Pentamidine

Pentamidine

Class

• Antiprotozoal agent
• Aromatic diamidine compound

Mechanism of Action

• Exact mechanism not fully understood.
• Interferes with protozoal DNA, RNA, phospholipid, and protein synthesis.
• Has activity against Pneumocystis jirovecii, Trypanosoma brucei, and Leishmania species.

Indications

1. Pneumocystis jirovecii pneumonia (PJP/PCP)
   • Treatment in patients intolerant to TMP-SMX.
   • Prophylaxis in immunocompromised patients (HIV/AIDS, transplant, oncology patients).
2. African trypanosomiasis (early hemolymphatic stage of T. brucei gambiense)
   • Not effective in CNS disease.
3. Leishmaniasis (off-label, less common).

Dosing

1. PJP Treatment

• IV: 4 mg/kg once daily infused over ≥60 minutes for 14–21 days.
• IM: 4 mg/kg once daily for 14–21 days (less preferred).

2. PJP Prophylaxis

• Inhalation (via nebulizer): 300 mg every 4 weeks (most common).
• IV alternative: 4 mg/kg every 2–4 weeks (rarely used).

3. African Trypanosomiasis

• IV or IM: 4 mg/kg once daily or on alternate days for 7–10 doses.

Adverse Effects

Systemic (IV/IM)

• Renal: nephrotoxicity, azotemia, acute tubular necrosis.
• Metabolic: hypo/hyperglycemia, pancreatitis, hypocalcemia, hypokalemia, hypomagnesemia.
• Hematologic: leukopenia, thrombocytopenia, anemia.
• Cardiac: QT prolongation, arrhythmias, hypotension.
• Hepatic: elevated transaminases.
• Others: rash, fever, nausea, vomiting.

Inhaled

• Cough, bronchospasm, wheezing, metallic taste.

Contraindications

• Hypersensitivity to pentamidine.
• Use cautiously in patients with renal impairment, diabetes, electrolyte imbalances, or cardiac disease.

Monitoring

• Renal function: BUN, serum creatinine.
• Electrolytes: glucose, potassium, calcium, magnesium.
• Liver function tests.
• ECG if prolonged therapy (risk of QT prolongation).
• CBC for cytopenias.
• Clinical: cough/bronchospasm for inhaled use.

Formulations

• IV/IM injection.
• Nebulized inhalation solution (for prophylaxis).

Key Points for Oncology/Immunocompromised Patients

• Alternative to TMP-SMX for PJP prophylaxis/treatment in patients with sulfa allergy, renal dysfunction, or severe cytopenias.
• Inhaled pentamidine is often chosen for prophylaxis in stem cell transplant recipients or HIV patients unable to tolerate TMP-SMX.
• Requires close monitoring for metabolic and renal toxicity.

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