diltiazem
| Product dosage: 180mg | |||
|---|---|---|---|
| Package (num) | Per pill | Price | Buy |
| 30 | $3.39 | $101.77 (0%) | 🛒 Add to cart |
| 60 | $2.72 | $203.54 $163.23 (20%) | 🛒 Add to cart |
| 90 | $2.51 | $305.31 $225.71 (26%) | 🛒 Add to cart |
| 120 | $2.38 | $407.08 $286.16 (30%) | 🛒 Add to cart |
| 180 | $2.27 | $610.61 $409.09 (33%) | 🛒 Add to cart |
| 270 | $2.20
Best per pill | $915.92 $594.49 (35%) | 🛒 Add to cart |
| Product dosage: 60mg | |||
|---|---|---|---|
| Package (num) | Per pill | Price | Buy |
| 60 | $0.82 | $49.37 (0%) | 🛒 Add to cart |
| 90 | $0.78 | $74.06 $70.53 (5%) | 🛒 Add to cart |
| 120 | $0.76 | $98.75 $91.69 (7%) | 🛒 Add to cart |
| 180 | $0.74 | $148.12 $133.00 (10%) | 🛒 Add to cart |
| 270 | $0.73 | $222.18 $196.48 (12%) | 🛒 Add to cart |
| 360 | $0.72
Best per pill | $296.24 $258.96 (13%) | 🛒 Add to cart |
Diltiazem hydrochloride is a calcium channel blocker primarily used in cardiovascular medicine, available in various formulations including immediate-release tablets, extended-release capsules, and intravenous preparations. This compound belongs to the benzothiazepine class and has established itself as a cornerstone in managing hypertension, angina pectoris, and certain arrhythmias since its FDA approval in the 1980s. What makes diltiazem particularly valuable in clinical practice is its balanced effect on both vascular smooth muscle and cardiac conduction tissue, though it leans more toward vascular selectivity compared to verapamil.
Diltiazem: Comprehensive Cardiovascular Protection - Evidence-Based Review
1. Introduction: What is Diltiazem? Its Role in Modern Medicine
Diltiazem functions as a calcium ion influx inhibitor (slow channel blocker or calcium antagonist) that directly impacts the movement of calcium ions during membrane depolarization in cardiac and vascular smooth muscle. Unlike dihydropyridine calcium channel blockers that predominantly affect vascular smooth muscle, diltiazem exerts significant effects on both the vasculature and cardiac conduction system, making it particularly useful for patients with coexisting hypertension and supraventricular arrhythmias.
In my early cardiology rotations, I remember being surprised by how often attending physicians reached for diltiazem when patients presented with rapid atrial fibrillation alongside elevated blood pressure - it addressed both issues with a single agent, which simplified medication regimens and improved adherence. The drug’s versatility stems from its multifaceted mechanism, which we’ll explore in detail.
2. Key Components and Bioavailability Diltiazem
Diltiazem hydrochloride is the active pharmaceutical ingredient, typically formulated with various excipients depending on the delivery system. The standard immediate-release tablet contains 30mg, 60mg, 90mg, or 120mg of the active compound, while extended-release formulations (Cardizem CD, Dilacor XR, Tiazac) provide 24-hour coverage with once-daily dosing.
Bioavailability varies significantly between formulations. The immediate-release version has approximately 40% absolute bioavailability due to extensive first-pass metabolism, primarily via cytochrome P450 3A4 in the liver. Extended-release formulations are engineered to maintain therapeutic concentrations throughout the dosing interval, with peak concentrations occurring between 10-14 hours post-administration. Protein binding ranges from 70-80%, and the elimination half-life is approximately 3-4.5 hours for immediate-release but extends to 5-8 hours for sustained-release products.
We’ve had some formulation challenges over the years - I recall when our hospital switched generic suppliers and we noticed subtle differences in blood pressure control in several established patients. The pharmacy team had to carefully review bioequivalence data before we felt comfortable with the transition.
3. Mechanism of Action Diltiazem: Scientific Substantiation
Diltiazem’s therapeutic effects derive from its inhibition of calcium ion influx through slow channels during membrane depolarization of cardiac and vascular smooth muscle. The drug binds to L-type calcium channels in their inactivated state, prolonging recovery time and reducing calcium availability for contraction.
In vascular smooth muscle, this produces coronary and peripheral vasodilation, decreasing systemic vascular resistance and afterload. In cardiac tissue, diltiazem depresses sinus node automaticity and atrioventricular node conduction velocity without significantly affecting normal sinoatrial node function or intra-atrial or intraventricular conduction times at therapeutic doses.
The electrophysiological effects are particularly interesting - diltiazem prolongs the AH interval and AV node refractory periods without significantly altering HV interval or QRS duration. This selective action makes it ideal for rate control in atrial fibrillation and flutter while having minimal impact on ventricular conduction.
I’ve found the vascular vs cardiac selectivity spectrum helpful when explaining to residents: if nifedipine is mostly vascular and verapamil has stronger cardiac effects, diltiazem sits comfortably in the middle, which explains its balanced clinical profile.
4. Indications for Use: What is Diltiazem Effective For?
Diltiazem for Chronic Stable Angina
Diltiazem improves exercise tolerance and reduces angina frequency by decreasing myocardial oxygen demand through reduced heart rate and afterload, while simultaneously increasing oxygen supply via coronary vasodilation. Multiple randomized trials have demonstrated its equivalence to beta-blockers for stable angina management.
Diltiazem for Hypertension
As monotherapy or in combination with other antihypertensives, diltiazem effectively lowers blood pressure through peripheral vasodilation and reduced vascular resistance. The extended-release formulations provide 24-hour coverage with smooth blood pressure control throughout the dosing interval.
Diltiazem for Atrial Fibrillation and Flutter
The drug’s effect on AV node conduction makes it particularly valuable for rate control in atrial fibrillation and flutter. Intravenous diltiazem can achieve rate control within 2-7 minutes, while oral formulations maintain control chronically.
Diltiazem for Vasospastic Angina
Diltiazem prevents coronary artery spasm in variant angina through direct effects on vascular smooth muscle, making it a first-line agent for this condition.
Diltiazem for Supraventricular Tachycardias
The drug can terminate and prevent reentrant tachycardias involving the AV node, such as AV nodal reentrant tachycardia.
We had a memorable case last year - a 58-year-old man with recurrent PSVT who failed adenosine in the ED. I ordered IV diltiazem and watched his rhythm convert to sinus within four minutes. His wife commented, “That’s the first time he’s stayed in normal rhythm since this started.” We transitioned him to oral diltiazem and he’s had only one breakthrough episode in ten months.
5. Instructions for Use: Dosage and Course of Administration
Dosing must be individualized based on indication, formulation, and patient characteristics:
| Indication | Formulation | Initial Dose | Titration | Maintenance |
|---|---|---|---|---|
| Hypertension | Extended-release | 180-240 mg daily | 2-week intervals | 180-480 mg daily |
| Chronic Stable Angina | Immediate-release | 30 mg QID | 1-2 day intervals | 120-320 mg daily in divided doses |
| Atrial Fibrillation (rate control) | Extended-release | 120-180 mg daily | - | 180-360 mg daily |
| IV for AF/Aflutter | Intravenous | 0.25 mg/kg over 2 min | 0.35 mg/kg after 15 min if needed | 5-15 mg/hour infusion |
Administration considerations: Extended-release capsules should be swallowed whole, not crushed or chewed. Diltiazem may be taken with or without food, though consistent administration relative to meals improves absorption consistency.
In practice, I usually start older patients or those with borderline blood pressure on the lower end of dosing ranges. I learned this the hard way early in my career when I started a 72-year-old woman on 240mg of extended-release diltiazem - her blood pressure dropped to 85/50 and she had a near-syncopal episode. We reduced to 120mg with much better tolerance.
6. Contraindications and Drug Interactions Diltiazem
Absolute contraindications:
- Sick sinus syndrome (except with functioning ventricular pacemaker)
- Second- or third-degree AV block (except with functioning ventricular pacemaker)
- Hypotension (systolic <90 mmHg)
- Acute myocardial infarction with pulmonary congestion on x-ray
- Hypersensitivity to diltiazem
Relative contraindications:
- Severe left ventricular dysfunction
- Liver impairment (requires dose reduction)
- Renal impairment (monitor closely)
- Pregnancy (Category C)
Significant drug interactions:
- Beta-blockers: Increased risk of bradycardia and AV block
- Digoxin: Increased digoxin levels by 20-50%
- Statins: Increased concentrations of simvastatin, lovastatin, atorvastatin
- Cyclosporine: Markedly increased cyclosporine levels
- CYP3A4 inhibitors/inducers: Altered diltiazem metabolism
I had a concerning interaction case last month - a transplant patient on cyclosporine was started on diltiazem for hypertension. Within two weeks, his cyclosporine levels doubled despite no dose change, and he developed nephrotoxicity. We missed checking levels sooner because the connection wasn’t immediately obvious to the covering resident.
7. Clinical Studies and Evidence Base Diltiazem
The evidence supporting diltiazem spans decades of rigorous investigation. The Multicenter Diltiazem Post-Infarction Trial demonstrated that in patients with non-Q-wave MI, diltiazem reduced the rate of reinfarction compared to placebo. The Nordic Diltiazem Study showed significant antianginal efficacy with improved exercise tolerance.
For hypertension, multiple trials including the VA Cooperative Study established diltiazem’s equivalence to other first-line agents with potentially better metabolic profile than beta-blockers or diuretics. The INVEST trial specifically compared calcium channel blocker-based strategies (verapamil) to beta-blocker based approaches, with implications for the entire class.
In electrophysiology, the Diltiazem Rate Control in Atrial Fibrillation Trial demonstrated superior rate control compared to digoxin, with more patients achieving target heart rates.
What’s interesting is that despite all this evidence, we still have debates in our cardiology department about first-line choices. Our electrophysiologists swear by diltiazem for rate control, while some of our heart failure specialists avoid it completely in reduced EF patients.
8. Comparing Diltiazem with Similar Products and Choosing a Quality Product
When comparing diltiazem to other calcium channel blockers:
Vs. Verapamil: Both affect cardiac conduction, but verapamil has stronger negative inotropy and constipation side effects. Diltiazem may be better tolerated.
Vs. Dihydropyridines (amlodipine, nifedipine): Dihydropyridines have minimal cardiac effects but cause more peripheral edema and reflex tachycardia. Diltiazem provides balanced cardiac and vascular effects.
Formulation considerations: Branded extended-release formulations (Cardizem LA, Tiazac) may offer more consistent 24-hour coverage than some generic equivalents, though most generic ER formulations are therapeutically equivalent.
Quality assessment should include verification of FDA approval, manufacturing standards, and consistency of clinical effect. I typically recommend patients stick with one manufacturer once they find a formulation that works well for them, as switching between generics can occasionally cause variations in effect.
9. Frequently Asked Questions (FAQ) about Diltiazem
How quickly does diltiazem work for blood pressure control?
Oral formulations begin reducing blood pressure within 30-60 minutes, with peak effects at 2-3 hours for immediate-release and 10-14 hours for extended-release. Full antihypertensive effect may take 2-4 weeks.
Can diltiazem be combined with beta-blockers?
Yes, but with caution due to additive effects on heart rate and AV conduction. Monitor for excessive bradycardia and consider lower doses of both medications.
What monitoring is required during diltiazem therapy?
Baseline and periodic ECG, blood pressure, heart rate, and liver function tests. Digoxin levels if co-administered.
Is diltiazem safe in elderly patients?
Yes, but start with lower doses due to increased sensitivity and potentially reduced clearance.
Can diltiazem be used in patients with diabetes?
Yes, and it may be preferable to beta-blockers as it doesn’t mask hypoglycemia symptoms or worsen insulin resistance.
10. Conclusion: Validity of Diltiazem Use in Clinical Practice
Diltiazem remains a valuable tool in cardiovascular therapeutics due to its balanced hemodynamic effects, proven efficacy across multiple indications, and generally favorable side effect profile. The drug’s versatility makes it particularly useful for patients with concomitant conditions like hypertension and atrial fibrillation.
The evidence base supporting diltiazem continues to grow, with recent studies exploring its potential in microvascular angina and its effects on endothelial function. While newer agents have emerged, diltiazem’s established safety profile and cost-effectiveness ensure its ongoing relevance in clinical practice.
I’ve been using diltiazem for over twenty years now, and it’s one of those medications that just works predictably. One patient particularly stands out - Margaret, a 68-year-old with hypertension and paroxysmal atrial fibrillation who had failed multiple medications due to side effects. We started her on extended-release diltiazem, and at her six-month follow-up, she brought in a log showing normal blood pressures and only two brief episodes of palpitations. “I finally feel like myself again,” she told me. Those are the moments that remind you why you chose this profession. She’s now been on the same dose for three years with excellent control and no significant side effects - sometimes the older drugs really are the best tools we have.