|Cardizem® CD; Cardizem®
Injectable; Cardizem® SR; Cardizem® Tablet; Dilacor™
XR; Tiamate®; Tiazac™|
|Apo®-Diltiaz; Novo-Diltazem; Nu-Diltiaz;
Calcium Channel Blocker
Capsule: Essential hypertension (alone or in combination) - sustained release
only; chronic stable angina or angina from coronary artery spasm
Injection: Atrial fibrillation or atrial flutter; paroxysmal supraventricular
Clinical effects on the fetus: Teratogenic and embryotoxic effects have been
demonstrated in small animals given doses 5-10 times the adult dose (mg/kg)
Breast-feeding/lactation: Freely diffuses into breast milk; however, the
American Academy of Pediatrics considers diltiazem to be compatible with
breast-feeding. Available evidence suggests safe use during breast-feeding.
Hypersensitivity to diltiazem or any component; sick sinus syndrome; second-
or third- degree AV block (except in patients with a functioning artificial
pacemaker); hypotension (systolic <90 mm Hg); acute MI and pulmonary
congestion by x-ray
Concomitant use with beta-blockers or digoxin can result in conduction
disturbances. Avoid concurrent I.V. use of diltiazem and a beta-blocker -
monitor closely when I.V. diltiazem is used. Use caution in left ventricular
dysfunction and CHF (can exacerbate condition). Symptomatic hypotension can
occur. Use with caution in hepatic or renal dysfunction.
>10%: Gastrointestinal: Gingival hyperplasia (21%)
1% to 10%:
Cardiovascular: Sinus bradycardia (1.5% to 6%), first-degree A-V block (1.8%
to 7.6%), EKG abnormality (4.1%), peripheral edema (dose-related 5.4% to 8%),
flushing (1.9% to 3%), hypotension (1%), palpitations (1.3%)
Central nervous system: Dizziness (3.4% to 7%), headache (4.5% to 12%),
somnolence (1.3%), insomnia (1%)
Gastrointestinal: Nausea (1.3% to 1.6%), constipation (1.6%), dyspepsia
Neuromuscular & skeletal: Weakness (2.8% to 5%)
Dermatological: Rash (1& to 1.5%)
Renal: Polyuria (1.3%)
<1% (Limited to important or life-threatening symptoms): Angina,
arrhythmia, second- or third-degree AV block, bundle branch block, congestive
heart failure, syncope, tachycardia, ventricular extrasystoles, abnormal dreams,
amnesia, depression, gait abnormalities, hallucinations, nervousness,
paresthesia, personality change, tremor, anorexia, diarrhea, dry mouth,
dysgeusia, thirst, vomiting, weight gain, petechiae, photosensitivity, pruritus,
urticaria, amblyopia, dyspnea, epistaxis, eye irritation, hyperglycemia,
hyperuricemia, impotence, muscle cramps, nasal congestion, nocturia,
osteoarticular pain, sexual difficulties, myoclonus, tinnitus
Case reports: Agranulocytosis, leukocytopenia (overdose), thrombocytopenia,
akathisia, mania, psychosis, Parkinsonian-like syndrome, TEN, Stevens-Johnson
syndrome, erythema multiforme, exfoliative dermatitis, gynecomastia
The primary cardiac symptoms of calcium blocker overdose includes hypotension
and bradycardia. The hypotension is caused by peripheral vasodilation,
myocardial depression, and bradycardia. Bradycardia results from sinus
bradycardia, second- or third-degree atrioventricular block, or sinus arrest
with junctional rhythm. Intraventricular conduction is usually not affected so
QRS duration is normal (verapamil does prolong the P-R interval and bepridil
prolongs the Q-T and may cause ventricular arrhythmias, including torsade de
In a few reported cases, overdose with calcium channel blockers has been
associated with hypotension and bradycardia, initially refractory to atropine
but becoming more responsive to this agent when larger doses (approaching 1 gram
per hour for more than 24 hours) of calcium chloride was administered.
CYP3A3/4 enzyme substrate; CYP3A3/4, 1A2, 2D6 enzyme inhibitor
Amiodarone use may lead to bradycardia, other conduction delays, and
decreased cardiac output; monitor closely if using together.
Azole antifungals may inhibit the calcium channel blocker's metabolism; avoid
this combination. Try an antifungal like terbinafine (if appropriate) or monitor
closely for altered effect of the calcium channel blocker.
Beta-blockers may have increased pharmacodynamic interactions with diltiazem
Calcium may reduce the calcium channel blocker's effects, particularly
Carbamazepine's serum concentration is increased and toxicity may result;
avoid this combination.
Cimetidine reduced diltiazem's metabolism; consider an alternative
Cyclosporine's serum concentrations are increased by diltiazem; avoid the
combination. Use another calcium channel blocker or monitor cyclosporine trough
levels and renal function closely.
Digoxin's serum concentration can be increased in some patients; monitor for
increased effects of digoxin.
HMG-CoA reductase inhibitors (atorvastatin, cerivastatin, lovastatin,
simvastatin): Serum concentration will likely be increased; consider
pravastatin/fluvastatin or a dihydropyridine calcium channel blocker.
Lithium neurotoxicity may result when diltiazem is added; monitor lithium
Midazolam's plasma concentration is increased by diltiazem; monitor for
prolonged CNS depression.
Moricizine's serum concentration is increased; monitor clinical response
Nafcillin decreases plasma concentration of diltiazem; avoid this
Nitroprusside's dose required reduction in patients started on diltiazem;
monitor blood pressure.
Protease inhibitor like amprenavir and ritonavir may increase diltiazem's
Rifampin increases the metabolism of calcium channel blockers; adjust the
dose of the calcium channel blocker to maintain efficacy.
Tacrolimus's serum concentrations are increased by diltiazem; avoid the
combination. Use another calcium channel blocker or monitor tacrolimus trough
levels and renal function closely.
Store injections in refrigerator at 2°C to
8°C (36°F to
46°F); stable for 24 hours
Inhibits calcium ion from entering the "slow channels" or select
voltage-sensitive areas of vascular smooth muscle and myocardium during
depolarization, producing a relaxation of coronary vascular smooth muscle and
coronary vasodilation; increases myocardial oxygen delivery in patients with
Onset of action: Oral: 30-60 minutes (including sustained release)
Absorption: 80% to 90%
Time to peak serum concentration: Short-acting tablets: Within 2-3 hours;
Sustained release: 6-11 hours
Distribution: Vd: 3-13 L/kg; appears in breast milk
Protein binding: 77% to 85%
Metabolism: Extensive first-pass metabolism; metabolized in the liver;
following single I.V. injection, plasma concentrations of
N-monodesmethyldiltiazem and desacetyldiltiazem are typically undetectable;
however, these metabolites accumulate to detectable concentrations following
24-hour constant rate infusion. N-monodesmethyldiltiazem appears to have 20% of
the potency of diltiazem; desacetyldiltiazem is about 50% as potent as the
Bioavailability: ~40% to 60% due to significant first-pass effect
Half-life: 4-6 hours, may increase with renal impairment; 5-7 hours with
Elimination: In urine and bile mostly as metabolites
Cardizem® SR: Initial: 60-120 mg twice daily;
adjust to maximum antihypertensive effect (usually within 14 days); usual range:
Cardizem® CD, Tiazac™:
Hypertension: Total daily dose of short-acting administered once daily or
initially 180 or 240 mg once daily; adjust to maximum effect (usually within 14
days); maximum: 480 mg/day; usual range: 240-360 mg/day
Cardizem® CD: Angina: Initial: 120-180 mg once
daily; maximum: 480 mg once/day
Hypertension: 180-240 mg once daily; maximum: 540 mg/day; usual range:
180-480 mg/day; use lower dose in elderly
Angina: Initial: 120 mg/day; titrate slowly over 7-14 days up to 480 mg/day,
I.V. (requires an infusion pump):
- Initial bolus dose: 0.25 mg/kg actual body weight over 2 minutes
(average adult dose: 20 mg)
- Repeat bolus dose (may be administered after 15 minutes if the
response is inadequate.): 0.35 mg/kg actual body weight over 2 minutes (average
adult dose: 25 mg)
- Continuous infusion (infusions >24 hours or infusion rates >15
mg/hour are not recommended.): Initial infusion rate of 10 mg/hour; rate may be
increased in 5 mg/hour increments up to 15 mg/hour as needed; some patients may
respond to an initial rate of 5 mg/hour.
If Cardizem® injectable is administered by continuous
infusion for >24 hours, the possibility of decreased diltiazem clearance,
prolonged elimination half-life, and increased diltiazem and/or diltiazem
metabolite plasma concentrations should be considered.
Conversion from I.V. diltiazem to oral diltiazem: Start oral
approximately 3 hours after bolus dose.
Oral dose (mg/day) is approximately equal to [rate (mg/hour) x 3 + 3] x
3 mg/hour = 120 mg/day
5 mg/hour = 180 mg/day
7 mg/hour = 240 mg/day
11 mg/hour = 360 mg/day
Dosing comments in renal/hepatic impairment: Use with caution as
extensively metabolized by the liver and excreted in the kidneys and bile.
Dialysis: Not removed by hemo- or peritoneal dialysis; supplemental dose is
Alcohol: Avoid use
Sustained release capsules may be opened and sprinkled on a spoonful of
applesauce. Applesauce should be swallowed without chewing, followed by drinking
a glass of water.
Liver function tests, blood pressure, EKG
Diltiazem is an effective antihypertensive alone or in combination with other
agents. Antihypertensive therapy should be individualized with consideration
given to the patient's concomitant diseases and compelling indications for
Diltiazem may be administered intravenously in the acute setting to attain
ventricular rate control in patients with atrial fibrillation or flutter.
Patients who respond, defined in general as at least a 20% decrease in
ventricular response rate or attaining a rate <100 beats/minute, can be
continued on oral therapy to maintain control. It is important to consider the
potential drug interaction with digoxin, as these agents are both used in this
|Mental Health: Effects
on Mental Status|
May cause dizziness, insomnia, nervousness, or sedation
Effects on Psychiatric
May produce leukopenia; use caution with clozapine and carbamazepine; lithium
levels may be increased or decreased; monitor serum lithium levels;
carbamazepine levels may be increased; monitor levels
|Dental Health: Local
No information available to require special precautions
Effects on Dental Treatment|
Calcium channel blockers cause gingival hyperplasia in approximately 1% of
patients. There have been fewer reports with diltiazem than with other CCBs. The
hyperplasia will usually disappear with cessation of drug therapy. Consultation
with physician is suggested.
Oral: Take as directed; do not alter dosage or discontinue therapy without
consulting prescriber. Do not crush or chew extended release form. Avoid (or
limit) alcohol and caffeine. You may experience dizziness or lightheadedness
(use caution when driving or engaging in tasks requiring alertness until
response to drug is known); nausea or vomiting (small frequent meals, frequent
mouth care, chewing gum, or sucking lozenges may help); constipation (increased
exercise, dietary fiber, fruit, or fluid may help); diarrhea (buttermilk, boiled
milk, or yogurt may help). Report chest pain, palpitations, irregular heartbeat,
unusual cough, difficulty breathing, swelling of extremities, muscle tremors or
weakness, confusion or acute lethargy, or skin rash. Pregnancy
precautions: Inform prescriber if you are or intend to be
Do not crush sustained release capsules
Capsule, sustained release, as hydrochloride: 60 mg, 90 mg, 120 mg, 180 mg,
240 mg, 300 mg
Cardizem® CD: 120 mg, 180 mg, 240 mg, 300 mg, 360 mg
Cardizem® SR: 60 mg, 90 mg, 120 mg
Cartia® XT: 120 mg, 180 mg, 240 mg, 300 mg
Dilacor™ XR: 180 mg, 240 mg
Diltia XT®: 120 mg, 180 mg, 240 mg
Tiazac®: 120 mg, 180 mg, 240 mg, 300 mg, 360 mg, 420 mg
Injection, as hydrochloride: 5 mg/mL (5 mL, 10 mL)
Cardizem®: 5 mg/mL (5 mL, 10 mL)
Tablet, as hydrochloride (Cardizem®): 30 mg, 60 mg, 90
mg, 120 mg
Tablet, extended release, as hydrochloride (Tiamate®):
120 mg, 180 mg, 240 mg
Diltiazem 12 mg/mL was found to be stable for up to 60 days at
5°C and 25°C in a 1:1 mixture of
Ora-Sweet® and Ora-Plus®, a 1:1
mixture of Ora-Sweet® SF and
Ora-Plus® and of cherry syrup
Anthony T, Jastremski M, Elliott W, et al,
"Charcoal Hemoperfusion for the Treatment of a Combined Diltiazem and Metoprolol Overdose,"
Ann Emerg Med, 1986, 15(11):1344-8.
Avila JR, Bejarano D, Gonzalez ML, et al,
"Elevation of Hepatic Enzymes After Cutaneous Reaction Caused by Diltiazem,"
Ann Pharmacother, 1995, 29(3):317-8.
Bertorini TE, Palmieri GMA, Griffin JW, et al,
"Effect of Chronic Treatment With the Calcium Antagonist Diltiazem in Duchenne Muscular Dystrophy,"
Neurology, 1988, 38(4):609-13.
Ellenbogen KA, Dias VC, and Cardello FP,
"Safety and Efficacy of Intravenous Diltiazem in Atrial Fibrillation or Atrial Flutter,"
Am J Cardiol, 1995, 75(1):45-9.
Fauville JP, Hantson P, Honore P, et al,
"Severe Diltiazem Poisoning With Intestinal Pseudo-Obstruction: Case Report and Toxicological Data,"
J Toxicol Clin Toxicol, 1995, 33(3):273-7.
Ferner RE, Odemuyiwa O, Field AB, et al,
"Pharmacokinetics and Toxic Effects of Diltiazem in Massive Overdose," Hum
Toxicol, 1989, 8(6):497-9.
Howarth DM, Dawson AH, Smith AJ, et al,
"Calcium Channel Blocking Drug Overdose: An Australian Series," Hum Exp
Toxicol, 1994, 13(3):161-6.
Kalin JR, Wood KM, and Lee AJ, "A Possible Suicide by Diltiazem Overdose,"
J Anal Toxicol, 1994, 18(3):180-2.
Proano L, Chiang WK, and Wang RY, "Calcium Channel Blocker Overdose," Am J
Emerg Med, 1995, 13(4):444-50.
Roberts D, Honcharik N, Sitar DS, et al,
"Diltiazem Overdose: Pharmacokinetics of Diltiazem and Its Metabolites and Effect of Multiple Dose Charcoal Therapy,"
J Toxicol Clin Toxicol, 1991, 29(1):45-52.
Snover SW and Bocchino V, "Massive Diltiazem Overdose," Ann Emerg Med,
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