TIAZAC
Clinical safety rating
cautionComprehensive 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 |
| Molecular Weight | 450.98 Da |
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 | Teratogenic effects observed in animal studies; use only if benefit outweighs risk. |
| 2nd trimester | May cause fetal hypotension, hypoxia, or growth restriction; monitor fetal heart rate. |
| 3rd trimester | Risk of neonatal hypotension, bradycardia, and hypocalcemia; avoid near term. |
Clinical note
Comprehensive clinical and safety monograph for TIAZAC (TIAZAC).
| Placental transfer | Crosses placenta; fetal serum levels approximately 50% of maternal levels. |
| Breastfeeding | Diltiazem is excreted into breast milk in small amounts. Monitor infant for bradycardia, hypotension, and poor feeding. |
| Lactation Rating | L3 (Moderately Safe) |
| 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. |
| 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. |
■ FDA Black Box Warning
None
| Serious Effects |
Severe hypotension (systolic < 90 mmHg)Sick sinus syndrome without pacemakerSecond- or third-degree AV block without pacemakerAtrial flutter/fibrillation with accessory bypass tract (e.g., WPW syndrome)Concurrent use with rifampinConcurrent use with ivabradine
| 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 |
| Food/Dietary | Avoid grapefruit juice and grapefruit products due to CYP3A4 inhibition, which can increase diltiazem levels. Limit sodium intake as part of hypertension management. No significant interaction with other foods. |
| Clinical Pearls | TIAZAC (diltiazem extended-release) is a nondihydropyridine calcium channel blocker used for hypertension and stable angina. Avoid use in patients with sick sinus syndrome or second/third-degree AV block without a pacemaker. It is a substrate of CYP3A4; monitor for interactions with strong inhibitors (e.g., ketoconazole) or inducers (e.g., rifampin). In hepatic impairment, start at lowest dose. Use with beta-blockers increases risk of bradycardia and heart failure. May cause gingival hyperplasia; stress good oral hygiene. |
| Patient Advice | Take TIAZAC exactly as prescribed, usually once daily. Swallow the capsule whole; do not crush, chew, or open. · Do not stop taking this medication abruptly, as it may worsen chest pain or blood pressure. · Avoid drinking grapefruit juice or eating grapefruit while on this drug, as it can increase side effects. · Common side effects include dizziness, headache, swelling in the ankles/feet, and constipation. Contact your doctor if you experience very slow heartbeat, fainting, or shortness of breath. · Inform your doctor about all other medications, especially beta-blockers, digoxin, or other blood pressure drugs. |
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