Sodium Stibogluconate

Usage

• Sodium stibogluconate is prescribed for the treatment of leishmaniasis, a parasitic disease transmitted by sandflies. This includes cutaneous (skin), visceral (internal organs), and mucosal (mucous membranes) forms of the disease. It has also been investigated for use in acute myeloid leukemia (AML).
• Pharmacological classification: Antiprotozoal agent, pentavalent antimonial.
• Mechanism of Action: While the exact mechanism isn’t fully elucidated, sodium stibogluconate is believed to inhibit the parasite’s essential metabolic processes, including glucose metabolism, fatty acid oxidation, and adenosine triphosphate (ATP) synthesis. This disrupts crucial cellular functions like DNA and RNA synthesis, leading to parasite death. The drug targets the amastigote form of the Leishmania parasite residing within macrophages.

Alternate Names

• International/Regional Variations: Pentostam, Stiboson.
• Brand Names: Pentostam.

How It Works

• Pharmacodynamics: Sodium stibogluconate primarily affects Leishmania parasites. It inhibits several metabolic pathways crucial for the parasite’s survival and replication. By targeting these pathways, it ultimately leads to parasite death.
• Pharmacokinetics: Administered intravenously (IV) or intramuscularly (IM). Its absorption following IM administration may be slower than IV. It’s primarily excreted via the kidneys. The drug is not extensively metabolized. Elimination is relatively slow.
• Mode of Action: The drug’s antileishmanial action is thought to involve inhibition of trypanothione reductase, a crucial enzyme for the parasite’s antioxidant defense. This leads to the build-up of toxic byproducts and subsequent parasite death. It specifically targets the amastigote form within macrophages.
• Elimination Pathways: Primarily renal excretion.

Dosage

Standard Dosage

Adults:

• Visceral Leishmaniasis: 20 mg/kg/day (up to a maximum of 850 mg) IV or IM for 20-28 days.
• Cutaneous Leishmaniasis: 20 mg/kg/day (up to a maximum of 850 mg) IV or IM for 10-20 days.
• Mucosal Leishmaniasis: 20 mg/kg/day (up to a maximum of 850 mg) IV or IM for 30 days.
• Administration should be via slow IV infusion (over at least 5 minutes) or deep IM injection.

Children:

• Similar to adult dosing (20 mg/kg/day, maximum 850 mg), but for children under 10 kg, a minimum dose of 200 mg daily is recommended. Pediatric safety considerations include careful monitoring for adverse effects due to potential immature organ function.

Special Cases:

• Elderly Patients: Caution advised due to potential age-related decline in organ function. Close monitoring is necessary.
• Patients with Renal Impairment: Contraindicated in significant renal impairment. Dose adjustment may be required in mild to moderate renal impairment.
• Patients with Hepatic Dysfunction: Contraindicated in hepatic impairment.
• Patients with Comorbid Conditions: Caution is advised in patients with cardiac disease, especially arrhythmias. Close cardiac monitoring (ECG) during administration is recommended.

Clinical Use Cases

Dosing for specific clinical settings generally follows the standard dosing recommendations for the respective form of leishmaniasis. There is not any specific information related to dosing for Intubation, Surgical Procedures, Mechanical Ventilation, Intensive Care Unit (ICU) Use, and Emergency Situations.

Dosage Adjustments

Dose adjustments are primarily based on renal function. For patients with mild to moderate renal impairment, dose reduction may be necessary. No specific guidelines are available, and adjustments should be made based on clinical judgment and close patient monitoring.

Side Effects

Common Side Effects

Nausea, vomiting, diarrhea, abdominal pain, anorexia, headache, lethargy, myalgia, arthralgia, fever, sweating, flushing, vertigo, epistaxis, gingival bleeding, rash, injection site pain (IV or IM), elevated liver enzymes. ECG changes (e.g., T-wave flattening or inversion, prolonged QT interval).

Rare but Serious Side Effects

Pancreatitis, cardiac arrhythmias (including torsades de pointes), hepatitis, renal failure, bone marrow suppression, anaphylaxis, pneumonia.

Long-Term Effects

Chronic complications from prolonged use are rare but may include cardiac conduction abnormalities.

Contraindications

• Hypersensitivity to sodium stibogluconate or any component of the formulation.
• Significant renal impairment.
• Hepatic impairment.
• Pregnancy.
• Breastfeeding.
• Concurrent use of amphotericin B or other QT-prolonging drugs.

Drug Interactions

• Amphotericin B: Increased risk of cardiotoxicity.
• QT Prolonging Agents: (e.g., certain antiarrhythmics, antidepressants, antipsychotics, quinolone antibiotics): Increased risk of torsades de pointes and other ventricular arrhythmias.
• Other Potential Interactions: While not extensively documented, it is essential to consider potential interactions with other medications metabolized by the liver or excreted by the kidneys.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: Information on pregnancy safety is limited. The drug is generally contraindicated during pregnancy due to potential fetal risks.
• Breastfeeding: Limited data suggests that small amounts of the drug may be excreted in breast milk. Breastfeeding is generally contraindicated during treatment.

Drug Profile Summary

• Mechanism of Action: Inhibits parasite metabolic processes, including glucose metabolism and ATP synthesis.
• Side Effects: Common: Nausea, vomiting, myalgia, arthralgia, elevated liver enzymes. Serious: Pancreatitis, cardiac arrhythmias, hepatitis.
• Contraindications: Hypersensitivity, renal impairment, hepatic impairment, pregnancy, breastfeeding, concurrent use of amphotericin B or QT-prolonging agents.
• Drug Interactions: Amphotericin B, QT-prolonging agents.
• Pregnancy & Breastfeeding: Contraindicated.
• Dosage: 20 mg/kg/day (max 850 mg) IV or IM. Duration depends on the type of leishmaniasis.
• Monitoring Parameters: ECG, complete blood count (CBC), liver function tests (LFTs), renal function tests, serum amylase and lipase.

Popular Combinations

• Sodium stibogluconate is sometimes used in combination with paromomycin for the treatment of visceral leishmaniasis, particularly in East Africa. This combination can shorten treatment duration and improve efficacy.
• Combining with allopurinol has been reported in some settings.

Precautions

• General Precautions: Baseline ECG, renal function tests, LFTs, and CBC are recommended before initiating therapy. Monitoring during therapy is essential, especially for cardiac, hepatic, and renal function.
• Specific Populations:
  • Pregnant Women: Contraindicated.
  • Breastfeeding Mothers: Contraindicated.
  • Children & Elderly: Close monitoring for adverse events.
• Lifestyle Considerations: No specific lifestyle considerations are consistently reported.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Sodium Stibogluconate?

A: The standard dosage is 20 mg/kg/day (maximum 850 mg) administered via slow IV infusion or deep IM injection. The duration of treatment varies depending on the type of leishmaniasis: 10-20 days for cutaneous, 28 days for visceral, and 30 days for mucosal leishmaniasis.

Q2: What are the common side effects of Sodium Stibogluconate?

A: Common side effects include nausea, vomiting, diarrhea, abdominal pain, headache, fatigue, muscle and joint pain, and elevated liver enzymes. Injection site pain is also common with both IV and IM administration.

Q3: What are the serious side effects of Sodium Stibogluconate?

A: Serious side effects can include pancreatitis, cardiac arrhythmias (including torsades de pointes), hepatitis, and renal impairment. Patients should be closely monitored for these adverse events.

Q4: What are the contraindications for Sodium Stibogluconate?

A: The drug is contraindicated in patients with hypersensitivity to the drug or its components, significant renal or hepatic impairment, pregnancy, and breastfeeding. It should not be used concurrently with amphotericin B or other drugs that prolong the QT interval.

Q5: How does Sodium Stibogluconate work?

A: Although the exact mechanism is not fully understood, it is believed to inhibit the parasite’s metabolic pathways, including glucose metabolism, fatty acid oxidation, and ATP synthesis, resulting in parasite death.

Q6: How is Sodium Stibogluconate administered?

A: It is administered either by slow intravenous infusion (over at least 5 minutes) or deep intramuscular injection. Intravenous administration is preferred due to less injection site pain and better tolerability.

Q7: What monitoring is required during Sodium Stibogluconate treatment?

A: Monitoring should include ECG, complete blood count, liver function tests, renal function tests, and serum amylase and lipase levels. The frequency of monitoring depends on the patient’s condition and risk factors.

Q8: Can Sodium Stibogluconate be used during pregnancy?

A: Sodium stibogluconate is generally contraindicated during pregnancy due to potential fetal risks. The benefits of treatment must be carefully weighed against the potential risks in individual cases.

Q9: Can Sodium Stibogluconate be used during breastfeeding?

A: It is generally contraindicated during breastfeeding, as small amounts of the drug can be excreted in breast milk. The safety of the drug in infants is not well established.

Q10: What should be done if a dose of Sodium Stibogluconate is missed?

A: If a dose is missed, it should be administered as soon as possible. However, if it is almost time for the next dose, the missed dose should be skipped, and the regular dosing schedule should be resumed. Doubling up on doses is not recommended.