General

Pronunciation:
dil-tye-a-zem

Trade Name(s)

• Cardizem
• Cardizem CD
• Cardizem LA
• Cartia XT
• Matzim LA
• Taztia XT
• Tiadylt ER
• Tiazac
• Tiazac XC 

Ther. Class.

antianginals

antiarrhythmics

(class IV)

antihypertensives

Pharm. Class.

calcium channel blockers

Indications

• Hypertension.
• Angina pectoris and vasospastic (Prinzmetal) angina.
• Supraventricular tachyarrhythmias and rapid ventricular rates in atrial flutter or fibrillation.

Action

Inhibits transport of calcium into myocardial and vascular smooth muscle cells, resulting in inhibition of excitation-contraction coupling and subsequent contraction.

Therapeutic Effect(s):

• Systemic vasodilation resulting in decreased BP.
• Coronary vasodilation resulting in decreased frequency and severity of attacks of angina.
• Reduction of ventricular rate in atrial fibrillation or flutter.

Pharmacokinetics

Absorption: Well absorbed, but rapidly metabolized after oral administration.

Distribution: Unknown.

Protein Binding: 70–80%.

Metabolism and Excretion: Primarily metabolized by the liver via the CYP3A4 isoenzyme. Excreted in the urine and feces.

Half-life: 3.5–9 hr.

TIME/ACTION PROFILE

Contraindication/Precautions

Contraindicated in:

• Hypersensitivity;
• Sick sinus syndrome;
• 2nd- or 3rd-degree AV block (unless an artificial pacemaker is in place);
• Systolic BP <90 mm Hg;
• Recent MI or pulmonary congestion;
• Concurrent use of rifampin;
• Lactation:  Lactation.

Use Cautiously in:

• Severe hepatic impairment (↓ dose recommended);
• Severe renal impairment;
• Serious ventricular arrhythmias or HF;
• OB:   Use during pregnancy only if potential maternal benefit justifies potential fetal risk;
• Pedi:   Safety and effectiveness not established in children;
• Geri:  ↓ dose and slower IV infusion rate recommended in older adults; ↑ risk of hypotension; consider age-related decrease in body mass, ↓ hepatic/renal/cardiac function, concurrent drug therapy, and other disease states.

Adverse Reactions/Side Effects

CV: peripheral edema, ARRHYTHMIA, bradycardia, chest pain, HF, hypotension, palpitations, syncope, tachycardia

Derm: dermatitis, erythema multiforme, flushing, photosensitivity, pruritus/urticaria, rash, STEVENS-JOHNSON SYNDROME (SJS), sweating

EENT: blurred vision, disturbed equilibrium, epistaxis, tinnitus

Endo: gynecomastia, hyperglycemia

GI: ↑ liver enzymes, anorexia, constipation, diarrhea, dry mouth, dyspepsia, nausea, vomiting

GU: dysuria, nocturia, polyuria, sexual dysfunction, urinary frequency

Hemat: anemia, leukopenia, thrombocytopenia

Metabolic: weight gain

MS: joint stiffness, muscle cramps

Neuro: abnormal dreams, anxiety, confusion, dizziness, drowsiness, dysgeusia, headache, nervousness, paresthesia, psychiatric disturbances, tremor, weakness

Resp: cough, dyspnea

Misc: gingival hyperplasia

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

• ↑ hypotension may occur when used with  fentanyl, other  antihypertensives,  nitrates, acute ingestion of  alcohol, or  quinidine.
• Antihypertensive effects may be ↓ by  NSAIDs.
• May ↑  digoxin  levels.
• May ↑ levels of and risk of myopathy from  simvastatin  and  lovastatin.
• Concurrent use with  beta blockers,  clonidine,  digoxin,  disopyramide,  ivabradine, or  phenytoin  may result in bradycardia, conduction defects, or HF; avoid concurrent use with ivabradine.
•  Phenobarbital  and  phenytoin  may ↑ metabolism and ↓ effectiveness.
• May ↓ metabolism of and ↑ risk of toxicity from  cyclosporine,  quinidine, or  carbamazepine.
•  Cimetidine  ↑ levels and effects.
• May ↑ or ↓ the effects of  lithium  or  theophylline.

Drug-Food:

Grapefruit juice ↑ levels and effect.

Route/Dosage

PO (Adults): 30–120 mg 3–4 times daily or 180–240 mg once daily as CD or XR capsules or LA tablets (up to 360 mg/day);  Concurrent simvastatin therapy:  Diltiazem dose should not exceed 240 mg/day and simvastatin dose should not exceed 10 mg/day.

IV (Adults): 0.25 mg/kg; may repeat in 15 min with a dose of 0.35 mg/kg. May follow with continuous infusion at 10 mg/hr (range 5–15 mg/hr) for up to 24 hr.

Availability (generic available)

Tablets: 30 mg, 60 mg, 90 mg, 120 mg

Extended-release capsules (Cardizem CD, Tiazac, Tiadylt ER, Cartia XT): 120 mg, 180 mg, 240 mg, 300 mg, 360 mg, 420 mg

Extended-release tablets (Cardizem LA, Matzim LA): 120 mg, 180 mg, 240 mg, 300 mg, 360 mg, 420 mg

Premixed infusion: 125 mg/125 mL D5W, 250 mg/250 mL D5W

Solution for injection: 5 mg/mL

Assessment

• Monitor BP and HR before therapy, during dose titration, and periodically during therapy. Monitor ECG at baseline then periodically during prolonged therapy.

  • Monitor intake and output and daily weight. Assess for signs/symptoms of HF (peripheral edema, rales/crackles, dyspnea, weight gain, jugular venous distention).  If HF occurs, discontinue diltiazem and treat appropriately.
• Assess for rash or signs/symptoms of SJS periodically during therapy (fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, hepatitis, eosinophila).  If rash occurs,  discontinue diltiazem and provide supportive care.
• Angina: Assess location, duration, intensity, and precipitating factors of patient's anginal pain.
• Hypertension: BP should be checked monthly when initiating or adjusting therapy and then every 3–6 mo once BP goals have been met.
• Arrhythmias: Monitor ECG continuously during administration. Report bradycardia or prolonged hypotension promptly. Emergency equipment and medication should be available. Monitor BP and HR before and frequently during administration.  If 3rd degree atrioventricular block occurs, discontinue diltiazem and institute appropriate supportive measures.
• Patients receiving digoxin concurrently with diltiazem, nifedipine, or verapamil should have routine serum digoxin level and be monitored for signs and symptoms of digoxin toxicity.

Lab Test Considerations:

Total serum calcium concentrations are not affected by calcium channel blockers.

• Monitor potassium periodically. Hypokalemia ↑ the risk of arrhythmias and should be corrected.
• Monitor renal and hepatic function periodically during long-term therapy. May ↑ liver enzymes after several days of therapy, which return to normal on discontinuation of therapy.

Implementation

• Do not confuse Cardizem with Cardene. Do not confuse diltiazem with diazepam.
• PO May be administered without regard to meals. May be administered with meals if GI irritation becomes a problem.
  •  DNC: Do not open, crush, break, or chew extended-release tablets.  Empty tablets that appear in stool are not significant.
  • Tiazac  capsules may be opened and contents sprinkled on a spoonful of applesauce. Swallow immediately without chewing and follow with full glass of water; do not store mixture or subdivide capsule contents.

Patient/Family Teaching

• Explain purpose and side effects of diltiazem. Instruct patient to take medication as directed, even if feeling well. Take missed doses as soon as possible unless almost time for next dose; do not double doses. May need to be discontinued gradually. Advise patient to read  Patient Information  before starting and with each Rx refill in case of changes.

  • Advise patients to avoid drinking grapefruit juice during therapy.
  • Instruct patient on technique for monitoring HR. Instruct patient to contact health care provider if HR <50 bpm.
  • Caution patient to change positions slowly to minimize orthostatic hypotension.
  • Advise patient to notify health care provider if rash, irregular heartbeat, dyspnea, swelling of hands and feet, pronounced dizziness, nausea, constipation, or hypotension occurs or if headache is severe or persistent.
  • May cause drowsiness or dizziness. Advise patient to avoid driving or other activities requiring alertness until response to the medication is known.
  • Geri:  Teach patient and family about risk for falls and how to ↓ risk in the home.
  • Instruct patient on importance of maintaining good dental hygiene and seeing dentist frequently for teeth cleaning to prevent tenderness, bleeding, and gingival hyperplasia (gum enlargement).
  • Instruct patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to avoid concurrent use of alcohol or OTC medications and herbal products, especially NSAIDs and cold preparations, without consulting health care provider.
  • Caution patient to wear protective clothing and use sunscreen to prevent photosensitivity reactions.
• Angina:

  Instruct patient on concurrent nitrate or beta blocker therapy to continue taking both medications as directed and use SL nitroglycerin as needed for anginal attacks.

  • Advise patient to contact health care provider if chest pain does not improve, worsens after therapy, or occurs with diaphoresis; or if shortness of breath or persistent headache occurs.
  • Caution patient to discuss exercise restrictions with health care provider before exertion.
• Hypertension:

  Encourage patient to comply with other interventions for hypertension (weight reduction, low-sodium diet, smoking cessation, moderation of alcohol consumption, regular exercise, and stress management). Medication controls but does not cure hypertension.

  • Instruct patient and family in proper technique for monitoring BP. Advise patient to take BP weekly and to report significant changes to health care provider.
• Rep:   Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected or if breastfeeding.

Evaluation/Desired Outcomes

• Decrease in BP.

• Decrease in frequency and severity of anginal attacks.

  • Decrease in need for nitrate therapy.
  • Increase in activity tolerance and sense of well-being.
• Suppression and prevention of supraventricular tachyarrhythmias.