DILTIAZEM HYDROCHLORIDE

Clinical safety rating: safe

Animal studies have demonstrated safety

How it works

Calcium channel blocker; inhibits calcium ion influx across cardiac and smooth muscle cells, decreasing myocardial contractility and oxygen demand, and dilating coronary and peripheral arteries.

What the body does with it

Metabolism	Metabolized primarily via CYP3A4; undergoes extensive first-pass metabolism.
Excretion	Renal (2-4% unchanged), hepatic metabolism to active metabolites (65%), fecal (30%)
Half-life	3.0-4.5 hours; up to 6 hours with repeated dosing, extended in hepatic impairment
Protein binding	70-80%, primarily to albumin
Volume of Distribution	5.3 L/kg; extensive tissue distribution
Bioavailability	Oral: 40-60% (extensive first-pass metabolism); IV: 100%
Onset of Action	Oral: 30-60 min; IV: 3 min for bolus
Duration of Action	Oral: 6-12 hours; IV: 1-3 hours after bolus

Classification & Brands

Dosing & administration

Oral: Immediate-release: 30-120 mg 3-4 times daily; Extended-release: 120-480 mg once daily. IV: Bolus 0.25 mg/kg over 2 min, then 0.35 mg/kg after 15 min; infusion 5-15 mg/hr.

Dosage form	INJECTABLE
Renal impairment	CRCl <10 mL/min: Use with caution; consider dose reduction by 25-50%. No specific guidelines for higher GFR.
Liver impairment	Child-Pugh A: No adjustment. Child-Pugh B: Reduce dose by 50%. Child-Pugh C: Avoid use or reduce dose by 75%.
Pediatric use	Oral: Immediate-release: 1-2 mg/kg/day divided every 6-8 hours; extended-release: 1.5-2 mg/kg/day divided every 12 hours. IV: Bolus 0.25 mg/kg, infusion 5-15 mcg/kg/min.
Geriatric use	Initiate at lower end of dosing range (e.g., immediate-release 30 mg twice daily or extended-release 120 mg once daily); titrate slowly. Monitor for hypotension and bradycardia.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

CYP3A4 inhibitors can increase levels and inducers can decrease levels Can cause bradycardia and heart failure.

Breastfeeding

Diltiazem is excreted into human breast milk. The milk-to-plasma (M/P) ratio is approximately 0.8 to 1.0, with estimated infant dose less than 1% of maternal weight-adjusted dose. Although considered compatible with breastfeeding by the American Academy of Pediatrics, caution is advised; monitor infant for bradycardia, hypotension, and gastrointestinal effects. Use lowest effective maternal dose.

Teratogenic Risk

Diltiazem hydrochloride is classified as FDA Pregnancy Category C. In animal studies, embryofetal toxicity and teratogenic effects (skeletal abnormalities) were observed at doses 5-10 times the maximum recommended human dose. There are no adequate and well-controlled studies in pregnant women. First trimester exposure may be associated with a small increased risk of congenital malformations, but data are limited. Second and third trimester use may cause uterine relaxation and potential for postpartum hemorrhage. Use only if potential benefit justifies risk to fetus.

Warnings & precautions

■ FDA Black Box Warning

None.

Side Effect Profile

Common Effects	angina
Serious Effects

Absolute Contraindications

Sick sinus syndrome (except in presence of pacemaker), second- or third-degree AV block (except in presence of pacemaker), hypotension (systolic <90 mm Hg), acute myocardial infarction with pulmonary congestion, hypersensitivity to diltiazem.

Clinical Precautions

Precautions

May cause hypotension, bradycardia, and heart block; caution in patients with impaired hepatic or renal function; avoid abrupt withdrawal; may increase risk of gastrointestinal obstruction in patients with pre-existing strictures.

Clinical Tips & Counseling

Drug interactions

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