CARDIZEM CD
Clinical safety rating
cautionComprehensive clinical and safety monograph for CARDIZEM CD (CARDIZEM CD).
Diltiazem is a calcium channel blocker that inhibits calcium ion influx across cardiac and vascular smooth muscle cell membranes, resulting in dilation of coronary arteries and peripheral arterioles, and decreased myocardial contractility and conduction velocity.
| Metabolism | Hepatic via CYP3A4; also undergoes deacetylation; substrate of P-glycoprotein. |
| Excretion | Renal: ~2-4% (unchanged), Hepatic metabolism to multiple metabolites; ~65% renal (metabolites), ~35% fecal/biliary. Total clearance: 5-7 mL/kg/min. |
| Half-life | Terminal elimination half-life: 6-8 hours (single dose), prolonged to 10-15 hours with multiple dosing or in elderly/hepatic impairment. Clinical context: Therapeutic steady-state achieved in 2-4 days. |
| Protein binding | 70-80% bound primarily to albumin (70%), also alpha-1 acid glycoprotein (10%). Binding saturable at high concentrations. |
| Volume of Distribution | Approximately 5.3 L/kg. Meaning: Extensive tissue distribution (3-5 L/kg); reflects high lipophilicity and wide distribution beyond plasma. |
| Bioavailability | Extended-release (Cardizem CD): ~40% (range 35-45%) due to extensive first-pass metabolism. Immediate-release: ~40-50%. IV: 100%. |
| Onset of Action | Extended-release (Cardizem CD): 3-5 days for maximal antianginal/antihypertensive effect; immediate-release oral: 30-60 min; IV: 2-3 min. |
| Duration of Action | Extended-release: 24 hours (once-daily dosing); immediate-release: 6-8 hours. Clinical note: Cardizem CD provides stable plasma levels over 24 hours. |
| Molecular Weight | 414.52 |
Hypertension: 180-360 mg once daily orally. Angina: 120-360 mg once daily orally. Maximum dose: 480 mg/day.
| Dosage form | CAPSULE, EXTENDED RELEASE |
| Renal impairment | No specific GFR-based adjustment required, but use caution in severe renal impairment (CrCl <30 mL/min). |
| Liver impairment | Child-Pugh Class A: start with 120 mg once daily. Child-Pugh Class B: start with 120 mg once daily, titrate cautiously. Child-Pugh Class C: contraindicated. |
| Pediatric use | Not approved for pediatric use; safety and efficacy not established. |
| Geriatric use | Start at lower end of dosing range (120 mg once daily) due to increased risk of hypotension and bradycardia; titrate slowly. |
| 1st trimester | Associated with embryotoxicity and teratogenicity in animal studies; use only if clearly needed. |
| 2nd trimester | May cause fetal harm; use only if potential benefit justifies risk. |
| 3rd trimester | Can cause uterine atony and hemorrhage; avoid near term. |
Clinical note
Comprehensive clinical and safety monograph for CARDIZEM CD (CARDIZEM CD).
| Placental transfer | Crosses the placenta (fetal-to-maternal ratio approximately 0.8-1.0 in animal studies). |
| Breastfeeding | Diltiazem is excreted into breast milk in small amounts but may accumulate in neonates due to immature hepatic clearance; monitor for bradycardia, lethargy, and hypotension. |
| Lactation Rating | L2 (Possibly Safe) |
| Teratogenic Risk | Diltiazem, the active ingredient in Cardizem CD, is classified as Pregnancy Category C. Animal studies have demonstrated embryotoxicity and teratogenicity (skeletal abnormalities) at doses 5-10 times the maximum recommended human dose. There are no adequate and well-controlled studies in pregnant women. In humans, exposure during the first trimester may be associated with a small increased risk of congenital anomalies, particularly cardiac defects, though data are limited. During the second and third trimesters, use may be associated with potential risks of fetal growth restriction and preterm labor due to maternal hypotension and decreased uteroplacental perfusion. The drug should only be used if the potential benefit justifies the potential risk to the fetus. |
| Fetal Monitoring | Monitor maternal blood pressure and heart rate regularly, especially during dose titration, to avoid excessive hypotension or bradycardia. Assess fetal heart rate and growth via ultrasound and nonstress testing, as uteroplacental insufficiency may occur. Monitor for signs of preterm labor and fetal distress. Electrocardiographic monitoring may be considered in mothers with preexisting cardiac conditions. |
| Fertility Effects | In animal studies, diltiazem has been associated with reduced spermatogenesis and fertility at high doses. Human data on fertility are lacking; however, calcium channel blockers have been reported to impair sperm motility and function in some studies, potentially reducing male fertility. The clinical significance is uncertain. |
■ FDA Black Box Warning
None
| Serious Effects |
Sick sinus syndrome (except in the presence of a functioning ventricular pacemaker)Second- or third-degree AV block (except in the presence of a functioning ventricular pacemaker)Hypotension (systolic < 90 mm Hg)Acute myocardial infarction with pulmonary congestionAtrial fibrillation or flutter with accessory bypass tract (e.g., WPW syndrome)Hypersensitivity to diltiazem
| Precautions | May cause hypotension, Risk of heart failure exacerbation in patients with impaired ventricular function, May slow AV conduction, leading to bradycardia or AV block, Hepatic and renal impairment caution, May exacerbate symptoms in patients with hypertrophic cardiomyopathy |
| Food/Dietary | Grapefruit juice may increase diltiazem serum concentrations; avoid concurrent ingestion. Alcohol may enhance hypotensive effects. No significant food restrictions otherwise. |
| Clinical Pearls | Diltiazem (Cardizem CD) is a nondihydropyridine calcium channel blocker; use with caution in patients with systolic heart failure (HFrEF) due to negative inotropic effects. Avoid concurrent use with beta-blockers due to risk of bradycardia and heart block. May increase dugoxin levels; monitor digoxin levels. Contraindicated in sick sinus syndrome or second/third-degree AV block without pacemaker. Also inhibits CYP3A4; monitor for interactions with statins (e.g., simvastatin dose limit 10 mg). |
| Patient Advice | Take capsule whole; do not crush or chew. May be taken without regard to meals. · Do not stop abruptly; gradual taper advised to avoid rebound hypertension or ischemia. · Report symptoms of bradycardia (dizziness, fainting) or heart failure (swelling, shortness of breath). · Avoid grapefruit juice as it may increase drug levels and risk of side effects. · Use sunscreen and protective clothing due to possible photosensitivity. |
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