Yes, Dapsone is a Recommended Alternative for PCP Prophylaxis When Bactrim Cannot Be Used
Dapsone is an established and guideline-recommended alternative agent for PCP prophylaxis in patients who cannot tolerate trimethoprim-sulfamethoxazole (TMP-SMZ), with a BI strength recommendation from the U.S. Public Health Service and Infectious Diseases Society of America. 1
Recommended Dapsone Dosing Regimens
For Adults
- Standard dose: 100 mg orally daily 1
- Alternative: 50 mg orally twice daily 1
- For enhanced toxoplasmosis coverage: Dapsone 50 mg daily PLUS pyrimethamine 50 mg weekly PLUS leucovorin 25 mg weekly 1
- Higher dose option: Dapsone 200 mg weekly PLUS pyrimethamine 75 mg weekly PLUS leucovorin 25 mg weekly 1
For Children
- Dose: 1 mg/kg/day orally (maximum 100 mg/day) to minimize toxicity 1
- Alternative: 2 mg/kg/day (maximum 100 mg/day) 1
- Alternative: 4 mg/kg weekly (maximum 200 mg/week) 1
- Tablets (25 mg or 100 mg) are crushable and can be given with or in food 1
Efficacy Compared to Other Agents
Dapsone demonstrates comparable efficacy to aerosolized pentamidine and atovaquone, though slightly less effective than TMP-SMZ. 2 In a comparative trial, only one episode of PCP occurred during 862 patient-months of dapsone prophylaxis, demonstrating excellent efficacy 3. However, daily dosing at 2 mg/kg in children showed superior PCP prevention (0 cases/100 patient-years) compared to weekly dosing (9.5 cases/100 patient-years) 4.
Critical Monitoring Requirements
Monthly complete blood counts with differential and platelet count are mandatory to assess for hematologic toxicity 1. This is the same monitoring recommended for HIV-uninfected children receiving TMP-SMZ for recurrent infections 1.
Key Adverse Effects to Monitor
- Rash (most common reason for discontinuation) 3
- Hemolytic anemia 2, 5
- Methemoglobinemia 2, 5
- Agranulocytosis 2
- Hepatic dysfunction 2
- Sulfone syndrome (rare but serious: fever, methemoglobinemia, hemolytic anemia, exfoliative dermatitis, transaminitis) 5
Important Clinical Caveats
Timing of Adverse Reactions
Most adverse reactions occur within the first 2 months of therapy. 5, 6 In one study, all nine patients who discontinued dapsone due to adverse reactions did so within the first 2 months 6. The sulfone syndrome specifically occurs within 2 months of initiating therapy at any dose (50-300 mg/day) 5.
Cross-Reactivity with TMP-SMZ
Prior TMP-SMZ intolerance does NOT reliably predict dapsone intolerance. 3 In a crossover study, 6 of 11 patients (55%) who were TMP-SMZ-intolerant successfully tolerated dapsone 3. However, approximately 40% of TMP-SMZ-intolerant patients will also be intolerant to dapsone 6.
Desensitization Option
Desensitization can be accomplished in many cases for patients who develop non-life-threatening reactions 2.
Contraindications
Screen for G6PD deficiency before initiating dapsone, as hemolytic anemia risk is significantly increased in these patients 2.
Cost Considerations
Dapsone is the most cost-effective PCP prophylaxis currently available, making it an attractive alternative when TMP-SMZ cannot be used 2.
Other Alternative Agents (If Dapsone Also Fails)
If dapsone cannot be tolerated, additional alternatives include: