What are the recommended doses of isoniazid (Isoniazid), valacyclovir (Valacyclovir), and cotrimoxazole (Cotrimoxazole) for prophylaxis in patients taking prednisone (Prednisone) >20mg?

Prophylactic Dosing for Patients on Prednisone >20mg Daily

For patients receiving prednisone ≥20 mg daily for ≥4 weeks, initiate trimethoprim-sulfamethoxazole for Pneumocystis jirovecii prophylaxis, consider valacyclovir for herpes zoster prevention, and screen for latent tuberculosis with isoniazid prophylaxis if indicated. 1

Pneumocystis jirovecii Pneumonia (PJP) Prophylaxis

Indication and Timing

• Trimethoprim-sulfamethoxazole (TMP-SMX) is the preferred agent for PJP prophylaxis in patients receiving prednisone equivalent ≥20 mg/day for ≥4 weeks 1
• This threshold represents a critical risk point where prophylaxis transitions from "consider" to "should implement" 1

Dosing Regimen

• TMP-SMX: One double-strength tablet (160 mg trimethoprim/800 mg sulfamethoxazole) daily is the standard prophylactic dose 1
• Alternative dosing: One double-strength tablet three times weekly if daily dosing is not tolerated 1

Alternative Agents (if TMP-SMX intolerant)

• Atovaquone 1500 mg daily 1
• Dapsone 100 mg daily (check G6PD levels before initiating) 1
• Pentamidine (aerosolized 300 mg monthly or IV) 1

Duration

• Continue prophylaxis throughout the period of prednisone ≥20 mg/day and for at least 4-6 weeks after tapering below this threshold 1

Herpes Zoster Prophylaxis

Indication

• Consider valacyclovir prophylaxis for patients on prednisone ≥20 mg/day for ≥6 weeks, particularly those with additional immunosuppression 1
• The risk of zoster reactivation increases substantially with prolonged high-dose corticosteroid exposure 1

Dosing Regimen

• Valacyclovir 500 mg daily is the typical prophylactic dose for immunosuppressed patients
• Continue throughout high-dose steroid therapy and consider extending 1-2 months after tapering 1

Tuberculosis Screening and Prophylaxis

Screening Requirements

• Screen all patients for latent tuberculosis before initiating prednisone ≥20 mg/day using interferon-gamma release assays (IGRAs) or tuberculin skin testing 1
• Prednisone >15 mg/day for ≥3 months represents a significant TB reactivation risk 2

Isoniazid Prophylaxis Dosing (if latent TB positive)

• Isoniazid 300 mg daily for 6-9 months is the standard regimen for latent TB treatment in immunosuppressed patients 2
• A 70% reduction in TB risk was demonstrated with any isoniazid prophylaxis, and 97% reduction with complete 6-month prophylaxis in steroid-exposed patients 2
• Alternative: Rifampin-based regimens may be considered but require careful drug interaction monitoring with other medications 2

Critical Timing Consideration

• Do not delay corticosteroid therapy for TB testing results in acute situations; initiate testing concurrently and add isoniazid prophylaxis if positive 1

Additional Fungal Prophylaxis

Indication for Fluconazole

• Consider fluconazole 400 mg weekly for patients receiving prednisone ≥20 mg/day for ≥6 weeks, particularly in endemic fungal areas or with additional immunosuppression 1
• This is a lower priority than PJP prophylaxis but should be considered in high-risk scenarios 1

Hepatitis B Screening and Prophylaxis

Pre-treatment Screening

• Screen for hepatitis B surface antigen (HBsAg) and anti-HBc before initiating prednisone ≥20 mg/day for ≥4 weeks 1
• Moderate-to-high dose corticosteroids (≥20 mg/day) for ≥4 weeks place HBsAg-positive patients at high risk for reactivation 1

Antiviral Prophylaxis (if HBsAg positive)

• Entecavir 0.5 mg daily or tenofovir 300 mg daily should be initiated before starting high-dose steroids 1
• Continue for at least 6 months after discontinuation of immunosuppressive therapy 1

Monitoring and Supportive Care

Essential Monitoring

• Blood glucose monitoring at least weekly initially, then as clinically indicated for steroid-induced hyperglycemia 1
• Gastric protection with proton pump inhibitors or H2 blockers for patients on NSAIDs or anticoagulants 1
• Calcium 1200-1500 mg daily plus vitamin D 800-1000 IU daily for osteoporosis prevention 1

Common Pitfalls to Avoid

• Do not wait for symptoms to initiate PJP prophylaxis—the threshold of prednisone ≥20 mg/day for ≥4 weeks is absolute 1
• Do not assume prior vaccination eliminates the need for prophylaxis—immunosuppression reduces vaccine efficacy 1
• Do not discontinue prophylaxis prematurely—continue until steroids are tapered below 20 mg/day for at least 4 weeks 1
• Sulfa allergies are common—have alternative PJP prophylaxis agents readily available 1
• Drug interactions matter—rifampin-based TB regimens can interact with multiple medications; isoniazid is generally safer 3