Does Reglan (Metoclopramide) Affect Tacrolimus Levels?
Yes, metoclopramide (Reglan) can increase tacrolimus whole blood trough concentrations and increase the risk of serious adverse reactions including neurotoxicity and QT prolongation. 1
Mechanism and Clinical Significance
The FDA drug label explicitly lists metoclopramide under "Other drugs" that may increase tacrolimus whole blood trough concentrations. 1
When metoclopramide is co-administered with tacrolimus, the FDA recommends monitoring tacrolimus whole blood trough concentrations and reducing the tacrolimus dose if needed. 1
The increased tacrolimus levels can lead to serious toxicity manifestations including nephrotoxicity, neurotoxicity, and QT prolongation. 1
Monitoring and Management Strategy
When starting metoclopramide in a patient on tacrolimus:
Check tacrolimus trough levels within 1-3 days of initiating metoclopramide, as levels can rise relatively quickly. 2
Continue monitoring tacrolimus levels every 2-3 days until stable therapeutic range is confirmed. 2
Be prepared to reduce tacrolimus dose by 25-33% if levels rise 20-50% above target, or by 50% if levels exceed 50% above target. 3
Target therapeutic ranges for tacrolimus:
- Lung transplant recipients: 10-15 ng/mL early post-transplant, then 5-10 ng/mL long-term. 3
- General transplant monitoring: 5-15 ng/mL is the standard recommended range. 4, 5
Critical Pitfalls to Avoid
Do not assume the interaction is negligible - while metoclopramide is not classified as a strong CYP3A4 inhibitor like azole antifungals, the FDA still explicitly warns about this interaction. 1
Do not wait for symptoms of toxicity - proactively monitor levels rather than waiting for clinical signs of tacrolimus toxicity such as tremor, confusion, or rising creatinine. 2, 5
Do not forget to recheck levels if metoclopramide is discontinued - tacrolimus levels may drop when the interacting drug is removed, potentially increasing rejection risk. 4, 2
Comparison to Other Drug Interactions
Metoclopramide's effect is less pronounced than strong CYP3A4 inhibitors (azole antifungals, protease inhibitors) which require immediate 67% dose reduction of tacrolimus. 1
However, metoclopramide's interaction is clinically significant enough to warrant the same monitoring recommendations as mild-to-moderate CYP3A4 inhibitors like calcium channel blockers and macrolide antibiotics. 1