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FUNGISOME® i.v.

FUNGISOME® i.v.

Amphotericin B is the most potent and broad-spectrum antifungal of all the drugs discovered in more than a century of global efforts. Amphotericin B has been in clinical use and has not shown any drug resistance. On one hand owing to its merits it earned the status of a Gold Standard while on the other hand the dose limiting and frequently fatal toxicities predominantly nephrotoxicity labeled it as Ampho- the- Terrible.

Despite the nephrotoxicity in two-thirds of the patients using Amphotericin B, hitherto no better drug could be discovered to replace its broad-spectrum and drug sensitivity- in fact the only antifungal free of drug resistance.

Amphotericin B- The only Broad-Spectrum Antifungal

Product name Candida Aspergillus Mucor Cryptococcus
FUNGISOME® i.v. Yes Yes Yes Yes
Fluconazole Variable No No Yes
Itraconazole Variable Yes No Yes
Voriconazole Variable Yes No Yes
Posaconazole Yes Yes Variable Yes
Caspofungin Variable Yes No No
Anidulafungin Yes Yes No No
Micafungin Yes Yes No No

In vitro antifungal activity of FUNGISOME® i.v.

FUNGISOME® i.v. was found to be very stable, safe and highly potent against commonly occurring fungal pathogen. MIC90 of FUNGISOME® i.v. was tested against 262 fungal pathogen clinical isolates. The in vitro activity of FUNGISOME® i.v. appears to be better and has broader-spectrum compared to Conventional Amphotericin B and other Lipid/Liposomal Amphotericin B.

MIC90 of FUNGISOME® i.v. is 2 to 16 times lower than Amphotericin B deoxycholate (Conventional Amphotericin B) for 262 isolates except one Paecilomyces lilacinus. All the isolates of Candida haemulonii are found to be sensitive to FUNGISOME® i.v. with MIC50 of 0.5mg/l, whereas Conventional Amphotericin B is resistant. FUNGISOME® i.v. is found to have broader spectrum of antifungal activity than Conventional Amphotericin B. These findings are in contrast with in vitro studies2,3 conducted with other Amphotericin B formulations, which indicated that other lipid formulations are equally or less active in vitro than Conventional Amphotericin B against Candida spp., Aspergillus flavus, Aspergillus fumigatus and Cryptococcus neoformans.

MIC Comparison of Lipid/Liposomal formulations with reference to Conventional Amphotericin B

Product Yeast Filamentous fungi
Ablecet1 0.51 ± 0.21 4.34 ± 0.61
AmBisome1 1.28 ± 0.24 5.68 ± 0.57
Amphotericin B1 0.29 ± 0.11 1.12 ± 0.19
Product Yeast Filamentous fungi
FUNGISOME® i.v. 2 0.125 (0.03-0.5) (0.06-2.0)
Amphotericin B2 0.5 (0.125-16.0) 0.5-4.0

References:

  1. Jessup C et al. A head- on comparison of the in vitro antifungal activity of conventional and lipid-based amphotericin B: a multicentric study. J Chemother. 2000.Feb;12(1):22-29.
  2. Rudramurthy SM et al. In vitro antifungal activity of Indian liposomal amphotericin B against clinical isolates of emerging species of yeast and loulds, and its comparison with amphotericin B deoxycholate, voriconazole, itraconazole and fluconazole. Mycoses. 2013;56:39-46.

Out of all Amphotericin B and Liposomal Amphotericin B formulations only FUNGISOME® i.v. is effective against
Candida aureus and Candida haemulonii

  • FUNGISOME® i.v. developed in India by combining Liposome- and Nano- Technologies along with strategic changes in composition have given a Nanosomal Amphotericin B which is most broad-spectrum , potent at lower dose and yet nephrosafe at high dose.
  • It has been administered for as long as 8.5months (256 days) and maximum total dose of 11.23g of Amphotericin B was administered without significant toxicity.
  • Theses distinguishing features of FUNGISOME® i.v. make it the best antifungal ever developed anywhere in the world for the treatment of systemic as well as superficial fungal infections and Visceral Leishmaniasis - vector borne parasitic disease commonly known in Indian sub-continent as Kala- Azar.
  • FUNGISOME® i.v. is also found to be effective in the treatment of Kala-Azar.
  • The below diagram showing the comparison of two trials; one with AmBisome and other with FUNGISOME® i.v. alone and FUNGISOME® i.v. with Miltefosine for the Treatment of Post Kala-Azar Dermal Leishmaniasis. In AmBisome group, the success rate was 83.16% , 10 cases of recurrence of Visceral Leishmaniasis and 32 cases of PKDL were reported. In FUNGISOME® i.v. group, there was 100% cure rate without any recurrence and PKDL cases
chart

* Mondal et. al. Relationship of Serum Antileishmanial Antibody With Development of Visceral Leishmaniasis, Post-kala-azar Dermal Leishmaniasis and Visceral Leishmaniasis Relapse. Front. Microbiol., 09 October 2019. doi.org

** Goswami R P et al. Combination Therapy against Indian Visceral Leishmaniasis with Liposomal Amphotericin B (FUNGISOME® i.v.) and Short- Course Miltefosine in Comparison to Miltefosine Monotherapy. Am J Trop Med Hyg, doi: 10.4269/ajtmh.19-0931,2020 doi.org

*** Chadha AA et. al. Treatment of Post Kala-Azar Dermal Leishmaniasis with FUNGISOME® i.v. – A Novel Indian Liposomal Amphotericin B. Indian J Drugs Dermatol. 6:28-31,2020. doi.org

Amphotericin B i.v. formulations Daily Dose mg (kg/day) Antifungal Efficacy
Liposomal Amphotericin B in Saline 1-3mg/kg/day1,2 > 90%
Phase II-94.0%3
Phase III- 90.9%3
Phase IV- 91.1%2
Liposomal Amphotericin B (AmBisome & its copies) 3-6mg/kg/day4,5 40-42%7
77 %8
Amphotericin B conventional/ Lipid Emulsion 1/2 - 5mg/kg/day6 31.69
Amphotericin B Lipid Complex 5mg/kg/day7 33.37
  1. Kshirsagar NA et al. (2005) J Postgrad Med 51 (Suppl 1):S5-15.
  2. Sanath SS et al. (2005) J Postgrad Med 51 (Suppl 1):S58-63.
  3. FUNGISOME® i.v. Product Insert.
  4. Ambisome® USA Product Insert/Information-February, 2019.
  5. Phosome Product Insert Information-(September,2013, Downloaded on February 22nd, 2020).
  6. Amphomul Literature
  7. Wingard et al. (2000) Clinical Infectious Diseases, 31(5):1155-1163.
  8. Ringdén O (2002) Journal of Antimicrobial Chemotherapy 49. (Suppl S1):51-55.
  9. Herbrecht R et al. (2002) New England Journal of Medicine, Vol. 347(6):408-415.
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Nephro-toxicity Hepato-toxicity
Amphotericin B Formulations Conventional Amphotericin B 34%-60%1
FUNGISOME® i.v./
AmBullet® i.v.
No Nephrotoxicity
reported 2,3,4,5
No Hepatotoxicity
Liposomal Amphotericin B 10%-20% 1
26.9%6
34%-60%1
Lipid Complex 42-63% 1 34%-60%1
Lipid Emulsion Not reported Data not available
Echinocandins Caspofungin 16.7% 7 22.4% 8
Anindulafungin 37.2% 8
Azoles Micafungin 23.2% 8
Fluconazole 8% 9
Itraconazole 5% 10 10% 10
Voriconazole 7% 11 19.2% 12
Posaconazole 5%-11% 13
  1. Richardson MD et al. Therapeutic Guidelines in Systemic Fungal Infections (3rd Edition), Current Medical Literature, page 43.
  2. Hegde S et al. (2005) Post-marketing study to assess the safety, tolerability and effectiveness of LAmB-Saline; An Indian Liposomal Amphotericin B preparation. Journal of Postgraduate Medicine. 51(suppl. 1): s58-s63.
  3. Kshirsagar NA et al. (2005) Liposomal Drug Delivery System from Laboratory to clinic. Journal of Postgraduate Medicine. 51(1): s5-s15.
  4. Bodhe PV et al. (2002) Open Label, Randomized comparative phase III safety an efficacy study with conventional Amphotericin B and liposomal Amphotericin B in patients with systemic fungal infection. JAPI. 50: 662-670.
  5. Jadhav MP et al. (2010) Liposomal Amphotericin B (LAmB-SalineTM) for the treatment of cryptococcal meningitis in HIV/AIDS patients in India; A multi-centric, randomized controlled trial. JPM. 56(2): 71-75.
  6. Walsh TJ et al. (1999)Liposomal Amphotericin B for empirical therapy in patients with persistent fever and neutropenia. New England Journal of Medicine. 340 (10): 764-771.
  7. Ellis M et al. (2006) An open study of the comparative efficacy and safety of Caspofungin and Liposomal Amphotericin B in treating invasive fungal infections or febrile neutropenia in patients with hematological malignancy. Journal of Medical Microbiology. 55:1357-1365.
  8. Vekeman F et al. (2018) Retrospective cohort study comparing the risk of severe hepatotoxicity in hospitalized patients treated with echinocandins for invasive candidiasis in the presence of cofounding by indication. BMC Infectious Disease. 18(1): 438.
  9. Fischer MA et al. (2005) The Hepatotoxicity of Antifungal Medications in Bone Marrow Transplant Recipients. Clinical Infectious Diseases. 41(3): 301-307.
  10. Park SH et al. Intravenous Itraconazole vs. Amphotericin B Deoxycholate for Empirical Antifungal Therapy in Patients with Persistent Neutropenia Fever. Korean J Intern Med. 21(3): 165-172.
  11. Walsh TJ et al. (2002) Voriconazole compared with Liposomal Amphotericin B for empirical therapy in patients with neutropenia and persistent fever. The N Engl J Med. 364(4):225-234.
  12. Vfend (Voriconazole) Product Monograph (Table 4 & 5, page 16,17).
  13. Tverdek FP et al. (2016) Antifungal agents and liver toxicity: a complex interaction. Expert Review of Anti-infective Therapy. 14(8): 765-776.
medicine

FUNGISOME® i.v. - A Patented Innovative Liposomal Amphotericin B in Saline Most Nephro-safe and Effective Formulation