fda anthrax advisory committee
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Presentation, Anthrax, Cipro FDA, Advisory Committee, Anti-InfectiveTRANSCRIPT
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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Events Leading to Anthrax SubmissionEvents Leading to
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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Events Leading to Anthrax SubmissionEvents Leading to
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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Events Leading to Anthrax SubmissionEvents Leading to
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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Events Leading to Anthrax SubmissionEvents Leading to
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
Pharmacokinetics/PharmacodynamicsPharmacokinetics/Pharmacodynamics
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Pharmacokinetics/PharmacodynamicsPharmacokinetics/Pharmacodynamics
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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CIPRO® Pediatric ExperienceCIPRO® Pediatric Experience
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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CIPRO® Pediatric ExperienceCIPRO® Pediatric Experience
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)
Ciprofloxacin Spontaneous ADE Reports1
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
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
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)
Total Number of Reports
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)
Total Number of Reports
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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Ciprofloxacin Spontaneous ADE Reports1
Ten Most Frequently Reported Serious Events (All Formulations)
Ciprofloxacin Spontaneous ADE Reports1
Ten Most Frequently Reported Serious Events (All Formulations)
Total Number of Reports
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
Total Number of Reports
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
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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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