diltiazem (Cardizem, Cardizem CD, Cardizem LA, Cartia XT, Dilacor, Dilacor XR, Dilatrate, Diltazem, Diltazem CD, Dilt-CD, Diltia XT, Diltiaz, Diltiaz CD, Diltiaz SR, Diltiazem CD, Diltiazem SR, Dilzem, Taztia XT, Tiazac)
Classes: Antidysrhythmics, IV; Calcium Channel Blockers; Calcium Channel Blockers, Non-dihydropyridine
Dosing and uses of Cardizem, Cardizem CD (diltiazem)
Adult dosage forms and strengths
capsule/tablet, extended release
- 120mg
- 180mg
- 240mg
- 300mg
- 360mg
- 420mg
injectable solution
- 5mg/mL
powder for injection
- 100mg
tablet
- 30mg
- 60mg
- 90mg
- 120mg
Angina
Conventional: 30 mg PO q6hr; increased every 1 or 2 days until angina controlled (usually 180-360 mg/day PO divided q6-8hr); not to exceed 360 mg/day
Cardizem CD, Cartia XT, Dilt-CD: 120-180 mg/day PO; titrate over 7-14 days; maintenance range usually 120-320 mg/day; not to exceed 480 mg/day
DilacorXR, Dilt-XR: 120 mg/day PO; titrate after 7-14 days; maintenance range usually 120-320 mg/day; not to exceed 540 mg/day
Tiazac, Taztia XT: 120-180 mg/day PO; titrate after 7-14 days; maintenance range usually 120-320 mg/day; not to exceed 540 mg/day
Cardizem LA, Matzim LA: 180 mg/day PO; titrate after 14 days; maintenance range usually 120-320 mg/day; not to exceed 360 mg/day
Hypertension
Cardizem CD, Cartia XT, Dilt-CD: 180-240 mg/day PO; titrate after 14 days; maintenance range usually 180-420 mg/day; not to exceed 480 mg/day
Dilacor XR, Dilt-XR: 180-240 mg/day PO; titrate after 14 days; maintenance range usually 180-420 mg/day; not to exceed 540 mg/day
Tiazac, Taztia XT: 120-240 mg/day PO; titrate after 14 days; maintenance range usually 180-420 mg/day; not to exceed 540 mg/day
Cardizem LA, Matzim LA: 180-240 mg/day PO; titrate after 14 days; maintenance range usually 120-540 mg/day
Extended-release twice-daily dosing: 60-120 mg PO q12hr; may be adjusted after 14 days; maintenance range usually 240-360 mg/day
Paroxysmal Supraventricular Tachycardia
0.25 mg/kg (average adult dose, 20 mg) direct IV over 2 minutes; after 15 minutes, may repeat bolus by administering 0.35 mg/kg actual body weight over 2 min (average adult dose, 25 mg) direct IV if first dose tolerated but response inadequate; some clinicians suggest additional doses q15min
Use weight-based dosing for lower-body-weight patients
Continuous infusion: 10 mg/hr IV initially; increased to no more than 15 mg/hr for up to 24 hours
Atrial Fibrillation/Flutter
0.25 mg/kg (usual adult dose, 20 mg) direct IV over 2 minutes; after 15 minutes, may repeat bolus by administering 0.35 mg/kg actual body weight over 2 min (average adult dose, 25 mg) direct IV if first dose tolerated but response inadequate; some clinicians suggest additional doses q15min
Use weight-based dosing for lower-body-weight patients
Continuous infusion: 10 mg/hr IV initially; increased to no more than 15 mg/hr for up to 24 hours
Dose Modifications
Renal Impairment
- Use caution; not studied
Hepatic Impairment
- Use caution; not studied
Pediatric dosage forms and strengths
capsule/tablet, extended release
- 120mg
- 180mg
- 240mg
- 300mg
- 360mg
- 420mg
injectable solution
- 5mg/mL
powder for injection
- 100mg
tablet
- 30mg
- 60mg
- 90mg
- 120mg
Hypertension (Off-label)
1.5-2 mg/kg/day PO divided q8hr; not to exceed 6 mg/kg/day, up to 360 mg/day
Cardizem, Cardizem CD (diltiazem) adverse (side) effects
>10%
Edema (2-15%)
Headache (5-12%)
1-10%
Dizziness (3-10%)
AV block (2-8%)
Peripheral edema (2-8%)
Bradyarrhythmia (2-6%)
Headache (1-5%)
Hypotension (2-4%)
Nausea (3%)
Vomiting (2%)
Vasodilation (2-3%)
Extrasystoles (2%)
Flushing (1-2%)
Drug-induced gingival hyperplasia (<2%)
Myalgia (2%)
Diarrhea (1-2%)
Constipation (2-4%)
Bronchitis (1-4%)
Sinus congestion (1-2%)
Dyspnea (1-6%)
Congestion (1-2%)
< 1%
Increased Alkaline phosphatase as well as ALT and ASt
CHF
Thrombocytopenia
Toxic epidermal necrolysis
Hemolytic anemia
Photosensitivity
Extrapyramidal symptoms
Syncope
Warnings
Contraindications
Hypersensitivity
Wolff-Parkinson-White syndrome, Lown-Ganong-Levine syndrome, symptomatic severe hypotension (systolic BP <90 mm Hg), sick sinus syndrome (if no pacemaker), 2°/3° (if no pacemaker); heart block
PO: Acute MI and pulmonary congestion
IV: Use in newborns (because of benzyl alcohol), concomitant beta-blocker therapy, cardiogenic shock, ventricular tachycardia (must determine whether origin is supraventricular or ventricular)
Cautions
May cause abnormally slow heart rates or second- or third-degree AV block’ patients with sick sinus syndrome are at increased risk of bradycardia (risk increases with agents known to slow cardiac conduction
Stevens-Johnson syndrome, toxic epidermal necrolusis, erythema multiforme and/or exfoliative dermatitis reported
Significant elevations in liver enzymes such as alkaline phosphatase, LDH, AST (SGOT), ALT (SGPT) and signs of acute hepatic injury reported; reversible upon discontinuation of drug therapy
Mild elevations of transaminases with and without concomitant elevation in alkaline phosphatase and bilirubin observed; elevations were usually resolved even with continued diltiazem treatment
Symptomatic hypotension with or without syncope reported
Peripheral edema occurs within 2-3 weeks of starting therapy
Use with caution in hypertrophic obstructive cariomyopathy, hepatic/renal impairment, left ventricular dysfunction
Concomitant use of diltiazem with beta-blockers or digitalis may result in additive effects on cardiac conduction; sinus bradycardia resulting in hospitalization reported with concurrent use of clonidine and other agents that slow cardiac conduction
May increase the risk of adverse cardiac events in patients with heart failure due to negative inotropic effects (risk directly related to the severity of baseline HF)
Pregnancy and lactation
Pregnancy category: C
Lactation: Drug enters breast milk; because of risk for serious adverse reactions in nursing infants from diltiazem, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Cardizem, Cardizem CD (diltiazem)
Mechanism of action
Nondihydropyridine calcium-channel blocker: Inhibits extracellular calcium ion influx across membranes of myocardial cells and vascular smooth muscle cells, resulting in inhibition of cardiac and vascular smooth muscle contraction and thereby dilating main coronary and systemic arteries; no effect on serum calcium concentrations; substantial inhibitory effects on cardiac conduction system, acting principally at AV node, with some effects at sinus node
Absorption
Bioavailability: 40% (PO)
Onset (hypertension): 30-60 min (IR); 3 min (IV)
Duration (SVT): 1-3 hr (IV bolus); 0.5-10 hr (following discontinuation of continuous IV infusion)
Peak serum time: 2-4 hr (IR); 10-14 hr (ER capsule); 11-18 hr (ER tablet)
Distribution
Protein bound: 70-80%
Vd: 3-13 L/kg
Metabolism
Metabolized via hepatic CYP3A4
Metabolites: Desacetyldiltiazem (active), 25-50% as potent as diltiazem in coronary vasodilation; N-monodesmethyldiltiazem (inactive)
Elimination
Half-life: 3-4.5 hr (IR); 6-9 hr (ER tablet), 5-10 hr (ER capsule); 3-4 hr (single dose IV); 4-5 hr (continuous infusion)
Clearance: 11.8 mL/min/kg
Excretion: Urine (2-4% as unchanged; 6-7% as metabolites), feces
Administration
IV Incompatibilities
Y-site: Allopurinol, amphotericin B, cefepime, cefoperazone, diazepam, furosemide, ketorolac, lansoprazole, pantoprazole, phenytoin, rifampin, thiopentaL
IV Compatibilities
Solution: D5W, Ns
Y-site (partial list): Acetazolamide (may be incompatible at higher concentrations), acyclovir (may be incompatible at higher concentrations), ceftriaxone, ciprofloxacin, clindamycin, digoxin, dobutamine, dopamine, epinephrine, erythromycin, fentanyl, fluconazole, heparin(?), labetalol, lidocaine, lorazepam, meperidine, metoclopramide, metronidazole, midazolam, milrinone, morphine sulfate, nafcillin (may be incompatible at higher concentrations), nitroglycerin, norepinephrine, potassium chloride, sodium bicarbonate, vancomycin
IV Preparation
IV push may be given by using undiluted 5 mg/mL injection
Infusion
- Accepted diluents are D5W, NS, and D5/½NS
- Add 25 mL of 5 mg/mL solution in 100 mL diluent (1 mg/mL solution)
- Add 50 mL of 5 mg/mL solution in 250 mL diluent (0.83 mg/mL solution)
- Add 50 mL of 5 mg/mL solution in 500 mL diluent (0.45 mg/mL solution)
- Dilute 1 monovial (100 mg) in 100 mL diluent (1 mg/mL solution)
- Dilute 2 monovials (200 mg) in 250 mL diluent (0.8 mg/mL solution)
- Dilute 2 monovials (200 mg) in 500 mL diluent (0.4 mg/mL solution)
IV Administration
Give bolus over 2 minutes with continuous ECG and BP monitoring
Response to bolus may require several minutes to reach maximum; response may persist for several hours after infusion is discontinued
Continuous infusion is done via infusion pump
Infusion for >24 hours is not recommended
Storage
Refrigerate liquid injection vials; protect from freezing
May store at room temperature for 1 month
Powder: Store at room temperature; do not freeze
Reconstituted solution stable at room temperature for 24 hours