Diltiazem

What it is

Diltiazem is a prescription calcium channel blocker taken by mouth (immediate- and extended-release forms), given intravenously in hospital, and compounded as a 2% cream for anal fissure. The US label for extended-release capsules covers high blood pressure and chronic stable or spasm-related angina.

What the research says

In a large trial in high blood pressure, diltiazem prevented heart attacks, strokes and cardiovascular deaths about as well as diuretics and beta-blockers, with fewer strokes. After a heart attack it did not reduce deaths, and in people whose heart pumped weakly it increased late heart failure. For fast atrial fibrillation in hospital it controls heart rate at least as well as metoprolol. Topical diltiazem heals anal fissures about as well as nitroglycerin ointment with far fewer headaches. It raises blood levels of some statins and other drugs cleared by the liver enzyme CYP3A4.

Evidence grade: Well established.

How it works

Drug class: Non-dihydropyridine calcium channel blocker (benzothiazepine)

Diltiazem blocks calcium entry into the muscle cells of blood vessel walls and the heart. The vessel walls relax, which lowers resistance to blood flow and lowers blood pressure. It also slows conduction through the heart's AV node, which is why it slows a fast heart rate and why it can cause a slow pulse or heart block. (Source 1)

What it is used for

• In NORDIL (10,881 people, open-label with blinded endpoints) the combined rate of stroke, heart attack and cardiovascular death was the same as with diuretics and beta-blockers (16.6 vs 16.2 events per 1,000 patient-years). Strokes were fewer (6.4 vs 7.9 per 1,000 patient-years); heart attacks were numerically more but not significantly. Evidence: established. (Source 2)
• Approved on the basis of symptom trials. We did not retrieve a systematic review of angina outcomes for this write-up; the label is the only source we read for this use. Evidence: limited. (Source 3)
• In MDPIT (2,466 people after myocardial infarction, placebo-controlled) diltiazem did not reduce total mortality; in people with ejection fraction below 40% late heart failure occurred in 21% on diltiazem versus 12% on placebo. Evidence: not-supported. (Source 4)
• A 2024 meta-analysis of 19 studies (3 randomised, 16 observational) found intravenous diltiazem achieved rate control more often than intravenous metoprolol (OR for metoprolol 0.61), with no significant difference in low blood pressure or slow pulse. Most included studies were observational. Evidence: limited. (Source 5)
• A meta-analysis of 9 randomised trials found healing rates equal to glyceryl trinitrate ointment, with far fewer headaches and fewer late recurrences. Evidence: limited. (Source 6)

Interactions

• Statins cleared by CYP3A4 (simvastatin, lovastatin) (pharmacokinetic study): Diltiazem raises statin blood levels several-fold, which can raise the risk of muscle damage. Pravastatin levels did not change. (Source 7)
• Other drugs cleared by CYP3A4 or P-glycoprotein (label): Diltiazem is both cleared by and blocks CYP3A4 and P-glycoprotein, so it can change levels of many other drugs and be changed by them. (Source 8)
• Grapefruit juice (pharmacokinetic study): In the review we read, diltiazem's absorption was not changed by grapefruit juice. The same review reports a rise in nifedipine absorption with double-strength juice only, and no change for verapamil. (Source 9)
• St John's wort (theoretical): St John's wort speeds up CYP3A4, the enzyme that clears diltiazem, and also P-glycoprotein, so it would be expected to lower diltiazem levels. This is inferred from studies of other drugs cleared this way, not from a study of diltiazem itself. (Source 10)
• Alcohol (label): In a laboratory (in vitro) test, alcohol made Cardizem CD capsules release diltiazem faster. The label says this may lead to faster absorption, higher exposure and dose-related side effects. This is a laboratory dissolution finding, not a study in people. (Source 11)

Stopping it

• In one small randomised study, stopping oral diltiazem about 17 hours before heart bypass surgery produced no withdrawal response, no severe ischaemia and no coronary spasm. We found no deprescribing trial of diltiazem outside surgery. (Source 12)

What goes wrong

After a heart attack, in people whose heart pumped weakly (ejection fraction under 40%), diltiazem increased late heart failure compared with placebo. (Source 4)

• Randomized trial, Moderate certainty.
• Size: 2,466 patients (subgroup with ejection fraction below 40%)
• Who: Adults after acute myocardial infarction.
• How long: Mean 25 months.
• Result: Late congestive heart failure 21% on diltiazem vs 12% on placebo (p = 0.004), an absolute difference of 9 percentage points.
• Funding: not stated on the page we read.

When ejection fraction < 40% late congestive heart failure appeared in 12% receiving placebo and 21% on diltiazem (p = 0.004).

Diltiazem increased AV block, slow heart rate and low blood pressure compared with placebo after a heart attack. (Source 4)

• Randomized trial, Moderate certainty.
• Size: 2,466 patients.
• Who: Adults after acute myocardial infarction.
• How long: Mean 25 months.
• Result: Rates not given on the page we read.
• Funding: not stated on the page we read.

Increased AV block, bradycardia and hypotension in diltiazem group.

Diltiazem markedly raises blood levels of simvastatin and lovastatin, raising the risk of statin muscle injury; pravastatin was not affected. (Source 7)

• Blood level study, Low certainty.
• Size: 10 healthy volunteers per study.
• Who: Healthy volunteers.
• How long: 14 days of diltiazem.
• Result: 5-fold increase in simvastatin AUC; the label adds that computer simulations project an 8- to 9-fold increase at 480 mg/day of diltiazem; 3- to 4-fold increase in lovastatin AUC; no significant change in pravastatin.
• Funding: manufacturer label (pharmacokinetic studies described in the label)

coadministration of a single 20 mg dose of simvastatin at the end of a 14-day regimen with 120 mg BID diltiazem SR resulted in a 5-fold increase in mean simvastatin AUC versus simvastatin alone

What the evidence supports

In people with high blood pressure, diltiazem prevented the combined outcome of stroke, heart attack and cardiovascular death as well as diuretics and beta-blockers did. (Source 2)

• Randomized trial, Moderate certainty.
• Size: 10,881 patients.
• Who: Adults aged 50-74 in Norway and Sweden with diastolic blood pressure of 100 mm Hg or more.
• How long: Not recorded in the page we read (trial ran about 4.5 years)
• Result: Primary endpoint 16.6 vs 16.2 events per 1000 patient-years; relative risk 1.00 (95% CI 0.87-1.15), p=0.97.
• Funding: not stated on the ACC summary page we read.

A primary endpoint occurred in 403 patients in the diltiazem group and in 400 in the diuretic and beta-blocker group (16.6 vs 16.2 events per 1000 patient-years; relative risk 1.00 [95% CI 0.87-1.15], p=0.97).

For fast atrial fibrillation, intravenous diltiazem achieved rate control more often than intravenous metoprolol, with no significant difference in low blood pressure or slow pulse; most included studies were observational. (Source 5)

• Meta-analysis, Low certainty.
• Size: 19 studies (3 RCTs, 16 observational)
• Who: Patients with atrial fibrillation and rapid ventricular rate.
• How long: Acute treatment.
• Result: Metoprolol vs diltiazem rate control OR 0.61 (95% CI 0.44 to 0.84); bradycardia OR 0.51 (0.22 to 1.22); hypotension OR 1.08 (0.72 to 1.61)
• Funding: not stated in the abstract.

Pooled analysis showed intravenous metoprolol resulted in a 39% lower rate control attainment compared to diltiazem (OR: 0.61; 95% CI: 0.44 to 0.84; p = 0.002).

Topical 2% diltiazem healed chronic anal fissures as often as glyceryl trinitrate, with fewer headaches and fewer late recurrences. (Source 6)

• Meta-analysis, Certainty not rated.
• Size: 9 RCTs (379 diltiazem, 351 GTN) for healing.
• Who: Adults with chronic anal fissure.
• How long: 6-12 weeks of treatment.
• Result: Healing RR 1.04 (0.93-1.16); headache RR 0.15 (0.07-0.34); late recurrence RR 0.51 (0.27-0.96)
• Funding: not stated in the abstract.

Nine RCTs compared rates of healing with topical DTZ (n= 379) and GTN (n= 351), there was no difference between the two groups [RR 1.04 (0.93-1.16), p= 0.48].

What the evidence does not support

After a heart attack, diltiazem did not reduce total deaths compared with placebo. (Source 4)

• Randomized trial, Moderate certainty.
• Size: 2,466 patients.
• Who: Adults aged 25-75 after documented acute myocardial infarction.
• How long: Mean 25 months (12-52)
• Result: No difference in total mortality; 11% fewer first recurrent cardiac events, not statistically significant.
• Funding: not stated on the page we read.

11% fewer first recurrent cardiac events (cardiac death or nonfatal reinfarction with diltiazem than placebo but not statistically significant).

Where the evidence is mixed

Diltiazem was followed by fewer strokes than diuretics and beta-blockers in NORDIL; heart attacks were numerically more but not significantly so. (Source 2)

• Randomized trial, Moderate certainty.
• Size: 10,881 patients.
• Who: Adults aged 50-74 with diastolic blood pressure of 100 mm Hg or more.
• How long: Not recorded in the page we read.
• Result: Stroke 6.4 vs 7.9 per 1000 patient-years (RR 0.80, 0.65-0.99, p=0.04); MI 7.4 vs 6.3 per 1000 patient-years (RR 1.16, 0.94-1.44, p=0.17). Absolute stroke difference about 1.5 per 1,000 patient-years.
• Funding: not stated on the page we read.

Fatal and non-fatal stroke occurred in 159 patients in the diltiazem group and in 196 in the diuretic and beta-blocker group (6.4 vs 7.9 events per 1000 patient-years; 0.80 [0.65-0.99], p=0.04)

In a small retrospective study of people with weak heart pumping and fast atrial fibrillation, intravenous diltiazem and metoprolol gave similar rate control and similar signs of worsening heart failure. (Source 13)

• Cohort study, Very low certainty.
• Size: 48 patients (34 diltiazem, 14 metoprolol)
• Who: Patients with heart failure with reduced ejection fraction in atrial fibrillation with rapid ventricular response.
• How long: Acute (30-60 minutes)
• Result: Rate control within 30 min 50% diltiazem vs 62% metoprolol (p = 0.49)
• Funding: not stated.

The primary outcome, successful rate control within 30 min, occurred in 62% of the metoprolol group and 50% of the diltiazem group (p = 0.49).

Where the research disagrees

Whether diltiazem is appropriate after a heart attack

• American College of Cardiology trial summary of MDPIT (quoting the NEJM 1988 manuscript), rct: Data demonstrates that diltiazem treatment is not appropriate for all patients after myocardial infarction. (Source 4)

How much

• Reference intake: Dosing is set by the prescriber. The Cardizem CD label is a position, not evidence; it describes once-daily extended-release dosing for hypertension (usual range studied 240 to 360 mg once daily) and for angina. (Source 14)
• Upper limit: The Cardizem CD label (revised 04/2025) states that individual patients may respond to doses of up to 480 mg once daily, for both hypertension and angina. This is the label's position. (Source 14)
• Studied: Label interaction studies gave healthy volunteers 120 mg diltiazem SR twice daily for 14 days. (Source 7)
• Studied: Anal fissure trials used 2% diltiazem cream twice daily for 6-12 weeks. (Source 6)

A common belief, and what the research shows

The belief: Every blood pressure calcium channel blocker interacts with grapefruit.

What the research shows: Grapefruit affects some calcium channel blockers more than others. For diltiazem the review we read says "Bioavailability of diltiazem is unaltered by grapefruit juice." Diltiazem's own important interactions are with drugs such as simvastatin.

Questions and answers

What is it?

Diltiazem is a prescription calcium channel blocker used for high blood pressure and angina, given intravenously for fast atrial fibrillation, and compounded as a cream for anal fissure. (Source 3)

What does it do in the body?

It relaxes the muscle in blood vessel walls, lowering resistance to blood flow and so lowering blood pressure. It also slows the heart's electrical conduction. (Source 1)

Is it good or bad for you?

It depends on the person. In high blood pressure it protected against heart attack, stroke and cardiovascular death as well as older drugs. After a heart attack in people with a weak heart, it increased heart failure. (Source 4)

How do you get more of it?

Does not apply. Diltiazem is a prescription medicine; there is no food or behaviour that supplies it, and the dose is set by the prescriber. (Source 3)

If it is harmful, what reduces it?

Diltiazem is cleared by the liver enzyme CYP3A4. Stopping it is a decision for the prescriber; one small surgical study found no rebound when it was stopped the evening before bypass surgery. (Source 12)

Why might someone be low in it or missing it?

Does not apply. Diltiazem is not a nutrient or a substance the body makes, so no one is deficient in it. (Source 7)

We searched: Label and trials read for this write-up; the question does not apply to a synthetic drug.

Which whole foods contain it or feed it?

No food contains diltiazem. Grapefruit juice, which affects some related drugs, did not change diltiazem's absorption in the studies summarised. (Source 9)

What happens if you do not have it?

Does not apply as a deficiency. In one small surgical study, stopping it did not cause spasm or severe ischaemia. (Source 12)

How can you test for it?

Blood levels of diltiazem are measured in research but are not a routine clinical test; its effect is judged by blood pressure, heart rate and symptoms. (Source 7)

We searched: Label and the trials read; no source we read describes a routine clinical blood test for diltiazem.

References

1. US FDA-approved labeling (Bausch Health), as posted on DailyMed. CARDIZEM CD (diltiazem hydrochloride) extended-release capsules - Prescribing Information, Clinical Pharmacology and Mechanisms of Action. 2025. Read the source
2. American College of Cardiology (ACC.org, Latest in Cardiology: Clinical Trials); ACC summary text, not the paper itself. NORDIL (Nordic Diltiazem Study) - clinical trial summary page (summarises Hansson L et al., Lancet 2000;356:359-365). 2002. Read the source
3. US FDA-approved labeling (Bausch Health), as posted on DailyMed. CARDIZEM CD (diltiazem hydrochloride) extended-release capsules - Prescribing Information, Indications and Usage. 2025. Read the source
4. American College of Cardiology (ACC.org, Latest in Cardiology: Clinical Trials); ACC summary text, not the paper itself. MDPIT (Multicenter Diltiazem Post Infarction Trial) - clinical trial summary page (summarises N Engl J Med 1988;319:385-392). 2003. Read the source
5. Cureus. Comparison of the Effectiveness and Safety of Metoprolol and Diltiazem in Atrial Fibrillation With Rapid Ventricular Rate Patients: A Systematic Review and Meta-Analysis. 2024. DOI 10.7759/cureus.56560. Read the source
6. Turkish Journal of Surgery. Topical diltiazem and glyceryl-trinitrate for chronic anal fissure: A meta-analysis of randomised controlled trials, abstract results. 2020. DOI 10.47717/turkjsurg.2020.4895. Read the source
7. US FDA-approved labeling (Bausch Health), as posted on DailyMed. CARDIZEM CD (diltiazem hydrochloride) extended-release capsules - Prescribing Information, Drug Interactions: Statins. 2025. Read the source
8. US FDA-approved labeling (Bausch Health), as posted on DailyMed. CARDIZEM CD (diltiazem hydrochloride) extended-release capsules - Prescribing Information, Precautions: Drug Interactions (general). 2025. Read the source
9. Australian Prescriber (NPS MedicineWise). Interactions between grapefruit juice and some drugs available in Australia (McNeece J, Aust Prescr 2002), diltiazem entry. 2002. Read the source
10. HelloPharmacist (interaction monograph, medically reviewed by Brian Staiger, PharmD; page updated September 2026). St. John's Wort + Diltiazem interaction, CYP3A4 substrates section. 2026. Read the source
11. US FDA-approved labeling (Bausch Health), as posted on DailyMed. CARDIZEM CD (diltiazem hydrochloride) extended-release capsules - Prescribing Information, Precautions: Drug Interactions: Alcohol. 2025. Read the source
12. Journal of Cardiothoracic Anesthesia. Diltiazem withdrawal before coronary artery bypass surgery. 1989. DOI 10.1016/S0888-6296(89)94525-0. Read the source
13. American Journal of Emergency Medicine. Metoprolol vs. diltiazem in the acute management of atrial fibrillation in patients with heart failure with reduced ejection fraction. 2018. Read the source
14. US FDA-approved labeling (Bausch Health), as posted on DailyMed. CARDIZEM CD (diltiazem hydrochloride) extended-release capsules - Prescribing Information, Dosage and Administration. 2025. Read the source