fda anthrax advisory committee

Presentation to FDA Anti-Infective Drug Products

Advisory Committee July 28, 2000

Presentation to FDA Anti-Infective Drug Products

Advisory Committee July 28, 2000

Proposed Use of Cipro for the indication of Post-Exposure Prophylaxis of Anthrax

Proposed Use of Cipro for the indication of Post-Exposure Prophylaxis of Anthrax

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CiprofloxacinAnthrax post-exposure prophylaxis

CiprofloxacinAnthrax post-exposure prophylaxis

Andrew S. Verderame

Associate Director, Regulatory Affairs

Bayer Corporation, Pharmaceutical Division

Andrew S. Verderame

Associate Director, Regulatory Affairs

Bayer Corporation, Pharmaceutical Division

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AgendaAgenda

Introduction and Proposed Labeling CIPRO Product Line Events Leading to the Submission Discussion of Indication and Submission Rationale for the use of Ciprofloxacin in this

indication Conclusion

Introduction and Proposed Labeling CIPRO Product Line Events Leading to the Submission Discussion of Indication and Submission Rationale for the use of Ciprofloxacin in this

indication Conclusion

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IntroductionIntroduction

On February 29, 2000 Bayer submitted an sNDA to FDA for all oral and I.V. CIPRO formulations to provide labeling for an anthrax post-inhalation exposure prophylaxis indication

According to FDA, this is the first antimicrobial drug application submitted for an indication resulting from the intentional use of a biological agent

On February 29, 2000 Bayer submitted an sNDA to FDA for all oral and I.V. CIPRO formulations to provide labeling for an anthrax post-inhalation exposure prophylaxis indication

According to FDA, this is the first antimicrobial drug application submitted for an indication resulting from the intentional use of a biological agent

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Proposed LabelingProposed Labeling

Proposed Indication for adults and pediatrics:

Anthrax (post-inhalation exposure prophylaxis) caused by Bacillus anthracis

Recommended Dosage* (BID)

Formulation Adults Pediatrics

Tablet/Suspension 500 mg 10-15 mg/kg

I.V. 400 mg 10-15 mg/kg

Recommended Duration* - 60 Days

Proposed Indication for adults and pediatrics:

Anthrax (post-inhalation exposure prophylaxis) caused by Bacillus anthracis

Recommended Dosage* (BID)

Formulation Adults Pediatrics

Tablet/Suspension 500 mg 10-15 mg/kg

I.V. 400 mg 10-15 mg/kg

Recommended Duration* - 60 Days* Inglesby TV, Henderson DA, Bartlett JG et al. JAMA 281:1735-1745, 1999

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Approved CIPRO® FormulationsApproved CIPRO® Formulations

Five formulations of ciprofloxacin have been approved in the US for a wide variety of indications:

Tablets Oral Suspension* Intravenous Solution Otic Suspension with hydrocortisone Ophthalmic Solution

Five formulations of ciprofloxacin have been approved in the US for a wide variety of indications:

Tablets Oral Suspension* Intravenous Solution Otic Suspension with hydrocortisone Ophthalmic Solution

* Approved for all CIPRO Tablet indications, and is the only fluoroquinolone with an approved oral liquid formulation

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Approved CIPRO® Oral and I.V. Indications

Approved CIPRO® Oral and I.V. Indications

Lower Respiratory Infections*

Skin and Skin Structure Infections*

Bone and Joint Infections* Urinary Tract Infections* Infectious Diarrhea* Complicated Intra-

Abdominal Infections* Empirical Therapy in Febrile

Neutropenic Patients*

Lower Respiratory Infections*

Skin and Skin Structure Infections*

Bone and Joint Infections* Urinary Tract Infections* Infectious Diarrhea* Complicated Intra-

Abdominal Infections* Empirical Therapy in Febrile

Neutropenic Patients*

Nosocomial Pneumonia* Chronic Bacterial Prostatitis Acute Sinusitis Acute Uncomplicated

Cystitis Typhoid Fever Urethral and Cervical

Gonococcal Infections

Nosocomial Pneumonia* Chronic Bacterial Prostatitis Acute Sinusitis Acute Uncomplicated

Cystitis Typhoid Fever Urethral and Cervical

Gonococcal Infections

* Includes Severe Infections

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Events Leading to Anthrax SubmissionEvents Leading to

Anthrax Submission

1990 - 1991

Gulf War Bayer provided 30 million CIPRO 500 mg Tablets to

the US Government

CIPRO Tablets distributed to air and ground troops

Bayer commended for meeting urgent production and delivery timelines

Department of Defense conducts anthrax Rhesus monkey testing

1990 - 1991

Gulf War Bayer provided 30 million CIPRO 500 mg Tablets to

the US Government

CIPRO Tablets distributed to air and ground troops

Bayer commended for meeting urgent production and delivery timelines

Department of Defense conducts anthrax Rhesus monkey testing

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Anthrax Submission

1998

U.S. Army Medical Research Institute of Infectious Diseases’ Medical Management of Biological Casualties Handbook (3rd Ed.) references ciprofloxacin 500 mg oral bid as a preferred antibiotic therapy for anthrax prophylaxis

1998

U.S. Army Medical Research Institute of Infectious Diseases’ Medical Management of Biological Casualties Handbook (3rd Ed.) references ciprofloxacin 500 mg oral bid as a preferred antibiotic therapy for anthrax prophylaxis

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Anthrax Submission

1999

The Centers for Disease Control’s Morbidity and Mortality Weekly Report published the recommended treatment guidelines for post-exposure prophylaxis of anthrax, including ciprofloxacin use as a drug of choice

The Working Group on Civilian Biodefense published their consensus statement in JAMA for Public Health Management following the use of anthrax as a biological weapon, also listing ciprofloxacin as a preferred agent

1999

The Centers for Disease Control’s Morbidity and Mortality Weekly Report published the recommended treatment guidelines for post-exposure prophylaxis of anthrax, including ciprofloxacin use as a drug of choice

The Working Group on Civilian Biodefense published their consensus statement in JAMA for Public Health Management following the use of anthrax as a biological weapon, also listing ciprofloxacin as a preferred agent

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Anthrax Submission

1999

Government agencies contacted Bayer regarding ciprofloxacin to provide advice and to help facilitate the Federal Government’s Emergency Preparedness Plans in the event of a bioterrorist attack

Internal Bayer discussions were held concerning the published recommendations and heightened awareness of potential bioterrorism and action plan created

1999

Government agencies contacted Bayer regarding ciprofloxacin to provide advice and to help facilitate the Federal Government’s Emergency Preparedness Plans in the event of a bioterrorist attack

Internal Bayer discussions were held concerning the published recommendations and heightened awareness of potential bioterrorism and action plan created

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Anthrax Submission

1999

Bayer submitted a detailed briefing package to the FDA to assess the regulatory position regarding the feasibility of an anthrax prophylaxis indication and the required content of a labeling supplement

FDA agreed that the information available was sufficient to file a supplemental application and encouraged Bayer to do so

1999

Bayer submitted a detailed briefing package to the FDA to assess the regulatory position regarding the feasibility of an anthrax prophylaxis indication and the required content of a labeling supplement

FDA agreed that the information available was sufficient to file a supplemental application and encouraged Bayer to do so

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Concurrent Events Concurrent Events

1998 -1999

August 1998 Bayer proposed a pediatric development program to FDA in complicated urinary tract infections

May 1999 FDA issued a Written Request Letter to Bayer requesting the initiation of clinical trials with ciprofloxacin in pediatric patients

Large scale pediatric studies began prior to year end 1999

1998 -1999

August 1998 Bayer proposed a pediatric development program to FDA in complicated urinary tract infections

May 1999 FDA issued a Written Request Letter to Bayer requesting the initiation of clinical trials with ciprofloxacin in pediatric patients

Large scale pediatric studies began prior to year end 1999

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Final Events Leading to Anthrax Submission

Final Events Leading to Anthrax Submission

Centers for Disease Control (CDC) contacted Bayer (Nov. 1999) to encourage submission of a labeling supplement to FDA

On February 29, 2000 Bayer submitted an sNDA to FDA for the CIPRO oral and IV formulations

Centers for Disease Control (CDC) contacted Bayer (Nov. 1999) to encourage submission of a labeling supplement to FDA

On February 29, 2000 Bayer submitted an sNDA to FDA for the CIPRO oral and IV formulations

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Rationale for the Use of CiprofloxacinRationale for the Use of Ciprofloxacin

Ciprofloxacin Pharmacokinetics

Review of Lower Respiratory Tract Infection Clinical Database

Review of ciprofloxacin safety in adults and pediatrics

Ciprofloxacin Pharmacokinetics

Review of Lower Respiratory Tract Infection Clinical Database

Review of ciprofloxacin safety in adults and pediatrics

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Pharmacokinetics/PharmacodynamicsPharmacokinetics/Pharmacodynamics

Bacillus anthracis is highly susceptible to ciprofloxacin (MIC90 = 0.06 µg/mL)

Ciprofloxacin half-life is approximately 4 hours

Protein binding is approximately 30%

The absolute bioavailability of the oral formulations is approximately 70%

Bacillus anthracis is highly susceptible to ciprofloxacin (MIC90 = 0.06 µg/mL)

Ciprofloxacin half-life is approximately 4 hours

Protein binding is approximately 30%

The absolute bioavailability of the oral formulations is approximately 70%

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Ciprofloxacin DoseCmax

(g/mL)AUC24h

(gh/mL)

Adult 500 mg PO BID 3.0 27.4

Adult 400 mg I.V. q 12h (1 hr infusion) 4.6 25.4

Pediatric 15 mg/kg PO BID 3.5 26.6

Pediatric 10 mg/kg I.V. q 12h (30 min infusion)Pediatric 10 mg/kg I.V. q 8h (1 hr infusion)

8.53.6 – 5.3

27.626.7- 37.4

Ciprofloxacin DoseCmax

(g/mL)AUC24h

(gh/mL)

Adult 500 mg PO BID 3.0 27.4

Adult 400 mg I.V. q 12h (1 hr infusion) 4.6 25.4

Pediatric 15 mg/kg PO BID 3.5 26.6

Pediatric 10 mg/kg I.V. q 12h (30 min infusion)Pediatric 10 mg/kg I.V. q 8h (1 hr infusion)

8.53.6 – 5.3

27.626.7- 37.4

• Plasma concentrations observed at the recommended dosages:

• The Cmin is approximately 0.2 g/mL

• The MIC90 of Bacillus anthracis is 0.06 µg/mL


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For optimal antibiotic effect the target values for Cmax/MIC and AUC/MIC should be at least 8-10 and

125, respectively

Cmax/MIC ratio = 50 for Bacillus anthracis

AUC0-12h/MIC ratio = 228 for Bacillus anthracis

For optimal antibiotic effect the target values for Cmax/MIC and AUC/MIC should be at least 8-10 and

125, respectively

Cmax/MIC ratio = 50 for Bacillus anthracis

AUC0-12h/MIC ratio = 228 for Bacillus anthracis

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Tissue PenetrationTissue Penetration

Tissue or Fluid Concentration(4 hours)

Concentration(12 hours)

Bronchial EpithelialLining Fluid

1.87 0.94 g/mL 0.42 0.10 g/mL

Alveolar Macrophages 34.6 22.2 g/mL 5.1 7.1 g/mL

Peripheral LymphFluid

1.0 g/mL* 0.25 g/mL

Tissue or Fluid Concentration(4 hours)

Concentration(12 hours)

Bronchial EpithelialLining Fluid

1.87 0.94 g/mL 0.42 0.10 g/mL

Alveolar Macrophages 34.6 22.2 g/mL 5.1 7.1 g/mL

Peripheral LymphFluid

1.0 g/mL* 0.25 g/mL

Concentration of ciprofloxacin in bronchial epithelial lining fluid, alveolar macrophages and peripheral lymph fluid remain above the target pathogen MIC for the entire dosing interval1,2

1 Gottfried et al Clin. Infect. Dis. 27(4): 968, 1998

2 Bergan et al Eur. J. Clin. Microbiol. Vol. 5 No. 4 pp. 458-461, 1986

* 3 hours

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CIPRO® Clinical DatabaseCIPRO® Clinical Database

The most widely studied fluoroquinolone

Bayer has sponsored over 850 ciprofloxacin clinical trials

Over 140,000 adults and 3,400 children have been treated in the ciprofloxacin protocols

Clinical trials have well defined the safety and efficacy of ciprofloxacin therapy

The most widely studied fluoroquinolone

Bayer has sponsored over 850 ciprofloxacin clinical trials

Over 140,000 adults and 3,400 children have been treated in the ciprofloxacin protocols

Clinical trials have well defined the safety and efficacy of ciprofloxacin therapy

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Review of US Lower Respiratory Tract Infection Clinical DatabaseReview of US Lower Respiratory Tract Infection Clinical Database

34 controlled studies included diseases such as Nosocomial Pneumonia, Community Acquired Pneumonia, Acute Exacerbations of Chronic Bronchitis, Pulmonary Exacerbations of Cystic Fibrosis

Comparators such as Ceftazidime, Ampicillin, Clarithromycin, Imipenem, Ceftriaxone, Amoxicillin/Clavulanic Acid, Cefaclor, Tobramycin, Cefuroxime, Erythromycin, Vancomycin

34 controlled studies included diseases such as Nosocomial Pneumonia, Community Acquired Pneumonia, Acute Exacerbations of Chronic Bronchitis, Pulmonary Exacerbations of Cystic Fibrosis

Comparators such as Ceftazidime, Ampicillin, Clarithromycin, Imipenem, Ceftriaxone, Amoxicillin/Clavulanic Acid, Cefaclor, Tobramycin, Cefuroxime, Erythromycin, Vancomycin

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Clinical Success Rates in the LRTI Pooled Studies

Clinical Success Rates in the LRTI Pooled Studies

86 85

0

20

40

60

80

100

CIPRO COMPARATORS

Treatment Group

Pe

rce

nt

Su

cc

es

s (

%)

N =

15

23

N =

16

89

86 85

0

20

40

60

80

100

CIPRO COMPARATORS

Treatment Group

Pe

rce

nt

Su

cc

es

s (

%)

N =

15

23

N =

16

89

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Review of Overall Clinical Trials Safety Database

Review of Overall Clinical Trials Safety Database

Over 1000 patients (including 104 children) have received ciprofloxacin for 60 days or longer in Bayer sponsored clinical trials worldwide

The most common indications included: osteomyelitis

cystic fibrosis

prostatitis

pyelonephritis

UTI prophylaxis

tuberculosis

Over 1000 patients (including 104 children) have received ciprofloxacin for 60 days or longer in Bayer sponsored clinical trials worldwide

The most common indications included: osteomyelitis

cystic fibrosis

prostatitis

pyelonephritis

UTI prophylaxis

tuberculosis

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Review of Global Clinical Trials Safety Database

Review of Global Clinical Trials Safety Database

Cipro Pts fromControlled

StudiesN = 12,799

(%)

ControlPatients

N = 11,980

(%)

Cipro PtsTreated 30 – 59

DaysN = 1,420

(%)

Cipro PtsTreated 60

DaysN = 1,051

(%)

Any Event 31.1 32.8 27.8 28.6

Nausea 5.5 5.0 8.9 3.8

Diarrhea 4.1 4.7 5.8 2.5

Vomiting 2.8 2.2 4.4 1.7

Headache 2.6 5.2 1.3 1.0

Rash 2.5 2.7 3.6 3.9

LFTAbnormal

2.1 2.1 3.2 2.6

AbdominalPain

1.7 1.8 1.4 3.6

Pruritus 1.3 1.1 1.4 1.5

Dizziness 1.1 1.3 0.7 0.6

Cipro Pts fromControlled

StudiesN = 12,799

(%)

ControlPatients

N = 11,980

(%)

Cipro PtsTreated 30 – 59

DaysN = 1,420

(%)

Cipro PtsTreated 60

DaysN = 1,051

(%)

Any Event 31.1 32.8 27.8 28.6

Nausea 5.5 5.0 8.9 3.8

Diarrhea 4.1 4.7 5.8 2.5

Vomiting 2.8 2.2 4.4 1.7

Headache 2.6 5.2 1.3 1.0

Rash 2.5 2.7 3.6 3.9

LFTAbnormal

2.1 2.1 3.2 2.6

AbdominalPain

1.7 1.8 1.4 3.6

Pruritus 1.3 1.1 1.4 1.5

Dizziness 1.1 1.3 0.7 0.6

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CIPRO® Pediatric ExperienceCIPRO® Pediatric Experience

Bayer has completed several pediatric clinical trials: Cystic Fibrosis, Meningococcal carriage, Diarrheal Diseases, Pneumonia, Neutropenia, etc.

Data available on over 3,400 CIPRO treated pediatric patients

No serious adverse events reported in the pediatric patients (n = 104) receiving at least 60 days of ciprofloxacin in clinical trials

Bayer has completed several pediatric clinical trials: Cystic Fibrosis, Meningococcal carriage, Diarrheal Diseases, Pneumonia, Neutropenia, etc.

Data available on over 3,400 CIPRO treated pediatric patients

No serious adverse events reported in the pediatric patients (n = 104) receiving at least 60 days of ciprofloxacin in clinical trials

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Review of Controlled Pediatric Clinical Trial Safety DatabaseReview of Controlled Pediatric Clinical Trial Safety Database

CIPRON = 167

(%)

CONTROLN = 178

(%)Any Event 51 44

LFT Abnormal 12 12

Vomiting 10 4

Rash 7 4

Nausea 7 3

Arthralgia 5 7

Joint Disorder 5 6

Abdominal Pain 4 4

Headache 4 3

Diarrhea 2 3

Pruritus 2 1

Dizziness 0 2

CIPRON = 167

(%)

CONTROLN = 178

(%)Any Event 51 44

LFT Abnormal 12 12

Vomiting 10 4

Rash 7 4

Nausea 7 3

Arthralgia 5 7

Joint Disorder 5 6

Abdominal Pain 4 4

Headache 4 3

Diarrhea 2 3

Pruritus 2 1

Dizziness 0 2

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Ciprofloxacin Global Clinical Trials Pediatric Safety Database

Ciprofloxacin Global Clinical Trials Pediatric Safety Database

All CiproPediatric Pts

N = 2,327(%)

All Cipro Pediatric PtsTreated 30 – 59 Days

N = 189(%)

All Cipro Pediatric Pts Treated 60 Days**

N = 104(%)

Any Event 13 20 17

Nausea 2 4 2

LFT Abnormal 2 2 1

Arthralgia 1 4 5

Diarrhea 1 2 0

Rash 1 1 2

Pruritus 1 1 2

Arthritis 1 1 0

Photosensitivity Reaction <1 2 3

Injection Site Sensitivity <1 0 2

Nervousness <1 0 2

Abnormal Kidney Function <1 2 0

All CiproPediatric Pts

N = 2,327(%)

All Cipro Pediatric PtsTreated 30 – 59 Days

N = 189(%)

All Cipro Pediatric Pts Treated 60 Days**

N = 104(%)

Any Event 13 20 17

Nausea 2 4 2

LFT Abnormal 2 2 1

Arthralgia 1 4 5

Diarrhea 1 2 0

Rash 1 1 2

Pruritus 1 1 2

Arthritis 1 1 0

Photosensitivity Reaction <1 2 3

Injection Site Sensitivity <1 0 2

Nervousness <1 0 2

Abnormal Kidney Function <1 2 0

Adverse Events* By Duration of TherapyAdverse Events* By Duration of Therapy

* Events reported in 2 or more patients treated for 30-59 or 60 days** None of these were considered serious by the reporting investigator

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After discussions with FDA on study design, two ciprofloxacin pediatric trials are currently ongoing

Complicated Urinary Tract Infection - Controlled, Randomized, Double-Blind Comparative Trial

Long-term (post-dosing) Observational Study in ciprofloxacin-treated Pediatric Patients

After discussions with FDA on study design, two ciprofloxacin pediatric trials are currently ongoing

Complicated Urinary Tract Infection - Controlled, Randomized, Double-Blind Comparative Trial

Long-term (post-dosing) Observational Study in ciprofloxacin-treated Pediatric Patients

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Despite prominent class labeling warnings and no promotion to the pediatric community, it is estimated that 14,000 prescriptions are written annually (0.1 % of all US CIPRO scripts) for patients younger than 10 years old, an additional 28,000 (0.2 %) for patients between 10-14, and 140,000 (1%) for patients between 15-17*

Approximately 4.5 million ciprofloxacin pediatric treatment courses worldwide over the last 13 years

* IMS Data

Despite prominent class labeling warnings and no promotion to the pediatric community, it is estimated that 14,000 prescriptions are written annually (0.1 % of all US CIPRO scripts) for patients younger than 10 years old, an additional 28,000 (0.2 %) for patients between 10-14, and 140,000 (1%) for patients between 15-17*

Approximately 4.5 million ciprofloxacin pediatric treatment courses worldwide over the last 13 years

* IMS Data

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CIPRO® - Review of Global Post-Marketing Safety Database

CIPRO® - Review of Global Post-Marketing Safety Database

Ciprofloxacin has been available for prescription use for 13 years

Over 250 million prescriptions written worldwide (over 5 billion individual doses) for all formulations

Ciprofloxacin has been available for prescription use for 13 years

Over 250 million prescriptions written worldwide (over 5 billion individual doses) for all formulations

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Ciprofloxacin Spontaneous ADE Reports1

Ten Most Frequently Reported Events(All Formulations)


Ten Most Frequently Reported Events(All Formulations)

Total Number of Reports

1. Rash 1232 (4.9 per 1 million patients)

2. Tendon Disorder 537 (2.1 per 1 million patients)

3. Arthralgia 476

4. Pruritus 466

5. Urticaria 457

6. Nausea 409

7. Diarrhea 396

8. Convulsion 3669. LFT Abnormal 365

10. Dizziness 344


1. Rash 1232 (4.9 per 1 million patients)

2. Tendon Disorder 537 (2.1 per 1 million patients)

3. Arthralgia 476

4. Pruritus 466

5. Urticaria 457

6. Nausea 409

7. Diarrhea 396

8. Convulsion 3669. LFT Abnormal 365

10. Dizziness 344

All Patient Exposures (N 250 million)

1 Bayer Global Drug Safety Database

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Most Frequently Reported Ciprofloxacin Spontaneous ADE Reports1 By Age (When Known)

(All Formulations)

Most Frequently Reported Ciprofloxacin Spontaneous ADE Reports1 By Age (When Known)

(All Formulations)

Age 18 (N 245 million)


Age 18 (N 4.5 million) Total Number of Reports

1. Rash 1026 1. Rash 322. Tendon 433

Disorder2. Arthralgia 24

3. Pruritus 394 3. Urticaria 244. Urticaria 380 4. Convulsion 155. Arthralgia 373 5. Face Edema 156. Nausea 334 6. Pruritus 157. Diarrhea 329 7. Fever 148. Convulsion 310 8. Anaphylactoid 13

Reaction9. LFT Abnormal 296 9. Nausea 1310. Dizziness 277 10. Photosensitivity 13

Reaction

Age 18 (N 245 million)


Age 18 (N 4.5 million) Total Number of Reports

1. Rash 1026 1. Rash 322. Tendon 433

Disorder2. Arthralgia 24

3. Pruritus 394 3. Urticaria 244. Urticaria 380 4. Convulsion 155. Arthralgia 373 5. Face Edema 156. Nausea 334 6. Pruritus 157. Diarrhea 329 7. Fever 148. Convulsion 310 8. Anaphylactoid 13

Reaction9. LFT Abnormal 296 9. Nausea 1310. Dizziness 277 10. Photosensitivity 13

Reaction1 Bayer Global Drug Safety Database

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Ten Most Frequently Reported Serious Events (All Formulations)


Ten Most Frequently Reported Serious Events (All Formulations)


1. Convulsion 215 (0.86 per 1 million patients)

2. Anaphylactoid Reaction 167

3. Rash 166

4. Tendon Rupture 142

5. Acute Kidney Failure 140

6. Tendon Disorder 128

7. LFT Abnormal 119

8. Thrombocytopenia 103

9. Kidney Failure 97

10. Kidney Function 96 Abnormal


1. Convulsion 215 (0.86 per 1 million patients)

2. Anaphylactoid Reaction 167

3. Rash 166

4. Tendon Rupture 142

5. Acute Kidney Failure 140

6. Tendon Disorder 128

7. LFT Abnormal 119

8. Thrombocytopenia 103

9. Kidney Failure 97

10. Kidney Function 96 Abnormal

All Patient Exposures (N 250 million)

1 Bayer Global Drug Safety Database

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SummarySummary

13 years of marketed clinical experience

Over 250 million prescriptions written worldwide

Ciprofloxacin pharmacokinetics supports expected efficacy in this indication

The extensive clinical trial and post-marketing experience with ciprofloxacin has defined its safety profile, including extended treatment durations

13 years of marketed clinical experience

Over 250 million prescriptions written worldwide

Ciprofloxacin pharmacokinetics supports expected efficacy in this indication

The extensive clinical trial and post-marketing experience with ciprofloxacin has defined its safety profile, including extended treatment durations

04/11/23 36

ConclusionsConclusions

Bayer Corporation, after discussions with several government agencies, has filed this supplement in response to a public health need

Given the seriousness of the indication and the extraordinary hazards that an anthrax release would entail, the risk / benefit ratio supports ciprofloxacin therapy for this proposed indication

Bayer Corporation, after discussions with several government agencies, has filed this supplement in response to a public health need

Given the seriousness of the indication and the extraordinary hazards that an anthrax release would entail, the risk / benefit ratio supports ciprofloxacin therapy for this proposed indication

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fda anthrax advisory committee

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