What are the dosing options for Cardizem (Diltiazem)?

Cardizem (Diltiazem) Dosing Options

For acute rate control in atrial fibrillation or flutter, administer an initial IV bolus of 0.25 mg/kg (typically 20 mg) over 2 minutes, followed by a second bolus of 0.35 mg/kg (typically 25 mg) if needed after 15 minutes, then maintain with a continuous infusion starting at 10 mg/hour (range 5-15 mg/hour). 1

Intravenous Administration

Acute Rate Control (Atrial Fibrillation/Flutter)

Initial Bolus Dosing:

• First dose: 0.25 mg/kg (15-20 mg for average patient) IV over 2 minutes 2, 1
• Second dose (if inadequate response): 0.35 mg/kg (20-25 mg for average patient) IV over 2 minutes, administered 15 minutes after first dose 2, 1
• Some patients may respond to a lower initial dose of 0.15 mg/kg, though duration of action may be shorter 1

Continuous Infusion:

• Initial rate: 10 mg/hour immediately following bolus 2, 1
• Alternative starting rate: 5 mg/hour may be appropriate for some patients 2, 1
• Titration: Increase in 5 mg/hour increments up to maximum of 15 mg/hour as needed for further heart rate reduction 2, 1
• Duration: Maximum 24 hours (infusions >24 hours not studied and not recommended) 1
• Efficacy: 74-83% of patients maintain therapeutic response throughout 24-hour infusion 3, 4

Supraventricular Tachycardia (SVT)

For reentrant PSVT:

• Initial dose: 20 mg (0.25 mg/kg) IV over 2 minutes 2
• Maintenance infusion: 10 mg/hour following bolus 2

Preparation for Continuous Infusion

Standard dilutions: 1

• 125 mg in 100 mL (final volume 125 mL) = 1 mg/mL concentration
• 250 mg in 250 mL (final volume 300 mL) = 0.83 mg/mL concentration
• 250 mg in 500 mL (final volume 550 mL) = 0.45 mg/mL concentration

Compatible diluents: Normal Saline, D5W, or D5W/0.45% NaCl 1

Storage: Keep refrigerated until use; use within 24 hours 1

Oral Administration

Immediate-Release Formulation

Angina (exertional or vasospastic):

• Starting dose: 30 mg four times daily (before meals and bedtime) 5
• Titration: Increase gradually at 1-2 day intervals in divided doses (3-4 times daily) 5
• Optimal range: 180-360 mg/day in divided doses 5
• Administration: May be swallowed whole, crushed, or chewed (do not split 30 mg tablets) 5

Transition from IV to oral:

• After achieving rate control with IV diltiazem, transition to oral long-acting formulation (180-360 mg/day) 6
• Discontinue IV infusion 4 hours after first oral dose 6
• 77% of patients maintain heart rate control during transition 6

Extended-Release Formulation

Rate control maintenance:

• Typical dosing: 120-360 mg daily 2
• Common transition dose: 300 mg/day (diltiazem CD) after IV therapy 6

Clinical Context and Indications

Primary Indications

Narrow-complex tachycardias: 2

• Stable narrow-complex tachycardias uncontrolled by adenosine or vagal maneuvers
• Recurrent SVT
• Ventricular rate control in atrial fibrillation or flutter

Coronary vasospasm:

• Moderate to high doses recommended for coronary spasm treatment 7

Pharmacodynamic Considerations

Plasma concentration-effect relationship: 8

• Mean plasma concentrations of 79 ng/mL, 172 ng/mL, and 294 ng/mL produce 20%, 30%, and 40% heart rate reduction respectively
• Strong correlation (r² = 0.78) between plasma diltiazem concentration and percent heart rate reduction
• EC50 (concentration achieving half-maximal effect) = 110 ng/mL

Pharmacokinetics: 8

• Elimination half-life: 6.8-6.9 hours after infusion
• Nonlinear pharmacokinetics with dose-dependent decrease in systemic clearance at higher infusion rates
• Principal metabolites (desacetyldiltiazem, N-desmethyldiltiazem) contribute minimally to pharmacodynamic effects

Critical Safety Considerations

Absolute Contraindications

Avoid diltiazem in: 2, 7

• Heart failure with reduced ejection fraction (HFrEF) or decompensated heart failure
• Pre-excited atrial fibrillation or flutter (WPW syndrome)
• Wide-complex tachycardias or rhythms consistent with ventricular tachycardia
• AV block greater than first degree or significant SA node dysfunction

Monitoring Requirements

Essential monitoring: 2, 7

• Hypotension: Most common adverse effect; monitor blood pressure closely
• Bradycardia: Watch for excessive heart rate reduction
• Heart failure: Monitor for precipitation or worsening in predisposed patients
• Resuscitation equipment: Should be readily available during administration 7

Dose Adjustments

Special populations: 1, 5

• Low body weight patients: Dose on mg/kg basis rather than fixed dosing
• Renal/hepatic impairment: Titrate with particular caution (specific dosing data unavailable)

Comparative Efficacy Data

IV continuous infusion vs. oral immediate-release: 9

• After IV loading dose, oral immediate-release diltiazem (median 30 mg) showed lower treatment failure rate (27%) compared to IV continuous infusion (46%) at 4 hours
• Treatment failure defined as heart rate >110 bpm at 4 hours or conversion to another agent

Infusion dose-response: 4

• 5 mg/hour infusion: 47% maintained response at 10 hours
• 10 mg/hour infusion: 68% maintained response
• 15 mg/hour infusion: 76% maintained response
• 18% conversion to sinus rhythm by end of infusion