Usage
Diltiazem is primarily prescribed for the management of:
- Hypertension: Lowers blood pressure by reducing peripheral vascular resistance.
- Chronic Stable Angina: Decreases the frequency and severity of angina attacks by improving myocardial oxygen supply and reducing oxygen demand.
- Prinzmetal’s Angina (Variant Angina): Prevents and treats episodes of angina caused by coronary artery spasm.
- Atrial Fibrillation and Atrial Flutter (AF/AFL): Controls the rapid ventricular rate associated with these arrhythmias.
- Paroxysmal Supraventricular Tachycardia (PSVT): Converts PSVT to normal sinus rhythm and controls heart rate.
Pharmacological Classification: Non-dihydropyridine Calcium Channel Blocker.
Mechanism of Action: Diltiazem inhibits the influx of calcium ions into vascular smooth muscle cells and cardiac myocytes, leading to vasodilation and decreased myocardial contractility. This results in lower blood pressure, reduced cardiac workload, and improved coronary blood flow.
Alternate Names
Diltiazem hydrochloride is the chemical name. There are no widely used alternate generic names.
Brand Names: Cardizem, Cardizem CD, Cartia XT, Dilt-XR, Dilacor XR, Tiazac, Taztia XT, Matzim LA.
How It Works
Pharmacodynamics: Diltiazem’s primary effects are vasodilation and decreased myocardial contractility. It also slows atrioventricular (AV) nodal conduction, which helps control heart rate in certain arrhythmias.
Pharmacokinetics:
- Absorption: Well-absorbed orally.
- Metabolism: Extensively metabolized by the liver, primarily via CYP3A4.
- Elimination: Excreted in urine and feces.
Mode of Action: Diltiazem binds to L-type calcium channels in vascular smooth muscle and cardiac muscle, blocking calcium influx and reducing intracellular calcium concentrations. This leads to relaxation of vascular smooth muscle, decreased peripheral vascular resistance, and reduced myocardial contractility.
Receptor Binding/Enzyme Inhibition: Binds to L-type calcium channels; metabolized by CYP3A4.
Elimination Pathways: Primarily hepatic metabolism, with subsequent renal and biliary excretion.
Dosage
Standard Dosage
Adults:
- Immediate-Release Tablets/Capsules: 30 mg orally four times daily initially, titrated up to 180-360 mg/day in divided doses.
- Extended-Release Capsules/Tablets: Dosage varies depending on the specific formulation and indication. Starting doses typically range from 60 mg twice daily to 240 mg once daily, with maximum doses up to 540 mg daily. Refer to individual product labeling for specific recommendations.
Children: Not generally recommended. Safety and efficacy not well established.
Special Cases:
- Elderly Patients: Start with lower doses and titrate cautiously.
- Patients with Renal Impairment: Dose adjustments are often necessary. Consult specific product information and clinical guidelines.
- Patients with Hepatic Dysfunction: Dose reduction required. Close monitoring is recommended.
- Patients with Comorbid Conditions: Adjustments may be needed depending on the specific comorbidity.
Clinical Use Cases
- Intubation: Not routinely administered during intubation itself but may be used to manage hypertension or arrhythmias.
- Surgical Procedures: May be used to manage hypertension or angina perioperatively.
- Mechanical Ventilation: Not specifically indicated for mechanical ventilation but can be continued if already part of the patient’s treatment regimen.
- Intensive Care Unit (ICU) Use: Frequently used to manage hypertension, angina, and arrhythmias.
- Emergency Situations: IV diltiazem is used for rapid rate control in PSVT, atrial fibrillation, and atrial flutter.
Dosage Adjustments:
Dose adjustments are necessary for patients with renal or hepatic dysfunction. Drug interactions should be carefully considered and appropriate dosage modifications made.
Side Effects
Common Side Effects:
- Headache
- Dizziness
- Edema (swelling)
- Bradycardia (slow heart rate)
- Flushing
- Nausea
- Constipation
Rare but Serious Side Effects:
- Hypotension (low blood pressure)
- AV block (heart block)
- Heart failure
- Hepatotoxicity (liver damage)
Long-Term Effects:
Generally well-tolerated with long-term use. Periodic monitoring of liver function and heart rate is recommended.
Adverse Drug Reactions (ADR): Angioedema, Stevens-Johnson syndrome.
Contraindications
- Sick sinus syndrome (except with a functioning pacemaker)
- Second- or third-degree AV block (except with a functioning pacemaker)
- Severe hypotension
- Hypersensitivity to diltiazem
- Acute myocardial infarction with pulmonary congestion
Drug Interactions
Diltiazem interacts with numerous drugs, including:
- Beta-blockers: Additive bradycardia and hypotension.
- Digoxin: Increased digoxin levels.
- CYP3A4 inhibitors (e.g., azole antifungals, macrolide antibiotics, grapefruit juice): Increased diltiazem levels.
- CYP3A4 inducers (e.g., rifampin, phenytoin): Decreased diltiazem levels.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: C (Consult product information)
- Fetal Risks: Potential for fetal harm, though limited data. Use with caution.
- Breastfeeding: Diltiazem is excreted in breast milk. Use with caution.
Drug Profile Summary
- Mechanism of Action: Calcium channel blocker, inhibits calcium influx into vascular smooth muscle and cardiac myocytes.
- Side Effects: Headache, dizziness, edema, bradycardia, flushing, nausea, constipation. Rarely, hypotension, AV block, heart failure.
- Contraindications: Sick sinus syndrome, AV block, severe hypotension, hypersensitivity.
- Drug Interactions: Beta-blockers, digoxin, CYP3A4 inhibitors/inducers.
- Pregnancy & Breastfeeding: Use with caution. Potential fetal risks and excretion in breast milk.
- Dosage: Varies depending on formulation and indication. See detailed dosage information above.
- Monitoring Parameters: Heart rate, blood pressure, liver function tests (periodically).
Popular Combinations
- Other antihypertensive medications (e.g., thiazide diuretics, ACE inhibitors, ARBs)
- Nitrates (for angina)
Precautions
- Monitor heart rate and rhythm, particularly in patients with pre-existing conduction abnormalities.
- Caution in patients with hepatic or renal impairment.
- Avoid grapefruit juice.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Diltiazem?
A: Dosage varies widely depending on the indication, formulation (immediate-release vs. extended-release), and patient-specific factors. See the detailed dosage section above for specifics. Always refer to the latest product information.
Q2: What are the common side effects of Diltiazem?
A: Common side effects include headache, dizziness, edema, bradycardia, flushing, nausea, and constipation.
Q3: How does Diltiazem differ from other calcium channel blockers?
A: Diltiazem is a non-dihydropyridine calcium channel blocker, meaning it has more pronounced effects on the heart than on blood vessels, compared to dihydropyridines like amlodipine.
Q4: Can Diltiazem be used in patients with heart failure?
A: Diltiazem should be used cautiously in patients with heart failure. Close monitoring is required, and dose adjustments may be necessary.
Q5: What are the contraindications to using Diltiazem?
A: Contraindications include sick sinus syndrome, second- or third-degree AV block, severe hypotension, and hypersensitivity to diltiazem.
Q6: How should Diltiazem be administered?
A: Diltiazem is available in oral (immediate-release and extended-release) and intravenous formulations. Extended-release tablets should be swallowed whole and not crushed or chewed.
Q7: Does Diltiazem interact with other medications?
A: Yes, Diltiazem interacts with numerous medications, including beta-blockers, digoxin, and drugs that affect CYP3A4 activity. Consult drug interaction resources for a complete list.
Q8: Can Diltiazem be used during pregnancy or breastfeeding?
A: Diltiazem should be used with caution during pregnancy and breastfeeding. Potential risks to the fetus and newborn should be carefully considered.
Q9: What monitoring is necessary for patients taking Diltiazem?
A: Monitor heart rate, blood pressure, and liver function tests periodically. Closely monitor patients with renal or hepatic impairment.
