What is pentamidine and for what is it used?

What is Pentamidine and What is it Used For?

Pentamidine is an aromatic diamidine antiprotozoal agent primarily used for the treatment and prophylaxis of Pneumocystis jirovecii (formerly P. carinii) pneumonia (PCP), particularly in immunocompromised patients including those with HIV/AIDS. 1

Primary Indications

Treatment of Active PCP

• Pentamidine isethionate is FDA-approved for the treatment of pneumonia due to Pneumocystis carinii at a dose of 4 mg/kg/day IV over 60-90 minutes for 14-21 days. 1
• It serves as an alternative therapy for patients who cannot tolerate or have failed trimethoprim-sulfamethoxazole (TMP-SMX), which remains the first-line agent. 2, 3
• The drug is particularly valuable in HIV-infected patients with AIDS who experience high rates of adverse reactions to TMP-SMX (40-65% in adults). 4

Prophylaxis Against PCP

• Aerosolized pentamidine at 300 mg monthly via Respirgard II jet nebulizer is effective for both primary and secondary prophylaxis of PCP in HIV-infected adults. 4
• Alternative dosing includes 60 mg every 2 weeks via Fisoneb ultrasonic nebulizer. 4
• However, TMP-SMX is superior to aerosol pentamidine for prophylaxis, with a 1-year PCP recurrence rate of 3.5% versus 18.5% (3.25-fold higher risk with pentamidine). 4

Emerging Indication: Human African Trypanosomiasis

• WHO guidelines (2025) recommend pentamidine as immediate interim treatment for rhodesiense HAT when definitive therapy (fexinidazole, suramin, or melarsoprol) is not immediately available. 4
• Pentamidine may be more rapidly available in non-endemic countries since it is stocked for PCP treatment. 4

Mechanism of Action

• Pentamidine interferes with protozoal nuclear metabolism by inhibiting DNA, RNA, phospholipid, and protein synthesis, though its exact mechanism is not fully understood. 1

Pharmacokinetics

• The drug distributes extensively with a volume of distribution of 821-2724 L, concentrating heavily in kidneys, liver, and lungs (70-1000 times peak serum concentration). 1
• Terminal half-life ranges from 6.4 to 9.4 hours after single doses, but extends to 2.8-12 days with repeated dosing due to deep tissue compartment accumulation. 1
• Up to 12% is excreted unchanged in urine, with detectable levels persisting 6-8 weeks after treatment cessation. 1, 5
• After aerosol administration, pentamidine is almost exclusively recovered from the lung with minimal systemic absorption. 5

Routes of Administration

Intravenous (Preferred for Treatment)

• 4 mg/kg/day infused over 60-90 minutes for 14-21 days. 2, 3, 1
• Produces higher systemic concentrations but carries greater risk of systemic toxicity. 5

Intramuscular

• Same dosing as IV but associated with local pain and sterile abscesses at injection sites. 5, 6

Aerosolized (Preferred for Prophylaxis)

• 300 mg monthly via Respirgard II nebulizer or 60 mg every 2 weeks via Fisoneb nebulizer. 4
• Optimal particle size is 1-2 microns mass median aerodynamic diameter (MMAD) for even alveolar distribution. 7
• Jet nebulizers like Respirgard II produce particles in this ideal range, while ultrasonic nebulizers produce larger particles. 7

Adverse Effects Profile

Systemic Toxicity (More Common with Parenteral Routes)

• Approximately 45-50% of patients receiving parenteral pentamidine experience adverse effects. 8
• Nephrotoxicity (azotemia, renal insufficiency). 4, 5
• Hypoglycemia (can be severe and delayed). 4, 1
• Hypotension (particularly with rapid IV infusion). 5, 8
• Hematologic abnormalities (leukopenia, thrombocytopenia). 3
• Pancreatitis. 4
• Hyperkalemia, especially in patients with reduced kidney function. 3

Local/Respiratory Effects (More Common with Aerosolized Route)

• Bronchospasm (up to 15% of patients). 4
• Cough (38% of patients). 4
• Burning sensation in throat and unpleasant taste. 4
• Pneumothorax. 4
• Chemical conjunctivitis. 4
• Aerosolized pentamidine is generally better tolerated than IV formulation, particularly in pediatric populations. 9

Clinical Considerations and Pitfalls

Breakthrough PCP with Aerosol Prophylaxis

• 5-25% of patients receiving aerosolized pentamidine develop breakthrough PCP. 4
• Atypical presentations are common, including upper-lobe infiltrates and extrapulmonary disease. 4

Environmental Contamination Risk

• Substantial environmental contamination occurs during aerosol administration from the delivery system and patient coughing, potentially transmitting Mycobacterium tuberculosis. 4
• Long-term effects on healthcare workers remain unknown. 4

Limited Spectrum

• Aerosol pentamidine provides no protection against other HIV-associated opportunistic infections, unlike TMP-SMX which may offer some protection against toxoplasmosis. 4

Pediatric Considerations

• Use of aerosolized pentamidine in young children is limited by their ability to use the nebulizer effectively. 4
• Adverse reactions to pentamidine appear less frequent in HIV-infected children (15%) compared to adults. 4

Drug Interactions

• Unlike atovaquone, pentamidine does not have documented interactions with rifampin, making it a suitable alternative for PCP prophylaxis/treatment in patients receiving tuberculosis therapy. 10

Cost Considerations

• Wholesale cost of pentamidine (300-mg vial) was $99 in 1991, compared to $19 for generic TMP-SMX (30 double-strength tablets). 4
• True cost includes drug delivery (labor, equipment, supplies), laboratory monitoring, and management of adverse reactions. 4