Pentamidine is a potent, broad spectrum antiinfective agent with activity against several parasitic worms, protozoa and fungi that has been used mainly in the treatment and the prophylaxis of Pneumocystis jiroveci (formerly carinii) infection in immunodeficient persons. Pentamidine is relatively toxic and therapy requires careful monitoring. Pentamidine has been associated with transient serum aminotransferase elevations during therapy and with rare instances of clinically apparent liver injury.
Pentamidine (pen tam' i deen) is an aromatic diamine that is active against a broad spectrum of infectious agents. Its mechanism of action is unknown, but it appears to be taken up and concentrated within microorganisms where it inhibits DNA, RNA and protein synthesis. Pentamidine has a broad spectrum of activity against several cestodes, trematodes and protozoan parasites such as Giardia, Cryptosporidium and Entamoeba. Pentamidine is also active against Pneumocystis jiroveci (formerly known as P. carinii), which is now considered a fungal agent. Pentamidine was approved for use in the United States in 1984 at which time a major indication was the prophylaxis and therapy of Pneumocystis jiroveci infection. In intervening years, pentamidine has been replaced by better tolerated and less toxic agents in treating Pneumocystis such as trimethoprim/sulfamethoxazole or dapsone with atovaquone. Pentamidine is also an alternative, second line therapy for leishmaniasis and trypanosomiasis. Pentamidine is not absorbed well by the oral route and is available in aerosol forms (300 mg) under the brand name of Nebupent and as a solution for injection under the name Pentam 300. For treatment of pneumocystis pneumonia, the recommended regimen is 3-4 mg/kg intravenously or intramuscularly once daily for 14 to 21 days. For pneumocystis prevention, the recommended regimen is 300 mg in nebulized form every 4 weeks. Pentamidine therapy is highly toxic and the side effects of intravenous therapy are often severe and can be fatal. These side effects include nausea, abdominal discomfort, dizziness, hypotension, tachycardia, headache, rash, fever, hypoglycemia, hyponatremia, renal insufficiency and allergic reactions, including Stevens Johnson syndrome.
Pentamidine has been associated with serum aminotransferase elevations in 9% to 15% of patients receiving 2 to 3 weeks of therapy for pneumocystis pneumonia. Clinically apparent liver injury has also been reported with its use, but always in association with multiple other severe complications, such as respiratory or renal failure and pancreatitis. The onset of injury is within days of starting therapy and is characterized by acute hepatic necrosis, marked elevations in serum aminotransferase levels, rapid development of prolongation of prothrombin time and minimal or no jaundice. Recovery is typically rapid and usually complete.
Mechanism of Injury
Pentamidine interferes with polyamine synthesis and RNA polymerase activity, which may account for its multiorgan toxicity.
Outcome and Management
Pentamidine is not very well tolerated, but its major toxicities are not hepatic, and the predominance of these other dose limiting toxicities may be the reason that liver injury is not more common. Pentamidine has not been associated with fatal acute liver failure or chronic liver injury.
Drug Class: Antifungal Agents
Pentamidine is not a typical antifungal agent and has a broad spectrum of activity that does not fit neatly into any antimicrobial class. Other agents used to treat or prevent Pneumocystis jiroveci pneumonia: Sulfamethoxazole/Trimethoprim, Dapsone, Atovaquone, Primaquine, Clindamycin
Drug Class: Antihelmintic Agents
Pentamidine – NebuPent® [Aerosol]
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