Caspofungin

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CaspofunginCaspofunginBreakthrough Treatment in the

Management of Patients with Invasive CandidiasisBreakthrough Treatment in the

Management of Patients with Invasive Candidiasis


Overview: Growing ThreatOverview: Growing Threat

• Serious fungal infections are on the rise

• Invasive Candida infections– 4th most common nosocomial bloodstream infection in the

United States*

• Serious fungal infections are on the rise

• Invasive Candida infections– 4th most common nosocomial bloodstream infection in the

United States*

* In a 3-year (1995-1998) surveillance study of 49 hospitals in the United States.

Adapted from Edmond MB et al Clin Infect Dis 1999;29:239-244.

Andriole VT J Antimicrob Chemother 1999;44:151-162; Uzun O, Anaissie EJ Ann Oncol 2000;11:1517-1521; Edmond MB, Wallace SE, McClish DK, Pfaller MA, Jones RN, Wenzel RP Clin Infect Dis 1999;29:239-244.

* In a 3-year (1995-1998) surveillance study of 49 hospitals in the United States.

Adapted from Edmond MB et al Clin Infect Dis 1999;29:239-244.

Andriole VT J Antimicrob Chemother 1999;44:151-162; Uzun O, Anaissie EJ Ann Oncol 2000;11:1517-1521; Edmond MB, Wallace SE, McClish DK, Pfaller MA, Jones RN, Wenzel RP Clin Infect Dis 1999;29:239-244.

Coagulase-negative staphylococci 3908 31.9Staphylococcus aureus 1928 15.7Enterococci 1354 11.1Candida species 934 7.6

Coagulase-negative staphylococci 3908 31.9Staphylococcus aureus 1928 15.7Enterococci 1354 11.1Candida species 934 7.6

Pathogen No. of Isolates Incidence (%)Pathogen No. of Isolates Incidence (%)


In an international surveillance study of bloodstream infections:

Species of Candida Most Commonly IsolatedIn an international surveillance study of bloodstream infections:

Species of Candida Most Commonly Isolated

Pfaller MA, Jones RN, Doern GV et al and The SENTRY Participant Group Antimicrob Agents Chemother 2000;44:747-751.Pfaller MA, Jones RN, Doern GV et al and The SENTRY Participant Group Antimicrob Agents Chemother 2000;44:747-751.

C. glabrata 16%

C. glabrata 16%

C. albicans 54%

C. albicans 54%C. parapsilosis

15%C. parapsilosis

15%

C. tropicalis 8%

C. tropicalis 8%

C. krusei 2%

C. krusei 2% other Candida

spp 5%other Candida

spp 5%

Adapted from Pfaller MA et al and The SENTRY Participant Group Antimicrob Agents Chemother 2000;44:747-751.Adapted from Pfaller MA et al and The SENTRY Participant Group Antimicrob Agents Chemother 2000;44:747-751.


High Rate of Mortality Associated with Candidal Bloodstream InfectionsHigh Rate of Mortality Associated with Candidal Bloodstream Infections

Patients with candidal bloodstream infectionsPatients with candidal bloodstream infections

Edmond MB, Wallace SE, McClish DK, Pfaller MA, Jones RN, Wenzel RP Clin Infect Dis 1999;29:239-244.Edmond MB, Wallace SE, McClish DK, Pfaller MA, Jones RN, Wenzel RP Clin Infect Dis 1999;29:239-244.

00

55

1010

1515

2020

2525

3030

3535

4040

454540%40%

25%25%

Per

cent

age

of P

atie

nts

Per

cent

age

of P

atie

nts

Patients with bacterial (non-candidal)

bloodstream infections

Patients with bacterial (non-candidal)

bloodstream infections

In a 3-year surveillance study of nosocomial bloodstream infections in 49 US hospitals:In a 3-year surveillance study of nosocomial bloodstream infections in 49 US hospitals:


Blumberg HM, Jarvis WR, Soucie JM et al and the NEMIS Study Group Clin Infect Dis 2001;33:177-186; Garber G Drugs 2001;61(suppl 1):1-12. National Epidemiology of Mycosis Survey (NEMIS) was a prospective, multicenter study conducted at 6 US sites from 1993-1995 to examine rates of risk factors for the development of candidal bloodstream infections (CBSIs) among patients in surgical and neonatal ICUs >48h. Among 4276 patients, 42 CBSIs occurred.

Blumberg HM, Jarvis WR, Soucie JM et al and the NEMIS Study Group Clin Infect Dis 2001;33:177-186; Garber G Drugs 2001;61(suppl 1):1-12. National Epidemiology of Mycosis Survey (NEMIS) was a prospective, multicenter study conducted at 6 US sites from 1993-1995 to examine rates of risk factors for the development of candidal bloodstream infections (CBSIs) among patients in surgical and neonatal ICUs >48h. Among 4276 patients, 42 CBSIs occurred.

Patients at High RiskPatients at High Risk

Potential risk factors include:

Non-Neutropenic

• Acute renal failure

• Parenteral nutrition

• Anti-anaerobic agents

• Prior vancomycin use

• Intralipid agents

• Prior surgery

• Indwelling triple-lumen catheters

Potential risk factors include:

Non-Neutropenic

• Acute renal failure

• Parenteral nutrition

• Anti-anaerobic agents


• Intralipid agents

• Prior surgery

• Indwelling triple-lumen catheters

Neutropenic

• Cancer

• Transplantation

• Broad spectrum anti-anaerobic antibiotic use


• Immunocompromised state

• Surgery

• Indwelling catheters

Neutropenic

• Cancer

• Transplantation

• Broad spectrum anti-anaerobic antibiotic use


• Immunocompromised state

• Surgery

• Indwelling catheters


Candidemia in Neutropenic Patients with Cancer: Clinical Characteristics* Candidemia in Neutropenic Patients with Cancer: Clinical Characteristics*

Broad-spectrum antibiotics in previous 2 weeks

Corticosteroids within previous 2 weeks

Chemotherapywithin previous 30 days

Abdominal surgerywithin previous 2 months

Intravenous hyperalimentationwithin previous 30 days

Concomitant infection within previous week

Central venous catheter (CVC) in place at time of positive

blood culture








blood culture

% with clinical characteristic% with clinical characteristic* Univariate analyses.

Adapted from Anaissie EJ et al Am J Med 1998;104:238-245.

Anaissie EJ, Rex JH, Uzun O, Vartivarian S Am J Med 1998;104:238-245.

* Univariate analyses.



Neutropenic (n=217)Neutropenic (n=217)

00 1001005050

56%56%

3%3%

39%39%

63%63%

98%98%

90%90%

89%89%


Candidemia in Non-Neutropenic Patients with Cancer: Clinical Characteristics*Candidemia in Non-Neutropenic Patients with Cancer: Clinical Characteristics*














blood culture








blood culture

% with clinical characteristic% with clinical characteristic

Non-Neutropenic (n=257)Non-Neutropenic (n=257)

00 1001005050

23%23%

29%29%

52%52%

61%61%

49%49%

80%80%

88%88%


Kartsonis NA. Presented at the 12th European Congress of Clinical Microbiology and Infectious Diseases. April 24-27, 2002. Milan, Italy. Kartsonis NA. Presented at the 12th European Congress of Clinical Microbiology and Infectious Diseases. April 24-27, 2002. Milan, Italy.

Caspofungin: New Class of Drug Caspofungin: New Class of Drug

Nucleoside AnalogsNucleoside Analogs

-(1,3)-D-glucan-(1,3)-D-glucan

ErgosterolPolyenes

Azoles

ErgosterolPolyenes

Azoles

Phospholipid bilayerof the fungal cell

membrane

Phospholipid bilayerof the fungal cell

membrane

Fungal cell wallFungal cell wall

-(1,6)-glucan-(1,6)-glucan

-(1,3)-D-glucan synthaseGlucan Synthesis

Inhibitor

-(1,3)-D-glucan synthaseGlucan Synthesis

Inhibitor

nucleus

Breakthrough Mechanism of Action: Targets the Pathogen, Not the Patient Breakthrough Mechanism of Action: Targets the Pathogen, Not the Patient


Caspofungin: Broad Spectrum of Activity Caspofungin: Broad Spectrum of Activity

Data on file, MSD; Bartizal K, Gill CJ, Abruzzo GK et al Antimicrob Agents Chemother 1997;41:2326-2332.Data on file, MSD; Bartizal K, Gill CJ, Abruzzo GK et al Antimicrob Agents Chemother 1997;41:2326-2332.

C. alb

ican

s

C. alb

ican

s

C. gla

brat

a

C. gla

brat

a

CANDIDA ALBICANSCANDIDA ALBICANS

C. par

apsil

osis

C. par

apsil

osis

C. tro

pica

lis

C. tro

pica

lisC. k

ruse

i

C. kru

sei

C. gui

llier

mon

dii

C. gui

llier

mon

dii

C. lip

olyt

ica

C. lip

olyt

ica

C. dub

linie

nsis

C. dub

linie

nsis

C. kef

yr

C. kef

yrC. l

usita

niae

C. lus

itani

aeC. r

ugos

a

C. rug

osa

A. fl

avus

A. fl

avus

A. fu

mig

atus

A. fu

mig

atus

A. te

rreu

s

A. te

rreu

sA.

nig

er

A. n

iger

A. n

idul

ans

A. n

idul

ans

CANDIDA NON-ALBICANS

CANDIDA NON-ALBICANS

ASPERGILLUSASPERGILLUS

Expanded Spectrum of In Vitro ActivityExpanded Spectrum of In Vitro Activity

C. pse

udot

ropi

calis

C. pse

udot

ropi

calis


Unique Mechanism of Action (MOA) Offers Favorable Resistance Profile Unique Mechanism of Action (MOA) Offers Favorable Resistance Profile

• Active in vitro against fluconazole-, amphotericin B-, or flucytosine-resistant Candida

• Not cross-resistant with azoles or polyenes

• Not intrinsically resistant to Candida isolates

• Active in vitro against fluconazole-, amphotericin B-, or flucytosine-resistant Candida

• Not cross-resistant with azoles or polyenes

• Not intrinsically resistant to Candida isolates

Data on file, MSD; Graybill JR Int J Clin Pract 2001;55(9):633-638; Pfaller MA, Jones RN, Doern GV et al Diagn Microbiol Infect Dis 1999;35:19-25.Data on file, MSD; Graybill JR Int J Clin Pract 2001;55(9):633-638; Pfaller MA, Jones RN, Doern GV et al Diagn Microbiol Infect Dis 1999;35:19-25.


Caspofungin: IndicationCaspofungin: Indication

• NEW: Invasive candidiasis including candidemia in neutropenic and non-neutropenic patients

In addition to:

• Invasive aspergillosis in patients who are refractory to or intolerant of standard therapies

• Esophageal candidiasis

• Oropharyngeal candidiasis

• NEW: Invasive candidiasis including candidemia in neutropenic and non-neutropenic patients

In addition to:

• Invasive aspergillosis in patients who are refractory to or intolerant of standard therapies

• Esophageal candidiasis

• Oropharyngeal candidiasis

Data on file, MSD.Data on file, MSD.


Caspofungin: Proven Antifungal Efficacy against Invasive CandidiasisCaspofungin: Proven Antifungal Efficacy against Invasive Candidiasis

Clinical Trial: Protocol 014

Caspofungin vs. Amphotericin B Deoxycholate in the Treatment of Invasive Candidiasis in Neutropenic and Non-Neutropenic Patients

Clinical Trial: Protocol 014

Caspofungin vs. Amphotericin B Deoxycholate in the Treatment of Invasive Candidiasis in Neutropenic and Non-Neutropenic Patients



Protocol 014: ObjectiveProtocol 014: Objective

To compare the proportion of caspofungin acetate patients with both a favorable clinical response and a favorable microbiological assessment at the time of discontinuing IV antifungal therapy with that of amphotericin B patients

To compare the proportion of caspofungin acetate patients with both a favorable clinical response and a favorable microbiological assessment at the time of discontinuing IV antifungal therapy with that of amphotericin B patients



Protocol 014: DesignProtocol 014: Design

• Multicenter, randomized, double-blind, comparative study

• To compare the proportion of caspofungin patients with a favorable clinical response and a favorable microbiological assessment at the time of discontinuing IV antifungal therapy with that of amphotericin B patients

• Patients (18 years old) stratified by neutropenic status

• Multicenter, randomized, double-blind, comparative study

• To compare the proportion of caspofungin patients with a favorable clinical response and a favorable microbiological assessment at the time of discontinuing IV antifungal therapy with that of amphotericin B patients

• Patients (18 years old) stratified by neutropenic status

Caspofungin: Amphotericin B:114 pts (92 with candidemia) 125 pts (92 with candidemia)

— 50 mg/day — 0.7–1.0 mg/kg/day (70 mg loading dose on day 1) neutropenic patients

— 0.6–0.7 mg/kg/daynon-neutropenic patients

Caspofungin: Amphotericin B:114 pts (92 with candidemia) 125 pts (92 with candidemia)

— 50 mg/day — 0.7–1.0 mg/kg/day (70 mg loading dose on day 1) neutropenic patients

— 0.6–0.7 mg/kg/daynon-neutropenic patients



Study treatment course (at least 10 days of IV study therapy; switch to oral fluconazole possible after day 10)

Study treatment course (at least 10 days of IV study therapy; switch to oral fluconazole possible after day 10)

Protocol 014: Study Design Flow Chart Protocol 014: Study Design Flow Chart

Kartsonis NA. Presented at the 12th European Congress of Clinical Microbiology and Infectious Diseases. April 24-27, 2002. Milan, Italy. Kartsonis NA. Presented at the 12th European Congress of Clinical Microbiology and Infectious Diseases. April 24-27, 2002. Milan, Italy.

Start of IV study therapy

Start of IV study therapy

Positive culture

collected

Positive culture

collected

< 4 days < 4 days

Last positive culture

Last positive culture

End of treatment

course

End of treatment

course

2-week post-therapy

follow-up

2-week post-therapy

follow-up

6- to 8-week post-therapy

follow-up

6- to 8-week post-therapy

follow-up

14 days14 days

Day 10 of IV Rx

Day 10 of IV Rx

End of all antifungal Rx

End of all antifungal Rx

End of IV Study Rx

End of IV Study Rx

2-week follow-up2-week

follow-up6- to 8-week

follow-up6- to 8-week

follow-up

Primary Efficacy

Time Point Primary Efficacy

Time Point

Secondary Efficacy

Time Points Secondary Efficacy

Time Points


Protocol 014: Efficacy Evaluation—Diagnostic CriteriaProtocol 014: Efficacy Evaluation—Diagnostic Criteria

• Favorable clinical response– Complete resolution of signs/symptoms of Candida

• Favorable microbiological response or presumptive eradication– Candida eradication from follow-up cultures

• Definition of comparability– 95.6% confidence interval (CI) difference

between groups

• Favorable clinical response– Complete resolution of signs/symptoms of Candida

• Favorable microbiological response or presumptive eradication– Candida eradication from follow-up cultures

• Definition of comparability– 95.6% confidence interval (CI) difference

between groups



Protocol 014: Primary Efficacy EndpointProtocol 014: Primary Efficacy Endpoint

• Proportion of patients with favorable overall response (favorable clinical and microbiological response) at end of IV therapy– Modified Intent-To-Treat (MITT): primary assessment

criteria• Patients received 1 day IV study therapy

– Evaluable Patients (EP): secondary assessment analysis• Patients met entry criteria, received IV study therapy 5

days, and had full efficacy evaluation at the end of IV study therapy

• Proportion of patients with favorable overall response (favorable clinical and microbiological response) at end of IV therapy– Modified Intent-To-Treat (MITT): primary assessment

criteria• Patients received 1 day IV study therapy

– Evaluable Patients (EP): secondary assessment analysis• Patients met entry criteria, received IV study therapy 5

days, and had full efficacy evaluation at the end of IV study therapy



Protocol 014: Caspofungin Demonstrates Comparable Efficacy Results in MITT Group Protocol 014: Caspofungin Demonstrates Comparable Efficacy Results in MITT Group

Caspofungin80/109

Caspofungin80/109

Perfect J. Presented at the 12th European Congress of Clinical Microbiology and Infectious Diseases. April 24-27, 2002. Milan, Italy; Data on file, MSD.Perfect J. Presented at the 12th European Congress of Clinical Microbiology and Infectious Diseases. April 24-27, 2002. Milan, Italy; Data on file, MSD.

00

1010

2020

3030

4040

5050

6060

7070

8080

9090

73.4%73.4%

61.7%61.7%

Amphotericin B71/115

Amphotericin B71/115

100100MITT (n=224)p=0.0861MITT (n=224)p=0.0861

Per

cent

age

Per

cent

age

Overall Response at End of IV Therapy (test of cure)Overall Response at End of IV Therapy (test of cure)


Protocol 014: Caspofungin Appeared to Have Efficacy vs. Amphotericin B in Evaluable Patients Analysis*Protocol 014: Caspofungin Appeared to Have Efficacy vs. Amphotericin B in Evaluable Patients Analysis*

* Evaluable patients analysis was a secondary analysis.

Perfect J. Presented at the 12th European Congress of Clinical Microbiology and Infectious Diseases. April 24-27, 2002. Milan, Italy; Data on file, MSD.

* Evaluable patients analysis was a secondary analysis.

Perfect J. Presented at the 12th European Congress of Clinical Microbiology and Infectious Diseases. April 24-27, 2002. Milan, Italy; Data on file, MSD.

Caspofungin71/88

Caspofungin71/88

00

1010

2020

3030

4040

5050

6060

7070

8080

9090 80.7%80.7%

64.9%64.9%

Amphotericin B63/97

Amphotericin B63/97

100100P

erce

ntag

eP

erce

ntag

e

EP (n=185)p=0.0346EP (n=185)p=0.0346

Overall Response at End of IV Therapy (test of cure)Overall Response at End of IV Therapy (test of cure)


Protocol 014: Caspofungin Demonstrates Similar Efficacy vs. Amphotericin B in Candidemia Protocol 014: Caspofungin Demonstrates Similar Efficacy vs. Amphotericin B in Candidemia

CaspofunginCaspofungin


00

1010

2020

3030

4040

5050

6060

7070

8080

9090

72.5%72.5%

62.5%62.5%

Amphotericin BAmphotericin B

100100

Per

cent

age

of P

atie

nts

Per

cent

age

of P

atie

nts

n=92n=92

n=94n=94


Protocol 014: Time to First Negative Blood Culture Protocol 014: Time to First Negative Blood Culture

Per

cent

age

Per

cent

age

Perfect J. Presented at the 12th European Congress of Clinical Microbiology and Infectious Diseases. April 24-27, 2002. Milan, Italy.Perfect J. Presented at the 12th European Congress of Clinical Microbiology and Infectious Diseases. April 24-27, 2002. Milan, Italy.

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24

0

10

20

30

40

50

60

70

80

90

100

Study DayStudy Day

Caspofungin Amphotericin B

Day 4 19.6% 19.1%Day 7 12.0% 9.0%Day 9 6.5% 6.4%

Caspofungin Amphotericin B

Day 4 19.6% 19.1%Day 7 12.0% 9.0%Day 9 6.5% 6.4%

Caspofungin (n=92)Caspofungin (n=92)Amphotericin B (n=94)Amphotericin B (n=94)


Protocol 014: Failure or Relapse Rates Protocol 014: Failure or Relapse Rates

Perfect J. Presented at the 12th European Congress of Clinical Microbiology and Infectious Diseases. April 24-27, 2002. Milan, Italy.Perfect J. Presented at the 12th European Congress of Clinical Microbiology and Infectious Diseases. April 24-27, 2002. Milan, Italy.

00

1010

2020

3030

4040

26.6%26.6%

6.4%6.4%

5050

Failure(End of IV

study therapy)

Failure(End of IV

study therapy)

38.2%38.2%

7.0%7.0%2.7%2.7%

16.5%16.5%

Relapse(6–8 weeks post-Rx)

Relapse(6–8 weeks post-Rx)

Toxicity requiring additional treatment

p=0.0277

Toxicity requiring additional treatment

p=0.0277

Caspofungin (n=109)70/50 mg

Amphotericin B (n=115)0.6–1.0 mg/kg

Caspofungin (n=109)70/50 mg

Amphotericin B (n=115)0.6–1.0 mg/kg


Protocol 014: Mortality Assessment Protocol 014: Mortality Assessment

* Attributable mortality was defined as meeting any one of the following criteria:— Positive Candida culture within 48 hours of death— Histopathological or microbiological evidence of Candida on autopsy— Candida infection identified as an investigator-determined cause of death

** Crude mortality was defined as the mortality rate from all causes of death.

Data on file, MSD; Perfect J. Presented at the 12th European Congress of Clinical Microbiology and Infectious Diseases. April 24-27, 2002. Milan, Italy.

* Attributable mortality was defined as meeting any one of the following criteria:— Positive Candida culture within 48 hours of death— Histopathological or microbiological evidence of Candida on autopsy— Candida infection identified as an investigator-determined cause of death

** Crude mortality was defined as the mortality rate from all causes of death.

Data on file, MSD; Perfect J. Presented at the 12th European Congress of Clinical Microbiology and Infectious Diseases. April 24-27, 2002. Milan, Italy.

Crude Mortality**(p=0.528)

Crude Mortality**(p=0.528)

00

1010

2020

3030

4040

4.4%4.4%

34.2%34.2%

5050

30.4%30.4%

7.2%7.2%

Caspofungin 70/50 mg

Amphotericin B 0.6–1.0 mg/kg



Attributable Mortality*(p=0.566)

Attributable Mortality*(p=0.566)


Protocol 014: Caspofungin Demonstrates a Favorable Safety Profile vs. Amphotericin B* Protocol 014: Caspofungin Demonstrates a Favorable Safety Profile vs. Amphotericin B*

AE=adverse event.

Data on file, MSD.

AE=adverse event.

Data on file, MSD.

00

1010

2020

3030

4040

5050

6060

7070

8080

9090

100100

Per

cent

age

of P

atie

nts

Per

cent

age

of P

atie

nts

42.1%42.1%

75.2%75.2%

2.6%2.6%

23.2%23.2%20.2%20.2%

48.8%48.8%

11.4%11.4%

26.4%26.4%

8.4%8.4%

24.8%24.8%

All drug-related

AEs

All drug-related

AEs

Infusion-related

systemic AEs

Infusion-related

systemic AEs

Drug-relateddiscontinuations

due to AEs

Drug-relateddiscontinuations

due to AEs

Hypokalemiarequiring potassium treatment

Hypokalemiarequiring potassium treatment

NephrotoxicityNephrotoxicity

48/11448/114

94/12594/125

3/1143/114

29/12529/12523/11423/114

61/12561/125

13/11413/114

33/12533/125

8/958/95

26/10526/105

* All p values were <0.03; 95% CI for relative riskof caspofungin vs. amphotericin B was <1.

* All p values were <0.03; 95% CI for relative riskof caspofungin vs. amphotericin B was <1.






Other Studies: Amphotericin B Therapy— Clinical Impact of Acute Renal Failure Other Studies: Amphotericin B Therapy— Clinical Impact of Acute Renal Failure

• 30% (212) of 707 amphotericin B–treated patients: acute renal failure (ARF)

• High mortality rate: 27% of 707 amphotericin B patients

• 30% (212) of 707 amphotericin B–treated patients: acute renal failure (ARF)

• High mortality rate: 27% of 707 amphotericin B patients

Study Design: To assess the mortality and resource utilization resulting from acute renal failure (ARF) associated with amphotericin B therapy; 707 adult admissions in which parenteral amphotericin B therapy was given were studied at a tertiary-care hospital.

Bates DW, Su L, Yu DT et al Clin Infec Dis 2001;32:686-693.

Study Design: To assess the mortality and resource utilization resulting from acute renal failure (ARF) associated with amphotericin B therapy; 707 adult admissions in which parenteral amphotericin B therapy was given were studied at a tertiary-care hospital.

Bates DW, Su L, Yu DT et al Clin Infec Dis 2001;32:686-693.

Patients with acute renal failure

Patients with acute renal failure

16%16%

54%54%

5050404030302020101000 1001009090808070706060

Patients without ARFPatients without ARFn=707n=70779/495

115/212


Other Studies: Caspofungin Maintains Favorable Safety/Tolerability ProfileOther Studies: Caspofungin Maintains Favorable Safety/Tolerability Profile

• Overall safety assessed in 876 patients

• 394 patients enrolled in Phase I studies

• Most patients with Candida infections had serious underlying medical conditions, including hematologic or other malignancy, recent major surgery, or HIV

• In a clinical study among patients with oropharyngeal or esophageal candidiasis, caspofungin (n=83) demonstrated a comparable tolerability profile vs. fluconazole (n=94)

• In a clinical study among patients with invasive candidiasis, caspofungin (n=114) demonstrated a superior tolerability profile to amphotericin B (n=125)

• In an open-label, noncomparative aspergillosis (n=69) study, caspofungin maintained its favorable profile

• Overall safety assessed in 876 patients

• 394 patients enrolled in Phase I studies

• Most patients with Candida infections had serious underlying medical conditions, including hematologic or other malignancy, recent major surgery, or HIV

• In a clinical study among patients with oropharyngeal or esophageal candidiasis, caspofungin (n=83) demonstrated a comparable tolerability profile vs. fluconazole (n=94)

• In a clinical study among patients with invasive candidiasis, caspofungin (n=114) demonstrated a superior tolerability profile to amphotericin B (n=125)

• In an open-label, noncomparative aspergillosis (n=69) study, caspofungin maintained its favorable profile



Caspofungin: Minimal Drug InteractionsCaspofungin: Minimal Drug Interactions

• Not a P450 (CYP) inhibitor

• No antagonistic interaction with amphotericin B or itraconazole

• Has been used with antirejection drugs tacrolimus and/or mycophenolate

• Not a P450 (CYP) inhibitor

• No antagonistic interaction with amphotericin B or itraconazole

• Has been used with antirejection drugs tacrolimus and/or mycophenolate

Data on file, MSD; Bartizal K et al Antimicrob Agents Chemother 1997;41:2326-2332.Data on file, MSD; Bartizal K et al Antimicrob Agents Chemother 1997;41:2326-2332.


Caspofungin: Dosing/AdministrationCaspofungin: Dosing/Administration

• Once-daily dosing with 50 mg standard dose

• 70 mg loading dose on day 1 for aspergillosis and invasive candidiasis

• No premedication necessary

• Recommended infusion time: 1 hour

• No dosage adjustment in many cases*

• Once-daily dosing with 50 mg standard dose

• 70 mg loading dose on day 1 for aspergillosis and invasive candidiasis

• No premedication necessary

• Recommended infusion time: 1 hour

• No dosage adjustment in many cases*

* For patients with moderate hepatic insufficiency (Child-Pugh score 7-9), a dose adjustment to 35 mg daily is recommended. There is no clinical experience in patients with severe hepatic insufficiency (Child-Pugh score >9).

Data on file, MSD.

* For patients with moderate hepatic insufficiency (Child-Pugh score 7-9), a dose adjustment to 35 mg daily is recommended. There is no clinical experience in patients with severe hepatic insufficiency (Child-Pugh score >9).

Data on file, MSD.


Conclusions: Caspofungin—The New Gold StandardConclusions: Caspofungin—The New Gold Standard

• Invasive candidiasis:– Caspofungin is comparable to amphotericin B

(MITT analysis)– Caspofungin appears to be superior to

amphotericin B (EP analysis)– Candidemia: Caspofungin is comparable to

amphotericin B

• Overall safety/tolerability profile:– Caspofungin has a favorable tolerability profile

• Invasive candidiasis:– Caspofungin is comparable to amphotericin B

(MITT analysis)– Caspofungin appears to be superior to

amphotericin B (EP analysis)– Candidemia: Caspofungin is comparable to

amphotericin B

• Overall safety/tolerability profile:– Caspofungin has a favorable tolerability profile



ReferencesReferences


ReferencesReferences

Documents

Caspofungin