TIAZAC
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TIAZAC (TIAZAC).
Diltiazem, a benzothiazepine calcium channel blocker, inhibits calcium ion influx across cardiac and vascular smooth muscle cell membranes, resulting in coronary vasodilation, peripheral vasodilation, decreased myocardial contractility, and decreased AV nodal conduction velocity.
| Metabolism | Hepatic via CYP3A4 isoenzyme; extensive first-pass metabolism; metabolites include N-desmethyl diltiazem (active) and others. |
| Excretion | Renal (2-4% unchanged, 60% as inactive metabolites); Fecal (30%); Biliary (minor) |
| Half-life | Terminal elimination half-life is 5-7 hours for immediate-release; for TIAZAC (extended-release), effective half-life is approximately 6-9 hours due to prolonged absorption |
| Protein binding | 70-80% bound to plasma proteins (albumin) |
| Volume of Distribution | Approximately 1.7 L/kg; suggests extensive tissue distribution |
| Bioavailability | Approximately 40% for oral immediate-release; extended-release formulation has comparable bioavailability with reduced peak-to-trough fluctuations |
| Onset of Action | Oral (extended-release): 2-3 hours to measurable reduction in blood pressure; peak effect at 6-12 hours |
| Duration of Action | 24 hours for antihypertensive effect with once-daily dosing; consistent plasma levels over 24 hours due to extended-release formulation |
Oral: 120-360 mg once daily; maximum 540 mg daily.
| Dosage form | CAPSULE, EXTENDED RELEASE |
| Renal impairment | No specific adjustment required; use with caution in severe renal impairment (CrCl <30 mL/min). |
| Liver impairment | Child-Pugh Class A: no adjustment; Child-Pugh Class B: reduce total dose by 50%; Child-Pugh Class C: reduce total dose by 60-70%. |
| Pediatric use | Not established; use in children <18 years is not recommended. |
| Geriatric use | Start at lower end of dosing range (120 mg daily); titrate slowly due to increased sensitivity and potential for hypotension. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TIAZAC (TIAZAC).
| Breastfeeding | Diltiazem is excreted into human breast milk at low concentrations. The milk-to-plasma ratio is approximately 0.4 to 0.8. Relative infant dose is estimated to be <1% of maternal weight-adjusted dose; considered compatible with breastfeeding. Monitor infant for potential adverse effects such as bradycardia, hypotension, or sedation. |
| Teratogenic Risk | TIAZAC (diltiazem) is classified as FDA Pregnancy Category C. First trimester: Limited human data; animal studies have shown embryotoxic and teratogenic effects at high doses. Second and third trimesters: No well-controlled studies; risk of fetal bradycardia, hypotension, and hypocalcemia due to calcium channel blockade. Use only if benefit outweighs risk. |
■ FDA Black Box Warning
None
| Serious Effects |
["Sick sinus syndrome (unless paced)","Second- or third-degree AV block (unless paced)","Hypotension (systolic < 90 mmHg)","Cardiogenic shock","Atrial fibrillation/flutter with accessory bypass tract (e.g., Wolff-Parkinson-White syndrome, Lown-Ganong-Levine syndrome)","Acute myocardial infarction with pulmonary congestion","Hypersensitivity to diltiazem"]
| Precautions | ["Bradycardia and heart block (risk increased with beta-blockers or digoxin)","Heart failure with reduced ejection fraction (may worsen in acute MI or pulmonary congestion)","Hypotension","Increased risk of gastrointestinal bleeding in elderly","Hepatic impairment (dose adjustment may be required)","Abrupt withdrawal may exacerbate angina or cause rebound hypertension","Concurrent use with CYP3A4 inhibitors (e.g., clarithromycin, itraconazole) increases diltiazem levels"] |
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| Fetal Monitoring | Maternal: blood pressure, heart rate, ECG in patients with conduction abnormalities. Fetal: heart rate monitoring during labor if used near term; consider fetal growth ultrasound if used long-term due to potential reduced uteroplacental perfusion. |
| Fertility Effects | Diltiazem has been associated with reversible decreases in sperm motility and count in some animal studies; human data are limited. No significant adverse effects on female fertility have been reported. Use of TIAZAC is unlikely to impair fertility, but caution is advised in patients attempting conception. |