Medrol Dose Pack Drug Interactions
Methylprednisolone (Medrol) interacts with multiple medications through cytochrome P450 enzyme pathways, anticoagulants, immunosuppressants, and other drug classes, requiring dose adjustments and careful monitoring to prevent serious adverse events. 1
Critical Pharmacokinetic Interactions
CYP3A4 Enzyme Interactions
Drugs that induce hepatic enzymes (phenobarbital, phenytoin, rifampin) increase methylprednisolone clearance and may require dose increases to maintain therapeutic effect. 1
Drugs that inhibit metabolism (troleandomycin, ketoconazole) decrease methylprednisolone clearance, necessitating dose reduction to avoid steroid toxicity. 1
- Aprepitant (antiemetic) significantly interacts with methylprednisolone through CYP3A4 inhibition and induction, altering plasma concentrations. 2
- These interactions are more pronounced with oral formulations due to first-pass metabolism. 2
Cyclosporine Interaction
Mutual inhibition of metabolism occurs with concurrent cyclosporine use, increasing the likelihood of adverse events from either drug, including convulsions. 1
Anticoagulant Interactions
The effect of methylprednisolone on oral anticoagulants is variable and unpredictable, with reports of both enhanced and diminished anticoagulant effects. 1
- Coagulation indices (INR) must be monitored closely to maintain desired anticoagulant effect when combining these medications. 1
- Corticosteroids significantly increase bleeding risk in patients on NOACs (non-vitamin K antagonist oral anticoagulants), with an adjusted hazard ratio of 1.53 for major bleeding events. 3
- Corticosteroids increase intracranial bleeding risk in anticoagulated patients (aHR 1.49). 3
Aspirin Interactions
Methylprednisolone may increase clearance of chronic high-dose aspirin, leading to decreased salicylate levels or increased salicylate toxicity risk upon methylprednisolone withdrawal. 1
- Use aspirin cautiously with corticosteroids in patients with hypoprothrombinemia. 1
Cardiovascular Drug Interactions
Diltiazem is both a substrate and moderate inhibitor of CYP3A4, creating potential interactions with methylprednisolone. 2
- Specific drug interactions listed for diltiazem include apixaban, cyclosporine, and simeprevir, which may be relevant when combined with corticosteroids. 2
Chemotherapy Agent Interactions
Chemotherapeutic agents metabolized by CYP3A4 (docetaxel, paclitaxel, etoposide, irinotecan, ifosfamide, vincristine, vinblastine) may have altered metabolism when combined with methylprednisolone. 2
- Although phase III trials did not adjust chemotherapy doses for these interactions, caution is warranted. 2
Oral Contraceptive Interactions
Methylprednisolone may affect oral contraceptive efficacy through enzyme induction, though this interaction is less documented than with other corticosteroids. 2
Common Pitfalls and Monitoring
Warfarin Management
- Monitor INR more frequently when initiating or discontinuing methylprednisolone in warfarinized patients. 1
- Expect unpredictable changes requiring dose adjustments in either direction. 1
Immunosuppression Considerations
- Patients on immunosuppressant doses should avoid exposure to chickenpox or measles and seek immediate medical attention if exposed. 1
Tumor Lysis Syndrome Risk
- In patients with hematological malignancies or solid tumors, methylprednisolone (alone or with chemotherapy) can precipitate tumor lysis syndrome. 1
- Monitor high-risk patients (high tumor burden, high proliferative rate) closely with appropriate precautions. 1
Adrenal Suppression
- Gradual dose reduction is essential to minimize drug-induced secondary adrenocortical insufficiency, which may persist for months after discontinuation. 1
- During stress periods following discontinuation, hormone therapy should be reinstituted. 1