What are the side effects of Diltiazem (Dilzem)?

Diltiazem Side Effects

Most Common Adverse Effects

The most frequently reported side effects of diltiazem are peripheral edema (2.4%), headache (2.1%), nausea (1.9%), dizziness (1.5%), rash (1.3%), and asthenia (1.2%), with hypotension being the most clinically significant adverse effect requiring monitoring. 1

Cardiovascular Side Effects

• Hypotension is the most common cardiovascular adverse effect requiring clinical attention, particularly during dose titration 2, 3
• Bradycardia occurs due to negative chronotropic effects on SA and AV nodes, with significantly increased risk when combined with beta-blockers 4, 3
• AV block (first-degree, and rarely second- or third-degree) can occur, affecting approximately 0.48% of patients (6 of 1243 patients) 1
• Worsening heart failure is a serious risk in patients with pre-existing ventricular dysfunction, occurring in 17% of hospitalized patients with EF <50% 3, 5
• Other cardiovascular effects include angina, arrhythmia, bundle branch block, congestive heart failure, flushing, palpitations, syncope, tachycardia, and ventricular extrasystoles (all <1%) 1

Peripheral Edema

• Peripheral edema occurs in 2.4% of patients, is dose-related, and more common in women 2, 3, 1
• Adding diuretics may help manage this side effect 2

Gastrointestinal Side Effects

• Constipation is particularly problematic in elderly individuals due to decreased intestinal motility 3
• Other GI effects include anorexia, diarrhea, dysgeusia, dyspepsia, dry mouth, thirst, vomiting, and weight increase (all <1%) 1
• GERD exacerbation may occur, potentially causing noncardiac chest pain that can confound clinical assessment in cardiac patients 3

Hepatic Effects

• Mild elevations of liver enzymes (alkaline phosphatase, SGOT, SGPT, LDH) can occur 1
• Acute hepatic injury is rare but serious, with significant enzyme elevations that are reversible upon discontinuation 1
• Liver function tests should be monitored if clinically indicated 2, 3

Neurological Side Effects

• Less common (<1%) neurological effects include abnormal dreams, amnesia, depression, gait abnormality, hallucinations, insomnia, nervousness, paresthesia, personality change, somnolence, and tremor 1
• Rare postmarketing reports include extrapyramidal symptoms 1

Dermatologic Reactions

• Rash occurs in 1.3% of patients 1
• Rare but serious skin reactions include acute generalized exanthematous pustulosis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, and exfoliative dermatitis 1
• Photosensitivity (including lichenoid keratosis and hyperpigmentation at sun-exposed areas), alopecia, and angioedema have been reported 1

Hematologic Effects

• Rare postmarketing reports include hemolytic anemia, increased bleeding time, leukopenia, purpura, and thrombocytopenia 1

Other Adverse Effects

• Gingival hyperplasia, hyperglycemia, hyperuricemia, impotence, muscle cramps, nasal congestion, nocturia, osteoarticular pain, polyuria, sexual difficulties, tinnitus, dyspnea, epistaxis, eye irritation, retinopathy, and myopathy have been reported (<1%) 1

Drug Interaction-Related Adverse Effects

• Diltiazem is both a CYP3A4 substrate and moderate CYP3A4 inhibitor, creating significant interaction potential 2, 3
• Severe bradycardia risk when combined with ivabradine 3
• Enhanced bradyarrhythmias and heart block when combined with beta-blockers 4, 3
• Increased drug levels of CYP3A4 substrates including apixaban, cyclosporine, simvastatin, itraconazole, bosutinib, ceritinib, cilostazol, everolimus, ibrutinib, idelalisib, lomitapide, olaparib, ranolazine, and simeprevir 2, 3

Critical Monitoring Requirements

• Blood pressure and heart rate should be monitored regularly during dose titration 2, 3
• ECG monitoring is recommended in patients with conduction system disease 3
• Signs and symptoms of heart failure should be monitored in at-risk patients, particularly those with reduced EF 3
• Liver function tests if clinically indicated 3

Important Clinical Pitfalls

• Avoid routine combination with beta-blockers due to increased risk of significant bradyarrhythmias and heart failure 4, 2
• Exercise extreme caution in patients with EF <50%, as worsening heart failure occurred in 17% of hospitalized patients with reduced ejection fraction versus 4.8% with preserved EF (p=0.005) 5
• Do not use in patients with second- or third-degree AV block without a pacemaker, sick sinus syndrome without a pacemaker, decompensated systolic heart failure, severe LV dysfunction, cardiogenic shock, or WPW syndrome with atrial fibrillation/flutter 2, 3, 1
• One case report documented periods of asystole (2-5 seconds) after a single 60 mg dose in a patient with Prinzmetal's angina 1