PENTAMIDINE ISETHIONATE
Clinical safety rating: safe
Animal studies have demonstrated safety
Pentamidine isethionate is a synthetic aromatic diamidine that interferes with protozoal DNA replication, transcription, and RNA processing. Its exact mechanism is unclear but may involve inhibition of dihydrofolate reductase, interference with polyamine synthesis, and binding to kinetoplast DNA.
| Metabolism | Pentamidine isethionate undergoes hepatic metabolism via multiple CYP450 enzymes, including CYP3A4, CYP2C8, and CYP2C19. Renal excretion is the primary route of elimination for unchanged drug and metabolites. |
| Excretion | Renal excretion accounts for approximately 60-70% of elimination, primarily as unchanged drug. Biliary/fecal elimination constitutes 10-20%, with the remainder undergoing metabolic clearance. |
| Half-life | Terminal elimination half-life is 18-24 hours in patients with normal renal function; prolongs to >48 hours in renal impairment, necessitating dose adjustment. |
| Protein binding | Approximately 90% bound, primarily to alpha-1-acid glycoprotein and albumin. |
| Volume of Distribution | 3-4 L/kg, indicating extensive tissue distribution (e.g., liver, kidney, lungs). |
| Bioavailability | Inhaled: 5-10% (systemic); IM: 100% (complete absorption); oral: <5% (not clinically used). |
| Onset of Action | Inhaled: 1-2 hours for prophylaxis of Pneumocystis jirovecii pneumonia; IV/IM: 30-60 minutes for therapeutic effect. |
| Duration of Action | Inhaled: 2-4 weeks for prophylaxis (weekly dosing); IV/IM: 24-48 hours therapeutic levels; prolonged accumulation with repeated dosing. |
Treatment of Pneumocystis jirovecii pneumonia (PCP): 4 mg/kg IV once daily for 21 days. Chemoprophylaxis of PCP: 300 mg inhalation via nebulizer every 4 weeks, or 4 mg/kg IV every 2-4 weeks. Treatment of leishmaniasis: 2-4 mg/kg IM or IV once daily or every other day for 14-30 doses.
| Dosage form | INJECTABLE |
| Renal impairment | CrCl >50 mL/min: no adjustment. CrCl 10-50 mL/min: extend dosing interval to every 24-36 hours. CrCl <10 mL/min: extend interval to every 48 hours or consider alternative therapy. |
| Liver impairment | No specific guidelines for Child-Pugh based adjustment. Use with caution in severe hepatic impairment; monitor for toxicity. |
| Pediatric use | Treatment of PCP: 4 mg/kg IV once daily for 14-21 days. Prophylaxis of PCP: for children ≥5 years: 300 mg inhalation monthly; for children <5 years: 4 mg/kg IV every 2-4 weeks. Leishmaniasis: 2-4 mg/kg IM or IV once daily or every other day for 14-30 doses. |
| Geriatric use | Start at lower end of dosing range (e.g., 3-4 mg/kg IV for PCP). Monitor renal function closely; adjust dose based on creatinine clearance. Increased risk of nephrotoxicity, hypotension, and hypoglycemia. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Other nephrotoxic drugs increase risk of toxicity Can cause severe hypotension hypoglycemia and nephrotoxicity.
| Breastfeeding | Excretion into human milk unknown; M/P ratio not established. Due to potential severe adverse effects (nephrotoxicity, hypoglycemia), breastfeeding is not recommended during therapy. |
| Teratogenic Risk | Pregnancy category C. First trimester: no adequate studies; potential teratogenic effects in animals (increased fetal resorptions, minor skeletal anomalies) suggest risk. Second and third trimesters: use only if clearly needed; no human data confirming teratogenicity, but embryotoxicity noted in animals. |
■ FDA Black Box Warning
WARNING: SEVERE HYPOTENSION, HYPOGLYCEMIA, AND CARDIAC ARRHYTHMIAS. Pentamidine isethionate can cause life-threatening hypotension, severe hypoglycemia, and QT prolongation leading to torsade de pointes. Resuscitative equipment and trained personnel must be available. Patients should be monitored for hypoglycemia, hypotension, and ECG changes.
| Common Effects | Hypotension |
| Serious Effects |
["Hypersensitivity to pentamidine or any component of the formulation","History of ventricular arrhythmias (e.g., torsade de pointes) due to risk of QT prolongation"]
| Precautions | ["Monitor blood glucose levels closely due to risk of severe hypoglycemia, which can be prolonged.","Risk of hypotension, especially with rapid IV administration; infuse over at least 60 minutes.","QT prolongation may occur; monitor ECG and electrolytes.","Renal toxicity: assess renal function before and during therapy.","Pancreatitis: discontinue if suspected.","Leukopenia and thrombocytopenia may occur.","Do not administer intramuscularly due to risk of sterile abscess.","Use caution in patients with diabetes, renal impairment, or electrolyte disturbances."] |
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| Fetal Monitoring |
| Monitor mother: renal function (BUN, creatinine), blood glucose (hypoglycemia risk), liver function tests, electrolytes, ECG (QT prolongation), blood pressure (hypotension), and complete blood count (pancytopenia). Fetal: growth and heart rate monitoring if used in later pregnancy. |
| Fertility Effects | Animal studies: impaired fertility in male rats (reduced spermatogenesis, testicular atrophy) and female rats (prolonged estrus cycle). Human data limited; potential for reversible oligospermia or azoospermia in males. |