DILTIAZEM HYDROCHLORIDE IN DEXTROSE 5%
Clinical safety rating: safe
CYP3A4 inhibitors can increase levels and inducers can decrease levels Can cause bradycardia and heart failure.
Diltiazem hydrochloride is a benzothiazepine calcium channel blocker that inhibits calcium ion influx across cardiac and smooth muscle cell membranes during depolarization. It acts primarily on vascular smooth muscle and cardiac myocytes, leading to vasodilation and reduced myocardial contractility, thereby decreasing myocardial oxygen demand. It also slows atrioventricular (AV) nodal conduction and prolongs the refractory period.
| Metabolism | Hepatic metabolism primarily via cytochrome P450 3A4 (CYP3A4) isoenzymes, undergoing N-demethylation and O-deacetylation; undergoes extensive first-pass metabolism; metabolites include desacetyldiltiazem (active, 40-50% potency) and N-desmethyldiltiazem. |
| Excretion | Renal: 2-4% unchanged; biliary/fecal: 60-65% as metabolites (primarily desacetyldiltiazem); remainder via hepatic metabolism and enterohepatic circulation. |
| Half-life | Terminal half-life 3.0-4.5 hours (single dose) extending to 5-6 hours with multiple dosing due to saturable metabolism. Increased in hepatic impairment (up to 14 hours) and elderly. |
| Protein binding | 70-80% bound primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Approximately 3-13 L/kg (mean 5.3 L/kg) indicating extensive tissue distribution; higher in females and elderly. |
| Bioavailability | Oral: 40-50% (first-pass metabolism); reduced to 30-40% with food; Intravenous: 100%. |
| Onset of Action | Intravenous: 3 minutes for antiarrhythmic effect; Oral immediate-release: 30-60 minutes; Oral extended-release: 2-3 hours (sustained effects). |
| Duration of Action | Intravenous: 1-3 hours (rate control); Oral immediate-release: 4-6 hours; Oral extended-release: 12-24 hours depending on formulation (e.g., Cardizem LA). Clinical effects on heart rate and blood pressure persist accordingly. |
Acute atrial fibrillation/flutter or PSVT: 0.25 mg/kg IV over 2 min (initial bolus), then 0.35 mg/kg IV over 2 min if needed after 15 min; maintenance IV infusion: 5-15 mg/hour titrated to effect. IV formulation is diltiazem HCl in D5W.
| Dosage form | SOLUTION |
| Renal impairment | No specific dosage adjustment required for GFR >30 mL/min. For GFR <30 mL/min or dialysis, use lower initial doses (0.15 mg/kg IV bolus) and titrate cautiously; monitor heart rate and blood pressure closely. |
| Liver impairment | Child-Pugh Class A: Reduce total daily dose by 20-30%. Child-Pugh Class B: Reduce dose by 50%. Child-Pugh Class C: Avoid use or use extreme caution with significant dose reduction (e.g., 75% reduction) and close monitoring. |
| Pediatric use | Not FDA-approved for pediatric use. Limited data: For supraventricular tachycardia (SVT), 0.25 mg/kg IV bolus over 2 min (max 20 mg), may repeat after 15 min at 0.35 mg/kg IV (max 25 mg). Continuous IV infusion: 0.11-0.21 mg/kg/hour (max 15 mg/hour). |
| Geriatric use | Start at lower end of dosing range; initial IV bolus of 0.15 mg/kg (adult: 0.25 mg/kg) and infusion at 5 mg/hour; titrate slowly due to increased risk of bradycardia, hypotension, and heart block. Avoid in elderly with sick sinus syndrome or pre-existing conduction defects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
CYP3A4 inhibitors can increase levels and inducers can decrease levels Can cause bradycardia and heart failure.
| FDA category | Animal |
| Breastfeeding | Diltiazem is excreted in breast milk with a milk-to-plasma ratio (M/P) of approximately 0.9. Limited data suggest that nursing infants may receive up to 1-5% of the maternal weight-adjusted dose. No adverse effects reported, but caution is advised; alternative agents preferred. |
| Teratogenic Risk | Diltiazem is classified as FDA Pregnancy Category C. First trimester: limited human data; animal studies have shown embryotoxicity and fetotoxicity at high doses. Second and third trimesters: may cause uterine relaxation and potential for hypotension in the fetus; risk of neonatal bradycardia, hypocalcemia, and hypoglycemia if used near term. |
■ FDA Black Box Warning
None
| Common Effects | angina |
| Serious Effects |
["Sick sinus syndrome (except in presence of functioning ventricular pacemaker)","Second- or third-degree AV block (except in presence of functioning ventricular pacemaker)","Hypotension (systolic blood pressure <90 mm Hg)","Acute myocardial infarction with pulmonary congestion","Cardiogenic shock","Known hypersensitivity to diltiazem or any component of the formulation","Concurrent use of intravenous diltiazem with intravenous beta-blockers (may potentiate bradycardia and hypotension)"]
| Precautions | ["May cause bradycardia and heart block; caution in patients with pre-existing conduction abnormalities (e.g., sick sinus syndrome, second- or third-degree AV block without pacemaker).","May exacerbate heart failure due to negative inotropic effects; avoid in patients with left ventricular dysfunction (ejection fraction <40%) unless clearly indicated.","Hypotension may occur, especially with rapid intravenous administration.","Use caution in patients with hepatic impairment; reduce dose as needed.","Use caution in patients with renal impairment.","Risk of increased bleeding when used concurrently with anticoagulants (e.g., warfarin) due to CYP3A4 inhibition.","May cause PR interval prolongation on ECG; monitor."] |
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| Fetal Monitoring | Maternal: Heart rate, blood pressure, ECG; signs of heart block or hypotension. Fetal: Heart rate monitoring during labor if used for tocolysis; ultrasound for fetal growth if used long-term in pregnancy. |
| Fertility Effects | Animal studies have shown reduced fertility and implantation at high doses. Human data are lacking; however, by altering calcium-dependent processes, potential for reversible effects on sperm and oocyte function. |
| Food/Dietary | Avoid grapefruit and grapefruit juice; may increase diltiazem concentrations. Limit alcohol intake as it can potentiate hypotensive effects. No other significant food interactions. |
| Clinical Pearls | Monitor blood pressure and heart rate during infusion; use with caution in patients with left ventricular dysfunction or AV block. Diltiazem can increase digoxin and cyclosporine levels. Avoid in patients with atrial fibrillation/flutter in the presence of WPW syndrome due to risk of ventricular fibrillation. |
| Patient Advice | This medication is given intravenously to treat certain heart rhythm disorders or high blood pressure. · Report any symptoms of dizziness, fainting, slow heart rate, or difficulty breathing. · Do not consume grapefruit juice while on diltiazem as it can increase drug levels. · Avoid alcohol, which can enhance the blood pressure-lowering effect. · Inform your doctor if you are pregnant, breastfeeding, or have liver/kidney disease. |