severe degree hepatic encephalopathy. Curr Med Res Opin. 1993;13:109-18.

11. Gillis JC, Brogden RN.. Rifaximin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic potential in conditions mediated by gastrointestinal bacteria. Drugs 1995;49:467-84.

12. Steffen R. Rifaximin: a nonabsorbed antimicrobial as a new tool for treatment of travelers’ diarrhea. J Travel Med. 2001;8:34-9.

13. DuPont HL, Ericsson CD, Mathewson JJ, et al. Rifaximin: a nonabsorbed antimicrobial in the therapy of travelers’ diarrhea. Digestion. 1998;59:708-14.

14. DuPont HL. Treatment of travelers’ diarrhea. J Travel Med. 2001;8:31-3.

15. Lawler JV, Wallace MR. Diagnosis and treatment of bacterial diarrhea. Curr Gastroenterol Rep. 2003;5:287-94.

16. Ericsson CD. Travelers’ diarrhoea. Int J Antimicrob Agents. 2003;21:116-24.

17. Miglio F, Valpiani D, Rossellini SR, et al. Rifaximin, a non-absorbable rifamycin, for the treatment of hepatic encephalopathy. A double-blind, randomised trial. Curr Med Res Opin. 1997;13:593-601.

18. Anon. Advice for travelers. Treat Guidelines Med Lett. 2004; 2:33-49.

19. Centers for Disease Control and Prevention. Health information for international travel, 2003–2004. Atlanta, GA: Department of Health and Human Services; 2003:184-91. From CDC website ()

More Rifaximin resources

• Rifaximin Side Effects (in more detail)
• Rifaximin Dosage
• Rifaximin Use in Pregnancy & Breastfeeding
• Rifaximin Support Group
• 14 Reviews for Rifaximin - Add your own review/rating

• Rifaximin MedFacts Consumer Leaflet (Wolters Kluwer)


• Rifaximin Professional Patient Advice (Wolters Kluwer)


• rifaximin Advanced Consumer (Micromedex) - Includes Dosage Information


• Xifaxan Prescribing Information (FDA)


• Xifaxan Consumer Overview

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Gen-Pantoprazole

Gen-Pantoprazole may be available in the countries listed below.

Ingredient matches for Gen-Pantoprazole

Pantoprazole

Pantoprazole sodium (a derivative of Pantoprazole) is reported as an ingredient of Gen-Pantoprazole in the following countries:

• Canada

International Drug Name Search

Céliprolol Zydus

Céliprolol Zydus may be available in the countries listed below.

Ingredient matches for Céliprolol Zydus

Celiprolol

Celiprolol hydrochloride (a derivative of Celiprolol) is reported as an ingredient of Céliprolol Zydus in the following countries:

• France

International Drug Name Search

Randil

Randil may be available in the countries listed below.

Ingredient matches for Randil

Ranitidine

Ranitidine is reported as an ingredient of Randil in the following countries:

• Dominican Republic

Ranitidine hydrochloride (a derivative of Ranitidine) is reported as an ingredient of Randil in the following countries:

• Dominican Republic

International Drug Name Search

Vitamina C Drawer

Vitamina C Drawer may be available in the countries listed below.

Ingredient matches for Vitamina C Drawer

Ascorbic Acid

Ascorbic Acid is reported as an ingredient of Vitamina C Drawer in the following countries:

• Argentina

International Drug Name Search

Benzocaine/Glycerin Spray

Pronunciation: BEN-zoe-kane/GLIS-er-in
Generic Name: Benzocaine/Glycerin
Brand Name: Cepacol Dual Relief

Benzocaine/Glycerin Spray is used for:

Temporarily relieving minor mouth or gum irritation, pain caused by canker sores, or minor sore throat.

Benzocaine/Glycerin Spray is a topical anesthetic and demulcent combination. It works by numbing and soothing the affected area.

Do NOT use Benzocaine/Glycerin Spray if:

• you are allergic to any ingredient in Benzocaine/Glycerin Spray or to other similar local anesthetics (eg, lidocaine, procaine)

Contact your doctor or health care provider right away if any of these apply to you.

Before using Benzocaine/Glycerin Spray:

Some medical conditions may interact with Benzocaine/Glycerin Spray. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

• if you are pregnant, planning to become pregnant, or are breast-feeding


• if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement


• if you have allergies to medicines, foods, or other substances

Some MEDICINES MAY INTERACT with Benzocaine/Glycerin Spray. Because little, if any, of Benzocaine/Glycerin Spray is absorbed into the blood, the risk of it interacting with another medicine is low.

Ask your health care provider if Benzocaine/Glycerin Spray may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Benzocaine/Glycerin Spray:

Use Benzocaine/Glycerin Spray as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Children younger than 12 years old should be supervised by an adult while using Benzocaine/Glycerin Spray.


• Shake well before each use.


• Spray 1 spray onto the affected area as directed by your doctor or on the package labeling. Do not use more than 1 spray per use.


• Do not use Benzocaine/Glycerin Spray more often than 4 times daily unless your doctor tells you otherwise.


• If you miss a dose of Benzocaine/Glycerin Spray and you are using it regularly, use it as soon as you remember. Continue to use it as directed by your doctor or on the package label. Do not use 2 doses at once.

Ask your health care provider any questions you may have about how to use Benzocaine/Glycerin Spray.

Important safety information:

• Do not get Benzocaine/Glycerin Spray in your eyes. If you get it in your eyes, rinse right away with cool water.


• Do NOT use more than the recommended dose without checking with your doctor.


• Do not use Benzocaine/Glycerin Spray for more than 2 days for sore throat or 7 days for sore mouth without checking with your doctor.


• Sore throat that is severe, persistent, or occurs with high fever, headache, rash, nausea, or vomiting may be serious. Check with your doctor right away if these symptoms occur.


• Benzocaine/Glycerin Spray is flammable. Do not store or use near an open flame or while smoking.


• Benzocaine/Glycerin Spray may cause harm if more than the amount used to treat pain is swallowed. If this occurs, contact your poison control center or emergency room right away.


• Do not use Benzocaine/Glycerin Spray in CHILDREN younger than 3 years old without first checking with the child's doctor or dentist; safety and effectiveness in these children have not been confirmed.


• Benzocaine/Glycerin Spray should not be used in CHILDREN younger than 6 months old; safety and effectiveness in these children have not been confirmed.


• PREGNANCY and BREAST-FEEDING: If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Benzocaine/Glycerin Spray while you are pregnant. It is not known if Benzocaine/Glycerin Spray is found in breast milk. If you are or will be breast-feeding while you use Benzocaine/Glycerin Spray, check with your doctor. Discuss any possible risks to your baby.

Possible side effects of Benzocaine/Glycerin Spray:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Numbness of the mouth or throat.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue).

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Benzocaine/Glycerin Spray may be harmful if swallowed.

Proper storage of Benzocaine/Glycerin Spray:

Store Benzocaine/Glycerin Spray between 68 and 77 degrees F (20 and 25 degrees C). Do not freeze. Store away from heat and light. Keep Benzocaine/Glycerin Spray out of the reach of children and away from pets.

General information:

• If you have any questions about Benzocaine/Glycerin Spray, please talk with your doctor, pharmacist, or other health care provider.


• Benzocaine/Glycerin Spray is to be used only by the patient for whom it is prescribed. Do not share it with other people.


• If your symptoms do not improve or if they become worse, check with your doctor.


• Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about Benzocaine/Glycerin Spray. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

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Baytril

Dosage Form: FOR ANIMAL USE ONLY
Baytril® (enrofloxacin)

Antibacterial Tablets for Dogs and Cats

CAUTION:

Federal (U.S.A.) law restricts this drug to use by or on the order of a licensed veterinarian.

Federal law prohibits the extralabel use of this drug in food-producing animals.

Baytril Description

Enrofloxacin is a synthetic chemotherapeutic agent from the class of the quinolone carboxylic acid derivatives. It has antibacterial activity against a broad spectrum of Gram negative and Gram positive bacteria (See Tables I and II). It is rapidly absorbed from the digestive tract, penetrating into all measured body tissues and fluids (See Table III).

Tablets are available in two sizes (22.7 and 68.0 mg enrofloxacin).

CHEMICAL NOMENCLATURE AND STRUCTURAL FORMULA:

1-cyclopropyl-7-(4-ethyl-1-piperazinyl)-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid.

ACTIONS:

Microbiology:

Quinolone carboxylic acid derivatives are classified as DNA gyrase inhibitors. The mechanism of action of these compounds is very complex and not yet fully understood. The site of action is bacterial gyrase, a synthesis promoting enzyme. The effect on Escherichia coli is the inhibition of DNA synthesis through prevention of DNA supercoiling. Among other things, such compounds lead to the cessation of cell respiration and division. They may also interrupt bacterial membrane integrity.1

Enrofloxacin is bactericidal, with activity against both Gram negative and Gram positive bacteria. The minimum inhibitory concentrations (MICs) were determined for a series of 39 isolates representing 9 genera of bacteria from natural infections in dogs and cats, selected principally because of resistance to one or more of the following antibiotics: ampicillin, cephalothin, colistin, chloramphenicol, erythromycin, gentamicin, kanamycin, penicillin, streptomycin, tetracycline, triple sulfa and sulfa/trimethoprim. The MIC values for enrofloxacin against these isolates are presented in Table I. Most strains of these organisms were found to be susceptible to enrofloxacin in vitro but the clinical significance has not been determined for some of the isolates.

The susceptibility of organisms to enrofloxacin should be determined using enrofloxacin 5 mcg disks. Specimens for susceptibility testing should be collected prior to the initiation of enrofloxacin therapy.

TABLE I — MIC Values for Enrofloxacin Against Canine and Feline Pathogens(Diagnostic laboratory isolates, 1984)

Organisms	Isolates	MIC Range (mcg/mL)
Bacteroides spp.	2	2
Bordetella bronchiseptica	3	0.125-0.5
Brucella canis	2	0.125-0.25
Clostridium perfringens	1	0.5
Escherichia coli	5*	≤0.016-0.031
Klebsiella spp.	11*	0.031-0.5
Proteus mirabilis	6	0.062-0.125
Pseudomonas aeruginosa	4	0.5-8
Staphylococcus spp.	5	0.125

The inhibitory activity on 120 isolates of seven canine urinary pathogens was also investigated and is listed in Table II.

TABLE II — MIC Values for Enrofloxacin Against Canine Urinary Pathogens (Diagnostic laboratory isolates, 1985)

Organisms	Isolates	MIC Range (mcg/mL)
E. coli	30	0.06-2.0
P. mirabilis	20	0.125-2.0
K. pneumoniae	20	0.06-0.5
P. aeruginosa	10	1.0-8.0
Enterobacter spp.	10	0.06-1.0
Staph. (coag. +)	20	0.125-0.5
Strep. (alpha hemol.)	10	0.5-8.0

Distribution in the Body: Enrofloxacin penetrates into all canine and feline tissues and body fluids. Concentrations of drug equal to or greater than the MIC for many pathogens (See Tables I, II and III) are reached in most tissues by two hours after dosing at 2.5 mg/kg and are maintained for 8-12 hours after dosing. Particularly high levels of enrofloxacin are found in urine. A summary of the body fluid/tissue drug levels at 2 to 12 hours after dosing at 2.5 mg/kg is given in Table III.

Table III — Body Fluid/Tissue distribution of Enrofloxacin in Dogs and Cats

	Single Oral Dose = 2.5 mg/kg (1.13 mg/lb)
	Post-treatment Enrofloxacin Levels
	Canine (n = 2)		Feline (n = 4)
Body Fluids (mcg/mL)	2 Hr.	8 Hr.	2 Hr.	12 Hr.
Bile	–	–	2.13	1.97
Cerebrospinal Fluid	–	–	0.37	0.10
Urine	43.05	55.35	12.81	26.41
Eye Fluids	0.53	0.66	0.45	0.65
Whole Blood	1.01	0.36	–	–
Plasma	0.67	0.33	–	–
Serum	–	–	0.48	0.18
Tissues (mcg/g) Hematopoietic System
Liver	3.02	1.36	1.84	0.37
Spleen	1.45	0.85	1.33	0.52
Bone Marrow	2.10	1.22	1.68	0.64
Lymph Node	1.32	0.91	0.49	0.21
Urogenital System
Kidney	1.87	0.99	1.43	0.37
Bladder Wall	1.36	0.98	1.16	0.55
Testes	1.36	1.10	1.01	0.28
Prostate	1.36	2.20	1.88	0.55
Ovaries	–	–	0.78	0.56
Uterine Wall	1.59	0.29	0.81	1.05
Gastrointestinal and Cardiopulmonary Systems
Lung	1.34	0.82	0.91	0.33
Heart	1.88	0.78	0.84	0.32
Stomach	3.24	2.16	3.26	0.27
Small Intestine	2.10	1.11	2.72	0.40
Large Intestine	–	–	0.94	1.10
Other
Fat	0.52	0.40	0.24	0.11
Skin	0.66	0.48	0.46	0.17
Muscle	1.62	0.77	0.53	0.29
Brain	0.25	0.24	0.22	0.12
Mammary Gland	0.45	0.21	0.36	0.30
Feces	1.65	9.97	0.37	4.18

Pharmacokinetics:

In dogs, the absorption and elimination characteristics of the oral formulation are linear (plasma concentrations increase proportionally with dose) when enrofloxacin is administered at up to 11.5 mg/kg, twice daily.2 Approximately 80% of the orally administered dose enters the systemic circulation unchanged. The eliminating organs, based on the drug’s body clearance time, can readily remove the drug with no indication that the eliminating mechanisms are saturated. The primary route of excretion is via the urine. The absorption and elimination characteristics beyond this point are unknown. In cats, no oral absorption information is available at other than 2.5 mg/kg, administered orally as a single dose. Saturable absorption and/or elimination processes may occur at greater doses. When saturation of the absorption process occurs, the plasma concentration of the active moiety will be less than predicted, based on the concept of dose proportionality.

Following an oral dose in dogs of 2.5 mg/kg (1.13 mg/lb), enrofloxacin reached 50% of its maximum serum concentration in 15 minutes and peak serum level was reached in one hour. The elimination half-life in dogs is approximately 21/2 - 3 hours at that dose, while in cats it is greater than 4 hours. In a study comparing dogs and cats, the peak concentration and the time to peak concentration were not different.

A graph indicating the mean serum levels following a dose of 2.5 mg/kg (1.13 mg/lb) in dogs (oral and intramuscular) and cats (oral) is shown in Figure 1.

Figure 1 - Serum Concentrations of Enrofloxacin Following a Single Oral or Intramuscular Dose at 2.5 mg/kg in Dogs and a Single Oral Dose at 2.5 mg/kg in Cats.

Breakpoint: Based on pharmacokinetic studies of enrofloxacin in dogs and cats after a single oral administration of 2.5 mg enrofloxacin/kg BW (i.e. half of the lowest-end single daily dose range for dogs and half the single daily dose for cats) and the data listed in Tables I and II, the following breakpoints are recommended for canine and feline isolates.

Zone Diameter (mm)	MIC (μg/mL)	Interpretation
≥ 21	≤ 0.5	Susceptible (S)
18 - 20	1	Intermediate (I)
≤ 17	≥ 2	Resistant (R)

A report of “Susceptible” indicates that the pathogen is likely to be inhibited by generally achievable plasma levels. A report of “Intermediate” is a technical buffer and isolates falling into this category should be retested. Alternatively the organism may be successfully treated if the infection is in a body site where drug is physiologically concentrated. A report of “Resistant” indicates that the achievable drug concentrations are unlikely to be inhibitory and other therapy should be selected.

Standardized procedures require the use of laboratory control organisms for both standardized disk diffusion assays and standardized dilution assays. The 5 μg enrofloxacin disk should give the following zone diameters and enrofloxacin powder should provide the following MIC values for reference strains.

QC strain		MIC (μg/mL)	Zone Diameter (mm)
E. coli	ATCC 25922	0.008 - 0.03	32 - 40
P. aeruginosa	ATCC 27853	1 - 4	15 - 19
S. aureus	ATCC 25923		27 - 31
S. aureus	ATCC 29213	0.03 - 0.12

INDICATIONS:

Baytril® (brand of enrofloxacin) Antibacterial Tablets are indicated for the management of diseases associated with bacteria susceptible to enrofloxacin. Baytril Antibacterial Tablets are indicated for use in dogs and cats.

EFFICACY CONFIRMATION:

Dogs: Clinical efficacy was established in dermal infections (wounds and abscesses) associated with susceptible strains of Escherichia coli, Klebsiella pneumoniae, Proteusmirabilis, and Staphylococcus intermedius; respiratory infections (pneumonia, tonsillitis, rhinitis) associated with susceptible strains of Escherichia coli and Staphylococcus aureus; and urinary cystitis associated with susceptible strains of Escherichia coli, Proteus mirabilis, and Staphylococcus aureus.

Cats: Clinical efficacy was established in dermal infections (wounds and abscesses) associated with susceptible strains of Pasteurella multocida, Staphylococcus aureus, and Staphylococcus epidermidis.

CONTRAINDICATIONS:

Enrofloxacin is contraindicated in dogs and cats known to be hypersensitive to quinolones.

Dogs: Based on the studies discussed under the section on Animal Safety Summary, the use of enrofloxacin is contraindicated in small and medium breeds of dogs during the rapid growth phase (between 2 and 8 months of age). The safe use of enrofloxacin has not been established in large and giant breeds during the rapid growth phase. Large breeds may be in this phase for up to one year of age and the giant breeds for up to 18 months. In clinical field trials utilizing a daily oral dose of 5.0 mg/kg, there were no reports of lameness or joint problems in any breed. However, controlled studies with histological examination of the articular cartilage have not been conducted in the large or giant breeds.

ADVERSE REACTIONS:

Dogs: Two of the 270 (0.7%) dogs treated with Baytril® (brand of enrofloxacin) Tablets at 5.0 mg/kg per day in the clinical field studies exhibited side effects, which were apparently drug-related. These two cases of vomition were self-limiting.

Post-Approval Experience: The following adverse experiences, although rare, are based on voluntary post-approval adverse drug experience reporting. The categories of reactions are listed in decreasing order of frequency by body system.

Gastrointestinal: anorexia, diarrhea, vomiting, elevated liver enzymes

Neurologic: ataxia, seizures

Behavioral: depression, lethargy, nervousness

Cats: No drug-related side effects were reported in 124 cats treated with Baytril® (brand of enrofloxacin) Tablets at 5.0 mg/kg per day for 10 days in clinical field studies.

Post-Approval Experience: The following adverse experiences, although rare, are based on voluntary post-approval adverse drug experience reporting. The categories of reactions are listed in decreasing order of frequency by body system.

Ocular: Mydriasis, retinal degeneration (retinal atrophy, attenuated retinal vessels, and hyperreflective tapeta have been reported), loss of vision. Mydriasis may be an indication of impending or existing retinal changes.

Gastrointestinal: vomiting, anorexia, elevated liver enzymes, diarrhea

Neurologic: ataxia, seizures

Behavioral: depression, lethargy, vocalization, aggression

For medical emergencies or to report adverse reactions, call 1-800-422-9874.

ANIMAL SAFETY SUMMARY:

Dogs: Adult dogs receiving enrofloxacin orally at a daily dosage rate of 52 mg/kg for 13 weeks had only isolated incidences of vomition and inappetence. Adult dogs receiving the tablet formulation for 30 consecutive days at a daily treatment of 25 mg/kg did not exhibit significant clinical signs nor were there effects upon the clinical chemistry, hematological or histological parameters. Daily doses of 125 mg/kg for up to 11 days induced vomition, inappetence, depression, difficult locomotion and death while adult dogs receiving 50 mg/kg/day for 14 days had clinical signs of vomition and inappetence.

Adult dogs dosed intramuscularly for three treatments at 12.5 mg/kg followed by 57 oral treatments at 12.5 mg/kg, all at 12 hour intervals, did not exhibit either significant clinical signs or effects upon the clinical chemistry, hematological or histological parameters.

Oral treatment of 15 to 28 week old growing puppies with daily dosage rates of 25 mg/kg has induced abnormal carriage of the carpal joint and weakness in the hindquarters.

Significant improvement of clinical signs is observed following drug withdrawal. Microscopic studies have identified lesions of the articular cartilage following 30 day treatments at either 5, 15 or 25 mg/kg in this age group. Clinical signs of difficult ambulation or associated cartilage lesions have not been observed in 29 to 34 week old puppies following daily treatments of 25 mg/kg for 30 consecutive days nor in 2 week old puppies with the same treatment schedule.

Tests indicated no effect on circulating microfilariae or adult heartworms (Dirofilaria immitis) when dogs were treated at a daily dosage rate of 15 mg/kg for 30 days. No effect on cholinesterase values was observed.

No adverse effects were observed on reproductive parameters when male dogs received 10 consecutive daily treatments of 15 mg/kg/day at 3 intervals (90, 45 and 14 days) prior to breeding or when female dogs received 10 consecutive daily treatments of 15 mg/kg/day at 4 intervals: between 30 and 0 days prior to breeding, early pregnancy (between 10th & 30th days), late pregnancy (between 40th & 60th days), and during lactation (the first 28 days).

Cats: Cats in age ranges of 3 to 4 months and 7 to 10 months received daily treatments of 25 mg/kg for 30 consecutive days with no adverse effects upon the clinical chemistry, hematological or histological parameters. In cats 7-10 months of age treated daily for 30 consecutive days, 2 of 4 receiving 5 mg/kg, 3 of 4 receiving 15 mg/kg, 2 of 4 receiving 25 mg/kg and 1 of 4 nontreated controls experienced occasional vomition. Five to 7 month old cats had no side effects with daily treatments of 15 mg/kg for 30 days, but 2 of 4 animals had articular cartilage lesions when administered 25 mg/kg per day for 30 days.

Doses of 125 mg/kg for 5 consecutive days to adult cats induced vomition, depression, incoordination and death while those receiving 50 mg/kg for 6 days had clinical signs of vomition, inappetence, incoordination and convulsions, but they returned to normal.

Enrofloxacin was administered to thirty-two (8 per group), six- to eight-month-old cats at doses of 0, 5, 20, and 50 mg/kg of body weight once a day for 21 consecutive days. There were no adverse effects observed in cats that received 5 mg/kg body weight of enrofloxacin.

The administration of enrofloxacin at 20 mg/kg body weight or greater caused salivation, vomition, and depression. Additionally, dosing at 20 mg/kg body weight or greater resulted in mild to severe fundic lesions on ophthalmologic examination (change in color of the fundus, central or generalized retinal degeneration), abnormal electroretinograms (including blindness), and diffuse light microscopic changes in the retina.

DRUG INTERACTIONS:

Compounds that contain metal cations (e.g., aluminum, calcium, iron, magnesium) may reduce the absorption of some quinolone-class drugs from the intestinal tract. Concomitant therapy with other drugs that are metabolized in the liver may reduce the clearance rates of the quinolone and the other drug.

Dogs: Enrofloxacin has been administered to dogs at a daily dosage rate of 10 mg/kg concurrently with a wide variety of other health products including anthelmintics (praziquantel, febantel, sodium disophenol), insecticides (fenthion, pyrethrins), heartworm preventatives (diethylcarbamazine) and other antibiotics (ampicillin, gentamicin sulfate, penicillin, dihydrostreptomycin). No incompatibilities with other drugs are known at this time.

Cats: Enrofloxacin was administered at a daily dosage rate of 5 mg/kg concurrently with anthelmintics (praziquantel, febantel), an insecticide (propoxur) and another antibacterial (ampicillin). No incompatibilities with other drugs are known at this time.

WARNINGS:

For use in animals only. In rare instances, use of this product in cats has been associated with Retinal Toxicity. Do not exceed 5 mg/kg of body weight per day in cats. Safety in breeding or pregnant cats has not been established. Keep out of reach of children.

Avoid contact with eyes. In case of contact, immediately flush eyes with copious amounts of water for 15 minutes. In case of dermal contact, wash skin with soap and water.

Consult a physician if irritation persists following ocular or dermal exposure. Individuals with a history of hypersensitivity to quinolones should avoid this product. In humans, there is a risk of user photosensitization within a few hours after excessive exposure to quinolones. If excessive accidental exposure occurs, avoid direct sunlight.

For customer service or to obtain product information, including Material Safety Data Sheet, call 1-800-633-3796.

PRECAUTIONS:

Quinolone-class drugs should be used with caution in animals with known or suspected Central Nervous System (CNS) disorders. In such animals, quinolones have, in rare instances, been associated with CNS stimulation which may lead to convulsive seizures.

Quinolone-class drugs have been associated with cartilage erosions in weight-bearing joints and other forms of arthropathy in immature animals of various species.

The use of fluoroquinolones in cats has been reported to adversely affect the retina. Such products should be used with caution in cats.

DOSAGE AND ADMINISTRATION:

Dogs: Administer orally at a rate to provide 5-20 mg/kg (2.27 to 9.07 mg/lb) of body weight. Selection of a dose within the range should be based on clinical experience, the severity of disease, and susceptibility of the pathogen. Animals which receive doses in the upper-end of the dose range should be carefully monitored for clinical signs that may include inappetance, depression, and vomition.

All tablet sizes are double scored for accurate dosing.
Weight of Dog	Once Daily Dosing Chart
	5.0 mg/kg	10.0 mg/kg	15.0 mg/kg	20.0 mg/kg
9.1 kg (20 lb)	2 x 22.7 mg tablets	1 x 22.7 mg plus 1 x 68 mg tablets	1 x 136 mg tablet	1 x 136 mg plus 2 x 22.7 mg tablets
27.2 kg (60 lb)	1 x 136 mg tablet	2 x 136 mg tablets	3 x 136 mg tablets	4 x 136 mg tablets

Cats: Administer orally at 5 mg/kg (2.27 mg/lb) of body weight. The dose for dogs and cats may be administered either as a single daily dose or divided into two (2) equal daily doses administered at twelve (12) hour intervals. The dose should be continued for at least 2-3 days beyond cessation of clinical signs, to a maximum of 30 days.

All tablet sizes are double scored for accurate dosing.
Weight of Cat	Once Daily Dosing Chart (5 mg/kg/day)
5 lb (2.27 kg)	1/2 x 22.7 mg tablet
10 lb (4.5 kg)	1 x 22.7 mg tablet
15 lb (6.8 kg)	1 and 1/2 x 22.7 mg tablets or 1/2 x 68 mg tablet

Palatability: Most dogs will consume Baytril® Taste Tabs® Tablets willingly when offered by hand. Alternatively the tablet(s) may be offered in food or hand-administered (pilled) as with other oral tablet medications. In cats, Baytril® Taste Tabs® Tablets should be pilled. After administration, watch the animal closely to be certain the entire dose has been consumed.

Dogs & Cats: The duration of treatment should be selected based on clinical evidence.

Generally, administration of Baytril Tablets should continue for at least 2-3 days beyond cessation of clinical signs. For severe and/or complicated infections, more prolonged therapy, up to 30 days, may be required. If no improvement is seen within five days, the diagnosis should be reevaluated and a different course of therapy considered.

The lower limit of the dose range in dogs and the daily dose for cats was based on efficacy studies in dogs and cats where enrofloxacin was administered at 2.5 mg/kg twice daily. Target animal safety and toxicology were used to establish the upper limit of the dose range for dogs and treatment duration for dogs and cats.

STORAGE:

Dispense tablets in tight containers only.

HOW SUPPLIED:

Taste Tabs® Code No.	Film Coated Code No.	Baytril Tablets Tablet Size	Tablets/Bottle
08711367	08713262	22.7 mg	100 Double Scored
08711375	08713289	22.7 mg	500 Double Scored
08711383	08713270	68.0 mg	50 Double Scored
08711391	08713297	68.0 mg	250 Double Scored
08711510	–	136.0 mg	50 Double Scored
08711405	–	136.0 mg	200 Double Scored

U.S. Patent No. 4,670,444

REFERENCES:

1. Dougherty, T.J. and Saukkonenn, J.J. Aug 1985. Membrane Permeability Changes Associated with DNA Gyrase Inhibitors in Escherichia coli. Antimicrobial Agents and Chemoth. V 53:200-206.


2. Walker, R.D. et al. Dec 1992. Pharmacokinetic Evaluation of Enrofloxacin Administered Orally to Healthy Dogs. Am. J. Res. V 53(12):2315-2319.

Bayer HealthCare LLC

Animal Health Division

Shawnee Mission, Kansas 66201 U.S.A.

©2004 Bayer HealthCare LLC                            October, 2004

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Baytril  enrofloxacin  tablet, film coated

Product Information Product Type PRESCRIPTION ANIMAL DRUG NDC Product Code (Source) 0859-2141 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength ENROFLOXACIN (ENROFLOXACIN) ENROFLOXACIN 22.7 mg

Inactive Ingredients Ingredient Name Strength No Inactive Ingredients Found

Product Characteristics Color PURPLE Score 4 pieces Shape ROUND Size 1mm Flavor Imprint Code B23 Contains

Packaging # NDC Package Description Multilevel Packaging 1 0859-2141-01 100 TABLET In 1 BOTTLE None 2 0859-2141-02 500 TABLET In 1 BOTTLE None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NADA	NADA140441	12/27/1988

Baytril  enrofloxacin  tablet, film coated

Product Information Product Type PRESCRIPTION ANIMAL DRUG NDC Product Code (Source) 0859-2142 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength ENROFLOXACIN (ENROFLOXACIN) ENROFLOXACIN 68 mg

Inactive Ingredients Ingredient Name Strength No Inactive Ingredients Found

Product Characteristics