No

Antibiotic, Miscellaneous

Treatment and prevention of pneumonia caused by Pneumocystis carinii; treatment of trypanosomiasis and visceral leishmaniasis

C

Hypersensitivity to pentamidine isethionate or any component (inhalation and injection)

Use with caution in patients with diabetes mellitus, renal or hepatic dysfunction; hypertension or hypotension; leukopenia, thrombocytopenia, asthma, hypo/hyperglycemia

Injection (I); Aerosol (A)

Cardiovascular: Chest pain (A - 10% to 23%)

Central nervous system: Fatigue (A - 50% to 70%); dizziness (A - 31% to 47%)

Dermatologic: Rash (31% to 47%)

Endocrine & metabolic: Hyperkalemia

Gastrointestinal: Anorexia (A - 50% to 70%), nausea (A - 10% to 23%)

Local: Local reactions at injection site

Renal: Increased creatinine (I - 23%)

Respiratory: Wheezing (A - 10% to 23%), dyspnea (A - 50% to 70%), coughing (A - 31% to 47%), pharyngitis (10% to 23%)

1% to 10%:

Cardiovascular: Hypotension (I - 4%)

Central nervous system: Confusion/hallucinations (1% to 2%), headache (A - 1% to 5%)

Dermatologic: Rash (I - 3.3%)

Endocrine & metabolic: Hypoglycemia <25 mg/dL (I - 2.4%)

Gastrointestinal: Nausea/anorexia (I - 6%), diarrhea (A - 1% to 5%), vomiting

Hematologic: Severe leukopenia (I - 2.8%), thrombocytopenia <20,000/mm³ (I - 1.7%), anemia (A - 1% to 5%)

Hepatic: Increased LFTs (I - 8.7%)

<1%: Hypotension <60 mm Hg systolic (I - 0.9%), tachycardia, arrhythmias, dizziness (I), fever, fatigue (I), hyperglycemia or hypoglycemia, hypocalcemia, pancreatitis, megaloblastic anemia, granulocytopenia, leukopenia, renal insufficiency, extrapulmonary pneumocystosis, irritation of the airway, pneumothorax, Jarisch-Herxheimer-like reaction, mild renal or hepatic injury

Symptoms of overdose include hypotension, hypoglycemia, cardiac arrhythmias

Treatment is supportive

CYP2C19 enzyme substrate

Do not refrigerate due to the possibility of crystallization; do not use NS as a diluent, NS is incompatible with pentamidine; reconstituted solutions (60-100 mg/mL) are stable for 48 hours at room temperature and do not require light protection; diluted solutions (1-2.5 mg/mL) in D₅W are stable for at least 24 hours at room temperature

Interferes with RNA/DNA, phospholipids and protein synthesis, through inhibition of oxidative phosphorylation and/or interference with incorporation of nucleotides and nucleic acids into RNA and DNA, in protozoa

Absorption: I.M.: Well absorbed

Distribution: Systemic accumulation of pentamidine does not appear to occur following inhalation therapy

Half-life, terminal: 6.4-9.4 hours; may be prolonged in patients with severe renal impairment

Elimination: 33% to 66% excreted in urine as unchanged drug

Children:

Treatment: I.M., I.V. (I.V. preferred): 4 mg/kg/day once daily for 10-14 days

Prevention:

I.M., I.V.: 4 mg/kg monthly or every 2 weeks

Inhalation (aerosolized pentamidine in children greater than or equal to 5 years): 300 mg/dose given every 3-4 weeks via Respirgard® II inhaler (8 mg/kg dose has also been used in children <5 years)

Treatment of trypanosomiasis: I.V.: 4 mg/kg/day once daily for 10 days

Adults:

Treatment: I.M., I.V. (I.V. preferred): 4 mg/kg/day once daily for 14-21 days

Prevention: Inhalation: 300 mg every 4 weeks via Respirgard® II nebulizer

Dialysis: Not removed by hemo or peritoneal dialysis or continuous arteriovenous or venovenous hemofiltration (CAVH/CAVHD); supplemental dosage is not necessary

Dosing adjustment in renal impairment: Adults: I.V.:

Cl_cr 10-50 mL/minute: Administer 4 mg/kg every 24-36 hours

Cl_cr <10 mL/minute: Administer 4 mg/kg every 48 hours

Avoid alcohol

Liver function tests, renal function tests, blood glucose, serum potassium and calcium, EKG, blood pressure

Sedation and dizziness are common; may cause confusion or hallucinations

May cause leukopenia; use caution with clozapine and carbamazepine

No information available to require special precautions

No effects or complications reported

I.V. or I.M. preparations must be given every day. For inhalant use as directed. Prepare solution and nebulizer as directed. Protect medication from light. You will be required to have frequent laboratory tests and blood pressure monitoring while taking this drug. PCP pneumonia may still occur despite pentamidine use. Maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake). Frequent mouth care or sucking on lozenges may relieve the metallic taste. Diabetics should check glucose levels frequently. You may experience dizziness or weakness with posture changes; rise or change position slowly. Report unusual confusion or hallucinations, chest pain, unusual bleeding, or rash. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Do not breast-feed.

Virtually indetectable amounts are transferred to healthcare personnel during aerosol administration; do not use NS as a diluent

Inhalation, as isethionate: 300 mg

Powder for injection, as isethionate, lyophilized: 300 mg

"1997 USPHS/IDSA Guidelines for the Prevention of Opportunistic Infections in Persons Infected With Human Immunodeficiency Virus," MMWR Morb Mortal Wkly Rep, 1997, 46(RR-12):1-46.

Centers for Disease Control, "Guidelines for Prophylaxis Against Pneumocystis carinii Pneumonia for Children Infected With Human Immunodeficiency Virus," JAMA, 1991, 265(13):1637-40, 1643-4.

Comtois R, Pouliot J, Gervais S, et al, "High Pentamidine Levels Associated With Hypoglycemia and Azotemia in a Patient With Pneumocystis carinii Pneumonia," Diagn Microbiol Infect Dis, 1992, 15(6):523-6.

Conte JE Jr, "Pharmacokinetics of Intravenous Pentamidine in Patients With Normal Renal Function or Receiving Hemodialysis," J Infect Dis, 1991, 163(1):169-75.

Cortese LM, Gasser RA, Jr, Bjornson DC, et al, "Prolonged Recurrence of Pentamidine-Induced Torsade de Pointes," Ann Pharmacother, 1992, 26(11):1365-9.

Goa KL and Campoli-Richards DM, "Pentamidine Isethionate. A Review of Its Antiprotozoal Activity, Pharmacokinetic Properties and Therapeutic Use in Pneumocystis carinii Pneumonia," Drugs, 1987, 33(3):242-58.

Hand IL, Wiznia AA, Porricolo M, et al, "Aerosolized Pentamidine for Prophylaxis of Pneumocystis carinii Pneumonia in Infants With Human Immunodeficiency Virus Infection," Pediatr Infect Dis J, 1994, 13(2):100-4.

Hughes WT, " Pneumocystis carinii Pneumonia: New Approaches to Diagnosis, Treatment, and Prevention," Pediatr Infect Dis J, 1991, 10(5):391-9.

Ito S and Koren G, "Estimation of Fetal Risk From Aerosolized Pentamidine in Pregnant Healthcare Workers," Chest, 1994, 106(5):1460-2.

Masur H, "Prevention and Treatment of Pneumocystis Pneumonia," N Engl J Med, 1992, 327(26):1853-60.

Monk JP and Benfield P, "Inhaled Pentamidine. An Overview of Its Pharmacological Properties and a Review of Its Therapeutic Use in Pneumocystis carinii Pneumonia," Drugs, 1990, 39(5):741-56.

Pelucio MT, Rothenhaus T, Smith M, et al, "Fatal Pancreatitis as a Complication of Therapy for HIV Infection," J Emerg Med, 1995, 13(5):633-7.

Sattler FR, Cowan R, Nielsen DM, et al, " Trimethoprim-Sulfamethoxazole Compared With Pentamidine for Treatment of Pneumocystis carinii Pneumonia in the Acquired Immunodeficiency Syndrome," Ann Intern Med, 1988, 109(4):280-7.

Singh G, el-Gadi SM, and Sparks RA, "Pancreatitis Associated With Aerosolized Pentamidine," Genitourin Med, 1995, 71(2):130-1.