Note: Dosage is expressed as mg of pentavalent antimony.
Leishmaniasis (off-label use):
Cutaneous, treatment: IM, IV: 20 mg/kg/day (CDC 2021a; HHS [OI adult 2021]; IDSA/ASTMH [Aronson 2016]). Duration of therapy is 10 to 20 days (CDC 2021a; IDSA/ASTMH [Aronson 2016]) except for patients with HIV where the duration is 28 days (HHS [OI adult 2021]).
Mucosal, treatment: IM, IV: 20 mg/kg/day for 28 days (CDC 2021a; IDSA/ASTMH [Aronson 2016]).
Visceral, treatment (alternative agent): IM, IV: 20 mg/kg/day for 28 days (CDC 2021a; HHS [OI adult 2021]; IDSA/ASTMH [Aronson 2016]).
Visceral, chronic maintenance therapy for patients with CD4 cell count <200 cells/mm3 (alternative agent): IM, IV: 20 mg/kg every 4 weeks. Note: Some experts suggest that therapy may be discontinued after a sustained (>3 to 6 months) increase in CD4 cell count to >200 to 350 cells/mm3 in response to antiretroviral therapy, although others suggest that it be continued indefinitely (HHS [OI adult 2021]).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Avoid use in significant impairment (McCarthy 2015).
Avoid use (WHO 2010).
Leishmaniasis: IM, IV: Refer to adult dosing.
Avoid use in significant impairment (McCarthy 2015).
Avoid use (WHO 2010).
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, Solution, as sodium: Equivalent to 100 mg of pentavalent antimony/mL (30 mL, 100 mL)
Sodium stibogluconate is not commercially available in the United States; it is available for the treatment of leishmaniasis through the Centers for Disease Control (CDC) Drug Service for patients that meet the eligibility criteria in the Investigational New Drug (IND) protocol. Contact the CDC Drug Service at 404-639-3670 or [email protected]. Additional information from the CDC is available at https://www.cdc.gov/laboratory/drugservice/formulary.html.
IM, IV: Administer IM or IV (preferred) over 5 to 10 minutes; IM injection may be painful because volume per dose may be large (McCarthy 2015; WHO 2010).
IM, IV: Administer IV (preferred) over 5 to 10 minutes; IM may also be used although IM injection may be painful because of high dose volume (McCarthy 2015; WHO 2010).
Leishmaniasis
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
1% to 10%: Gastrointestinal: Diarrhea (≤2%), nausea (≤2%), vomiting (≤2%)
Frequency not defined:
Cardiovascular: Flattened T wave on ECG, inversion T wave on ECG, prolonged QT interval on ECG
Central nervous system: Headache, lethargy, malaise
Endocrine & metabolic: Increased amylase
Gastrointestinal: Abdominal pain, anorexia, increased serum lipase (transient)
Hematologic & oncologic: Change in platelet count (decreased; transient), decreased hemoglobin (transient), decreased white blood cell count (transient)
Neuromuscular & skeletal: Arthralgia, myalgia
Respiratory: Cough (transient), pneumonia
<1%, postmarketing, and/or case reports: Diaphoresis, facial flushing, fever, hemorrhage (from nose or gums), jaundice, pancreatitis, rigors, skin rash, substernal pain, vertigo
Concerns related to adverse effects:
• Altered cardiac conduction: ECG changes, including T-wave inversion, prolonged QT interval, and arrhythmia may occur and appear to be dose and duration dependent. Cardiotoxicity and sudden death have been reported (rare). Discontinue immediately if prolongation of a corrected QT interval >0.5 seconds or other signs of cardiotoxicity (eg, significant arrhythmia, concave ST segments) occur. (Herwaldt 1992; WHO 2010)
• Hematologic effects: Anemia, leukopenia, and thrombocytopenia may occur during treatment; periodically monitor CBC. If possible, iron deficiency should be corrected prior to therapy initiation (WHO 1995; WHO 2010).
• Hepatotoxicity: Elevated liver enzymes may occur; periodically monitor LFTs. Discontinue use if hepatotoxicity occurs (WHO 2010).
• Musculoskeletal effects: Arthralgias and myalgias, sometimes severe and persisting for weeks after treatment, may occur (McCarthy 2015).
• Pancreatitis: Pancreatic enzyme elevations are common; pancreatitis is less common but may occur. Avoid use in patients with preexisting pancreatic disease (WHO 2010).
Disease-related concerns:
• Cardiac disease: Avoid use in patients with preexisting cardiac disease (WHO 2010).
• Hepatic impairment: Avoid use in patients with preexisting hepatic disease (WHO 2010).
• Renal impairment: Use is not recommended in patients with significant renal impairment (McCarthy 2015).
Special populations:
• Elderly: Patients of advanced age are at higher risk for toxicity-related mortality; use with caution (WHO 2010).
None known.
Amisulpride (Oral): May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk C: Monitor therapy
Amphotericin B: May enhance the cardiotoxic effect of Sodium Stibogluconate. Management: Consider separating courses of sodium stibogluconate and amphotericin B by at least 14 days. Correct electrolyte imbalances prior to initiating amphotericin B and closely monitor cardiac status. Risk D: Consider therapy modification
Amphotericin B Deoxycholate: May enhance the cardiotoxic effect of Sodium Stibogluconate. Specifically, arrhythmia and sudden cardiac death risks may be increased. Management: Consider separating courses of sodium stibogluconate and amphotericin B deoxycholate by at least 14 days. Correct electrolyte imbalances prior to initiating amphotericin B deoxycholate and closely monitor cardiac status. Risk D: Consider therapy modification
Chloroquine: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Chloroquine. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Clofazimine: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Clofazimine. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Domperidone: QT-prolonging Agents (Moderate Risk) may enhance the QTc-prolonging effect of Domperidone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Gadobenate Dimeglumine: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Gadobenate Dimeglumine. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Halofantrine: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Halofantrine. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Haloperidol: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Haloperidol. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Lofexidine: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Lofexidine. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Midostaurin: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Midostaurin. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Ondansetron: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Ondansetron. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Pentamidine (Systemic): QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Pentamidine (Systemic). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Pimozide: May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk X: Avoid combination
Piperaquine: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Piperaquine. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Probucol: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Probucol. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Agents (Highest Risk): May enhance the QTc-prolonging effect of Sodium Stibogluconate. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
QT-prolonging Antidepressants (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Antipsychotics (Moderate Risk): QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Class IC Antiarrhythmics (Moderate Risk): QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Class IC Antiarrhythmics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Kinase Inhibitors (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Miscellaneous Agents (Moderate Risk): May enhance the QTc-prolonging effect of Sodium Stibogluconate. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of QT-prolonging Miscellaneous Agents (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Quinolone Antibiotics (Moderate Risk): QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Quinolone Antibiotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Moderate Risk). QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of QT-prolonging Miscellaneous Agents (Moderate Risk). Risk X: Avoid combination
Use of sodium stibogluconate in pregnancy has been described; however, the risk of spontaneous abortion may be increased in comparison to use of other agents (Mueller 2006). Untreated leishmaniasis may also lead to spontaneous abortion, as well as babies born small for gestational age and congenital leishmaniasis (WHO 2010). Pregnancy may activate previous maternal infection (Meinecke 1999). Maternal infection is likely transmitted to the baby during delivery (Meinecke 1999; Mescouto-Borges 2013). Lesions observed in cutaneous leishmaniasis may be larger in pregnant women (Morgan 2007). Other agents are recommended for the treatment of visceral leishmaniasis in pregnant women (Mueller 2006; WHO 2010).
Sodium stibogluconate is excreted in breast milk (Berman 1989).
A protein-rich diet is recommended during therapy (WHO 1995).
Baseline and weekly EKG, serum creatinine, liver function tests, serum amylase, and CBC; patients requiring >20 days of treatment should begin twice-weekly EKG monitoring during week 3 of therapy; twice-weekly or more frequent EKG monitoring may be indicated in certain patients (eg, elderly, underlying cardiac, renal, or hepatic disease) (Herwaldt 1992; McCarthy 2015)
Exact mechanism of action is unknown. Proposed mechanisms include conversion to trivalent form of antimony that affects glucose metabolism, fatty acid beta oxidation, and adenosine triphosphate (ATP) formation; forms a complex with adenine nucleosides, acting as an inhibitor of Leishmania purine transporters or interfere with purine salvage pathway; and activation of host immune system (McCarthy 2015).
Absorption: IM: Well absorbed (McCarthy 2015)
Half-life elimination: ~10 hours (McCarthy 2015)
Excretion: Urine (80% as unchanged drug [over 6 hours]) (WHO 1995)
