FUNGISOME^TM i.v. is a sterile, yellow liquid product for intravenous infusion. Each ml of FUNGISOMETM i.v. infusion contains 1 mg of Amphotericin B intercalated in liposomes. It is available in three presentations of 10ml, 25ml and 50ml.

Each ml of FUNGISOME^TM i.v. contains 1mg of AmphotericinB USP in liposomes.

Amphotericin B is a macrolide polyene antibiotic produced by strain of Streptomyces nodosus.

Liposomes are artificial vesicles, composed of concentric lipid bilayers which enclose an aqueous space.  Amphotericin B being lipophilic is intercalated into the lipid bilayer.

Amphotericin B shows a high order of in vitro activity against many species of fungi viz. Histoplasma capsulatum, Cryptococcus immitis, Candida sp., Blastomyces dermatitidis, Rhodotorula, Cryptococcus neoformans, Sporothrix schenckii, Mucor sp.,  Aspergillus sp., Malassezia furfur, Trichosporon beigelii, Saccharomyces cerevisiae, Scedosporium sp., Paecilomyces sp., Penicillium sp., Fusarium sp., Bipolaris sp., Exophiala sp., Cladophialophora sp., Absidia sp., Apophysomyces sp., Cunninghamella sp., Rhizomucor sp., Rhizopus sp. and Saksenaea sp.These fungi are inhibited by concentrations of Amphotericin B ranging from 0.03 to 1 µg/ml in vitro.  Amphotericin B also has activity against species of Leishmania and is found to be effective in the treatment of Kala-Azar.  It has minimal or no effect on bacteria and viruses.

Patients treated with conventional*Amphotericin B develop toxicities such as nephrotoxicity, cardiotoxicity, CNS toxicity, electrolyte disturbances besides acute reactions like fever, chills, nausea, vomiting, etc.  

*Conventional Amphotericin B is micellar suspension of Amphotericin B in deoxycholate

FUNGISOME^TM i.v.  is a liposomal formulation strategically designed to provide remarkably improved therapeutic efficacy and much less toxicity as compared to conventional Amphotericin B which is proven in pre-clinical studies

In Aspergillus pneumonia FUNGISOME^TM i.v. delivered higher drug concentration for longer duration in lungs while it allowed lower concentrations in kidneys as compared to conventional Amphotericin B. In leishmaniasis FUNGISOME^TM i.v. was better tolerated even in dosage of 5mg/kg as compared to 0.8 mg/kg of conventional Amphotericin   B.

In clinical studies, FUNGISOME^TM i.v.  was effective in systemic fungal infections and leishmaniasis cases that did not respond to conventional Amphotericin B and other standard drugs.
Pharmacokinetic parameters of FUNGISOME^TM i.v. were comparable to conventional Amphotericin B.

Pharmacokinetics, after single dose administration of FUNGISOME^TM i.v.
(1 mg/kg body wt.)

FUNGISOME^TM i.v. is indicated in disseminated and invasive systemic fungal infections and also in patients of leishmaniasis.

It has been found to be effective even in cases resistant to standard antifungal drugs and antileishmanial drugs.

Read this section carefully and follow the instructions before administration of FUNGISOME^TM i.v.

Follow the instructions given in product insert.

Follow the instructions given in product insert.

Follow the instructions given in product insert.

The duration of treatment should be decided on the basis of clinical, radiological, histopathological and microbiological assessment. It is advisable to discontinue FUNGISOMETM i.v. treatment only after confirmation of clearance of infection as judged by histopathological and microbiological report.                                        

FUNGISOME^TM i.v. therapy has been administered for as long as 8.5 months (256 days) and maximum total dose of 11.23gms of Amphotericin B was administered without significant toxicity¹ .

After infection of Kala-Azar in the body, Leishmanial parasites (amastigote) are taken up by macrophages and liposomes are also taken up by macrophages thus both the drug and the parasites are present in the same cell for close encounter. There is passive targeting of the drug. This is why FUNGISOME^TMi.v. the Liposomal Amphotericin B is the most effective formulation for the cure of Kala-Azar.

FUNGISOME^TM i.v. has been used in the treatment of visceral leishmaniasis in a dose of 1mg/kg body wt/day for 21 days.  Successful results have also been achieved with the dose of 2mg/kg body wt/day for 10 days or 3mg/kg body wt/day for 7 days. In difficult to treat cases, physician may recommend the treatment for longer duration.

Pediatric patients of systemic fungal infections and visceral leishmaniasis have been treated successfully with doses comparable to adults on a per kilogram body weight basis without any significant adverse effect.

Candidemia in neonates has been treated with FUNGISOME^TM i.v. It is essential to monitor serum levels of electrolytes and withhold FUNGISOME^TM i.v. if serum electrolyte values are below normal range. Mortality has been reported due to electrolyte imbalance possibly related FUNGISOME^TM i.v.  If vomiting is induced by therapy, subsequent administration of FUNGISOME^TM i.v. is recommended on empty stomach to minimize chances of related aspiration.

Based on studies done till now, no specific dosage alteration or precautions are recommended.

Patients with high creatinine levels have been administered FUNGISOME^TM i.v.  If rise in creatinine is noted following FUNGISOME^TM i.v. administration, dose can be reduced to 0.8 mg/kg body wt/day.
In patients with high bilirubin or liver enzymes (SGOT, SGPT) before or during FUNGISOME^TM i.v. treatment, dose should be reduced to 0.8 mg/kg body wt/day.
Further dose alterations or discontinuation should be individualized.

In view of the toxicity of Amphotericin B, use of FUNGISOME^TM i.v. is best avoided, unless the benefits outweigh the risks.

FUNGISOME^TM i.v. is contraindicated in patients who have developed serious hypersensitivity reaction during previous administration of FUNGISOME^TM i.v. or its lipid constituents. Relative contraindications to FUNGISOME^TM i.v. include previous serious reaction to other forms of Amphotericin B (conventional Amphotericin B or other lipid formulations of Amphotericin B). Experience with such cases is limited.
One patient who developed bronchospasm after conventional Amphotericin B did not suffer bronchospasm with FUNGISOME^TM i.v.

In a comparative study FUNGISOME^TM i.v. produced fewer and less severe adverse effects than conventional Amphotericin B. Specifically, adverse effects viz. fever, chills, headache, backache, drowsiness, thrombophlebitis, nausea, vomiting, chestpain, palpitation, apnea, bronchospasm that occur with conventional Amphotericin B have been noted with FUNGISOME^TM i.v. also, but to a much lesser degree.
The problem of fever or rigor could be avoided to some extent by lowering the rate of infusion.

If any serious adverse effects are noted, the infusion should be stopped and the drug withdrawn.
Renal, hepatic, hematological parameters along with serum electrolytes levels should be monitored regularly during treatment. If any deterioration occurs in these parameters, administration of the drug should cease immediately.  Subsequent dosage should be administered on the basis of above mentioned parameters.
Amphotericin B is known to be nephrotoxic.  If the creatinine exceeds 2.5 mg%, dosage should be reduced or discontinued till renal function improves.  Hypokalemia during FUNGISOME^TM i.v.  therapy should be treated appropriately.
In neonates, if fall in packed cell volume (PCV) occurs, it should be treated with transfusions.
Do not use FUNGISOME^TM i.v. if there is any evidence of crystals, foreign material or foreign particle in the bottle.

The use of FUNGISOME^TM i.v. Indian liposomal formulation of Amphotericin B enables to overcome dose related nephrotoxicity of Amphotericin B, thus allowing concomitant use of nephrotoxic drugs and bone marrow suppressants with due precautions and on the advice of the treating physician.

Drug interactions due to possible hypokalemia with FUNGISOME^TM i.v. must be borne in mind and hypokalemia appropriately managed

A.  Unopened bottles of FUNGISOME^TM i.v. must be stored refrigerated at 2-8°C. 
B.  Sonicated FUNGISOME^TM i.v. may be stored for upto 24 hours at 2-8°C. If
   not used within 24 hours of sonication, discard FUNGISOME^TM i.v.
C.  If stored after sonication, shake well before use.
D.  Do not store partially used vial for future patient use.