CARDIZEM
Clinical safety rating
cautionComprehensive clinical and safety monograph for CARDIZEM (CARDIZEM).
Diltiazem inhibits calcium influx into cardiac and vascular smooth muscle cells during depolarization by binding to L-type calcium channels. This results in coronary vasodilation, decreased myocardial oxygen demand, and negative chronotropic and inotropic effects.
| Metabolism | Hepatic via CYP3A4; undergoes extensive first-pass metabolism; metabolites: desacetyl diltiazem (active, 40-50% potency), N-demethylated, and deacetylated forms. |
| Excretion | Primarily hepatic metabolism with extensive first-pass effect; approximately 2-4% excreted unchanged in urine; fecal excretion accounts for about 65% of dose as metabolites; renal excretion accounts for about 35% of dose as metabolites. |
| Half-life | Terminal elimination half-life is 3.0-4.5 hours in healthy adults; may be prolonged to 7-9 hours in elderly, hepatic impairment, or renal impairment; clinically relevant for dosing frequency. |
| Protein binding | 77-87% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | 3-5 L/kg; large Vd indicates extensive tissue binding and distribution. |
| Bioavailability | Oral: 40-50% due to significant first-pass metabolism (range 30-60% across individuals); IV: 100%. |
| Onset of Action | IV: 2-3 minutes; immediate-release oral: 30-60 minutes; extended-release oral: 60-120 minutes. |
| Duration of Action | IV: 1-3 hours (dose-dependent); immediate-release oral: 4-6 hours; extended-release oral: 12-24 hours depending on formulation. |
| Molecular Weight | 414.52 |
Oral: 30-120 mg three to four times daily; extended-release: 120-360 mg once daily. IV: Initial 0.25 mg/kg (max 25 mg) bolus over 2 minutes, may repeat in 15 minutes (0.35 mg/kg); maintenance: 5-15 mg/hour continuous infusion.
| Dosage form | INJECTABLE |
| Renal impairment | No specific dose adjustment for renal impairment; use with caution in severe renal dysfunction (CrCl <30 mL/min) with close monitoring of heart rate and blood pressure. |
| Liver impairment | Child-Pugh Class A: No adjustment. Class B: Reduce total daily dose by 25-50%. Class C: Avoid use; if necessary, consider further dose reduction with careful monitoring. |
| Pediatric use | Oral: 1.5-2 mg/kg/day divided every 6-8 hours, maximum 3.5 mg/kg/day. Extended-release not recommended in children. IV: Use only with caution; dosing not well established; typical initial bolus 0.1-0.3 mg/kg over 2 minutes, maximum 10 mg; infusion 0.5-5 mcg/kg/min. |
| Geriatric use | Start at lower end of dosing range: oral immediate-release 30 mg three times daily; extended-release 120 mg once daily. Increase slowly. IV: Lower initial bolus (0.15-0.2 mg/kg) and infusion rates (2-5 mg/hour). Monitor for hypotension and bradycardia. |
| 1st trimester | Teratogenic effects observed in animal studies; may cause fetal bradycardia, cardiac malformations. Use only if benefit outweighs risk. |
| 2nd trimester | Risk of fetal bradycardia, hypotension. Monitor fetal heart rate. Avoid use if possible. |
| 3rd trimester | May cause uterine relaxation, maternal hypotension, fetal bradycardia. Avoid near term due to risk of cervical ripening inhibition. |
Clinical note
Comprehensive clinical and safety monograph for CARDIZEM (CARDIZEM).
| Placental transfer | Crosses placenta; fetal serum levels approximately 50% maternal levels. |
| Breastfeeding | Diltiazem is excreted in breast milk in low levels; no adverse effects reported in infants. However, theoretical risk of cardiovascular effects. Use with caution. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | No adequate studies in pregnant women. In animal studies, diltiazem (Cardizem) has been shown to cause skeletal abnormalities and increased fetal mortality at doses 5-10 times the maximum recommended human dose. Based on animal data and human experience with calcium channel blockers, risk cannot be ruled out. Use only if potential benefit justifies risk to fetus. Category C. |
| Fetal Monitoring | Monitor maternal blood pressure, heart rate, and ECG for bradycardia, AV block, or hypotension. Monitor fetal heart rate and growth via ultrasound, especially if used for hypertension or arrhythmias in pregnancy. |
| Fertility Effects | No significant human data on fertility effects. Animal studies show no impairment of fertility at therapeutic doses. |
■ FDA Black Box Warning
There is no FDA black box warning for CARDIZEM (diltiazem).
| Serious Effects |
Hypersensitivity to diltiazemSevere hypotension (systolic BP <90 mmHg)Second- or third-degree AV block (without pacemaker)Sick sinus syndrome (without pacemaker)Atrial fibrillation/flutter with accessory bypass tract (WPW or LGL syndrome)Cardiogenic shockConcurrent use of ivabradineConcurrent use of dantrolene (risk of hyperkalemia)
| Precautions | Symptomatic hypotension, Bradycardia or heart block (especially in sick sinus syndrome or AV block without pacemaker), Worsening heart failure in patients with reduced ventricular function, Hepatic injury (rare but elevated liver enzymes reported), Concomitant use with beta-blockers may increase risk of bradycardia and heart failure, Digitalis toxicity risk increased when used with digoxin, May exacerbate myasthenia gravis, Acute generalized exanthematous pustulosis (AGEP) and other severe cutaneous reactions, Gradual withdrawal recommended for chronic therapy to avoid angina exacerbation, May lower blood pressure, use with caution in patients with hypotension, Use in renal impairment: monitor carefully |
| Food/Dietary | Avoid grapefruit and grapefruit juice as they inhibit CYP3A4 and can increase diltiazem levels, leading to toxicity. High-fat meals may increase absorption of some extended-release formulations; take with consistent meals. Alcohol may increase the risk of hypotension and dizziness. Maintain adequate hydration and avoid excessive salt intake to control blood pressure. |
| Clinical Pearls | Cardizem (diltiazem) is a non-dihydropyridine calcium channel blocker used for hypertension, angina, and atrial fibrillation/atrial flutter. It is contraindicated with IV beta-blockers due to risk of bradycardia and heart block. In AF, use IV form for rate control but avoid in WPW due to risk of ventricular pre-excitation. Diltiazem is metabolized by CYP3A4; caution with strong inhibitors like clarithromycin or grapefruit juice. For hypertension, start at 30 mg TID or extended-release once daily. Monitor heart rate and PR interval; avoid in sick sinus syndrome or second/third-degree AV block without pacemaker. |
| Patient Advice | Take this medication exactly as prescribed; do not crush or chew extended-release capsules. · Avoid grapefruit and grapefruit juice while taking this medication. · If you miss a dose, take it as soon as you remember unless it is almost time for your next dose; do not double the dose. · Do not stop taking this medication abruptly, as it may worsen your condition. · Common side effects include dizziness, headache, and swelling in the ankles/feet; contact your doctor if you experience slow heartbeat, shortness of breath, or fainting. · This medication may cause dizziness or lightheadedness; avoid driving or operating machinery until you know how it affects you. |
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