DILT-CD
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DILT-CD (DILT-CD).
Diltiazem inhibits calcium ion influx during depolarization of cardiac and vascular smooth muscle cells, thereby reducing intracellular calcium levels. It decreases sinoatrial and atrioventricular nodal conduction and dilates coronary and peripheral arteries.
| Metabolism | Hepatic via CYP3A4; undergoes deacetylation and N-demethylation. |
| Excretion | Renal 2-4% unchanged; extensive hepatic metabolism; 60-70% fecal, 30-40% renal as metabolites |
| Half-life | Terminal elimination half-life 7-10 hours; clinically relevant in hepatic impairment (prolonged to 14-20 hours) and in elderly |
| Protein binding | 85-90% bound to plasma proteins (primarily albumin and alpha-1-acid glycoprotein) |
| Volume of Distribution | 3-5 L/kg; large Vd indicates extensive tissue binding, with highest concentrations in liver, lung, and spleen |
| Bioavailability | Oral immediate-release: 40-60% (first-pass effect); oral sustained-release: 30-50%; IV: 100% |
| Onset of Action | Oral: 30-60 minutes (immediate-release); IV: 2-5 minutes; sustained-release: 2-3 hours |
| Duration of Action | Oral immediate-release: 6-8 hours; oral sustained-release: 12-24 hours; IV: 1-4 hours depending on infusion rate |
180-360 mg PO once daily (extended-release); 300-540 mg PO once daily for hypertension; 120-480 mg PO once daily for angina; IV: 0.25 mg/kg bolus over 2 min, then 5-15 mg/hr continuous infusion.
| Dosage form | CAPSULE, EXTENDED RELEASE |
| Renal impairment | No dosage adjustment required for mild-moderate renal impairment; use caution and consider dose reduction in severe renal impairment (CrCl <30 mL/min) due to potential accumulation. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 25-50%; Child-Pugh C: contraindicated or use with extreme caution, reduce dose by at least 50%. |
| Pediatric use | Not FDA-approved for pediatric use; off-label dosing for hypertension: extended-release initial 2.5-5 mg/kg/day PO once daily, max 10 mg/kg/day up to 360 mg daily; for supraventricular tachycardia: IV bolus 0.1-0.3 mg/kg over 2 min, may repeat after 30 min, max 10 mg/dose. |
| Geriatric use | Start at lower end of dosing range (e.g., 120 mg PO once daily for hypertension); titrate slowly; monitor for hypotension, bradycardia, and constipation; consider reduced initial dose due to altered pharmacokinetics. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DILT-CD (DILT-CD).
| Breastfeeding | Diltiazem is excreted into breast milk in small amounts; the estimated infant dose is approximately 1% of the maternal weight-adjusted dose. The milk-to-plasma ratio (M/P) is reported as 0.5-1.0. Caution is advised due to potential cardiovascular effects in the nursing infant, though limited data suggest low risk. Monitor infant for bradycardia and hypotension. |
| Teratogenic Risk | DILT-CD is a formulation of diltiazem, a calcium channel blocker. In animal studies, diltiazem has been associated with fetal skeletal abnormalities and reduced fetal weight at high doses. Human data are limited; however, diltiazem is generally avoided in the first trimester due to potential teratogenic effects. In the second and third trimesters, use is cautioned due to risks of maternal hypotension and possible fetal hypoxia. Diltiazem crosses the placenta and may cause fetal bradycardia. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Sick sinus syndrome (except with functioning pacemaker)","Second- or third-degree AV block (except with pacemaker)","Hypotension (systolic <90 mmHg)","Acute myocardial infarction with pulmonary congestion","Known hypersensitivity to diltiazem","Concomitant use with dantrolene (risk of ventricular fibrillation)","Concurrent use with ivabradine"]
| Precautions | ["May cause bradycardia, heart block, or heart failure exacerbation","Use caution in patients with impaired left ventricular function","May cause hypotension, especially in patients with aortic stenosis","May increase digoxin and cyclosporine levels","Abrupt withdrawal may exacerbate angina","Hepatic impairment may require dose adjustment","Avoid use in patients with sick sinus syndrome or second/third-degree AV block without pacemaker"] |
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| Fetal Monitoring | Monitor maternal blood pressure and heart rate regularly. Fetal heart rate monitoring is recommended given the risk of bradycardia. Assess fetal growth via ultrasound due to potential for intrauterine growth restriction (IUGR). Monitor for signs of maternal hypotension, especially when used with other antihypertensives. |
| Fertility Effects | Diltiazem has been associated with reversible decreases in sperm motility and count in animal studies. In humans, data are limited; however, calcium channel blockers may impair sperm function. No significant effects on female fertility are reported, but caution is warranted. |