Pentamidine

Agent: pentamidine

Pentamidine is the primary alternative to TMP/SMX for patients with Pneumocystis pneumonia, which was once extremely common but is becoming less so with effective anti-HIV therapy. It is also very toxic, so familiarity with its extensive adverse effects is required. It can be given either intravenously or by inhalation, and the route de-pends upon its indication.

Spectrum

Like-a-parasite-but-technically-a-fungus: Pneumocystis jirovecii

Protozoa: Trypanosoma, Leishmania

Adverse Effects (IV pentamidine)

Cardiovascular: Hypotension can occur with rapid infusion of pentamidine; the drug should be infused over at least an hour. Cases of QT prolongation with ventricular arrhythmia have also been reported.

Metabolic: Pentamidine is toxic to the pancreas, leading to dysglycemias in up to 25% of patients. The course of this toxicity may initially manifest as hypoglycemia because pentamidine-induced pancreatic injury causes release of insulin from islet cells. Later,  continuing injury can cause a decrease in pancreatic function, with hypoinsulinemia and hyperglycemia. Continued use may lead to irreversible damage, leaving patients with diabetes mellitus. Other manifestations of pancreatitis may also occur.

Renal: Nephrotoxicity is common with pentamidine, although it is generally reversible upon drug discontinuation. Electrolyte disturbances, including hypokalemia and hypocalcemia, may also occur.

Respiratory: Administration of pentamidine as an inhalation may induce bronchoconstriction,  especially in patients with asthma. Pretreatment with an inhaled bronchodilator may attenuate these effects.

Important Facts

• In clinical trials of pentamidine as treatment for Pneumocystis pneumonia, pentamidine appears to be equal in efficacy to TMP/SMX; how-ever, only about half of patients could tolerate a full course of IV pentamidine without discontinuing the drug or decreasing the dose. Careful monitoring (ECG, metabolic panel) and supportive care interventions (electrolyte re-placement, glucose, or insulin as appropriate)  are necessary. Also, dosage adjustment in patients with renal insufficiency is recommended.

• Once-monthly inhaled pentamidine has reasonable efficacy as a second-line agent for prophylaxis against  Pneumocystis  pneumonia. However, unlike TMP/SMX prophylaxis, cases of extrapulmonary Pneumocystis infection have been reported in patients on inhaled pentamidine. Inhaled pentamidine also does not protect against Toxoplasma disease or bacterial pneumonia as TMP/SMX does.

What It’s Good For

IV pentamidine is an alternative drug for treatment of severe  Pneumocystis  pneumonia; inhaled pentamidine is an alternative for prophylaxis against Pneumocystis pneumonia. IV pentamidine is an alternative drug for treatment for leishmaniasis and trypanosomiasis.

Don’t Forget!

Watch out for overlapping toxicities with pentamidine and other drugs the patient may be on. Patients receiving pentamidine are often severely ill and may be on drugs like insulin, furosemide,  aminoglycosides, and antiarrhythmics that may exacerbate pentamidine’s myriad adverse effects.

References

Gallagher ,J.C. and MacDougall ,c. (2012). Antibiotics Simplified. Second Edition. Jones & Bartlett Learning, LLC.