DILACOR XR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DILACOR XR (DILACOR XR).
Diltiazem inhibits calcium ion influx across cardiac and vascular smooth muscle cells, resulting in dilation of coronary and systemic arteries, decreased myocardial contractility, and reduced sinoatrial and atrioventricular conduction velocity.
| Metabolism | Extensively metabolized in the liver via CYP3A4; undergoes deacetylation and N-demethylation. |
| Excretion | Renal (70% as metabolites, 3-4% as unchanged drug); biliary/fecal (25-30%) |
| Half-life | Terminal half-life: 6-12 hours (prolonged in elderly, hepatic impairment, or with CYP3A4 inhibitors) |
| Protein binding | 98-99% bound to serum albumin and alpha-1-acid glycoprotein |
| Volume of Distribution | 1.1-1.8 L/kg (high Vd indicates extensive tissue binding) |
| Bioavailability | Oral: 40-50% (first-pass metabolism; food does not affect extent) |
| Onset of Action | Oral: 30-120 minutes (extended-release formulation) |
| Duration of Action | 24 hours (once-daily dosing for sustained antihypertensive effect) |
180 to 240 mg orally once daily, administered on an empty stomach; maximum dose 480 mg once daily.
| Dosage form | CAPSULE, EXTENDED RELEASE |
| Renal impairment | GFR 30-60 mL/min: initiate at 120 mg once daily, titrate cautiously; GFR <30 mL/min: not recommended due to risk of accumulation. |
| Liver impairment | Child-Pugh Class A: initiate at 120 mg once daily; Child-Pugh Class B or C: avoid use. |
| Pediatric use | Safety and effectiveness in pediatric patients have not been established; no dosing recommendations. |
| Geriatric use | Start at low end of dosing range (120 mg once daily) due to increased systemic exposure and risk of hypotension; titrate slowly. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DILACOR XR (DILACOR XR).
| Breastfeeding | Diltiazem is excreted in human breast milk. The milk-to-plasma (M/P) ratio ranges from 0.7 to 0.9. Limited data suggest infant exposure is low (approximately 1% of maternal weight-adjusted dose). No adverse effects reported in breastfed infants. Caution advised; monitor infant for bradycardia, hypotension, and sedation. Alternative agents may be preferred. |
| Teratogenic Risk | DILACOR XR (diltiazem) is a calcium channel blocker with limited human pregnancy data. In animal studies, at doses up to 5 times the maximum recommended human dose, no teratogenic effects were observed. However, embryofetal toxicity (increased fetal loss, growth retardation) occurred at maternally toxic doses. First trimester: No adequate human studies; risk cannot be excluded. Second and third trimesters: Use only if clearly needed; may cause maternal hypotension and reduced uteroplacental blood flow, potentially leading to fetal hypoxia and growth restriction. U.S. FDA Pregnancy Category C. |
■ FDA Black Box Warning
None.
| Serious Effects |
Sick sinus syndrome (except in presence of functioning ventricular pacemaker), second- or third-degree AV block (except with pacemaker), hypotension (systolic < 90 mm Hg), acute myocardial infarction with pulmonary congestion, hypersensitivity to diltiazem, concurrent use of ivabradine.
| Precautions | May cause hypotension, bradycardia, and heart block; avoid in patients with sick sinus syndrome or second- or third-degree AV block without a pacemaker; caution in patients with congestive heart failure; may increase risk of digitalis toxicity; abrupt withdrawal may worsen angina. |
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| Fetal Monitoring | Monitor maternal blood pressure, heart rate, and cardiac function throughout pregnancy. Watch for signs of hypotension or heart block. Fetal monitoring: assess fetal growth via ultrasound every 4-6 weeks due to potential reduced uteroplacental perfusion. Assess fetal heart rate and variability. In third trimester, consider non-stress tests or biophysical profiles. Monitor for neonatal bradycardia and hypotension after delivery. |
| Fertility Effects | No specific studies on human fertility. In animal studies, diltiazem at high doses caused reduced spermatogenesis and sperm motility in male rats, and decreased implantation in female rats. Relevance to humans is unknown. May theoretically affect uterine contractility or ovulation; no significant impact reported in clinical use. |