What medications interact with prednisone?

Medication Interactions with Prednisone

Prednisone has several important drug interactions that can affect its metabolism, efficacy, and safety profile, requiring dosage adjustments or alternative medications in certain cases. 1

Major Drug Interactions

Medications that Increase Prednisone Effects

• Antifungal drugs: May require dose adjustment of prednisone 1
• Grapefruit juice: May increase prednisone levels, potentially requiring lower doses 1
• Liquorice: Can potentiate prednisone effects, possibly requiring dose reduction 1
• Ketoconazole: Increases unbound prednisolone concentrations 2
• Estrogen-containing oral contraceptives: Increase unbound prednisolone concentrations 2
• Ritonavir and other protease inhibitors: May significantly increase prednisolone concentrations 1

Medications that Decrease Prednisone Effects

• Anti-epilepsy medications/barbiturates: May require higher prednisone doses 1
• Antituberculosis drugs: May necessitate increased prednisone dosing 1
• Etomidate: May require higher prednisone doses 1
• Topiramate: May require higher prednisone doses 1
• Microsomal liver enzyme inducers: Decrease prednisolone concentrations 2
• Rifampin: Induces CYP3A4, potentially reducing prednisone effectiveness 3
• Phenytoin, carbamazepine, phenobarbital: Induce prednisone metabolism, potentially causing rapid elimination 1

Specific Medication Interactions

• Warfarin: Prednisone enhances warfarin's anticoagulant effect by inhibiting vitamin K1 absorption through the NPC1L1 pathway, requiring close PT-INR monitoring 4
• Immunosuppressants: Tacrolimus, cyclosporine, and sirolimus concentrations may be affected when co-administered with prednisone 1
• TNF-alpha inhibitors: When combined with prednisone, may increase risk of hepatitis B reactivation in patients with positive HBsAg 1

Medications with Minimal Interactions

• Lansoprazole/Omeprazole: No significant effect on prednisone absorption, biotransformation, or disposition 5
• Azathioprine/6-mercaptopurine: Appear to have lowest potential for interaction with prednisone 1

Clinical Management of Interactions

Monitoring Recommendations

1. Hepatitis B screening: Essential before combining prednisone with immunosuppressants, especially TNF-alpha inhibitors 1
2. Blood glucose monitoring: Particularly important with long-term prednisone use 6
3. Blood pressure monitoring: Regular checks recommended during prednisone therapy 6
4. PT-INR monitoring: More frequent monitoring when initiating or discontinuing prednisone in patients on warfarin 4

Dosage Considerations

• Short-term use (<2 weeks): Generally associated with fewer significant drug interactions 3
• High-dose therapy (>20mg/day): Higher risk of drug interactions and adverse effects 1
• Long-term therapy (>3 months): Increases risk of interactions, particularly with drugs affecting CYP3A4 1

Special Populations

• Liver disease patients: May have altered prednisone metabolism but generally limited effects on prednisolone disposition 7
• Kidney disease patients: May experience increased unbound prednisolone concentrations 2
• Elderly patients: May be more sensitive to medication effects and potential interactions 3

Common Pitfalls to Avoid

• Failing to screen for hepatitis B before initiating prednisone with other immunosuppressants
• Overlooking the need for increased prednisone doses when co-administered with enzyme inducers
• Not monitoring warfarin efficacy when starting or stopping prednisone therapy
• Assuming that short-term, low-dose prednisone (<10mg/day for <2 weeks) carries the same interaction risk as higher doses or longer treatment

Remember that the clinical significance of many interactions depends on prednisone dose, duration of therapy, and individual patient factors. Monitoring for both therapeutic effects and adverse reactions is essential when prednisone is used with potentially interacting medications.