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FUNGISOME™ when used for
treatment of invasive fungal infections has shown
negligible nephrotoxicity. This is evident from
the PhaseI, PhaseII, PhaseIII and Phase IV data as
well as several case studies. Excerpts from various
published reports are given below.
Pharmacokinetics and tolerance of liposomal
amphotericin B in patients. Gokhale PC,
Barapatra RJ, Advani SH, Kshirsagar NA, and Pandya
SK. J Antimicrobial Chemotherapy 1993(32);
133-139
Twelve adult patients aged 16-63 y and weighing 39-
75 kg, were include in this study. These patients
were suffering from ………
chronic renal failure and transplant rejection (1)
or chronic renal failure and histoplasmosis (1),
renal and hepatosplenic candidiasis(1).
The rise in serum creatinine in one patient may be
due to chronic renal failure associated with
histoplasma infection of the kidneys.
The Possible explanation for rise in blood urea
nitrogen may be poor oral intake and chronic renal
failure
There were no dose-limiting toxicities observed
with liposomal amphotericin B in this study.
Treatment of candiduria with liposomal
amphotericin B (L-AmpB-LRC) in children. Gokhale
PC, Kshirsagar NA, Khan MU, Pandya SK, Merchant RH,
Mehta KP, Colaco MP. J. Antimicrob Chemother
1993; 33: 889-891.
Successful treatment of candiduria in three children
with nephrotic syndrome using liposomal amphotericin
B.
Liposomal amphotericin B was well tolerated in
all the three children.
None of the patients showed any deterioration in
renal function, which was normal before starting
liposomal amphotericin B.
Drug treatment of systemic fungal infection: our
experience with liposomal Amphotericin B.
Kshirsagar NA, Gokhale PC, and Pandya SK. Indian
J of Hematology and Blood Transfusion 1993;
11:72-79.
Nephrotoxicity or hepatotoxicity has not been
observed even in patients with pre-existing liver
disease on doses up to 3mg/kg/day. One of the
patients of candidemia was a case of renal
transplant receiving cyclosporine. Treatment with
liposomal amphotericin B could be successfully
completed to achieve complete cure.
Liposomes as Drug delivery systems in
leishmaniasis. Kshirsagar NA, Gokhale PC, Pandya
SK. JAPI 1995; 43(1):46-48.
A patient with renal transplant and receiving
immunosuppressive therapy had developed
hepatosplenomegaly and was diagnosed as visceral
leishmaniasis…….L-AmpB-LRC, 0.8mg/kg/day was
administered for 14 days. At the end of which LD
bodies had disappeared from bone marrow aspirate.
During this period his creatinine remained stable
Safety and efficacy of Liposomal Amphotericin B
(L-AMP-LRC-1) in patients with cryptococcal
meningitis. Kotwani RN, Gokhale PC, Bodhe PV,
Kirodian BG, Kshirsagar NA. JAPI 2001; 49:1086-1090.
A 23 year old male, who had received a renal
transplant …… His serum creatinine level of
6mg/dl.…….A subsequent examination of the CSF
revealed confluent growth of Cryptococcus neoformans
on culture…… Therapy with liposomal amphotericin
B was started at a dose of 0.8mg/kg on alternate
days. This dose was given in view of his high
serum creatinine concentration. It was felt that in
the presence of impaired renal function this dose
would prove adequate. After the fifth dose of
liposomal amphotericin B, the clinical condition of
the patient improved. He received a total dose of
1400mg of amphotericin B. Since he was receiving
immunosuppressive therapy, liposomal amphotericin B
was continued at a dose of 1mg/kg/week as
prophylaxis. After six weeks the treatment was
stopped.
Safety and efficacy of Liposomal Amphotericin B
(L-AMP-LRC-1) in patients with cryptococcal
meningitis. Kotwani RN, Gokhale PC, Bodhe PV,
Kirodian BG, Kshirsagar NA. JAPI 2001; 49:1086-1090.
In spite of prolonged therapy with liposomal
amphotericin B there was no deterioration in kidney
function. One patient who showed an increase in
levels of blood urea nitrogen had received treatment
with the aminoglycoside, amikacin. After stopping
amikacin treatment the levels reversed to the
pre-treatment values.
A major advantage of liposomal amphotericin B was
observed in renal transplant patients in whom
administration of conventional amphotericin B was
not possible due to its potential nephrotoxicity. It
was encouraging that liposomal amphotericin B could
be given safely to patients even in the setting of
kidney dysfunction.
Open label, randomized, comparative Phase III safety
and efficacy study with conventional Amphotericin B
and Liposomal amphotericin B in patients with
systemic fungal infections. Bodhe PV, Kotwani RN,
Kirodian BG, Kshirsagar NA, Pandya SK. JAPI 2002;
50: 662-670.
Six patients had received 44-136 infusions of L-AmpB-
LRC-1(2.2-6.2g of total ampB). In none of these
patients was thetre a significant increase in
creatinine, except in one case of renal
transplant with mucormycosis: serum creatinine
rose from pretreatment value of 2.6 to 3.9 mg %
(normal limits 0.6-1.1mg %). However this did not
warrant dose reduction or discontinuation of therapy
Among patients treated with conventional
amphotericin B, one of these was a case was of
chronic renal failure with mucormycosis: his
creatinine increased to 11.8mg% from pretreatment
value of 5.6mg%and he required repeated dialysis to
complete 40 doses of amphotericin B. In another
patient c-Amp B treatment was discontinued for 4
days due to rise in serum creatinine to 2.5mg%.
In the phase three safety and efficacy study
Liposomal amphotericin B was found to be less
nephrotoxic than c-Amp B and could be administered
to patients who had renal problems or had undergone
renal transplant.
Liposomal Drug Delivery System from Laboratory to
patients; Our experience. Kshirsagar NA, and
Kirodian BG. Proc. Indian Natn Sci Acad. (PINSA)
2002; 4:333-348.
Data on patients who had received more than 40 doses
of amphotericin B or liposomal amphotericin B was
specifically analyzed for effect on creatinine.
(patients who received lower doses had no
significant alteration in creatinine.)
Eleven patients received 44-147 infusions of
liposomal amphotericin B (2.2-10.99gm). Three had
renal disease, two having had renal transplant. In
none of these patients was there any significant
increase in creatinine.
One patient was a case of multiple myeloma with
chronic renal failure and renal transplant. His
creatinine had risen to 6.7mg% with 12 doses of c-AmpB
while no rise in creatinine occurred after 75
doses of liposomal amphotericin B.
Five patients had been treated with only plain
amphotericin B. One of these was a case of chronic
renal failure , his creatinine increased to 11.8mg%
and he required repeated dialysis to complete 40
doses of amphotericin B.
Treatment of Neonatal Candidiasis with Liposomal
Amphotericin B (L-AMP-LRC-1) Phase II study.
Kotwani RN, Bodhe PV, Kirodian BG, Mehta KP, Ali US,
Kshirsagar NA Indian Pediatrics, 2003;
40:545-550.
Three patients had serum creatinine above normal
before onset of treatment. There was no rise
during or after treatment in creatinine in any
patient, values were (mean ± SD) 0.76 ± 0.46 and
0.73 ± 0.25 mg % pre and post treatment
respectively.
Post-marketing study to assess the safety,
tolerability and effectiveness of FUNGISOME™. An
Indian Liposomal Amphotericin B Preparation Sanath
SS, Gogtay NJ, Kshirsagar NA, J Postgrad Med, 2005;
51(1): 58-62.
Of 109 patients treated with FUNGISOME™ none
showed increase in serum creatinine by more than
twice the baseline value. Data of the 4 patients
with pre-existing renal dysfunction, who had
received more than 40 doses (each received 40, 56,
57 and 76 infusions respectively) of FUNGISOME™
was specially analyzed for the effect on creatinine
( baseline serum creatinine 2.5mg/dl). Patient who
received lower than 40 doses also did not have any
significant alteration in creatinine.
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