Is there an interaction between diltiazem (calcium channel blocker) and modafinil (wakefulness-promoting agent)?

Drug Interaction Between Diltiazem and Modafinil

There is no documented clinically significant interaction between diltiazem and modafinil, but caution is warranted due to diltiazem's CYP3A4 inhibitory properties which could theoretically affect modafinil metabolism.

Pharmacological Properties and Metabolism

• Diltiazem is a non-dihydropyridine calcium channel blocker that acts as a moderate inhibitor of CYP3A4 and P-glycoprotein 1
• Diltiazem is primarily used for hypertension, angina, and rate control in atrial fibrillation/flutter 1
• Modafinil is a wakefulness-promoting agent that undergoes hepatic metabolism, partially through CYP3A4 pathways 1

Potential Interaction Mechanism

• Diltiazem's inhibition of CYP3A4 could theoretically increase plasma concentrations of drugs metabolized through this pathway 1
• While no specific studies have documented an interaction between diltiazem and modafinil, the theoretical risk exists based on their metabolic pathways 1
• Similar CYP3A4 inhibitors have been shown to affect the metabolism of other drugs, as demonstrated with tacrolimus where diltiazem significantly increased drug concentrations 2

Clinical Implications

• None of the major cardiovascular guidelines specifically mention an interaction between diltiazem and modafinil 1
• Diltiazem is known to have multiple drug interactions due to its effects on CYP3A4, which requires monitoring when used with certain medications 1
• The clinical significance of any potential interaction would depend on individual patient factors including hepatic function, age, and concomitant medications 1

Monitoring Recommendations

• If concurrent therapy is necessary, monitor for:
  • Increased modafinil effects (headache, nausea, anxiety, insomnia) 1
  • Changes in blood pressure and heart rate, as both medications can affect cardiovascular parameters 1
  • Consider starting with lower doses of modafinil if initiating therapy in a patient already on diltiazem 1

Special Considerations

• Patients with hepatic impairment may be at higher risk for interactions due to altered drug metabolism 1
• Elderly patients may be more sensitive to potential interactions due to age-related changes in pharmacokinetics 1
• The risk-benefit ratio should be assessed when considering concomitant use, particularly in patients with cardiovascular disease 1

Common Pitfalls

• Assuming no interaction exists simply because it's not explicitly documented in guidelines 1
• Failing to monitor for subtle changes in drug effects when combining medications that share metabolic pathways 2
• Not considering the potential for additive cardiovascular effects, as both medications can influence heart rate and blood pressure 1, 3