Usual Adult Dose for Pneumocystis Pneumonia

Manufacturer recommendation: 4 mg/kg IM or IV once a day for 14 to 21 days
Centers for Disease Control and Prevention (CDC) recommendation: 3 to 4 mg/kg IV once a day for 21 days

Usual Adult Dose for Pneumocystis Pneumonia Prophylaxis

300 mg administered via the Respirgard(R) II nebulizer every 4 weeks
Prophylactic therapy should be continued as long as the patient is at risk for Pneumocystis jiroveci pneumonia.

Usual Adult Dose for Leishmaniasis

Cutaneous leishmaniasis:
CDC recommendation: 2 to 3 mg/kg IM or IV once a day or every second day for 4 to 7 doses

The following regimens have been recommended for visceral leishmaniasis: 2 to 4 mg/kg IM or IV once a day or every other day for up to 15 doses
or
4 mg/kg IM or IV 3 times a week for 5 to 25 weeks or longer, depending on response
or
4 mg/kg IM or IV once every 2 or 3 days for up to 15 doses

Pentamidine was considered a second-line agent for visceral leishmaniasis; however, due to suboptimal efficacy and toxicity, it is rarely used. Stibogluconate sodium, amphotericin B, and amphotericin B liposomal are considered first-line agents.

Usual Adult Dose for Trypanosomiasis

First (hemolymphatic) stage infection due to Trypanosoma brucei gambiense or T brucei rhodesiense:
CDC recommendation: 4 mg/kg IM or IV once a day for 7 to 10 days

Pentamidine is a second-line agent for African trypanosomiasis caused by T brucei rhodesiense. Suramin is the first-line agent.

Usual Pediatric Dose for Pneumocystis Pneumonia

5 months or older:
Manufacturer recommendation: 4 mg/kg IM or IV once a day for 14 to 21 days
CDC recommendation: 3 to 4 mg/kg IM or IV once a day for 21 days

Usual Pediatric Dose for Pneumocystis Pneumonia Prophylaxis

5 years or older:
CDC recommendation: 300 mg administered via the Respirgard(R) II nebulizer once a month
Prophylactic therapy should be continued as long as the patient is at risk for Pneumocystis jiroveci pneumonia.

Usual Pediatric Dose for Leishmaniasis

Cutaneous leishmaniasis:
CDC recommendation: 2 to 3 mg/kg IM or IV once a day or every second day for 4 to 7 doses

Usual Pediatric Dose for Trypanosomiasis

First (hemolymphatic) stage infection due to T brucei gambiense or T brucei rhodesiense:
CDC recommendation: 4 mg/kg IM or IV once a day for 7 to 10 days

Pentamidine is a second-line agent for African trypanosomiasis caused by T brucei rhodesiense. Suramin is the first-line agent.

Renal Dose Adjustments

Parenteral: The manufacturer recommends caution when administering this drug to patients with renal dysfunction. Efficacy and safety of alternative dosing regimens have not been established for patients with renal impairment.

Liver Dose Adjustments

Parenteral: The manufacturer recommends caution when administering this drug to patients with liver dysfunction. Efficacy and safety of alternative dosing regimens have not been established for patients with hepatic impairment.

Precautions

Fatalities due to severe hypotension, hypoglycemia, acute pancreatitis, and cardiac arrhythmias have occurred with IM and IV pentamidine. Therefore, parenteral pentamidine use should be limited to patients with demonstrated Pneumocystis jiroveci (formerly, P carinii) and patients should be closely monitored for signs of serious side effects.

Sudden and severe hypotension has occurred after a single IM or IV dose of pentamidine and is more likely with rapid IV administration. Patients should receive the drug while lying down and blood pressure should be monitored closely during administration and several times thereafter until blood pressure is stable. Equipment for emergency resuscitation should be available.

Extravasations have been reported, progressing to ulceration, tissue necrosis, and/or sloughing at the injection site in some cases. Surgical debridement and skin grafting have been required in a few of these cases and long-term sequelae have been reported. Precautions should be taken to prevent extravasation, including proper positioning of the IV needle or catheter and close observation during administration. The pentamidine injection should be stopped immediately if extravasation occurs and restarted in another vein. The extravasation should be managed symptomatically.

Cautious use is recommended in patients with hypertension, hypotension, ventricular tachycardia, hypoglycemia, hyperglycemia, hypocalcemia, pancreatitis, leukopenia, thrombocytopenia, anemia, and Stevens-Johnson syndrome.

Pentamidine has induced hypoglycemia associated with pancreatic islet cell necrosis and high plasma insulin concentrations. Hyperglycemia and diabetes mellitus (with or without preceding hypoglycemia) have been reported, sometimes several months after pentamidine treatment. Blood glucose concentrations should be monitored daily during pentamidine treatment and several times thereafter.

Before, during, and after therapy with pentamidine, monitoring of blood urea nitrogen (BUN), serum creatinine, blood glucose, complete blood count, platelet count, liver function tests (including serum bilirubin, alkaline phosphatase, AST, and ALT), serum calcium, and electrocardiogram is recommended. Serum creatinine, BUN, and blood glucose should be checked daily.

Concomitant or sequential administration of other nephrotoxic drugs should be avoided if possible, or closely monitored.

Patients receiving inhaled pentamidine prophylaxis may still be at risk of developing acute Pneumocystis pneumonia (PCP). Patients with symptoms of a pulmonary infection should be thoroughly evaluated for PCP and other infections. Pentamidine use may result in atypical presentation of PCP, including altered radiographic results and clinical features. The presence of PCP should be excluded in symptomatic patients before initiating prophylaxis. The dose of nebulized pentamidine is insufficient for the treatment of PCP. Extrapulmonary pneumocystosis has been reported and should be considered when evaluating patients with unexplained symptoms.

The extent and consequence of pentamidine accumulation after inhalation is unknown. Patients should be monitored closely for the development of adverse reactions, as with parenteral pentamidine.

Inhaled pentamidine has been associated with acute pancreatitis and should be discontinued if signs or symptoms of pancreatitis occur.

Safety and efficacy of parenteral pentamidine have not been established in pediatric patients less than 5 months of age. Safety and efficacy of nebulized pentamidine have not been established in pediatric patients less than 17 years of age.

Dialysis

Data not available; however, pentamidine is not appreciably removed by hemodialysis or peritoneal dialysis

Other Comments

Parenteral pentamidine should be administered via IV infusion over 60 to 120 minutes or via deep IM injection.

Pentamidine for oral inhalation should be administered via the Respirgard(R) II nebulizer following reconstitution (one vial [300 mg] dissolved in 6 mL sterile water for injection). The dose should be delivered until the nebulizer chamber is empty (about 30 to 45 minutes). Pentamidine for oral inhalation should not be mixed with other drugs. The Respirgard(R) II nebulizer should not be used to administer bronchodilators.

Some patients, especially those with a history of smoking or asthma, may experience bronchospasm or cough with inhaled pentamidine. Pretreatment with an inhaled bronchodilator may minimize this reaction.