DILTZAC
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DILTZAC (DILTZAC).
Diltiazem is a calcium channel blocker that inhibits calcium ion influx across cardiac and vascular smooth muscle cells, resulting in dilation of coronary and systemic arteries and decreased myocardial contractility and conduction velocity.
| Metabolism | Hepatic via CYP3A4; undergoes extensive first-pass metabolism |
| Excretion | Renal: 60-70% as metabolites, 2-4% unchanged; Biliary/Fecal: 20-30% as metabolites. |
| Half-life | Terminal elimination half-life: 3.5-5.0 hours (healthy adults). Prolonged in elderly (6-8 hours) and in hepatic impairment (10-12 hours). |
| Protein binding | 80-85% bound to plasma proteins (albumin and alpha-1-acid glycoprotein). |
| Volume of Distribution | 5-6 L/kg (suggests extensive tissue distribution). |
| Bioavailability | Oral immediate-release: 40-60% (due to extensive first-pass hepatic metabolism). Extended-release: 30-40%. Intravenous: 100%. |
| Onset of Action | Oral: 30-60 minutes (immediate-release), 2-4 hours (extended-release). Intravenous: 3-5 minutes. |
| Duration of Action | Oral immediate-release: 4-6 hours. Oral extended-release: 12-24 hours (depending on formulation: CD, SR, XR). Intravenous: 1-3 hours (hemodynamic effects). |
Oral: 30-120 mg 3-4 times daily; maximum 480 mg/day. IV: 0.25 mg/kg over 2 min, then 0.35 mg/kg after 15 min if needed; continuous infusion 5-15 mg/hour.
| Dosage form | CAPSULE, EXTENDED RELEASE |
| Renal impairment | No adjustment required for GFR >30 mL/min. For GFR 10-30 mL/min, reduce dose by 25%. For GFR <10 mL/min, reduce dose by 50%. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 50%. Child-Pugh C: reduce dose by 75%. |
| Pediatric use | Oral: 1-3 mg/kg/day divided 3-4 times; maximum 3 mg/kg/day. IV: 0.25 mg/kg over 2 min; may repeat 0.35 mg/kg after 15 min; infusion 5-15 mcg/kg/min. |
| Geriatric use | Start at lowest dose (30 mg 3-4 times daily) due to increased bioavailability and reduced clearance; titrate slowly. IV dose: 0.2 mg/kg over 2 min. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DILTZAC (DILTZAC).
| Breastfeeding | Diltiazem is excreted in breast milk with low levels. Milk-to-plasma ratio is approximately 0.28. Caution advised; monitor infant for bradycardia and hypotension. |
| Teratogenic Risk | First trimester: No definitive evidence of teratogenicity in animal studies; human data limited. Second and third trimesters: Chronic use may cause fetal bradycardia, hypoxia, and growth restriction due to maternal hypotension and reduced placental perfusion. |
| Fetal Monitoring |
■ FDA Black Box Warning
None.
| Serious Effects |
Sick sinus syndrome (except with pacemaker), second- or third-degree AV block (except with pacemaker), hypotension (systolic <90 mm Hg), cardiogenic shock, acute myocardial infarction with pulmonary congestion, hypersensitivity to diltiazem, concomitant use of ivabradine, and concurrent use with strong CYP3A4 inhibitors when diltiazem is given intravenously.
| Precautions | May cause heart block, bradycardia, exacerbation of heart failure, hypotension, and hepatotoxicity. Monitor liver function, ECG, and blood pressure. Avoid abrupt discontinuation; taper gradually. |
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| Monitor maternal heart rate, blood pressure, and ECG; fetal monitoring for heart rate decelerations and growth ultrasound in chronic use. |
| Fertility Effects | No known significant impact on fertility in humans; animal studies show no impairment at therapeutic doses. |