Dosing of Ivabradine and Diltiazem
Ivabradine (Tablet) Dosing
For inappropriate sinus tachycardia (IST), start ivabradine at 2.5 mg twice daily and titrate up to 7.5 mg twice daily based on heart rate response and symptom control. 1
Standard Dosing Protocol
- Initial dose: 2.5 mg twice daily 1
- Target dose: 5-7.5 mg twice daily 1
- Maximum dose: 7.5 mg twice daily 1
Clinical Evidence and Efficacy
- In the pivotal randomized crossover trial, ivabradine at 2.5-7.5 mg twice daily reduced daytime heart rate from 98.4 ± 11.2 bpm to 84.7 ± 9.0 bpm (p<0.001) compared to placebo 1
- Observational studies using 15 mg total daily dose (7.5 mg twice daily) showed mean heart rate reduction from 94.0 ± 10.0 to 74.6 ± 5.2 bpm 2
- Long-term studies demonstrate sustained efficacy at 5-7.5 mg twice daily, with mean heart rate decreasing from 97 ± 6 bpm to 79 ± 8 bpm at 6 months 3
Combination Therapy Considerations
- When combined with beta-blockers (e.g., metoprolol succinate 95 mg daily), ivabradine 7.5 mg twice daily provides additive heart rate reduction and complete symptom resolution in refractory cases 1
- Monitor closely for excessive bradycardia (<50 bpm) when combining with beta-blockers 1
Important Safety Information
- Phosphenes (visual brightness disturbances) occur in 3% of patients but are usually transient 1
- Excellent safety profile demonstrated in large heart failure trials (SHIFT, BEAUTIFUL) 1
- Well-tolerated even in combination with beta-blockers in the majority of patients 1
Diltiazem (Injection) Dosing
For acute rate control in atrial fibrillation or focal atrial tachycardia, administer diltiazem 0.25 mg/kg IV over 2 minutes, followed by a second bolus of 0.35 mg/kg if needed after 15 minutes, then maintain with continuous infusion at 5-15 mg/hour. 4
IV Bolus Dosing
- Initial bolus: 0.25 mg/kg (approximately 15-20 mg for average adult) IV over 2 minutes 4, 5
- Second bolus (if needed): 0.35 mg/kg IV 15 minutes after first dose 4
- Onset of action: 2-7 minutes 4
Continuous Infusion Protocol
- Starting rate: 5-15 mg/hour 4
- Titration: Increase in 5 mg/hour increments as needed 4
- Maximum rate: 15 mg/hour 4
- Target heart rate: 60-80 bpm at rest or <100 bpm with >20% reduction from baseline 4
Lower-Dose Strategy for Safety
- Evidence suggests doses ≤0.2 mg/kg may be equally effective with significantly lower hypotension risk (18% vs 34.9% with standard dose) 6
- Consider starting with lower doses in elderly patients or those at risk for hypotension 6
Transition to Oral Therapy
- Timing: Initiate oral diltiazem once stable rate control achieved for 15-30 minutes after IV bolus 4
- Initial oral dose: 30-60 mg immediate-release every 6 hours (120-240 mg/day total) 4
- Maintenance oral dose: 120-360 mg daily (immediate-release in divided doses or extended-release once daily) 4, 7
- Monitor continuously for 2-4 hours after starting oral therapy 4
Critical Contraindications (Absolute)
- Heart failure with reduced ejection fraction (LVEF ≤40%) 4
- Pre-excited atrial fibrillation (WPW syndrome with AF/flutter) 4, 5
- Second or third-degree AV block without pacemaker 4, 7
- Severe hypotension (SBP <90 mmHg) 4, 7
- Cardiogenic shock 7
- Sick sinus syndrome without pacemaker 7, 5
Common Adverse Effects and Monitoring
- Hypotension (18-42% depending on dose) - most common adverse effect 4
- Bradycardia - monitor heart rate continuously 4
- Heart block - avoid in PR interval >0.24 seconds 4
- Negative inotropic effects - contraindicated in systolic heart failure 4
Important Clinical Pitfalls
- Never combine routinely with beta-blockers due to risk of profound bradycardia, AV block, and heart failure 4, 7
- Do not use for wide-complex tachycardias unless supraventricular origin confirmed 7
- Diltiazem is a CYP3A4 substrate and moderate inhibitor - reduce warfarin dose by 50% and digoxin by 30-50% when initiating 7
- In heart failure patients, use digoxin or amiodarone instead 4