Pentamidine
1. Pentamidine isethionate for injection (Pentam-300®, APP Pharmaceuticals); available in 15-ml vials as 300 mg of lyophilized powder for reconstitution.
2. Pentamidine isethionate for aerosolization (Nebu-Pent®, APP Pharmaceuticals); available in 15-ml vials as 300 mg of lyophilized powder.
3. Dosing recommendations are usually based on the pentamidine isethionate formulation, which is labeled according to the weight of the isethionate salt compound. A mesylate salt compound is also available; dosing of the mesylate salt is based on the weight of pentamidine alone; 1.74 mg of pentamidine isethionate is equivalent to 1 mg of pentamidine alone.
4. Inhaled and injectable pentamidine can also be found under other names in other countries, including Pentacarinat®.
Peak levels achieved at end of intravenous (IV) infusion or 40 minutes following intramuscular (IM) administration. Half-life: 6–9 hours. Distributes to kidneys, liver, spleen, lungs. Unknown metabolism. Excreted unchanged in the urine. Aerosol administration results in low systemic absorption.
Do not reconstitute with sodium chloride (precipitation will occur).
• IM: dissolve the 300 mg contents of the vial in 3 ml sterile water. Administer the calculated dose via deep IM injection.
• IV: dissolve the 300 mg contents of the vial in 3 ml sterile water. Further dilute the calculated dose in 250 ml 5% dextrose in water. Infuse the calculated dose over 1–2 hours to a supine patient; monitor blood pressure.
• Inhaled: dissolve the 300 mg contents of the vial in 6 ml sterile water. Transfer into Respirgard II nebulizer reservoir. Using a 40–50 pounds per square inch (PSI) air or oxygen source, set the flow rate at 5–7 liters per minute.
Administration of parenteral pentamidine has been associated with severe hypotension, hypoglycemia, pancreatitis, cardiac arhythmias and death. Extravasation of IV preparation can lead to necrosis. Sterile abscesses can occur at IM administration site.
• Renal: nephrotoxicity common. Hyperkalemia, hypocalcemia, hypomagnesemia.
• Endocrine: damages pancreatic islet cells; can lead to insulin release, hypoglycemia and eventual diabetes.
• Gastrointestinal: anorexia, nausea, vomiting common. Pancreatitis and hepatitis.
• Cardiac: prolonged QT prolongation and torsades de pointes.
• Respiratory: inhalational administration induces cough and bronchospasm.
Do not administer with other drugs associated with QT prolongation (particularly arthemether, lumefantrine, nilotinib, quinine, chloroquine, ciprofloxacin, tetrabenazine, thioridazine, ziprasidone). As a substrate of CYP2C19, levels may be decreased by strong CYP2C9 inducers, such as carbamazepine, phenytoin, ritonavir and rifampin. Avoid concurrent use with other nephrotoxins, including amphotericin B, aminoglycosides and foscarnet.
Leishmania resistance reported. Resistance may relate to decreased transport across protozoal membranes (for Trypanosoma) and into mitochrondria (for Leishmania).
Monitor glucose, electrolytes, renal function, hepatic function, blood pressure and EKG-QTc.
Bray PG, Barrett MP, Ward SA, Koning HP. Pentamidine uptake and resistance in pathogenic protozoa: past, present, and future. Trends Parasitol. 2003;19:232–239.
Ena J, Amador C, Pasqau F, et al. Once-a-month administration of intravenous pentamidine to patients infected with Human Immunodeficiency Virus as prophylaxis for Pneumocystis carinii pneumonia. Clin Inf Dis. 1994;18:901–904.
Lexi-Comp Online. Available at http://online.lexi.com (last accessed 1st March 2012)
O’Brien JG, Dong BJ, Coleman RL, et al. A 5-year retrospective review of adverse drug reactions and their risk factors in Human Immunodeficiency Virus-infected patients who were receiving intravenous pentamidine therapy for Pneumocystic carinii pneumonia. Clin Inf Dis. 1997;24:854–859.
Soto-Mancipe J, Grogl M, Berman JD. Evaluation of pentamidine for the treatment of cutaneous leishmaniasis in Colombia. Clin Inf Dis. 1993;16:417–425.