Diltiazem interactions to avoid

Drug interactions | Food interactions | Other interactions | Avoiding interactions | When to see a doctor

Diltiazem is a prescription cardiac medication belonging to a class of drugs known as calcium channel blockers. It has multiple approved uses related to the cardiac system including hypertension, angina, myocardial infarction (heart attack), and arrhythmias (irregular heart rhythm). There are many off-label uses of diltiazem as well. 

Diltiazem has documented interactions with many types of medications. This includes other drugs used for blood pressure and cardiac function, as well as drugs used for seizures, anxiety, stomach acid, and cholesterol. Diltiazem can interact with many drugs, and it is important to be aware of these interactions if you are taking diltiazem or considering starting therapy. Interactions can vary in severity and may intensify diltiazem side effects or alter how effective diltiazem or other medications may be.

Diltiazem drug interactions

Diltiazem interacts with a wide span of drugs, including prescriptions, over-the-counter medications, and herbal supplements. These can include other heart medications and medications used for seizures, anxiety, or acid reflux to name a few. Many of these interactions are due to diltiazem’s effect of blocking CYP3A4, a common enzyme important to the metabolism of other drugs. Some of the most common are detailed below. This is not intended to be an all-inclusive list, and you should consult your healthcare professional for more information and medical advice on additional interaction possibilities.

HMG CoA Reductase Inhibitors (Statins)

Statin drugs are some of the most commonly used and effective prescription drugs for lowering cholesterol. They are processed and metabolized by the cytochrome P450 enzyme system, including CYP3A4 for some of the statins. Diltiazem is an inhibitor of the enzyme responsible for the metabolism of some statins. When given together, this interaction can lead to increased statin levels in the blood. This can lead to adverse effects such as fibromyalgia, a tingling nerve pain. This can sometimes be managed by maintaining a lower dose of the statin, but the best choice may be choosing a statin that isn’t dependent on the same enzyme that diltiazem inhibits for metabolism. Pravastatin, though known to be a less intense statin, may be the safest choice with diltiazem.

Examples: Major interaction: Mevacor (lovastatin), Zocor (simvastatin),  Lipitor (atorvastatin)

Benzodiazepines

Benzodiazepines are primarily used to treat anxiety disorders, though they can sometimes be used for muscle relaxation as well. Several of the benzodiazepines are metabolized by CYP3A4. When diltiazem and these benzodiazepines are given together, it leads to an increased blood concentration of the benzodiazepine. This can be dangerous, especially at higher doses of the benzodiazepine drug, as levels can be increased by up to two times the original level. This can lead to prolonged sedation and respiratory depression, which can be dangerous. If a benzodiazepine and diltiazem must be given together, Ativan (lorazepam) or Restoril (temazepam) would be the safer choices as their metabolism is less dependent on 3A4.

Examples: Xanax (alprazolam), Klonopin (clonazepam), Valium (diazepam), Dalmane (flurazepam), Halcion (triazolam), Dormicom (midazolam)

Beta Blockers

Beta blockers are a separate class of cardiac drugs intended for hypertension, tachycardia, myocardial infarction, arrhythmias, and congestive heart failure. Generally speaking, beta blockers decrease the rate and force of the contraction of the heart as well as smooth muscle relaxation effects in the periphery. You should never give intravenous beta blockers with intravenous calcium channel blockers. Fatal heart attacks can result. The oral formulations can be co-administered with extreme caution. These drugs have similar effects on heart rate and smooth muscle contraction, and the additive effects can be dangerous. 

Examples: Trandate (labetalol), Brevibloc (esmolol), Lopressor (metoprolol), Sectrol (acebutolol), Inderal LA (propranolol), Tenormin (atenolol)

Alpha-1 Adrenoreceptor Blockers

Alpha-1 receptor blocking medications are primarily used to treat benign prostatic hypertrophy (BPH). In patients with BPH, the alpha-1 receptors in the blood vessels and prostate are stimulated and cause contraction, making you feel as though you need to urinate more frequently, but then also making it more difficult when you do so. Alpha-1 receptor blockers allow a relaxation of these muscles and a decrease in the symptoms of BPH. Using these drugs with diltiazem can result in low blood pressure. Additionally, these drugs are metabolized by CYP3A4, and diltiazem will slow the metabolism of these drugs. This can increase side effects related to both drugs.

Examples: Uroxatral (alfuzosin), Flomax (tamsulosin)

Anxiolytic Drugs

Non-benzodiazepine anxiolytic drugs should be used with extreme caution when in combination with diltiazem. Some are metabolized by CYP3A4, and administration with diltiazem can increase the blood levels of the anxiolytic multiple folds. This will exacerbate adverse events such as headache, drowsiness, weakness, and gastrointestinal effects such as nausea and vomiting. Consider using a lower dose of the anxiolytic if they must be used together.

Examples: Buspar (buspirone), Latuda (lurasidone)

Barbiturates

Barbiturate drugs are CYP3A4 inducers. Diltiazem is metabolized by 3A4, and co-administration with barbiturates can lead to sub-therapeutic levels of diltiazem. This will mean that you may not have the intended effects of diltiazem, such as blood pressure lowering. If they must be given together, blood pressure, heart rate, and the presence of chest pain should be closely monitored.

Examples: Amytal (amobarbital), Fioricet (butalbital/APAP/caffeine), Donnatal (belladonna/phenobarbital)

Anticonvulsants

One particular anticonvulsant is a  strong inducer of 3A4. Coadministration of this medication with diltiazem can decrease diltiazem levels to be undetectable. This could lead to cardiac effects such as high blood pressure, arrhythmias, and chest pain. It is best if an anticonvulsant that is not a 3A4 inducer is used with diltiazem. 

Examples: Trileptal (carbamazepine)

Digoxin

Digoxin is a prescription drug that regulates the heart rhythm. The dosing of digoxin must be tapered and is unique to each patient. When diltiazem and Digoxin are taken together, digoxin levels can increase by up to 20%. This can lead to an extremely low heart rate (bradycardia) or a complete heart block. 

This list is not all-inclusive of diltiazem interactions. Other medications that can interact with diltiazem include atazanavir, rifampin, amlodipine, cimetidine, cyclosporine, erythromycin, verapamil, and itraconazole. Consult your prescriber or pharmacist for a complete list.

Diltiazem food interactions

The presence of food does not appear to have any effect on diltiazem absorption, with the exception of grapefruit. Diltiazem can be taken with or without food.

Diltiazem and grapefruit

Grapefruit is a CYP3A4 inhibitor. Drinking grapefruit juice or consuming the fruit can cause a clinically significant increase in systemic exposure to diltiazem. Clinically, there does not seem to be a significant impact on blood pressure, but caution should be used when consuming grapefruit and taking diltiazem.

Other diltiazem interactions

There are a few other items that can affect diltiazem absorption and use. Alcohol and some herbal supplements should be used cautiously or avoided when taking diltiazem.

Diltiazem and alcohol 

Consuming alcohol while taking diltiazem can have additive effects on blood pressure. This can lead to lower blood pressure, orthostatic hypotension, dizziness, or syncope. Alcohol may also affect the release mechanism in controlled-release formulations of diltiazem. It has been shown to speed up the release of controlled-release and extended-release capsules.

Diltiazem and disease/CBD/illicit drugs/vitamins/herbal supplements/etc. 

Some red yeast rice products contain a statin drug derivative in them. It is best to avoid red yeast rice supplements or be diligent in reading the product labeling. Co-enzyme Q10 (CoQ10) can also lower blood pressure on its own, and the effect can be additive with diltiazem. Patients should be monitored for blood pressure being too low. St. John’s Wort, commonly used to help with symptoms of depression, can decrease plasma concentrations of diltiazem because it is a strong 3A4 inducer.

How to minimize diltiazem interactions

Before starting diltiazem therapy. Be sure your prescriber is aware of all the medications you take, including OTC medications and supplements. The best way to avoid an interaction is to be proactive. While on diltiazem, make sure any new drugs you begin taking are checked against diltiazem by your pharmacist. 

When to talk to a healthcare provider about diltiazem interactions

If you suspect you are experiencing drug interactions related to diltiazem, you should speak to your prescriber or pharmacist immediately. When taking blood pressure medication, you should keep a blood pressure monitor at home to keep tabs on your blood pressure. You should check it anytime you are feeling dizzy or feel that your heart is beating abnormally. Seek help immediately if your blood pressure is too high or too low.