Verelan


verapamil hydrochloride

Apo-Verap, Apo-Verap SR, Calan, Calan SR, Cordilox MR (UK), Covera-HS, Dom-Verapamil SR, Gen-Verapamil, Gen-Verapamil SR, Half Securon (UK), Isoptin, Isoptin SR, Med Verapamil, Novo-Veramil, Nu-Verap, Nu-Verap SR, PHL-Verapamil SR, PMS-Verapamil SR, Riva-Verapamil SR, Securon SR (UK), Univer (UK), Verapress (UK), Vera-Til SR (UK), Verelan, Verelan PM, Vertab SR (UK), Zolvera (UK)

Pharmacologic class: Calcium channel blocker

Therapeutic class: Antianginal, antiarrhythmic (class IV), antihypertensive

Pregnancy risk category C

Action

Decreases conduction of sinoatrial and atrioventricular (AV) nodes by inhibiting calcium influx into cardiac and vascular smooth muscle cells, inhibiting excitatory contraction. These effects prolong AV node refractoriness and decrease myocardial oxygen consumption.

Availability

Capsules (extended-release): 100 mg, 120 mg, 180 mg, 200 mg, 240 mg, 300 mg, 360 mg

Capsules (sustained-release): 120 mg, 180 mg, 240 mg, 360 mg

Injection: 2.5 mg/ml in 2- and 4-ml vials, ampules, and syringes

Tablets (extended-release): 120 mg, 180 mg, 240 mg

Tablets (immediate-release): 40 mg, 80 mg, 120 mg

Indications and dosages

Angina

Adults: Initially, 80 mg (immediate-release) P.O. t.i.d.; may titrate at daily or weekly intervals to 360 mg/day. Or initially, 180 mg (extended-release) P.O. once daily at bedtime, titrated up to 480 mg/day at bedtime.

Supraventricular tachyarrhythmias (SVTs)

Adults: 5 to 10 mg (0.075 to 0.15 mg/kg) I.V. bolus over 2 minutes; may give additional 10 mg after 30 minutes if response inadequate. Or 240 to 480 mg (immediate-release) P.O. daily in three or four divided doses.

To control ventricular rate in chronic atrial flutter or atrial fibrillation in patients receiving digoxin

Adults: 240 to 320 mg P.O. daily in three or four divided doses

Hypertension

Adults: Initially, 180 mg (extended-release tablet) or 200 mg (extended-release capsule) P.O. daily at bedtime. For maintenance, may titrate up to 480 mg (extended-release tablet) or 400 mg (extended-release capsule) P.O. daily at bedtime. Or initially, 80 mg (immediate-release tablet) P.O. t.i.d.; may titrate at daily or weekly intervals up to 360 to 480 mg/day. Or initially, 240 mg (sustained-release capsule) P.O. q day in morning; for maintenance, may titrate up to 240 mg P.O. b.i.d. or 480 mg P.O. once daily in morning. Titrate based on response.

Dosage adjustment

• Renal or hepatic impairment

• Concurrent digoxin therapy

Off-label uses

• Ventricular tachycardia

• Migraine headache prophylaxis

• Neurogenic bladder

• Premature labor

Contraindications

• Hypersensitivity to drug or other calcium channel blockers

• Sick sinus syndrome

• Second- or third-degree AV block (except in patients with artificial pacemakers)

• Hypotension

• Heart failure, severe ventricular dysfunction, or cardiogenic shock (except when associated with SVTs)

• Atrial flutter or atrial fibrillation associated with accessory bypass tracts (such as Wolff-Parkinson-White or Lown-Ganong-Levine syndrome)

Precautions

Use cautiously in:

• renal or severe hepatic impairment; first-degree AV block; idiopathic hypertrophic cardiomyopathy; neuromuscular transmission defects (such as Duchenne's muscular dystrophy); respiratory depression; digital ulcers, ischemia, or gangrene

• elderly patients

• pregnant or breastfeeding patients.

Administration

• Give I.V. over at least 2 minutes.

• Discontinue disopyramide 48 hours before starting verapamil. Don't restart disopyramide for at least 24 hours after verapamil therapy ends.

Adverse reactions

CNS: anxiety, confusion, dizziness, syncope, drowsiness, headache, jitteriness, abnormal dreams, disturbed equilibrium, psychiatric disturbances, asthenia, paresthesia, tremor, fatigue

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

EENT: blurred vision, epistaxis, tinnitus

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

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

Hematologic: anemia, leukopenia, thrombocytopenia

Metabolic: hyperglycemia

Musculoskeletal: joint stiffness, muscle cramps

Respiratory: cough, dyspnea, shortness of breath, pulmonary edema

Skin: dermatitis, flushing, diaphoresis, photosensitivity, pruritus, urticaria, rash, erythema multiforme, Stevens-Johnson syndrome

Other: gingival hyperplasia, edema, weight gain

Interactions

Drug-drug. Antihypertensives: additive hypotension

Aspirin: increased risk of bleeding

Beta-adrenergic blockers, other antiarrhythmics: additive adverse cardiovascular reactions

Carbamazepine, cyclosporine: increased blood levels of these drugs

CYP450-3A4 inducers (such as rifampin): decreased verapamil blood level

CYP450-3A4 inhibitors (such as erythromycin, ritonavir): increased verapamil blood level

Digoxin: increased digoxin blood level, greater risk of toxicity

Lithium: increased or decreased lithium blood level

Neuromuscular blockers (succinylcholine, tubocurarine, vecuronium): prolonged neuromuscular blockade

Theophylline: decreased verapamil clearance, increased blood level, and possible toxicity

Drug-diagnostic tests. Alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, blood urea nitrogen, glucose, lactate dehydrogenase: increased levels

Granulocytes: decreased count

Drug-food. Coffee, tea: increased caffeine blood level

Grapefruit juice: increased verapamil blood level and effects

Drug-herbs. Black catechu: increased drug effects

Cola nut, guarana: increased caffeine blood level

Ephedra (ma huang), St. John's wort: reduced hypotensive effect of verapamil

Yerba maté: decreased clearance of this herb

Drug-behaviors. Alcohol use: additive hypotension

Patient monitoring

• With I.V. use, monitor vital signs and ECG continuously.

• Assess blood pressure when therapy begins and when dosage is adjusted.

• Watch closely for signs and symptoms of heart failure.

Monitor for signs and symptoms of erythema multiforme (fever, rash, sore throat, mouth sores, cough, iris lesions). Report early indications immediately, before condition can progress to Stevens-Johnson syndrome.

• Assess CBC. Watch for blood dyscrasias.

• Monitor blood glucose level. Stay alert for hyperglycemia in diabetic patients.

Patient teaching

• Instruct patient to avoid chewing, breaking, or crushing extended-release form.

Advise patient to immediately report rash, unusual bleeding or bruising, fainting, and (in long-term use) fatigue, nausea, or yellowing of skin or eyes.

• Caution patient not to take with grapefruit juice.

• Instruct patient to limit caffeine intake and avoid alcohol.

• Advise patient to seek medical advice before using over-the-counter medications or herbs.

• Tell patient to avoid sun exposure and to wear sunscreen and protective clothing when going outdoors.

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

verapamil

(ver-ap-a-mil) verapamil,

Calan

(trade name),

Calan SR

(trade name),

Isoptin SR

(trade name),

Verelan

(trade name),

Verelan PM

(trade name)

Classification

Therapeutic: antianginals
Pharmacologic: calcium channel blockers
Pregnancy Category: C

Indications

Management of hypertension, angina pectoris, and/or vasospastic (Prinzmetal’s) angina.Management of supraventricular arrhythmias and rapid ventricular rates in atrial flutter or fibrillation.Prevention of migraine headache.

Action

Inhibits the transport of calcium into myocardial and vascular smooth muscle cells, resulting in inhibition of excitation-contraction coupling and subsequent contraction.Decreases SA and AV conduction and prolongs AV node refractory period in conduction tissue.

Therapeutic effects

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

Pharmacokinetics

Absorption: 90% absorbed after oral administration, but much is rapidly metabolized, resulting in bioavailability of 20–25%.Distribution: Small amounts enter breast milk.Protein Binding: 90%.Metabolism and Excretion: Mostly metabolized by the liver (primarily by CYP3A4).Half-life: 4.5–12 hr.

Time/action profile (cardiovascular effects)

ROUTEONSETPEAKDURATION
PO1–2 hr30–90 min†3–7 hr
PO-ERunknown5–7 hr24 hr
IV1–5 min‡3–5 min2 hr‡
†Single dose; effects from multiple doses may not be evident for 24–48 hr.‡Antiarrhythmic effects; hemodynamic effects begin 3–5 min after injection and persist for 10–20 min.

Contraindications/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;HF, severe ventricular dysfunction, or cardiogenic shock, unless associated with supraventricular tachyarrhythmias;Concurrent IV beta blocker therapy.Use Cautiously in: Severe hepatic impairment (dose ↓ recommended);History of serious ventricular arrhythmias or HF; Geriatric: Dose ↓/slower IV infusion rates recommended (↑ risk of hypotension); Obstetric / Lactation: Safety not established.

Adverse Reactions/Side Effects

Central nervous system

  • abnormal dreams
  • anxiety
  • confusion
  • dizziness/lightheadedness
  • drowsiness
  • extrapyramidal reactions
  • headache
  • jitteriness
  • nervousness
  • psychiatric disturbances
  • weakness

Ear, Eye, Nose, Throat

  • blurred vision
  • disturbed equilibrium
  • epistaxis
  • tinnitus

Respiratory

  • cough
  • dyspnea
  • shortness of breath

Cardiovascular

  • arrhythmias (life-threatening)
  • hf (life-threatening)
  • bradycardia
  • chest pain
  • hypotension
  • palpitations
  • peripheral edema
  • syncope
  • tachycardia

Gastrointestinal

  • ↑ liver enzymes
  • anorexia
  • constipation
  • diarrhea
  • dry mouth
  • dysgeusia
  • dyspepsia
  • nausea
  • vomiting

Genitourinary

  • dysuria
  • nocturia
  • polyuria
  • sexual dysfunction
  • urinary frequency

Dermatologic

  • stevens-johnson syndrome (life-threatening)
  • dermatitis
  • erythema multiforme
  • flushing
  • photosensitivity
  • pruritus/urticaria
  • rash
  • sweating

Endocrinologic

  • gynecomastia
  • hyperglycemia

Hematologic

  • anemia
  • leukopenia
  • thrombocytopenia

Metabolic

  • weight gain

Musculoskeletal

  • joint stiffness
  • muscle cramps

Neurologic

  • paresthesia
  • tremor

Miscellaneous

  • gingival hyperplasia

Interactions

Drug-Drug interaction

Additive hypotension may occur when used concurrently with fentanyl, other antihypertensives, nitrates, acute ingestion of alcohol, or quinidine.Antihypertensive effects may be ↓ by concurrent use of NSAIDs.Serum digoxin levels may be ↑.Concurrent use with beta blockers, digoxin, disopyramide, clonidine, or phenytoin may result in bradycardia, conduction defects, or HF.↑ risk of hypotension and bradycardia with erythromycin, clarithromycin, telithromycin, or ritonavir.May ↓ metabolism of and ↑ risk of toxicity from cyclosporine, prazosin, quinidine, or carbamazepine.May ↓ effectiveness of rifampin.↑ the muscle-paralyzing effects of nondepolarizing neuromuscular-blocking agents.Effectiveness may be ↓ by coadministration with vitamin D compounds and calcium.May alter serum lithium levels.May ↑ doxorubicin and paclitaxel levels.May ↑ risk of bleeding with aspirin.↑ caffeine levels with caffeine-containing herbs (cola nut, guarana, mate, tea, coffee).Grapefruit juice ↑ serum levels and effect.

Route/Dosage

Oral (Adults) 80–120 mg 3 times daily, ↑ as needed. Patients with hepatic impairment or geriatric patients—40 mg 3 times daily initially. Extended-release preparations—120–240 mg/day as a single dose; may be ↑ as needed (range 240–480 mg/day).Oral (Children up to 15 yr) 4–8 mg/kg/day in divided doses.Intravenous (Adults) 5–10 mg (75–150 mcg/kg); may repeat with 10 mg (150 mcg/kg) after 15–30 min.Intravenous (Children 1–15 yr) 2–5 mg (100–300 mcg/kg); may repeat after 30 min (initial dose not to exceed 5 mg; repeat dose not to exceed 10 mg).Intravenous (Children <1 yr) 0.75–2 mg (100–200 mcg/kg); may repeat after 30 min.

Availability (generic available)

Tablets: 40 mg, 80 mg, 120 mg Cost: Generic — 40 mg $21.85 / 100, 80 mg $10.83 / 100Extended-release tablets (Isoptin SR): 120 mg, 180 mg, 240 mg Cost: Generic — 120 mg $31.44 / 100, 180 mg $35.98 / 100, 240 mg $27.80 / 100Extended-release capsules (Verelan PM): 100 mg, 200 mg, 300 mg Cost: Generic — 100 mg $195.84 / 100, 200 mg $252.23 / 100, 300 mg $366.98 / 100Extended-release capsules (Verelan): 120 mg, 180 mg, 240 mg, 360 mg Cost: Generic — 120 mg $130.25 / 100, 180 mg $135.16 / 100, 240 mg $152.54 / 100, 360 mg $209.94 / 100Solution for injection: 2.5 mg/mL In combination with: trandolapril (Tarka); see combination drugs.

Nursing implications

Nursing assessment

  • Monitor BP and pulse before therapy, during dosage titration, and periodically throughout therapy. Monitor ECG periodically during prolonged therapy. Verapamil may cause prolonged PR interval.
    • Monitor intake and output ratios and daily weight. Assess for signs of HF (peripheral edema, rales/crackles, dyspnea, weight gain, jugular venous distention).
    • Patients receiving digoxin concurrently with calcium channel blockers should have routine serum digoxin levels and be monitored for signs and symptoms of digoxin toxicity.
  • Assess for rash periodically during therapy. May cause Stevens-Johnson syndrome. Discontinue therapy if severe or if accompanied with fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, hepatitis and/or eosinophilia.
  • Angina: Assess location, duration, intensity, and precipitating factors of patient’s anginal pain.
  • Arrhythmias: Monitor ECG continuously during administration. Notify health care professional promptly if bradycardia or prolonged hypotension occurs. Emergency equipment and medication should be available. Monitor BP and pulse before and frequently during administration.
  • Lab Test Considerations: Total serum calcium concentrations are not affected by calcium channel blockers.
    • Monitor serum potassium periodically. Hypokalemia ↑ risk of arrhythmias and should be corrected.
    • Monitor renal and hepatic functions periodically during long-term therapy. May cause ↑ hepatic enzymes after several days of therapy, which return to normal on discontinuation of therapy.

Potential Nursing Diagnoses

Decreased cardiac output (Indications)
Acute pain (Indications)

Implementation

  • Oral: Administer verapamil with meals or milk to minimize gastric irritation.
    • Do not open, crush, break, or chew sustained-release capsules or tablets. Empty tablets that appear in stool are not significant.
  • Intravenous Administration
  • Intravenous: Patients should remain recumbent for at least 1 hr after IV administration to minimize hypotensive effects.
  • Diluent: Administer undiluted.Concentration: 2.5 mg/mL.
  • Rate: Administer over 2 min. Geriatric: Administer over 3 min.
  • Y-Site Compatibility: alemtuzumab, alfentanil, amikacin, aminocaproic acid, amphotericin B lipid complex, anidulafungin, argatroban, ascorbic acid, atracurium, atropine, aztreonam, benztropine, bivalirudin, bleomycin, bumetanide, buprenorphine, butorphanol, calcium chloride, calcium gluconate, carboplatin, carmustine, caspofungin, cefazolin, cefotaxime, cefotetan, cefoxitin, ceftriaxone, cefuroxime, chlorpromazine, ciprofloxacin, cisplatin, clindamycin, cyanocobalamin, cyclophosphamide, cyclosporine, cytarabine, dactinomycin, daptomycin, dexamethasone, dexmedetomidine, dexrazoxane, digoxin, diltiazem, diphenhydramine, dobutamine, docetaxel, dolasetron, dopamine, doxorubicin hydrochloride, doxorubicin liposomal, doxycycline, enalaprilat, ephedrine, epinephrine, epirubicin, epotein alfa, eptifibatide, erythromycin, esmolol, etoposide, etoposide phosphate, famotidine, fenoldopam, fentanyl, fluconazole, fludarabine, gemcitabine, gentamicin, glycopyrrolate, granisetron, heparin, hydrocortisone sodium succinate, hydromorphone, idarubicin, ifosfamide, imipenem/cilastatin, insulin, irinotecan, isoproterenol, ketorolac, labetalol, leucovorin calcium, levofloxacin, lidocaine, linezolid, lorazepam, magnesium sulfate, mannitol, mechlorethamine, meperidine, metaraminol, methotrexate, methyldopate, methylprednisolone sodium succinate, metoclopramide, metoprolol, metronidazole, midazolam, milrinone, mitoxantrone, morphine, moxifloxacin, multivitamins, mycophenolate, nalbuphine, naloxone, nesiritide, nitroglycerin, nitroprusside, norepinephrine, octreotide, ondansetron, oxaliplatin, oxytocin, paclitaxel, palonosetron, pamidronate, pancuronium, papaverine, pemetrexed, penicillin G, pentamidine, pentazocine, phentolamine, phenylephrine, phytonadione, potassium acetate, potassium chloride, procainamide, prochlorperazine, promethazine, propranolol, protamine, pyridoxime, quinupristin/dalfopristin, ranitidine, rocuronium, sodium acetate, streptokinase, succinylcholine, sufentanil, tacrolimus, teniposide, theophylline, thiamine, ticarcillin/clavulanate, tirofiban, tobramycin, tolazoline, vancomycin, vasopressin, vecuronium, vinblastine, vincristine, vinorelbine, voriconazole, zoledronic acid
  • Y-Site Incompatibility: acyclovir, albumin, aminophylline, amphotericin B cholesteryl, amphotericin B colloidal, amphotericin B liposome, ampicillin, ampicillin/sulbactam, azathioprine, cefoperazone, ceftazidime, chloramphenicol, dantrolene, diazepam, diazoxide, ertapenem, fluorouracil, folic acid, foscarnet, furosemide, ganciclovir, indomethacin, pantoprazole, pentobarbital, phenobarbital, phenytoin, piperacillin/tazobactam, propofol, sodium bicarbonate, thiotepa, tigecycline, trimethoprim/sulfamethoxazole

Patient/Family Teaching

  • Advise 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 avoid large amounts (6–8 glasses of grapefruit juice/day) during therapy.
    • Instruct patient on correct technique for monitoring pulse. Instruct patient to contact health care professional if heart rate is <50 bpm.
    • Caution patient to change positions slowly to minimize orthostatic hypotension.
    • May cause drowsiness or dizziness. Advise patient to avoid driving or other activities requiring alertness until response to the medication is known.
    • 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 professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications, especially cold preparations.
    • Advise patient to notify health care professional if irregular heartbeats, rash, dyspnea, swelling of hands and feet, pronounced dizziness, nausea, constipation, or hypotension occurs or if headache is severe or persistent.
    • 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 professional if chest pain does not improve, worsens after therapy, or occurs with diaphoresis; if shortness of breath occurs; or if severe, persistent headache occurs.
    • Caution patient to discuss exercise restrictions with health care professional 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 professional.

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 atrial tachyarrhythmias.

Ver·e·lan

(vĕr′ə-lən) A trademark for the drug verapamil.

Verelan®

Verapamil, see there.