CARDIZEM SR
Clinical safety rating
cautionComprehensive clinical and safety monograph for CARDIZEM SR (CARDIZEM SR).
Diltiazem inhibits calcium ion influx across cardiac and vascular smooth muscle cell membranes during depolarization, leading to negative inotropic, chronotropic, and dromotropic effects, and vasodilation.
| Metabolism | Primarily hepatic via CYP3A4; undergoes extensive first-pass metabolism. |
| Excretion | Renal: 2-4% unchanged; hepatic metabolism: ~60-70% (including active metabolites); fecal: ~30-40%. |
| Half-life | 3.0-4.5 hours for diltiazem; metabolites (e.g., desacetyldiltiazem) up to 10 hours. Clinical context: dosing interval adjustment in hepatic impairment. |
| Protein binding | Approximately 70-80%, primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | 3.1-5.1 L/kg; large Vd indicates extensive tissue distribution (e.g., myocardium, vascular smooth muscle). |
| Bioavailability | Oral (sustained-release): approximately 40-50% due to first-pass metabolism; variable among formulations. |
| Onset of Action | Oral (sustained-release): 2-4 hours to significant antihypertensive or antianginal effect. |
| Duration of Action | Sustained-release: 12-24 hours, depending on dose and formulation; sustained effect allows once or twice daily dosing. |
| Molecular Weight | 414.52 |
Oral: Initial dose 60-120 mg twice daily; titrate to maximum 360 mg/day divided into two doses.
| Dosage form | CAPSULE, EXTENDED RELEASE |
| Renal impairment | For GFR < 10 mL/min: Use with caution and reduce dose by 25-50%; consider extended dosing interval. |
| Liver impairment | Child-Pugh Class B: Reduce dose by 50%; Child-Pugh Class C: Use not recommended. |
| Pediatric use | Safety and efficacy not established; no specific weight-based dosing guidelines available. |
| Geriatric use | Initial dose 60 mg twice daily; titrate slowly due to increased risk of bradycardia and hypotension. |
| 1st trimester | Avoid; limited data, but animal studies show teratogenicity and fetal harm at high doses. |
| 2nd trimester | Use only if clearly needed; may cause fetal bradycardia and hypotension. |
| 3rd trimester | Use with caution; may cause uterine relaxation and delay labor. |
Clinical note
Comprehensive clinical and safety monograph for CARDIZEM SR (CARDIZEM SR).
| Placental transfer | Crosses placenta; fetal/maternal ratio approximately 0.15-0.44. |
| Breastfeeding | Diltiazem is excreted in breast milk in low concentrations; monitor infant for bradycardia and hypotension. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | FDA Pregnancy Category C. No adequate studies in pregnant women. In animal studies, diltiazem has been shown to cause embryofetal toxicity (skeletal abnormalities, reduced fetal weight) at doses 5-10 times the maximum recommended human dose. Risk to fetus cannot be ruled out; use only if potential benefit justifies potential risk. |
| Fetal Monitoring | Monitor maternal blood pressure and heart rate regularly. Fetal heart rate monitoring during labor if used for hypertension. Assess for signs of heart failure or edema. Periodic liver and renal function tests recommended. |
| Fertility Effects | No specific studies on human fertility. Animal studies at high doses showed reduced fertility and impaired spermatogenesis. Clinical relevance unknown. |
■ FDA Black Box Warning
None.
| 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 <90 mmHg)Acute myocardial infarction with pulmonary congestionKnown hypersensitivity to diltiazem
| Precautions | Cardiac conduction abnormalities: bradycardia, AV block, sick sinus syndrome, Heart failure: use with caution in patients with compromised ventricular function, Hypotension, Hepatic impairment, Concomitant use with beta-blockers may increase risk of bradycardia and AV block, Abrupt discontinuation may exacerbate angina |
| Food/Dietary | Grapefruit and grapefruit juice increase diltiazem levels by inhibiting CYP3A4 metabolism; avoid concurrent use. No other significant food restrictions. Alcohol may enhance hypotensive effects and increase risk of dizziness. |
| Clinical Pearls | Cardizem SR is a sustained-release calcium channel blocker indicated for hypertension and angina. Onset: 2-3 hours, duration: 12-24 hours. Avoid concurrent use with beta-blockers due to risk of bradycardia and heart block. Contraindicated in sick sinus syndrome (unless pacemaker), second- or third-degree AV block, hypotension (SBP <90 mmHg), and acute MI with pulmonary congestion. Monitor liver function and renal function; dose adjustment needed in hepatic impairment. Use caution in patients with decreased left ventricular function (ejection fraction <40%). Do not crush or chew capsules; swallow whole. |
| Patient Advice | Take this medication exactly as prescribed, with or without food, at the same time each day. · Swallow the capsule whole; do not crush, chew, or open it. · Avoid grapefruit and grapefruit juice while on this medication; they can increase the drug's effect and risk of side effects. · Do not stop taking this medication suddenly; abrupt discontinuation may worsen chest pain or increase blood pressure. · Contact your healthcare provider if you experience slow heartbeat, fainting, dizziness, shortness of breath, or swelling of the legs/ankles. · Limit alcohol consumption as it may increase the risk of side effects such as dizziness or fainting. · Inform your doctor if you are pregnant, planning to become pregnant, or breastfeeding. · Keep all appointments to check your blood pressure and heart rhythm. |
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