Calcium Channel Blockers

amlodipine (Norvasc®):	bepridil (Vascor®):
diltiazem (Cardizem ®):	felodipine (Plendil®):
isradipine (Dynacirc®):	nicardipine (cardene®):
nifedipine (Procardia®):	nisoldipine (Sular®):
verapamil (Isoptin ® )

amlodipine (Norvasc®):

Adult (usual) Angina: 5-10 mg po qd.
Hypertension initial: 5 mg po qd; maintenance 5-10 mg po qd.
FDA labeled indications: Angina, stable or unstable; Hypertension. Small, fragile, or elderly individuals, or patients with hepatic insufficiency may be started on 2.5 mg once daily and this dose may be used when adding Norvasc® to other antihypertensive therapy.

Titration: In general, titration should proceed over 7 to 14 days so that the physician can fully assess the patient's response to each dose level.
[Supplied: 2.5, 5, 10mg tab]

Studies in Patients with Congestive Heart Failure:

Study: (PRAISE-2) randomized patients with NYHA class III (80%) or IV (20%) heart failure without clinical symptoms or objective evidence of underlying ischemic disease, on stable doses of ACE inhibitor (99%), digitalis (99%) and diuretics (99%), to placebo (n=827) or NORVASC (n=827) and followed them for a mean of 33 months. There was no statistically significant difference between NORVASC and placebo in the primary endpoint of all cause mortality (95% confidence limits from 8% reduction to 29% increase on NORVASC). With NORVASC there were more reports of pulmonary edema.

bepridil (Vascor®):

Use - Treatment of chronic stable angina; due to side effect profile, reserve for patients who have been intolerant of other antianginal therapy; bepridil may be used alone or in combination with nitrates or beta-blockers
Mechanism of Action- Bepridil, a type 4 calcium antagonist, possesses characteristics of the traditional calcium antagonists, inhibiting calcium ion from entering the "slow channels" or select voltage-sensitive areas of vascular smooth muscle and myocardium during depolarization and producing a relaxation of coronary vascular smooth muscle and coronary vasodilation. However, bepridil may also inhibit fast sodium channels (inward), which may account for some of its side effects (eg, arrhythmias); a direct bradycardia effect of bepridil has been postulated via direct action on the S-A node.

Dosing: Adults: Oral: Initial: 200 mg/day, then adjust dose at 10-day intervals until optimal response is achieved; usual dose: 300 mg/day; maximum daily dose: 400 mg
Dosage adjustment in renal impairment: Risk of toxic reactions is greater in patients with renal impairment; dose selection should be cautious, usually starting at the low end of the dosage range

Elderly: Peak concentrations and half-life are markedly increased in the elderly (>74 years); dose selection should be cautious, usually starting at the low end of the dosage range
Supplied
Tablet, as hydrochloride: 200 mg, 300 mg

diltiazem (Cardizem ®):

Adult (usual) Oral:
Angina: (regular release tablets) initial 30 mg po qid; usual dose 180-360 mg po daily (maximum 360 mg daily). Angina: (extended release capsule; Dilacor(R) XR), initial 120 mg po qd; usual dose 120-480 mg once daily, maximum 540 mg/day. Hypertension: (Cardizem SR), initial 60-120 mg po q12h.; usual dose 120-180 mg bid, maximum 360 mg/day. Hypertension: ( Dilacor(R) XR): initial, 120-240 mg orally once daily; titrate after 14 days; usual dose, 240-360 mg orally once daily, maximum 540 mg/day.

Arrhythmia: (IV bolus), initial 0.25 mg/kg (or 20 mg) IV over 2 minutes; if inadequate response, may give second bolus 0.35 mg/kg (25 mg) after 15 min Arrhythmia: (IV continuous infusion), initial 5-10 mg/hr; increase in 5 mg/hr increments up to 15 mg/hr maintained for up to 24 hr.

Higher doses - Continuous infusion ??:

Crit Care Med. 2001 Jun;29(6):1149-53. Amiodarone versus diltiazem for rate control in critically ill patients with atrial tachyarrhythmias.
Group 1 received diltiazem in a 25-mg bolus followed by a continuous infusion of 20 mg/hr for 24 hrs, group 2 received amiodarone in a 300-mg bolus, and group 3 received amiodarone in a 300-mg bolus followed by 45 mg/hr for 24 hrs. CONCLUSION: Sufficient rate control can be achieved in critically ill patients with atrial tachyarrhythmias using either diltiazem or amiodarone. Although diltiazem allowed for significantly better 24-hr heart rate control, this effect was offset by a significantly higher incidence of hypotension requiring discontinuation of the drug. Amiodarone may be an alternative in patients with severe hemodynamic compromise.

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 10.
5 mg/hour = 180 mg/day;
7 mg/hour = 240 mg/day
11 mg/hour = 360 mg/day

[Supplied: Immediate release tablets: 30, 60, 90, 120 mg. Sustained released capsules (SR): 60, 90, 120mg. Extended release capsules (CD): 120,180,240,300,360 mg. Vials (IV): 25, 50, 125 mg (5 mg/ml) ]

felodipine (Plendil®):

Mechanism of Action
Inhibits calcium ions 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 vasospastic angina

Administration: avoid taking with grapefruit juice. Dose adjustments should be made at intervals of not less than 2 weeks. o not crush or chew extended release tablets; swallow whole.

Dosage
Adults: hypertension: Oral: 2.5-10 mg once daily; usual initial dose: 5 mg; increase by 5 mg at 2-week intervals, as needed; maximum: 10 mg
Usual dose range (JNC 7) for hypertension: 2.5-20 mg once daily
Elderly: Begin with 2.5 mg/day
Dosing adjustment/comments in hepatic impairment: Initial: 2.5 mg/day; monitor blood pressure

[Supplied 2.5 mg, 5 mg, 10 mg ER tab]

isradipine (Dynacirc®):

Mechanism of Action
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 vasospastic angina

Dosing: Hypertension:
Oral: Adults: 2.5 mg twice daily; antihypertensive response occurs in 2-3 hours; maximal response in 2-4 weeks; increase dose at 2- to 4-week intervals at 2.5-5 mg increments; usual dose range (JNC 7): 2.5-10 mg/day in 2 divided doses. Note: Most patients show no improvement with doses >10 mg/day except adverse reaction rate increases; therefore, maximal dose in older adults should be 10 mg/day.

Supplied
Capsule (DynaCirc®): 2.5 mg, 5 mg
Tablet, controlled release (DynaCirc® CR): 5 mg, 10 mg

nicardipine (cardene®):

INDICATIONS - Chronic stable angina (immediate-release product only); management of essential hypertension (immediate and sustained release; parenteral only for short time that oral treatment is not feasible)

Dosage Adults:
Oral:
Immediate release: Initial: 20 mg 3 times/day; usual: 20-40 mg 3 times/day (allow 3 days between dose increases).
Sustained release: Initial: 30 mg twice daily, titrate up to 60 mg twice daily.

Note: The total daily dose of immediate-release product may not automatically be equivalent to the daily sustained-release dose; use caution in converting.

I.V. (dilute to 0.1 mg/mL):
Acute hypertension: Initial: 5 mg/hour increased by 2.5 mg/hour every 15 minutes to a maximum of 15 mg/hour; consider reduction to 3 mg/hour after response is achieved. Monitor and titrate to lowest dose necessary to maintain stable blood pressure.

Substitution for oral therapy (approximate equivalents):
20 mg every 8 hours oral, equivalent to 0.5 mg/hour I.V. infusion
30 mg every 8 hours oral, equivalent to 1.2 mg/hour I.V. infusion
40 mg every 8 hours oral, equivalent to 2.2 mg/hour I.V. infusion

Dosing adjustment in renal impairment: Titrate dose beginning with 20 mg 3 times/day (immediate release) or 30 mg twice daily (sustained release). Specific guidelines for adjustment of I.V. nicardipine are not available, but careful monitoring/adjustment is warranted.

Dosing adjustment in hepatic impairment: Starting dose: 20 mg twice daily (immediate release) with titration. Specific guidelines for adjustment of I.V. nicardipine are not available, but careful monitoring/adjustment is warranted.

Supplied
Capsule (Cardene®): 20 mg, 30 mg
Capsule, sustained release (Cardene® SR): 30 mg, 45 mg, 60 mg
Injection, solution (Cardene® IV): 2.5 mg/mL (10 mL)

nifedipine (Procardia®):

Use - Angina and hypertension (sustained release only), pulmonary hypertension

WARNING
The use of sublingual short-acting nifedipine in hypertensive emergencies and pseudoemergencies is neither safe nor effective and SHOULD BE ABANDONED! Serious adverse events (cerebrovascular ischemia, syncope, heart block, stroke, sinus arrest, severe hypotension, acute myocardial infarction, ECG changes, and fetal distress) have been reported in relation to such use.

Mechanism of Action
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 vasospastic angina

Dosing: Oral:
Adolescents and Adults: ( Note: When switching from immediate release to sustained release formulations, total daily dose will start the same)

Initial: 30 mg once daily as sustained release formulation, or if indicated, 10 mg 3 times/day as capsules
Usual dose: 10-30 mg 3 times/day as capsules or 30-60 mg once daily as sustained release
Maximum dose: 120-180 mg/day

Increase sustained release at 7- to 14-day intervals

Dosing adjustment in hepatic impairment: Reduce oral dose by 50% to 60% in patients with cirrhosis.

Supplied
Capsule, liquid-filled: 10 mg, 20 mg
Tablet, extended release: 30 mg, 60 mg, 90 mg
Adalat® CC, Nifediac™ CC, Procardia XL®: 30 mg, 60 mg, 90 mg
Afeditab™, Nifedical™ XL: 30 mg, 60 mg

nisoldipine (Sular®):

Use - Management of hypertension, alone or in combination with other antihypertensive agents.

Mechanism of Action- As a dihydropyridine calcium channel blocker, structurally similar to nifedipine, nisoldipine impedes the movement of calcium ions into vascular smooth muscle and cardiac muscle. Dihydropyridines are potent vasodilators and are not as likely to suppress cardiac contractility and slow cardiac conduction as other calcium antagonists such as verapamil and diltiazem; nisoldipine is 5-10 times as potent a vasodilator as nifedipine.

Adults: Oral: Initial: 20 mg once daily, then increase by 10 mg/week (or longer intervals) to attain adequate control of blood pressure; usual dose range (JNC 7): 10-40 mg once daily; doses >60 mg once daily are not recommended. A starting dose not exceeding 10 mg/day is recommended for the elderly and those with hepatic impairment.

Supplied
Tablet, extended release: 10 mg, 20 mg, 30 mg, 40 mg

verapamil (Isoptin ® )

Adult (usual):
Angina: (extended-release) initial: 180 mg po qd at bedtime. Titrate up to 480 mg at bedtime- maximum 540 mg at bedtime. (immediate release) initial: 80 mg po tid - may titrate at daily or weekly intervals to 360 mg daily.
Arrhythmias, supraventricular: (immediate-release) initial: 240-320 mg po daily in 3-4 divided doses. Non-digitalized patients may require up to 480 mg daily in 3-4 divided doses. Arrhythmias, supraventricular: 5-10 mg IV (0.075-0.15 mg/kg) IV bolus over 2 min. May give additional 10 mg after 30 minutes if no response.
Hypertension: (extended-release) initial, 180 mg tablet po qd at bedtime OR 200 mg capsule po qd at bedtime. Maintenance: titrate up to 480 mg TAB qd at hs or 400 mg capsule po qd at hs.
Hypertension: (immediate-release) initial- 80 mg po tid. May titrate at daily or weekly intervals to 360-480 mg daily. Hypertension: (sustained-release) initial: 240 mg orally once daily in the morning. Maintenance (based on response): titrate up to 240 mg bid (tablet) or 480 mg (capsule) once a day in the morning.
Migraine headache, prophylaxis: 80 mg po 3-4 times daily.

[Supplied:
Immediate release tablet: 40, 80, 120mg.
Sustained release tablets (SR): 120, 180, 240 mg.
Sustained released capsules (Verelan): 120,180,240,360mg.
Covera HS (extended release tab): 180,240mg.
Verelan PM (ER cap): 100,200,300mg. ]
-----------------------------------

Dosing (Adults):
Angina: Oral: Initial: 80-120 mg twice daily (elderly or small stature: 40 mg twice
daily); range: 240-480 mg/day in 3-4 divided doses

Hypertension: Oral:
Immediate release: 80 mg 3 times/day; usual dose range (JNC 7): 80-320 mg/day in 2 divided doses.
Sustained release: 240 mg/day; usual dose range (JNC 7): 120-360 mg/day in 1-2 divided doses; 120 mg/day in the elderly or small patients (no evidence of additional benefit in doses >360 mg/day).
Extended release:
Covera-HS®: Usual dose range (JNC 7): 120-360 mg once daily (once-daily dosing is recommended at bedtime)
Verelan® PM: Usual dose range: 200-400 mg once daily at bedtime

Arrhythmia (SVT): I.V.: 2.5-5 mg (over 2 minutes); second dose of 5-10 mg (~0.15 mg/kg) may be given 15-30 minutes after the initial dose if patient tolerates, but does not respond to initial dose; maximum total dose: 20 mg

Disclaimer

Listed dosages are for - Adult patients ONLY. PLEASE READ THE DISCLAIMER CAREFULLY BEFORE ACCESSING OR USING THIS SITE. BY ACCESSING OR USING THIS SITE, YOU AGREE TO BE BOUND BY THE TERMS AND CONDITIONS SET FORTH IN THE DISCLAIMER. GlobalRPH does not directly or indirectly practice medicine or provide medical services and therefore assumes no liability whatsoever of any kind for the information and data accessed through the Service or for any diagnosis or treatment made in reliance thereon.

David F. McAuley, Pharm.D., R.Ph. GlobalRPh Inc.

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