Propranolol and Methotrexate Interaction
No clinically significant pharmacokinetic or pharmacodynamic interaction exists between propranolol and methotrexate, and they can be safely co-administered without dose adjustments or additional monitoring beyond standard methotrexate protocols.
Evidence for Lack of Interaction
The available guideline evidence does not identify propranolol as a drug that interacts with methotrexate. When guidelines specifically list drugs that may increase methotrexate toxicity, propranolol is notably absent from these comprehensive lists 1.
Beta-blockers like propranolol are only mentioned in the context of interactions with other medications (specifically ozanimod), not with methotrexate 1. The mechanism of concern with ozanimod involves additive effects on heart rate when beta-blockers are combined with calcium channel blockers, which is unrelated to methotrexate pharmacology 1.
Drugs That Actually Interact with Methotrexate
To provide context, the following drug classes DO interact with methotrexate and should be monitored or avoided 1, 2, 3, 4:
- NSAIDs (reduce renal secretion of methotrexate) 1, 3, 4
- Proton pump inhibitors like omeprazole (may reduce renal elimination) 2, 5
- Penicillins and piperacillin/tazobactam (interfere with renal secretion) 1, 3, 6
- Trimethoprim-sulfamethoxazole (synergistic folate antagonism) 1, 4, 7
- Hepatotoxic drugs including barbiturates 1, 3
Standard Methotrexate Monitoring Applies
When a patient takes both propranolol and methotrexate, follow routine methotrexate monitoring protocols 1, 3:
- CBC and platelet counts: Every 2-4 weeks initially, then every 1-3 months once stable 1, 3
- Liver function tests: Monthly 1, 3
- Renal function (BUN/creatinine): Every 2-3 months 1, 3
- Folic acid supplementation: 1-5 mg daily (except on methotrexate dosing day) to reduce toxicity 1, 3
Clinical Bottom Line
Propranolol does not appear in any methotrexate drug interaction lists from major dermatology or rheumatology guidelines 1. The pharmacokinetic profile of propranolol—which primarily affects hepatic metabolism of other drugs through CYP enzyme interactions and liver blood flow changes 8—does not overlap with methotrexate's elimination pathway, which is predominantly renal 1, 3. No additional precautions, monitoring, or dose adjustments are needed when these two medications are prescribed together.