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Action

Inhibits calcium from entering myocardial and vascular smooth-muscle cells, thereby depressing myocardial and smooth-muscle contraction and decreasing impulse formation and conduction velocity. As a result, systolic and diastolic pressures decrease.

Availability

Capsules (extended-release, sustained-release): 60 mg, 90 mg, 120 mg, 180 mg, 240 mg, 300 mg, 360 mg, 420 mg

Injection: 5 mg/ml in 10-ml vials, 100-mg Monovial

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

Indications and dosages

➣ Angina pectoris and vasospastic (Prinzmetal's) angina; hypertension; supraventricular tachyarrhythmias; atrial flutter or fibrillation

Adults: 30 to 90 mg P.O. three to four times daily (tablets), or 60 to 120 mg P.O. b.i.d. (sustained-release), or 180 to 240 mg P.O. once daily (extended-release), adjusted after 14 days as needed, up to a total daily dosage of 360 mg. Or 0.25 mg/kg by I.V. bolus over 2 minutes; if response is inadequate after 15 minutes, may give 0.35 mg/kg over 2 minutes; may follow with continuous I.V. infusion at 10 mg/hour (at a range of 5 to 15 mg/hour) for up to 24 hours.

Dosage adjustment

• Severe hepatic or renal impairment

• Elderly patients

Off-label uses

• Unstable angina, coronary artery bypass graft surgery

• Tardive dyskinesia

• Migraine

• Hyperthyroidism

• Raynaud's phenomenon

Contraindications

• Hypersensitivity to drug

• Atrial flutter or fibrillation associated with shortened refractory period (Wolff-Parkinson-White syndrome, with I.V. use)

• Recent myocardial infarction or pulmonary congestion

• Cardiogenic shock, concurrent I.V. beta-blocker therapy, ventricular tachycardia, neonates (with I.V. use, because of benzyl alcohol in syringe formulation)

• Sick sinus syndrome, second- or third-degree atrioventricular block (except in patients with ventricular pacemakers)

• Hypotension (systolic pressure below 90 mm Hg)

Precautions

Use cautiously in:

• severe hepatic or renal impairment, heart failure

• history of serious ventricular arrhythmias

• concurrent use of I.V. diltiazem and I.V. beta blockers

• elderly patients

• pregnant or breastfeeding patients

• children (safety not established).

Administration

• When giving I.V., dilute in dextrose 5% in water or normal saline solution.

• Give I.V. bolus dose over 2 minutes; a second bolus may be given after 15 minutes.

• Administer continuous I.V. infusion at a rate of 5 to 15 mg/hour.

☞ When giving by continuous I.V. infusion, make sure emergency equipment is available and that patient has continuous ECG monitoring with frequent blood pressure monitoring.

• Don't crush tablets or sustained-release capsules; they must be swallowed whole.

• Withhold dose if systolic blood pressure falls below 90 mm Hg, diastolic pressure is below 60 mm Hg, or apical pulse is slower than 60 beats/minute.

Adverse reactions

CNS: headache, abnormal dreams, anxiety, confusion, dizziness, drowsiness, nervousness, psychiatric disturbances, asthenia, paresthesia, syncope, tremor

CV: peripheral edema, bradycardia, chest pain, hypotension, palpitations, tachycardia, arrhythmias, heart failure

EENT: blurred vision, tinnitus, epistaxis

GI: nausea, vomiting, diarrhea, constipation, dyspepsia, dry mouth

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

Hematologic: anemia, leukopenia, thrombocytopenia

Metabolic: hyperglycemia

Musculoskeletal: joint stiffness, muscle cramps

Respiratory: cough, dyspnea

Skin: rash, dermatitis, flushing, diaphoresis, photosensitivity, pruritus, urticaria, erythema multiforme

Other: unpleasant taste, gingival hyperplasia, weight gain, decreased appetite, Stevens-Johnson syndrome

Interactions

Drug-drug. Beta-adrenergic blockers, digoxin, disopyramide, phenytoin: bradycardia, conduction defects, heart failure

Carbamazepine, cyclosporine, quinidine: decreased diltiazem metabolism, increased risk of toxicity

Cimetidine, ranitidine: increased blood level and effects of diltiazem

Fentanyl, nitrates, other antihypertensives, quinidine: additive hypotension

HMG-CoA reductase inhibitors, imipramine, sirolimus, tacrolimus: increased blood levels of these drugs

Lithium: decreased lithium blood level, reduced antimanic control

Nonsteroidal anti-inflammatory drugs: decreased antihypertensive effect of diltiazem

Theophylline: increased theophylline effects

Drug-diagnostic tests. Hepatic enzymes: increased levels

Drug-food. Grapefruit juice: increased blood level and effects of diltiazem

Drug-behaviors. Acute alcohol ingestion: additive hypotension

Patient monitoring

• Check blood pressure and ECG before starting therapy, and monitor closely during dosage adjustment period. Withhold dose if systolic pressure is below 90 mm Hg.

☞ Monitor for signs and symptoms of heart failure and worsening arrhythmias.

• Supervise patient during ambulation.

Patient teaching

• Instruct patient to swallow extended-release capsules whole and not to crush or chew them.

• Advise patient to change position slowly to minimize light-headedness and dizziness.

• Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration and alertness.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, foods, and behaviors mentioned above.

Action

Blocks alpha₁-adrenergic receptors, promoting vasodilation. Also reduces urethral resistance, relieving obstruction and improving urine flow and other symptoms of benign prostatic hypertrophy (BPH).

Availability

Tablets: 1 mg, 2 mg, 4 mg, 8 mg

Tablets (extended-release): 4 mg, 8 mg

Indications and dosages

➣ Hypertension

Adults: 1 mg P.O. once daily. May increase dosage gradually q 2 weeks, up to 2 to 16 mg daily, as needed.

➣ BPH

Adults: 1 mg P.O. once daily. May increase dosage gradually, up to 8 mg daily, as needed. Or, initially 4 mg (extended-release) P.O. daily. May increase dosage to 8 mg daily, as needed, at 3- to 4-week intervals.

Off-label uses

• Pheochromocytoma

• Syndrome X

Contraindications

• Hypersensitivity to drug, its components, or quinazoline derivatives

Precautions

Use cautiously in:

• renal or mild or moderate hepatic impairment, coronary insufficiency, or preexisting severe GI narrowing

• severe hepatic impairment (extended-release form not recommended)

• intraoperative floppy iris syndrome

• concurrent use of strong CYP3A4 inhibitor (such as atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, or voriconazole), phosphodiesterase-5 (PDE-5) inhibitors

• elderly patients

• pregnant or breastfeeding patients (extended-release form not recommended in breastfeeding patients)

• children (safety not established).

Administration

• Give initial immediate-release dose at bedtime to minimize orthostatic hypotension and syncope.

• Give initial extended-release dose at breakfast.

• Be aware that extended-release tablets aren't indicated for hypertension.

• Be aware that prostate carcinoma should be ruled out before giving drug for BPH.

• Know that incidence of orthostatic hypotension increases greatly when daily dosage exceeds 4 mg and that it usually occurs within 6 hours of administration.

☞ If new or worsening signs or symptoms of angina pectoris occur, discontinue drug.

Adverse reactions

CNS: dizziness, vertigo, headache, depression, drowsiness, fatigue, nervousness, weakness, asthenia

CV: orthostatic hypotension, chest pain, palpitations, tachycardia, arrhythmias

EENT: abnormal or blurred vision, conjunctivitis, epistaxis, rhinitis, pharyngitis

GI: nausea, vomiting, diarrhea, constipation, abdominal discomfort, flatulence, dry mouth

GU: decreased libido, sexual dysfunction

Respiratory: dyspnea

Musculoskeletal: joint pain, arthritis, gout, myalgia

Skin: flushing, rash, pruritus

Other: edema

Interactions

Drug-drug. Clonidine, nitrates, other antihypertensives: decreased antihypertensive effect

Drugs that reduce GI motility leading to markedly prolonged GI retention times (such as anticholinergics): increased systemic exposure to doxazosin

PDE-5 inhibitors: increased risk of symptomatic hypotension

Drug-diagnostic tests. Neutrophils, white blood cells: decreased counts

Drug-food. Any food: increased drug plasma C_max (extended-release form)

Patient monitoring

• Monitor blood pressure with patient lying down and standing up every 2 to 6 hours after initial dose or after a dosage increase (when orthostatic hypotension is most likely to occur).

Patient teaching

• Tell patient to swallow extended-release tablets whole and not to chew, divide, cut, or crush them.

• Caution patient not to drive or perform other activities requiring alertness for 12 to 24 hours after first dose.

• Tell patient to move slowly when sitting up or standing, to avoid dizziness or light-headedness from sudden blood pressure decrease.

• Advise patient to report episodes of dizziness or palpitations.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.