Diltiazem and Cyclosporine Injection: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Diltiazem
Cyclosporine Injection
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
Increased cycloSPORINE exposure, an increased risk of cycloSPORINE toxicity (renal dysfunction, cholestasis, paresthesias) and an increased dilTIAZem exposure
Interaction Deep Dive
Coadministration of cycloSPORINE (a P-gp and CYP3A4 substrate) with dilTIAZem (a P-gp and CYP3A4 inhibitor) may increase the exposure of cycloSPORINE3. If these agents are to be administered concurrently, monitor cycloSPORINE exposure, especially when dilTIAZem therapy is initiated, adjusted, or discontinued. Coadministration of dilTIAZem and cycloSPORINE (a P-gp inhibitor) may also increase the exposure of dilTIAZem 8. DilTIAZem, verapamil, and niCARdipine have been shown to greatly increase cycloSPORINE blood levels. In contrast, NIFEdipine, isradipine and nitrendipine have been shown to have no effect on cycloSPORINE concentrations 6.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated metabolism of dilTIAZem; inhibition of P-gp-mediated efflux transport of cycloSPORINE; inhibition of P-gp-mediated efflux transport of dilTIAZem
Literature reports
9 reports — tap to read
a) A study involving the coadministration of cycloSPORINE and dilTIAZem in 14 renal transplant patients found a number of alterations in the pharmacokinetics of cycloSPORINE. Maximum concentrations were raised from a mean of 280 ng/mL to 600 ng/mL and the time to peak was prolonged from three hours to five hours. CycloSPORINE trough blood levels increased as the dose of dilTIAZem increased. To maintain the desired cycloSPORINE trough level, doses were reduced by an average of 60%. Peak concentrations of cycloSPORINE were not as high when dilTIAZem was given two hours after cycloSPORINE 9.
b) In two studies, the administration of dilTIAZem to renal transplant patients was shown to increase the serum level of cycloSPORINE 1011. Although the precise mechanism of action of the interaction is unclear, dilTIAZem has been said to increase cycloSPORINE absorption, inhibit metabolism, and decrease the volume of distribution. In one study, dilTIAZem 60 mg given twice daily inhibited human cytochrome P450 activity. This led to an increase in cycloSPORINE activity and resulted in a reduced incidence of transplant failure or rejection episodes. The addition of dilTIAZem to cycloSPORINE therapy increases the trough levels of cycloSPORINE by 70% and increases the area under the 12-hour concentration-time curve by 50%. Although the cycloSPORINE-sparing effect may be desirable, it is also associated with a worsening of certain cycloSPORINE side effects 10.
c) The interaction between dilTIAZem and cycloSPORINE has great economic implications for patients receiving daily cycloSPORINE therapy. Since dilTIAZem increases the level of cycloSPORINE, the net effect was a significant reduction in the total dosage and drug cost of cycloSPORINE 111. In one study, concurrent use of dilTIAZem resulted in a mean cost savings of 14% over one year; rejection rate, time to rejection onset, and survival rate were not different from patients receiving cycloSPORINE alone 5.
d) One case report describes a 49-year-old female patient with a single lung transplant who did not experience increased cycloSPORINE levels when on dilTIAZem therapy. Average trough cycloSPORINE concentrations fell by 33% when dilTIAZem was given concurrently. When dilTIAZem is prescribed for its cycloSPORINE-sparing effect, the benefit must be proven and can't be assumed 12.
e) A pharmacokinetic study was conducted to define the dose-response relationship between cycloSPORINE and dilTIAZem. Eight kidney transplant recipients stabilized on cycloSPORINE therapy were started on dilTIAZem 10 mg daily and increased to a maximum dose of 180 mg daily. Results showed that cycloSPORINE AUC increased following dilTIAZem 10 mg daily, and the rate of increase slowed after the dose of dilTIAZem reached 60 mg daily. However, the cycloSPORINE AUC did continue to increase up to the maximum dose of dilTIAZem tested. These results suggest that if dilTIAZem is being administered for its cycloSPORINE-sparing effect, the dose needed may be less than previous thought. In a patient not on previous dilTIAZem therapy, the dose should be initiated at 30 mg daily and increased to 60 mg daily and then 60 mg twice daily, depending on the magnitude of response. DilTIAZem should be administered concurrently with cycloSPORINE to maximize this interaction. If no benefit from dilTIAZem 60 mg twice daily is noted, dilTIAZem therapy should be discontinued, since increasing the dose further will not necessarily cause a cycloSPORINE-sparing effect 13.
f) Twelve adult renal transplant recipients receiving a microemulsion formulation of cycloSPORINE were assessed to determine the effect of dilTIAZem coadministration. All patients had a therapeutic concentration of cycloSPORINE when dilTIAZem 180 mg daily was initiated. The average daily dose of microemulsion cycloSPORINE decreased from 5 mg/kg to 3.9 mg/kg when dilTIAZem was added. Renal function remained stable during the 12-month follow-up time period 14.
g) In a retrospective chart review involving 103 patients receiving cycloSPORINE in capsule form, the effect of verapamil and dilTIAZem on cycloSPORINE levels appeared to be independent of the dosage. All patients were receiving a long-acting form of the calcium channel blocker and had been stabilized on their cycloSPORINE dose for two or more weeks. Doses of dilTIAZem ranging from 120 mg daily to 480 mg daily did not affect the cycloSPORINE plasma level index. These results suggest that once the dose of cycloSPORINE is adjusted when a patient is started on dilTIAZem, further dosage adjustments of cycloSPORINE are not necessary as long as the dose of dilTIAZem is only altered but not discontinued 7.
h) Neurotoxicity induced by a supratherapeutic blood concentration of cycloSPORINE has been reported in a 76-year-old female patient taking cycloSPORINE 100 mg twice daily for steroid-resistant aplastic anemia and thrombocytopenia. Other medications included dilTIAZem 180 mg daily, predniSONE 10 mg three times daily, and famotidine 20 mg daily. Following 13 days of cycloSPORINE therapy, the patient was admitted to the hospital with somnolence that quickly progressed to total unresponsiveness. Her cycloSPORINE blood concentration was 903 ng/mL (normal 100 ng/mL to 300 ng/mL) on admit. She regained consciousness 36 hours after the discontinuation of cycloSPORINE, and her toxic cycloSPORINE level was attributed to a drug interaction with dilTIAZem 2.
i) A pharmacokinetic interaction between dilTIAZem and cycloSPORINE has been observed during studies involving renal and cardiac transplant patients. In renal and cardiac transplant recipients, a reduction of cycloSPORINE trough dose ranging from 15% to 48% was necessary to maintain concentrations similar to those seen prior to the addition of dilTIAZem 8. DilTIAZem, verapamil, and niCARdipine have been shown to greatly increase cycloSPORINE blood levels. In contrast, NIFEdipine, isradipine and nitrendipine have been shown to have no effect on cycloSPORINE concentrations 6.
Common questions
Can I take Diltiazem and Cyclosporine Injection together?
Increased cycloSPORINE exposure, an increased risk of cycloSPORINE toxicity (renal dysfunction, cholestasis, paresthesias) and an increased dilTIAZem exposure Always confirm with your pharmacist or prescriber before making any change.
How serious is the Diltiazem and Cyclosporine Injection interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "delayed". Effects tend to build up gradually over days to weeks.
How strong is the evidence for this interaction?
The evidence is graded "established". Well documented — supported by controlled studies or strong clinical data.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Diltiazem or Cyclosporine Injection need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (14)
- Shennib H & Auger JL: Diltiazem improves cyclosporine dosage in cystic fibrosis lung transplant recipients. J Heart Lung Transplant 1994; 13:292-296.
- Jiang TT, Huang W, & Patel D: Cyclosporine-induced encephalopathy predisposed by diltiazem in a patient with aplastic anemia. Ann Pharmacother 1999; 33:750-751. DOI
- Product Information: NEORAL(R) oral soft gelatin capsules oral solution, cyclosporine modified oral soft gelatin capsules oral solution. Novartis Pharmaceuticals Corporation (per FDA), East Hanover, NJ, 2023. DailyMed
- Product Information: SANDIMMUNE(R) oral capsules, oral solution, intravenous injection, cyclosporine oral capsules, oral solution, intravenous injection. Novartis Pharmaceuticals Corporation (per FDA), East Hanover, NJ, 2023. DailyMed
- Patton PR, Brunson ME, Pfaff WW, et al: A preliminary report of diltiazem and ketoconazole: their cyclosporine-sparing effect and impact on transplant outcome. Transplantation 1994; 57:889-892. PubMed
- Yee GC & McGuire TR: Pharmacokinetic drug interactions with cyclosporin (Part II). Clin Pharmacokinet 1990; 19:400-415. PubMed
- Jacob LP, Malhotra D, Chan L, et al: Absence of a dose-response of cyclosporine levels to clinically used doses of diltiazem and verapamil. Am J Kidney Dis 1999; 33:301-303. DOI
- Product Information: CARDIZEM(R) oral tablets, diltiazem hydrochloride oral tablets. Bausch Health US LLC (per FDA), Bridgewater, NJ, 2025. DailyMed
- Masri MA, Shakuntala V, Shanwaz M, et al: Pharmacokinetics of cyclosporine in renal transplant patients on diltiazem. Transplant Proc 1994; 26:1921.
- Brockmoller J, Neumayer H, Wagner K, et al: Pharmacokinetic interaction between cyclosporine and diltiazem. Eur J Clin Pharmacol 1990; 38:237-242.
- McCauley J, Ptachcinski R, & Shapiro R: The cyclosporine-sparing effects of diltiazem in renal transplantation. Transplant Proc 1989; 21:3955-3957.
- Jones TE & Morris RG: Diltiazem does not always increase blood cyclosporin concentration. Br J Clin Pharmacol 1996; 42:642-644. DOI
- Jones TE, Morris RG, & Mathew TH: Diltiazem-cyclosporin pharmacokinetic interaction--dose-response relationship. Br J Clin Pharmacol 1997; 44:499-504. PubMed
- Mezzano S, Flores C, Ardiles L, et al: Study of Neoral kinetics in adult renal transplantation treated with diltiazem. Transplant Proc 1998; 30:1660-1662. PubMed
Keep reading about Diltiazem
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