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Diltiazem is an oral and parenteral non-dihydropyridine calcium channel blocker. It is useful in many clinical scenarios as an antihypertensive, anti-arrhythmic, and as an anti-anginal.[1]
FDA-approved Indications:
Diltiazem also has utility in numerous off-label indications. A select few are listed below.
Non-FDA-approved Indications[2]:
Diltiazem is available in many dosage forms and strengths, making it imperative to be cautious when prescribing, dispensing, and administering this medication. There are numerous brand names for oral diltiazem (capsules and tablets), and available strengths include 30 mg, 60 mg, 90 mg, 120 mg, 180 mg, 240 mg, 300 mg, 360 mg, 420 mg.
Diltiazem is a non-dihydropyridine calcium channel blocker. Therapeutic effects occur through various mechanisms. Primarily, diltiazem inhibits the inflow of calcium ions into the cardiac smooth muscle during depolarization. Reduced intracellular calcium concentrations equate to increased smooth muscle relaxation resulting in arterial vasodilation and, therefore, decreased blood pressure. Diltiazem is a potent coronary artery vasodilator and is consequently used for chronic angina and in those patients with coronary vasospasm. Vasospasm of the coronary arteries can lead to debilitating conditions such as myocardial infarction.
Diltiazem is a negative inotrope (decreased force) and negative chronotrope (decreased rate). The combination, along with coronary artery vasodilation, leads to decreased myocardial oxygen demand, decreased heart rate, and reduced blood pressure.
In the United States, diltiazem is FDA-approved as an oral and intravenous formulation. Compounded topical preparations of diltiazem are used off-label.[3][4]
Consult the package insert for the formulation you are using by brand name because pharmacokinetics vary significantly between different brands. The following represent the dosing variances by condition using generic names under various trade names.
Recommended Dosages
Hypertension
Chronic Stable Angina
Atrial Arrhythmia/Paroxysmal Supraventricular Tachycardia
*Increase based on clinical response to 180mg to 360mg/day
Common adverse effects of diltiazem therapy include edema, bradycardia, dizziness, headache, and fatigue. Rarer, yet more severe adverse effects include congestive heart failure, myocardial infarction, and hepatotoxicity. Diltiazem is indicated for the treatment of arrhythmias and consequently, the potential to worsen or create new arrhythmias such as extrasystole and AV block.
Diltiazem is extensively metabolized through the CYP450 system and requires careful medication profile review. Concomitant use alongside potent CYP450 inhibitors may increase diltiazem concentrations leading to adverse effects even at clinically recommended doses. Concomitant administration with agents that slow cardiac conduction can further potentiate adverse effects such as AV block or bradycardia.
Specific clinical scenarios are contraindicated to the use of diltiazem. Due to its mechanism of actions, patients with a systolic blood pressure of less than 90mmHg are ineligible for diltiazem pharmacotherapy. Additional contraindications include sick sinus syndrome and second/third-degree AV block, without a functioning ventricular pacemaker and acute myocardial infarction with pulmonary congestion on X-ray.
Additional contraindications are in place for intravenous administration. These include concomitant or recent administration of intravenous beta-blockers; cardiogenic shock; atrial fibrillation or flutter associated with an accessory bypass tract (i.e., Wolff-Parkinson-White syndrome); and ventricular tachycardia.
Therapeutic monitoring includes periodic assessments of blood pressure, heart rate, and electrocardiograms. When treating hypertension and arrhythmias, objective findings serve to assess the efficacy of therapy, while subjective findings, such as a patient's frequency and severity of chest pain, are used to evaluate efficacy when treating chronic angina. A complete blood count (CBC) lab test is also performed at baseline to track potential changes in electrolytes and kidney and liver function.
For the treatment of hypertension during pregnancy, recommendations state to use an alternative agent as diltiazem has shown adverse fetal effects in animal studies. If a patient is controlled on diltiazem for the treatment of hypertrophic cardiomyopathy, diltiazem therapy may continue, but additional fetal monitoring is required.
Additional monitoring is required when using diltiazem parenterally. When treating arrhythmias, an IV bolus is administered over two minutes. Continuous blood pressure and ECG monitoring are necessary during the bolus administration.
Potential diltiazem overdose can lead to profound bradycardia and conduction delays by suppression of SA and AV nodes. These may manifest as dizziness, lightheadedness, and fatigue. Further toxicities can lead to worsened arrhythmias, hyperglycemia, and end-organ dysfunction. Moderate toxicity is treatable with fluids, but ACLS protocol may be required when treating severe bradycardia and hypotension.[5][6]
Diltiazem is a substrate of the CYP450 enzyme, and careful monitoring is warranted when given concomitantly with inducers or inhibitors. Potent inducers/inhibitors can lead to new arrhythmias or worsen existing arrhythmias. Potent inhibitors can increase diltiazem concentration leading to mentioned toxicities. A pharmacist or other clinician should conduct a medication profile review when initiating new medications for patients on diltiazem.[7]
Diltiazem has been widely used in practice for many clinical indications. Proper dosage and frequency are essential to enhance patient care and improve outcomes. Providers should verify drug, dose, and patient factors prior to administration. One common error that occurs with diltiazem therapy is an incorrect dose administered to the patient. Diltiazem is available in many brand names with differing recommended dosages and differing maximum daily doses. Double-checking doses can help ensure the patient is receiving appropriate therapeutic management in both the inpatient and outpatient settings. Pharmacists and other providers should also check for potential drug interactions with other medications of the patient's profile. This vigilance will limit possible drug interactions.
Diltiazem possesses negative inotropic effects and is generally avoided in patients with congestive heart failure, but diltiazem is also on the Beers Criteria. These factors highlight the importance of avoiding diltiazem in heart failure patients, especially in the elderly, due to potential fluid retention and heart failure exacerbation.
| [1] | Weiner DA,Cutler SS,Klein MD, Efficacy and safety of sustained-release diltiazem in stable angina pectoris. The American journal of cardiology. 1986 Jan 1 [PubMed PMID: 3510525] |
| [2] | Islam S,Masiakos P,Schnitzer JJ,Doody DP,Ryan DP, Diltiazem reduces pulmonary arterial pressures in recurrent pulmonary hypertension associated with pulmonary hypoplasia. Journal of pediatric surgery. 1999 May [PubMed PMID: 10359169] |
| [3] | Knight JS,Birks M,Farouk R, Topical diltiazem ointment in the treatment of chronic anal fissure. The British journal of surgery. 2001 Apr [PubMed PMID: 11298624] |
| [4] | Sajid MS,Whitehouse PA,Sains P,Baig MK, Systematic review of the use of topical diltiazem compared with glyceryltrinitrate for the nonoperative management of chronic anal fissure. Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland. 2013 Jan [PubMed PMID: 22487078] |
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