Israel - English - Ministry of Health
ןולעב )תוחיטב ןולעב )תוחיטב
םושירה רפסמו תילגנאב רישכת םש
PENTOSTAM , 102-10-24710
םושירה לעב םש
GlaxoSmithKline (ISRAEL) Ltd
אפורל ןולעב אפורל ןולעב תורמחהה
Special Warnings and
There have been some reports of cardiac
arrhythmias and sudden death when
amphotericin B deoxycholate is
administered soon after sodium
stibogluconate for retreatment of visceral
leishmaniasis. Electrolyte imbalances
should be corrected prior to
administration of amphotericin B
deoxycholate, and patients appropriately
ונמוס תורמחה רדגב םניאש םייוניש ןולעב
The format of this leaflet was determined by the Ministry of Health
and its content was checked and approved in July 2013
Formulation and Strength
Injections of sodium stibogluconate containing the equivalent of 100 mg/ml
Water for injection
Sodium stibogluconate is indicated for the following diseases:
Visceral leishmaniasis (Kala Azar);
South American mucocutaneous leishmaniasis.
Sodium stibogluconate may also be of value in the treatment of leishmaniasis
recidivans and diffuse cutaneous leishmaniasis in the New World.
Note: Cutaneous and diffuse cutaneous leishmaniasis caused by Leishmania
aethiopica infections are unresponsive to treatment with pentavalent antimony
compounds, including sodium stibogluconate injection, at conventional
dosage, but may respond slowly at higher dosage.
Dosage and Administration
Except where otherwise stated, all doses should be given by the intravenous
or intramuscular route (see Warnings and Precautions).
Due to the presence of particulates (size range 20 to 300 microns) sodium
stibogluconate solution should be drawn up through a sterile filter immediately
prior to administration. These particulates are insoluble complexes formed
by an interaction between product preservative and the antioxidant in the
rubber stopper. Filters of pore size 5 microns or less and membrane types
polyvinylidene difluoride, polyethersulphone, polysulphone, nylon, surfactant-
free cellulose acetate and mixed cellulose esters have been shown to be suitable.
Where sterile filters are not available the risks and benefits of administering
unfiltered sodium stibogluconate therapy should be assessed by the clinician
on an individual basis.
All dosage recommendations are based on the findings of the WHO Expert
Committee on leishmaniasis, which met in 1984. There are no special
recommendations for different age groups.
10 to 20 mg pentavalent antimony (0.1-0.2 ml sodium stibogluconate injection)
per kg bodyweight to a maximum of 850 mg (8.5 ml sodium stibogluconate
injection) daily for a minimum period of 20 days.
Patients should be examined for evidence of relapse after 2 and 6 months,
and in Africa after twelve months.
Cutaneous Leishmaniasis not caused by L. aethiopica
The dosage regimen outlined for visceral leishmaniasis is recommended.
Alternatively, single, non-inflamed nodular lesions known not to be due to
L. braziliensis may be treated with intralesional injections of 100 to 300 mg
pentavalent antimony (1-3 ml sodium stibogluconate injection) repeated once
or twice if necessary at intervals of 1 to 2 days. Infiltration must be thorough
and produce complete blanching of the base of the lesion.
Individuals with cutaneous leishmaniasis due to L. braziliensis should be treated
systemically for several days after the lesion is healed.
Note: After successful treatment of L. braziliensis, anti-leishmania antibody
titres decline steadily over 4-24 months.
Patients with parasitologically confirmed leishmaniasis should be treated
with 20 mg pentavalent antimony (0.2 ml sodium stibogluconate injection)
per kg bodyweight to a maximum of 850 mg (8.5 ml sodium stibogluconate
injection) daily, continuing this dosage for several days longer than it takes
to achieve parasitological and clinical cure.
In the event of relapse, a further course should be given for at least twice
the previous duration.
Diffuse cutaneous leishmaniasis in the New World and leishmaniasis
Owing to the rarity of these conditions, precise data on dosage are not
available. A dose of 10 to 20 mg pentavalent antimony (0.1-0.2 ml sodium
stibogluconate injection) per kg bodyweight to a maximum of 850 mg (8.5
ml sodium stibogluconate injection) may be given daily for 2-3 weeks. If there
is a response then treatment should be maintained until several days after
clinical cure of leishmaniasis recidivans and for several months after clinical
and parasitological cure of diffuse cutaneous leishmaniasis.
There is little information on the effects of sodium stibogluconate on elderly
individuals. If treatment of cutaneous leishmaniasis is necessary then local
infiltration is preferred. The normal precautions should be strictly adhered to
when treating older patients for visceral leishmaniasis.
- Sodium stibogluconate injection should not be given to any patient with
significantly impaired renal function.
- Sodium stibogluconate injection should not be given to any patient who
has experienced a serious adverse reaction to a previous dose.
Warnings and Precautions
Intravenous injection should be filtered immediately prior to use (see Dosage
and Administration). Administer very slowly over 5 min to reduce the risk of
local thrombosis. In the unlikely event of coughing, vomiting or substernal
pain occurring, administration should be discontinued immediately. In such
cases, extreme care should be taken if sodium stibogluconate is re-administered
by this route.
Successful treatment of mucocutaneous leishmaniasis may induce severe
inflammation around the lesion. In cases of pharyngeal or tracheal involvement,
this may be life-threatening. Under such circumstances, corticosteroids may
Very rarely, anaphylactic shock may develop during treatment, for which
adrenalin injection and appropriate supportive measures should be given
Prolongation of the QTc interval has been observed in some patients taking
sodium stibogluconate and appears to be dose-related. There have also
been reports of fatal cardiac arrhythmias in patients receiving higher dose
antimonial therapy for visceral leishmaniasis. Therefore, ECG monitoring
is recommended before and during therapy with sodium stibogluconate.
Where ECG monitoring is not available, the risks and benefits of sodium
stibogluconate therapy should be assessed on an individual basis.
If clinically significant prolongation of QTc interval occurs, sodium stibogluconate
should be discontinued. Electrocardiographic changes, notably alterations in
T-wave amplitude may be expected in the majority of patients given sodium
stibogluconate. These appear to be reversible on cessation of therapy and
are not of serious significance.
Sodium stibogluconate should be used cautiously in patients with cardiovascular
disease, a history of ventricular arrhythmias or other risk factors known to
predispose towards QT prolongation: for example, those with congenital QTc
prolongation or taking concomitant drugs known to significantly prolong the
QT interval (e.g. class
anti-arrhythmics such as sotalol and amiodarone).
As there appears to be a dose relationship in the development of ECG
abnormalities, prior exposure to antimonial therapy should be considered
when assessing a patient’s suitability for initiating or continuing therapy with
Patients who have recently received other antimonial drugs should be monitored
closely for signs of antimony intoxication such as bradycardia and cardiac
arrhythmias during administration of sodium stibogluconate.
There have been some reports of cardiac arrhythmias and sudden death when
amphotericin B deoxycholate is administered soon after sodium stibogluconate
for retreatment of visceral leishmaniasis. Electrolyte imbalances should be
corrected prior to administration of amphotericin B deoxycholate, and patients
Intercurrent infections, such as pneumonia, should be sought and treated
High concentrations of antimony are found in the livers of animals after
repeated dosage with pentavalent antimony.
Sodium stibogluconate should therefore be used with caution in patients
with hepatic disease. However, some abnormalities of liver function may be
expected in cases of visceral leishmaniasis. In such patients the benefit of
pentavalent antimony treatment outweighs the risk. Sodium stibogluconate
may induce mild elevation of hepatic enzymes in serum which later return
No interactions with sodium stibogluconate have been reported.
There is no information on whether sodium stibogluconate interferes with
the accuracy of routine biochemical tests.
Pregnancy and Lactation
Although no effects on the foetus have been reported, sodium stibogluconate
should be withheld during pregnancy unless the potential benefits to the
patient outweigh the possible risk to the foetus.
Children should not be breast-fed by mothers receiving sodium
Ability to perform tasks that require judgement, motor or
Approximately 1 to 2% of patients complain of nausea, vomiting and/or
diarrhoea and a slightly higher number of abdominal pain.
Other common side effects include anorexia, malaise, myalgia, arthralgia,
headache and lethargy.
ECG changes, including reduction in T-wave amplitude, T-wave inversion and
QT prolongation have been observed (see Warnings and Precautions).
Transient coughing immediately following injection was reported with varying
frequency during several trials.
Intravenous injection of sodium stibogluconate may cause transient pain along
the course of the vein and eventually thrombosis of that vein.
Transient rises in serum lipase and amylase may occur during treatment with
sodium stibogluconate. Symptomatic pancreatitis has also been reported.
During some early trials of sodium stibogluconate, pneumonia occurred in a
small number of patients treated for visceral leishmaniasis and this occasionally
proved fatal. Pneumonia is a feature of the visceral leishmaniasis disease
process; however it has been associated with the toxicity profile of trivalent
antimony. It is, therefore, not possible to determine whether these cases were
due to the disease or to sodium stibogluconate.
Other (rarely reported) side effects include fever, rigor, sweating, vertigo,
facial flushing, worsening of lesions on the cheek, bleeding from the nose
or gum, substernal pain, jaundice and rash.
Transient reductions in platelets, white blood cells and haemoglobin have
Symptoms and Signs
The main symptoms of antimony overdosage are gastro-intestinal disturbances
(nausea, vomiting and severe diarrhoea). Haemorrhagic nephritis and hepatitis
may also occur.
There is only limited information on the use of chelating agents in the treatment
of intoxication by antimony compounds.
Dimercaprol has been reported to be effective; a dose of 200 mg by i.m.
injection every six hours until recovery is complete has been suggested.
2,3-Dimercaptosuccinic acid (DMSA) may also be effective treatment.
Mechanism of Action
The mode of action of sodium stibogluconate is unknown. In vitro exposure
of amastigotes to 500 mg pentavalent antimony/ml results in a greater
than 50% decrease in parasite DNA, RNA protein and purine nucleoside
triphosphate levels. It has been postulated that the reduction in ATP (adenosine
triphosphate) and GTP (guanosine triphosphate) synthesis contributes to
decreased macromolecular synthesis.
During daily administration there is a slow accumulation of sodium stibogluconate
into the central compartment so that tissue concentrations reach a theoretical
maximum level after at least 7 days.
Following i.v. or i.m. administration of sodium stibogluconate, antimony is
excreted rapidly via the kidneys, the majority of the dose being detected in
the first twelve-hour urine collection. This rapid excretion is reflected by a
marked fall in serum or whole blood antimony levels to approximately 1 to
4% of the peak level by 8 h after an i.v. dose.
The expiry date of the product is indicated on the label and packaging.
Store below 25
C. Protect from light.
Do not freeze.
100 ml vial: The contents should not be used more than one month after
removing the first dose.
Keep out of the reach of children.
Nature and Contents of Container
Neutral, amber glass vial sealed with a chlorobutyl rubber closure and aluminium
collar with polypropylene flip-top cover.
Pack size: 100 ml
Use and Handling
Sodium stibogluconate should be filtered immediately prior to use (see
Dosage and Administration).
Glaxo Operations (UK) Limited, Barnard Castle, UK.
License Holder and Importer
GlaxoSmithKline (Israel) Ltd., 25 Basel St., Petach Tikva
Pen DR v2 21824