Diltiazem works by relaxing the smooth muscle in the walls of arteries, resulting in them opening and allowing blood to flow more easily. Additionally, it acts on the heart to prolong the period until it can beat again. It does this by blocking the entry of calcium into the cells of the heart and blood vessels. It is a class IV antiarrhythmic.
Diltiazem was approved for medical use in the United States in 1982. It is available as a generic medication. In the United States the wholesale cost per day of the by mouth formulation is less than 0.70 USD as of 2018. In 2016 it was the 63rd most prescribed medication in the United States with more than 12 million prescriptions. An extended release formulation is also available.
Because of its vasodilatory effects, diltiazem is useful for treating hypertension. Calcium channel blockers are well tolerated, and especially effective in treating low-renin hypertension.
Contraindications and precautions
In congestive heart failure, patients with reduced ventricular function may not be able to counteract the inotropic and chronotropic effects of diltiazem, the result being an even higher compromise of function.
With SA node or AV conduction disturbances, the use of diltiazem should be avoided in patients with SA or AV nodal abnormalities, because of its negative chronotropic and dromotropic effects.
Intravenous diltiazem should be used with caution with beta-blockers because, while the combination is most potent at reducing heart rate, there are rare instances of dysrhythmia and AV node block.
Quinidine should not be used concurrently with calcium channel blockers because of reduced clearance of both drugs and potential pharmacodynamic effects at the SA and AV nodes.
Concurrent use of fentanyl with diltiazem, or any other CYP3A4 inhibitors, as these medications decrease the breakdown of fentanyl and thus increases its effects.
180 mg Cardizem capsule
Diltiazem is a potent vasodilator, increasing blood flow and variably decreasing the heart rate via strong depression of A-V node conduction. Its pharmacological activity is somewhat similar to verapamil, another nondihydropyridine (non-DHP) calcium channel blocker. Chemically, it is based upon a 1,4-thiazepinering, making it a benzothiazepine-type calcium channel blocker.
Diltiazem is also being used in the treatment of anal fissures. It can be taken orally or applied topically with increased effectiveness. When applied topically, it is made into a cream form using either vaseline or Phlojel. Phlojel absorbs the diltiazem into the problem area better than the vaseline base. It has good short term success rates. Like all nonsurgical treatments of anal fissure, it does not address the long term problem of increased basal anal tone and does not decrease the subsequent recurrence rate that can vary between 40 and 60%.
^Claas, Steven A; Glasser, Stephen P (2005). "Long-acting diltiazem HCL for the chronotherapeutic treatment of hypertension and chronic stable angina pectoris". Expert Opinion on Pharmacotherapy. 6 (5): 765–76. doi:10.1517/146565184.108.40.2065. PMID15934903.
^Gabrielli, Andrea; Gallagher, T James; Caruso, Lawrence J; Bennett, Neil T; Layon, A Joseph (2001). "Diltiazem to treat sinus tachycardia in critically ill patients: A four-year experience". Critical Care Medicine. 29 (10): 1874–79. doi:10.1097/00003246-200110000-00004. PMID11588443.
^Wattanasuwan, N; Khan, IA; Mehta, NJ; Arora, P; Singh, N; Vasavada, BC; Sacchi, TJ (2001). "Acute Ventricular Rate Control in Atrial Fibrillation : IV Combination of Diltiazem and Digoxin vs IV Diltiazem Alone". Chest. 119 (2): 502–06. doi:10.1378/chest.119.2.502. PMID11171729.
^Basile, Jan (2004). "The Role of Existing and Newer Calcium Channel Blockers in the Treatment of Hypertension". The Journal of Clinical Hypertension. 6 (11): 621–29, quiz 630–31. doi:10.1111/j.1524-6175.2004.03683.x.
^Ramoska, E; Spiller, H; Winter, M; Borys, D (1993). "A one-year evaluation of calcium channel blocker overdoses: Toxicity and treatment". Annals of Emergency Medicine. 22 (2): 196–200. doi:10.1016/S0196-0644(05)80202-1. PMID8427431.
^Ohno, Y; Hisaka, A; Suzuki, H (2007). "General framework for the quantitative prediction of CYP3A4-mediated oral drug interactions based on the AUC increase by coadministration of standard drugs". Clinical Pharmacokinetics. 46 (8): 681–96. doi:10.2165/00003088-200746080-00005. PMID17655375.
^Edoute, Yeouda; Nagachandran, Pradeep; Svirski, Boris; Ben-Ami, Haim (2000). "Cardiovascular Adverse Drug Reaction Associated with Combined β-Adrenergic and Calcium Entry-Blocking Agents". Journal of Cardiovascular Pharmacology. 35 (4): 556–59. doi:10.1097/00005344-200004000-00007. PMID10774785.
^Narimatsu, Akihiro; Norio Taira (August 1976). "Effects on Atrio-Ventricular Conduction of Calcium-Antagonistic Coronary Vasodilators, Local Anaesthetics and Quinidine Injected into the Posterior and the Anterior Septal Artery of the Atrio-Ventricular Node Preparation of the Dog". Naunyn-Schmiedeberg's Archives of Pharmacology. 294 (2): 169–77. doi:10.1007/bf00507850. PMID1012337.
^O'Connor, Stephen E; Grosset, Alain; Janiak, Philip (1999). "The pharmacological basis and pathophysiological significance of the heart rate-lowering property of diltiazem". Fundamental & Clinical Pharmacology. 13 (2): 145–53. doi:10.1111/j.1472-8206.1999.tb00333.x. PMID10226758.
^Montastruc, JL; Senard, JM (1992). "Médicaments anticalciques et prophylaxie de la migraine" [Calcium channel blockers and prevention of migraine]. Pathologie et Biologie (in French). 40 (4): 381–88. PMID1353873.
^Kim, KE (1991). "Comparative clinical pharmacology of calcium channel blockers". American Family Physician. 43 (2): 583–88. PMID1990741.
^Paterna, S; Martino, SG; Campisi, D; Cascio Ingurgio, N; Marsala, BA (1990). "Evaluation of the effects of verapamil, flunarizine, diltiazem, nimodipine and placebo in the prevention of hemicrania. A double-blind randomized cross-over study". La Clinica Terapeutica. 134 (2): 119–25. PMID2147612.
^Peroutka, Stephen J (1983). "The Pharmacology of Calcium Channel Antagonists: a Novel Class of Anti-migraine Agents?". Headache: The Journal of Head and Face Pain. 23 (6): 278–83. doi:10.1111/j.1526-4610.1983.hed2306278.x.
^Kishioka, S; Ko, MC; Woods, JH (2000). "Diltiazem enhances the analgesic but not the respiratory depressant effects of morphine in rhesus monkeys". European Journal of Pharmacology. 397 (1): 85–92. doi:10.1016/S0014-2999(00)00248-X. PMID10844102.
^Verma, V; Mediratta, PK; Sharma, KK (2001). "Potentiation of analgesia and reversal of tolerance to morphine by calcium channel blockers". Indian Journal of Experimental Biology. 39 (7): 636–42. PMID12019755.
^Jonas, Marion; Neal, Keith R; Abercrombie, John F; Scholefield, John H (2001). "A randomized trial of oral vs. topical diltiazem for chronic anal fissures". Diseases of the Colon & Rectum. 44 (8): 1074–78. doi:10.1007/BF02234624.
^Nash, GF; Kapoor, K; Saeb-Parsy, K; Kunanadam, T; Dawson, PM (2006). "The long-term results of diltiazem treatment for anal fissure". International Journal of Clinical Practice. 60 (11): 1411–13. doi:10.1111/j.1742-1241.2006.00895.x. PMID16911570.
^Sajid, MS; Rimple, J; Cheek, E; Baig, MK (2007). "The efficacy of diltiazem and glyceryltrinitrate for the medical management of chronic anal fissure: a meta-analysis". International Journal of Colorectal Disease. 23 (1): 1–6. doi:10.1007/s00384-007-0384-x. PMID17846781.