Important Drug Interactions for the Calcium Channel Blocker Diltiazem

Patients taking the widely prescribed calcium channel blocker diltiazem (CARDIZEM, CARTIA XT, TAZTIA XT, TIAZAC) should be aware that it has clinically important interactions with many other prescription medications.

Diltiazem initially was approved by the Food and Drug Administration (FDA) in 1982 and is used to treat hypertension (high blood pressure) and angina (chest pain that often spreads to the shoulders, arms and neck and that is caused by inadequate blood flow to the heart).[1]

The list of drugs that can interact with diltiazem and result in potential harm includes certain antibiotics, beta blockers, cholesterol-lowering statins and drugs for treating abnormal heart rhythms (see Table, below, for examples).[2],[3]

Examples of Oral Drugs That Have Clinically Important Interactions With Diltiazem

†Brand-name combination products were excluded.
*Designated as Limited Use
**Designated as Do Not Use
***The 80-milligram dose of simvastatin is designated as Do Not Use.

Beta blockers and clonidine[4],[5]

Beta blockers (such as atenolol [TENORMIN] and metoprolol [KAPSPARGO SPRINKLE, LOPRESSOR, TOPROL-XL]) are a large family of medications widely used to treat hypertension. Certain beta blockers also are approved for treating abnormal heart rhythms, angina, heart failure, heart attacks or migraines.

Patients with hypertension, angina and other heart conditions often are appropriately prescribed both a calcium channel blocker, such as diltiazem, and a beta blocker. Patients need to be aware that such concomitant (concurrent) use of diltiazem with any beta blocker may cause low blood pressure, a very low heart rate and abnormal heart rhythms, which could lead to light-headedness and fainting.

These adverse effects can occur because both diltiazem and beta blockers can slow the heart rate, interfere with electrical impulses that control the beating of the heart and decrease the strength of heart muscle contractions. Patients — particularly those with heart failure and the elderly — who are taking diltiazem and a beta blocker need to have their heart function, blood pressure and heart rate monitored carefully.

Similarly, concomitant use of diltiazem with the hypertension drug clonidine (CATAPRES, KAPVAY), which Public Citizen’s Health Research Group has designated as Do Not Use, can cause a dangerously low heart rate, which in some cases has required hospitalization and treatment with a pacemaker.

Increase toxicity of other drugs[6],[7]

Diltiazem can inhibit certain liver enzymes involved in the metabolism (breakdown) of many other drugs. As a result, concomitant use of diltiazem with these drugs can increase the blood levels of the interacting drugs, potentially leading to toxicity. The following are some notable examples of such interactions.

Statins

Concomitant use of diltiazem with atorvastatin (LIPITOR), lovastatin (ALTOPREV) or simvastatin (FLOLIPID, ZOCOR) can lead to toxic blood levels of these cholesterollowering statins.

For example, studies in healthy volunteers found that concomitant use of diltiazem with lovastatin increased lovastatin blood levels on average by as much as fourfold. Likewise, a single dose of diltiazem taken concomitantly with simvastatin caused a fivefold increase in simvastatin blood levels.

Statin toxicity can cause myopathy (muscle disease), which can result in muscle pain and weakness, and, in more severe cases, rhabdomyolysis (muscle breakdown), which can lead to sudden kidney failure. Patients who need to take both diltiazem and one of these three statins need to be alert for muscle pain, tenderness and weakness.

Colchicine

Concomitant use of diltiazem with the gout drug colchicine (COLCRYS, GLOPERBA, MITIGARE) can lead to markedly increased blood levels of colchicine and potentially fatal colchicine toxicity. Patients with impaired kidney or liver function in particular should never use these drugs concomitantly.

Colchicine toxicity typically causes gastrointestinal symptoms, including abdominal pain, nausea, vomiting and diarrhea.[8] It also can cause muscle pain and weakness and impair the bone marrow’s ability to make red and white blood cells, resulting in severe anemia and increasing the risk of serious infections, respectively. In extreme cases, colchicine toxicity can progress to failure of multiple vital organs and death.

Fentanyl and flibanserin

Concomitant use of diltiazem with the super-potent opioid fentanyl (ACTIQ, DURAGESIC, FENTORA, LAZANDA, SUBSYS) or flibanserin (ADDYI) — a drug approved by the FDA to treat hypoactive sexual desire disorder in women that Public Citizen’s Health Research Group has designated as Do Not Use — can lead to potentially dangerous fentanyl or flibanserin toxicity, respectively. Fentanyl toxicity can lead to sedation and depressed breathing, and flibanserin toxicity can cause severe low blood pressure and fainting.

Erythromycin

Concomitant use of diltiazem with the antibiotic erythromycin (E.E.S., ERY-TAB, ERYC, ERYPED, ERYTHROCIN) can increase erythromycin levels in the blood and cause prolongation of the QT interval. QT prolongation is a change in the electrical activity of the heart that can lead to a fatal heart rhythm disturbance called torsades de pointes, which can cause cardiac arrest and sudden death. One study showed that concomitant treatment with diltiazem and erythromycin increased the risk of heart-related death fivefold.

What You Can Do

If you need treatment with diltiazem, review all of your other medications with your doctor to assess for potentially significant drug interactions. If you are taking certain medications that interact with diltiazem, you may need to adjust the dosage of the interacting drug or undergo more frequent monitoring of the blood levels of the interacting drug, or your doctor may advise you to take a different drug for your hypertension or angina. Be aware that other drugs not listed in this article also may have dangerous interactions with diltiazem.
 

References

[1] Bausch Health US. Label: diltiazem extended-release capsules (CARDIZEM CD). April 2020. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=1042fa13-e6af-46b9-8008-6c941f0978b1&type=display . Accessed September 30, 2020.

[2] IBM Micromedex. Drug interactions. http://www.micromedexsolutions.com/home/dispatch. Search term: “diltiazem.” Accessed September 30, 2020.

[3] Bausch Health US. Label: diltiazem extended-release capsules (CARDIZEM CD). April 2020. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=1042fa13-e6af-46b9-8008-6c941f0978b1&type=display. Accessed September 30, 2020.

[4] IBM Micromedex. Drug interactions. http://www.micromedexsolutions.com/home/dispatch. Search term: “diltiazem.” Accessed September 30, 2020.

[5] Bausch Health US. Label: diltiazem extended-release capsules (CARDIZEM CD). April 2020. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=1042fa13-e6af-46b9-8008-6c941f0978b1&type=display. Accessed September 30, 2020.

[6] IBM Micromedex. Drug interactions. http://www.micromedexsolutions.com/home/dispatch. Search term: “diltiazem.” Accessed September 30, 2020.

[7] Bausch Health US. Label: diltiazem extended-release capsules (CARDIZEM CD). April 2020. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=1042fa13-e6af-46b9-8008-6c941f0978b1&type=display . Accessed September 30, 2020.

[8] Takeda Pharmaceuticals America. Label: colchicine (COLCRYS). January 2019. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d6adc880-5499-4691-93f3-27c87902d5fc. Accessed September 30, 2020.