Diltiazem Formulation Selection When Switching from Daily to Twice Daily Dosing
When switching from daily extended-release (ER) Cardizem (diltiazem) 120mg to twice-daily dosing, you should switch to immediate-release (IR) formulation, not continue with ER formulation.
Rationale for Formulation Selection
- Extended-release diltiazem is specifically designed for once-daily dosing with a recommended dosage range of 120-360 mg once daily 1, 2
- When twice-daily dosing is required, immediate-release formulation is the appropriate choice, as extended-release formulations are specifically designed for their longer duration of action 1, 2
- The American College of Cardiology guidelines clearly distinguish between extended-release formulations (used once daily) and immediate-release formulations (used multiple times daily) 1
Pharmacokinetic Considerations
- Extended-release diltiazem has a half-life of 12 hours compared to 4.5-12 hours for immediate-release formulation, making the extended-release version inappropriate for twice-daily dosing 1
- Dividing an extended-release formulation for twice-daily use disrupts the intended pharmacokinetic profile and may lead to unpredictable drug levels 3, 4
- Studies comparing once-daily versus twice-daily diltiazem administration used different formulations specifically designed for their respective dosing schedules 5, 6
Clinical Implications
- Using extended-release formulation twice daily may result in higher than intended peak concentrations and potential adverse effects including hypotension, edema, heart failure exacerbation, and bradycardia 1, 2
- Immediate-release diltiazem is specifically formulated for multiple daily dosing regimens and provides more consistent blood levels when administered twice daily 6
- Research has shown that when switching between formulations, using the appropriate formulation for the intended dosing frequency is crucial for maintaining therapeutic efficacy 4, 7
Dosing Recommendations
- For twice-daily dosing, use immediate-release diltiazem at 60mg twice daily to maintain the equivalent total daily dose of 120mg 1
- If extended-release formulation must be used (though not recommended), total daily dose should not exceed the maximum recommended daily dose of 360mg 1, 2
- When converting between formulations, maintain the same total daily dose but use the appropriate formulation for the intended dosing frequency 4
Common Pitfalls to Avoid
- Do not split or crush extended-release tablets as this destroys the extended-release mechanism and may cause dose dumping 2
- Avoid assuming that all diltiazem formulations are interchangeable; they have different release characteristics designed for specific dosing intervals 5, 6
- Be aware that inappropriate use of extended-release formulations multiple times daily may increase the risk of adverse effects, particularly hypotension and bradycardia 1, 2