Immediate-Release Oral Diltiazem Dosing
For immediate-release oral diltiazem, the standard dosing regimen is 30 to 90 mg administered four times daily (every 6 hours), with most patients requiring titration within this range to achieve therapeutic effect. 1
Standard Dosing Parameters
The FDA-approved immediate-release formulation requires frequent dosing due to its short duration of action and plasma elimination half-life of approximately 3.0 to 4.5 hours 2:
- Starting dose: 30 mg four times daily 1
- Usual therapeutic range: 30 to 90 mg four times daily 1
- Maximum daily dose: 360 mg total (90 mg four times daily) 1
Pharmacokinetic Considerations
Immediate-release diltiazem tablets achieve detectable plasma levels within 30 to 60 minutes, with peak plasma concentrations occurring 2 to 4 hours after administration 2. The short half-life necessitates the four-times-daily dosing schedule to maintain therapeutic plasma levels in the range of 50 to 200 ng/mL 2.
The dose-response relationship is non-linear: when increasing from 120 mg daily (30 mg four times daily) to 240 mg daily (60 mg four times daily), the area-under-the-curve increases 2.3-fold, and from 240 mg to 360 mg daily, it increases 1.8-fold 2. This means higher doses produce disproportionately greater drug exposure.
Titration Strategy
Begin with 30 mg four times daily and increase gradually based on clinical response 1. The American College of Cardiology guidelines emphasize cautious, progressive titration over several weeks to reach effective control while monitoring for adverse effects 3.
Key monitoring parameters during titration 3:
- Blood pressure and heart rate at each dose adjustment
- Signs of hypotension (the most common adverse effect)
- Bradycardia or conduction abnormalities
- Peripheral edema (dose-related, more common in women)
Clinical Context and Limitations
Immediate-release nifedipine is specifically NOT recommended for unstable angina/NSTEMI except with concomitant beta blockade 1, though this caveat applies less stringently to diltiazem given its heart rate-slowing properties. However, the four-times-daily dosing requirement of immediate-release diltiazem makes it impractical for most patients in contemporary practice.
The choice between diltiazem and other calcium channel blockers depends on baseline heart rate: diltiazem is preferred in patients with relative tachycardia due to its negative chronotropic effects, whereas dihydropyridines like nifedipine or amlodipine are preferred with relative bradycardia 1.
Absolute Contraindications
Do not use immediate-release diltiazem in 1, 3:
- Second or third-degree AV block without a functioning pacemaker
- Sick sinus syndrome without a pacemaker
- Decompensated systolic heart failure or severe left ventricular dysfunction
- Wolff-Parkinson-White syndrome with atrial fibrillation/flutter
- Cardiogenic shock
- Hypotension
Common Pitfalls
Avoid combining diltiazem with beta-blockers without careful monitoring, as this significantly increases the risk of bradyarrhythmias, heart block, and heart failure 1, 3. When combination therapy is necessary for refractory symptoms, the drugs may act synergistically to depress left ventricular function and sinus/AV node conduction 1.
Hepatic dysfunction requires dose adjustment since diltiazem undergoes extensive hepatic metabolism, with cirrhotic patients showing a 69% increase in drug exposure 2. Renal dysfunction does not significantly alter diltiazem pharmacokinetics 2.
Drug Interactions
Diltiazem is both a CYP3A4 substrate and moderate CYP3A4 inhibitor 3. Exercise caution with medications such as apixaban, itraconazole, cyclosporine, simvastatin, and other CYP3A4 substrates or inhibitors, as significant drug-drug interactions may occur 3.
Practical Consideration
In modern clinical practice, extended-release formulations (120-360 mg once daily) have largely replaced immediate-release diltiazem due to improved adherence with once-daily dosing and more stable plasma concentrations 3, 4. The immediate-release formulation remains relevant primarily for initial dose-finding in select patients or when rapid titration is needed, though even for acute rate control, intravenous formulations are preferred 5, 6.