verapamil

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

Therapeutic effects:

Reduction in BP.
Reduction in frequency and severity of angina episodes.
Reduction of ventricular rate during atrial fibrillation or atrial flutter.
Prevention and/or termination of supraventricular tachycardia.

Pharmacokinetics ⬆ ⬇

Absorption: 90% absorbed after oral administration, but much is rapidly metabolized, resulting in bioavailability of 20–25%.

Distribution: Well distributed to tissues.

Protein Binding: 90%.

Metabolism/Excretion: Primarily metabolized by the liver via the CYP3A4 isoenzyme. Primarily excreted in urine (4% as unchanged drug).

Half-Life: 4.5–12 hr.

Time/Action Profile ⬆ ⬇

(cardiovascular effects)

ROUTE	ONSET	PEAK	DURATION
PO	1–2 hr	30–90 min‡	3–7 hr
PO-extended release	unknown	5–7 hr	24 hr
IV	1–5 min‡	3–5 min	2 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.

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Sick sinus syndrome;
2nd- or 3rd-degree heart block (unless an artificial pacemaker is in place);
Systolic BP <90 mm Hg;
HF, severe left ventricular dysfunction, or cardiogenic shock, unless associated with supraventricular tachyarrhythmias;
Concurrent IV beta blocker therapy;
Lactation: Lactation.

Use Cautiously in:

Severe hepatic impairment (dose ↓ recommended);
History of serious ventricular arrhythmias;
OB: Safety not established in pregnancy;
Geri: Dose /slower IV infusion rates recommended in older adults ( risk of hypotension).

Adv. Reactions/Side Effects ⬆ ⬇

CV: ARRHYTHMIAS, bradycardia, chest pain, HF, hypotension, palpitations, peripheral edema, 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

Metab: weight gain

MS: joint stiffness, muscle cramps

Neuro: abnormal dreams, anxiety, confusion, dizziness/lightheadedness, drowsiness, dysgeusia, extrapyramidal reactions, headache, jitteriness, nervousness, paresthesia, psychiatric disturbances, tremor, weakness

Resp: cough, dyspnea

Misc: gingival hyperplasia

Interactions ⬆ ⬇

Drug-drug:

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.
May ↑ levels and the risk of toxicity of digoxin.
Concurrent use with beta blockers, digoxin, clonidine, or ivabradine may result in bradycardia or conduction defects; avoid concurrent use with ivabradine.
↑risk of hypotension and bradycardia with erythromycin, clarithromycin, or ritonavir.
May ↑ levels and the risk of toxicity of cyclosporine, quinidine, theophylline, or carbamazepine.
Rifampin and phenobarbital may ↓ levels and effectiveness.
↑the muscle-paralyzing effects of nondepolarizing neuromuscular-blocking agents.
May alter lithium levels.
May ↑ risk of bleeding with aspirin.
May ↑ levels and the risk of toxicity of sirolimus, temsirolimus, or everolimus; consider ↓ dose of sirolimus, temsirolimus, everolimus, and verapamil.
↑risk of myopathy with simvastatin and lovastatin; do not exceed 10 mg/day of simvastatin and 20 mg/day of lovastatin.

Drug-Natural Products:

↑caffeine levels with caffeine-containing herbs (cola nut, guarana, mate, tea, coffee).

Grapefruit juice↑ levels and the risk of toxicity.

Route/Dosage ⬆ ⬇

PO (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).
PO (Children ≤15 yr): 4–8 mg/kg/day in divided doses.
IV (Adults ): 5–10 mg (75–150 mcg/kg); may repeat with 10 mg (150 mcg/kg) after 15–30 min.
IV (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).
IV (Children <1 yr): 0.75–2 mg (100–200 mcg/kg); may repeat after 30 min.

Availability ⬆ ⬇

(Generic available)

Immediate-release tablets: 40 mg; 80 mg; 120 mg
Extended-release capsules (Verelan): 120 mg; 180 mg; 240 mg; 360 mg
Extended-release capsules (Verelan PM): 100 mg; 200 mg; 300 mg
Extended-release tablets: 120 mg; 180 mg; 240 mg
Solution for injection: 2.5 mg/mL
In combination with: trandolapril.

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 SJS. 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.

Implementation ⬆ ⬇

PO: Administer verapamil with meals or milk to minimize gastric irritation.
- DNC: Swallow extended-release tablets and capsules whole; do not open, crush, break, or chew. Empty tablets that appear in stool are not significant.

IV Administration:

IV: Patients should remain recumbent for at least 1 hr after IV administration to minimize hypotensive effects.
Diluent: Administer undiluted.Concentration: 2.5 mg/mL.

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.
- Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected and avoid breastfeeding during therapy.
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.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

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