For a patient intolerant to trimethoprim‑sulfamethoxazole because of severe allergy, renal insufficiency, hyperkalemia, or cytopenias, how should inhaled pentamidine be used for Pneumocystis jirovecii pneumonia prophylaxis (dose, administration schedule, monitoring, alternative agents, and duration of therapy)?

Inhaled Pentamidine for PJP Prophylaxis in TMP-SMX Intolerant Patients

For patients unable to tolerate TMP-SMX, inhaled pentamidine should be administered at 300 mg monthly via Respirgard II nebulizer or 60 mg every 2 weeks via Fisoneb nebulizer, with prophylaxis continued lifelong in immunosuppressed patients. 1

Dosing and Administration

Respirgard II Jet Nebulizer (Preferred Monthly Regimen)

• Dose: 300 mg pentamidine isethionate diluted in 6 mL sterile water 1
• Delivery: Air flow of 6 L/min from 50-PSI compressed air source until reservoir is dry 1
• Frequency: Once monthly 1

Fisoneb Ultrasonic Nebulizer (Biweekly Regimen)

• Loading phase: 60 mg pentamidine in 3 mL sterile water, five doses spaced 24-72 hours apart over first 2 weeks 1
• Maintenance: 60 mg every 2 weeks thereafter 1
• Administration time: 15-20 minutes until reservoir is dry 1

Pre-Treatment Requirements

Bronchospasm Prevention

• Administer albuterol 2 puffs (100 mcg each) 10 minutes before each pentamidine treatment to prevent cough, wheezing, and chest pain 1
• If bronchospasm occurs during treatment, provide immediate beta2 agonist intervention and pretreat all subsequent doses 1

Tuberculosis Screening (Critical)

Before initiating pentamidine, complete tuberculosis evaluation including: 1

• Medical history for TB symptoms
• Tuberculin skin test
• Chest radiograph
• If cough or infiltrate present: acid-fast bacilli smears and sputum cultures

Before each subsequent treatment, evaluate for TB symptoms or other active pulmonary disease 1

Absolute Contraindications

Do not administer pentamidine to patients with prior history of: 1

• Hypoglycemia from any form of pentamidine
• Pancreatitis from pentamidine
• Cardiac arrhythmia from pentamidine
• Severe hypotension from pentamidine

Special Populations Requiring Caution

• Severe pulmonary function abnormalities: Use with extreme caution only after considering all alternatives, as efficacy and safety not established in this population 1

Monitoring During Prophylaxis

Clinical Surveillance

Monitor closely for breakthrough PCP, as no prophylactic regimen is 100% effective 1

Atypical PCP Presentations on Pentamidine

Be alert for: 1

• Upper-lobe infiltrates (unusual pattern with aerosol prophylaxis)
• Pneumothorax
• Extrapulmonary pneumocystosis
• Reduced diagnostic yield of bronchoalveolar lavage and induced sputum

Adverse Event Monitoring

During IV pentamidine (if used instead of inhaled): monitor for hypotension, hypoglycemia, pancreatitis, and nephrotoxicity 2

Administration Environment (Infection Control)

Administer in individual rooms or booths with: 1

• Negative-pressure ventilation relative to adjacent areas
• Room air exhausted directly outside, away from windows and air-intake ducts
• Healthcare workers wear particulate respirators if patient has or is at high risk for TB 1

After treatment: 1

• Patients should not return to common waiting areas until coughing subsides
• Allow adequate time for air clearance before next patient uses room

Duration of Therapy

Continue prophylaxis for the patient's lifetime while immunosuppression persists 1

If prophylaxis is discontinued, patient immediately returns to high risk for PCP 1

Alternative Agents When Pentamidine Cannot Be Used

If neither TMP-SMX nor aerosol pentamidine can be administered, consider in unusual situations: 1

• Intravenous pentamidine (4 mg/kg once daily) 2
• Atovaquone (750 mg orally twice daily with food for mild-moderate disease) 2
• Dapsone (must rule out G6PD deficiency first) 3
• Clindamycin plus primaquine (must rule out G6PD deficiency) 2

Note: These alternatives have insufficient data and are not generally recommended as first-line prophylactic regimens 1

Common Pitfalls to Avoid

• Failure to pretreat with bronchodilators: Results in poor tolerance and discontinuation (7.6% discontinuation rate for aerosolized pentamidine due to adverse events) 4
• Using non-approved nebulizers: Only Respirgard II and Fisoneb have established efficacy 1
• Inadequate TB screening: Risk of TB transmission to healthcare workers and other patients 1
• Missing atypical PCP presentations: Upper-lobe disease and pneumothorax are more common with aerosol prophylaxis 1

Breakthrough PCP Management

If PCP develops despite adherence to pentamidine prophylaxis: 1

• Causes may include poor adherence, improper aerosol device use, or poor pulmonary ventilatory distribution
• Treat acute episode (some experts prefer different agent than prophylactic agent, though no data support this)
• After successful treatment, TMP-SMX remains preferred for subsequent prophylaxis if patient can tolerate it 1