antifungal comparison

1. MICAFUNGIN VS.
CASPOFUNGIN IN
HSCT

2. Invasive fungal infections
 Invasive fungal infections are a significant
and often lethal problem in transplant
patients.
 They are at risk for these infections as a
result of their general health status,
technical complications of surgery, and
immunosuppression.

3. FUNGAL INFECTIONS IN
TRANSPLANTATION
 The incidence of invasive fungal infections in solid organ transplant
recipients varies according to the type of transplant.
 Most of these infections are due to Candida spp., Aspergillus spp. or
Cryptococcus spp.
 Currently, overall mortality due to invasive fungal infections in solid
organ transplant recipients ranges between 25%-80% and half of these
deaths are directly related to the fungal infection.

5. CANDIDIASIS/
ASPERGILLOSIS
 Candidiasis is the most common
invasive fungal infection in SOT
recipients and accounts for 50–60%
infections.
 Candida species, particularly Candida
albicans, are frequent colonizers of
the human gastrointestinal,
respiratory and reproductive tracts,
and the skin.

6. CANDIDIASIS/
ASPERGILLOSIS
 The majority of invasive candidiasis is
from an endogenous source – usually
the skin or gut.
 Aspergillosis is the next most common
infection, accounting for 20–25% of
fungal infections.
 In lung transplant recipients,
aspergillosis is the most common
infection

7. DISTRIBUTION OF FUNGAL PATHOGENS
CAUSING INVASIVE FUNGAL INFECTIONS IN
TRANSPLANT RECIPIENTS
Ther Adv Infect Dis (2013) 1(3) 85105

8. INCIDENCE IN HSCT
 The incidence of invasive fungal infections in patients
receiving hematopoietic stem cell transplantation (HSCT) is
between 14% and 25%; these infections are associated with a
high rate of mortality
Therapeutics and Clinical Risk Management 2007:3(1)

9. NANTIFUNGALS
ERGOSTEROL SYNTHESIS
INHIBITORS
Voriconazole
Itraconazole
Posaconazole
Fluconazole

10.  Caspofungin, micafungin, and anidulafungin are semisynthetic
echinocandin derivatives with clinical use due to their solubility,
antifungal spectrum, and pharmacokinetic properties.
 All these preparations so far have low oral bioavailability, so
must be given intravenously only.
ECHINOCANDINS

11. MECHANISM OF ACTION
Inhibits the synthesis of β 1,3 – D- glucan via noncompetitive inhibition of
the enzyme 1,3-β glucan synthase and are thus called "penicillin of
antifungals“ resulting in the inhibition of cell wall, leading to lysis and
death.

12. FUNGICIDAL AND FUNGISTATIC
ACTION
 Echinocandins exhibit fungicidal activity against Candida
species, including triazole-resistant isolates, and
fungistatic activity against Aspergillus species.

13. PHARMACOKINETICS
 Due to the large molecular weight of echinocandins, they
have poor oral bioavailability and are administered by
intravenous infusion.
 In addition, their large structures limit penetration into
cerebrospinal fluid, urine, and eyes.
 In plasma, echinocandins have a high affinity to serum
proteins.
 Echinocandins do not have primary interactions with
CYP450 or P-glycoprotein pumps.

14. • Broad range (especially against all Candida), thus can be given
empirically in febrile neutropenia and stem cell transplant.
• Can be used in case of azole-resistant Candida or use as a second-
agent for refractory aspergillosis
• Long half-life
 Not an inhibitor, inducer, or substrate of the cytochrome P450 system,
or P-glycoprotein, thus minimal drug interactions
 No dose adjustment is necessary based on age, gender, race
ADVANTAGES OF
ECHINOCANDINS

15. MOLECULAR COMPARISON
Therapeutics and Clinical Risk Management 2007:3(1)

16. PHARMCOKINETICS
COMPARISON
Therapeutics and Clinical Risk Management 2007:3(1)

17. COMPARATIVE PHARMACOKINETICS
• Caspofungin has triphasic nonlinear pharmacokinetics.
• Micafungin and anidulafungin have linear elimination.

18. MIC AGAINST CANDIDA
SPECIES

19. COMPARISON OF INDICATIONS
Indication Caspofungin Micafungin
Invasive candidiasis Yes Yes
Neutropenic patients Yes Yes
Pediatric patients 12 months or
above
Yes
Neonates No Yes
Prophylaxis in HSCT patients or expected
neutropenic patients
Adults No Yes
Pediatric patients No Yes
Neonates No Yes
Oesophageal candidiasis No Yes
Invasive aspergillosis
Salvage Yes No
Empiric therapy in febrile neutropenia Yes No

20. MICAFUNGIN is the Only drug approved by FDA for prophylaxis
of candida infection in HSCT patient
Indication Dose
Adult Paediatrics 30 kg
or less
Paediatrics greater
than 30 kg
Prophylaxis of Candida
Infections in HSCT
Recipients
50 mg daily** 1 mg/kg/day
(maximum 50 mg daily)
**50 mg micafungin is equivalent to 50.86 mg micafungin sodium

21. DOSAGE COMPARISON IN
DIFFERENT INDICATIONS
 LD=loading dose. MD=maintenance dose
Therapeutics and Clinical Risk Management 2007:3(1)

22. COMPARISON OF DRUG
INTERACTIONS
Micafungin has less drug drug interaction as compared to caspofungin

23. ADVERSE EFFECT COMPARISON
Therapeutics and Clinical Risk Management 2007:3(1)

24. *70 mg loading dose on Day 1
†8 weeks in chronic disseminated candidiasis or Candida endophthalmitis; switch to oral
fluconazole permitted after 10 days in patients meeting protocol-specified criteria
‡Time from last dose day of protocol-defined antifungal therapy to final evaluation
Micafungin
100 mg/day
CAS
50 mg/day*
Treatment
period† Max 4 weeks†
Randomisation
(1:1:1)
6 weeks‡
Post-treatment
period
Phase III study micafungin vs.
caspofungin Study design
Micafungin
150
mg/day
Pappas PG, et al. Clin Infect Dis 2007; 45:883–93 CAS = caspofungin
Patients were stratified by
region and APACHE II score
(≤ 20 or > 20)

25. Phase III study micafungin vs.
caspofungin: treatment success
Pappas PG, et al. Clin Infect Dis 2007; 45:883–93
n = 191 n = 188n = 199
Caspofungin
50 mg/day*
Treatmentsuccessrate(%)
76.4
71.4 72.3
0
20
40
60
80
n = 191 199 188
Micafungin
100 mg/day
Micafungin
150 mg/day
*Loading dose 70 mg; mITT population

26. Phase III study micafungin vs.
caspofungin: treatment success by
Candida species
C. albicans Any non- C. glabrata C. tropicalis C. parapsilosis C. krusei
albicans
Pappas PG, et al. Clin Infect Dis 2007; 45:883–93
Non-albicans Candida spp.
*Loading dose 70 mg; mITT population
Micafungin 100 mg/day
(n = 191)
Treatmentsuccessrate(%)
p = NS
p = 0.07 (NS)
Micafungin 150 mg/day
(n = 199)
Caspofungin 50 mg/day*
(n = 188)
p = NS p = NSp = NS p = NS
0
10
20
30
40
50
60
70
80
90
100
n = 92 102 83 104 102 114 28 34 33 31 33 32 29 21 42 8 8 4
77.2
69.6
73.5 75.0
71.6 71.1
85.7 88.2
66.7 67.7
60.6
75.0 75.9
71.4
64.3
75.0
62.5
75.0

27. Phase III study micafungin vs.
caspofungin: treatment success by
neutropenic status
Overall Non-neutropenic
Pappas PG, et al. Clin Infect Dis 2007; 45:883-93
n = 199
Micafungin
100 mg/day
17
Treatmentsuccessrate(%)
0
100
80
60
40
20
Micafungin
150 mg/day
Caspofungin
50 mg/day*
182 188 11177
Neutropenic
191 22169
76.4
81.8
71.4
52.9
72.3
63.6
75.7
73.1 72.9
*Loading dose 70 mg; mITT population