Introduction
Cardizem (diltiazem hydrochloride) is a calcium channel blocker belonging to the benzothiazepine class. It is widely prescribed for cardiovascular conditions, primarily for its antianginal, antiarrhythmic, and antihypertensive properties. First approved by the FDA in the 1980s, Cardizem remains a cornerstone therapy in cardiovascular medicine due to its favorable efficacy and safety profile.
Mechanism of Action
Cardizem exerts its therapeutic effects through selective inhibition of calcium ion influx across the cell membrane of cardiac and vascular smooth muscle. This inhibition results in:
- Coronary and peripheral vasodilation
- Reduced myocardial oxygen demand
- Decreased atrioventricular (AV) nodal conduction
- Negative chronotropic and inotropic effects
The drug preferentially acts on vascular smooth muscle over cardiac muscle, making it particularly effective for vasospastic conditions while having less negative inotropic effect compared to verapamil.
Indications
FDA-approved indications:
- Hypertension (monotherapy or combination therapy)
- Chronic stable angina
- Vasospastic angina (Prinzmetal's variant angina)
- Supraventricular tachyarrhythmias (including atrial fibrillation and flutter)
Off-label uses may include:
- Raynaud's phenomenon
- Esophageal spasm
- Migraine prophylaxis
Dosage and Administration
Hypertension:- Immediate-release: 30-120 mg three times daily
- Extended-release: 180-480 mg once daily
- Immediate-release: 30-120 mg three or four times daily
- Extended-release: 120-480 mg once daily
- IV bolus: 0.25 mg/kg over 2 minutes, may repeat with 0.35 mg/kg after 15 minutes
- IV infusion: 5-15 mg/hour
- Renal impairment: Reduce dose by 50% if CrCl < 30 mL/min
- Hepatic impairment: Start with lowest dose and titrate slowly
- Elderly: Initiate at lower end of dosing range
Pharmacokinetics
Absorption: Well absorbed orally (80-90%) but undergoes extensive first-pass metabolism Distribution: Vd: 3-8 L/kg; Protein binding: 70-80% Metabolism: Extensive hepatic metabolism via CYP3A4 Elimination: Half-life: 3-4.5 hours (immediate-release); 5-8 hours (extended-release) Excretion: Primarily hepatic (60%) with renal elimination of metabolitesContraindications
- Sick sinus syndrome (except with functioning pacemaker)
- Second- or third-degree AV block (except with functioning pacemaker)
- Hypotension (<90 mmHg systolic)
- Acute myocardial infarction with pulmonary congestion
- Hypersensitivity to diltiazem or components
- Concurrent IV beta-blocker administration
- Wolff-Parkinson-White syndrome with atrial fibrillation
Warnings and Precautions
Black Box Warning: None Important Precautions:- Hepatic impairment: May require dose reduction
- Congestive heart failure: Use with caution
- Elderly patients: Increased sensitivity
- Abrupt withdrawal: May cause rebound angina
- Peripheral edema: Common side effect
- Dermatological reactions: Rare but serious
Drug Interactions
Major Interactions:- Beta-blockers: Increased risk of bradycardia and heart block
- Digoxin: Increased digoxin levels (15-20%)
- CYP3A4 inhibitors (ketoconazole, erythromycin): Increased diltiazem levels
- CYP3A4 inducers (rifampin): Decreased diltiazem levels
- Statins: Increased risk of myopathy with simvastatin and lovastatin
- Cyclosporine: Increased cyclosporine levels
Adverse Effects
Common (>10%):- Headache
- Dizziness
- Edema
- Flushing
- Bradycardia
- Nausea
- Constipation
- Fatigue
- Rash
- AV block
- Hepatotoxicity
- Gingival hyperplasia
- Photosensitivity
- Stevens-Johnson syndrome
Monitoring Parameters
Baseline:- Blood pressure and heart rate
- ECG
- Liver function tests
- Renal function
- Blood pressure at each visit
- Heart rate and rhythm
- Signs of heart failure
- Peripheral edema
- Liver function (periodically)
- Hypertension: BP <140/90 mmHg (individualized)
- Angina: Reduced frequency of attacks
- Arrhythmias: Control of ventricular rate
Patient Education
Key Points:- Take exactly as prescribed; do not stop abruptly
- Extended-release tablets must be swallowed whole
- Report any signs of edema, shortness of breath, or dizziness
- Avoid grapefruit juice (may increase drug levels)
- Rise slowly from sitting/lying position to prevent dizziness
- Inform all healthcare providers about Cardizem use
- Use caution when driving or operating machinery
- Regular blood pressure monitoring recommended
- Store at room temperature (15-30°C)
- Keep in original container
- Protect from moisture
References
1. FDA Prescribing Information: Cardizem (diltiazem hydrochloride) 2. Brunton LL, Hilal-Dandan R, Knollmann BC. Goodman & Gilman's: The Pharmacological Basis of Therapeutics. 13th ed. 3. Micromedex Solutions: Diltiazem Drug Information 4. American College of Cardiology/American Heart Association Guidelines for Hypertension Management (2017) 5. Journal of Cardiovascular Pharmacology: Diltiazem clinical studies (Various issues) 6. Clinical Pharmacology and Therapeutics: Calcium channel blocker pharmacokinetics (Volume 95, Issue 5) 7. European Heart Journal: Management of atrial fibrillation (2016) 8. New England Journal of Medicine: Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (2002)
Note: This information is for educational purposes only and does not replace professional medical advice. Always consult with a healthcare provider for personalized medical guidance.