Calcium Channel Blockers
| 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.
| 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
Clevidipine -cleviprex ®
| INDICATIONS AND USAGE
Cleviprex is a dihydropyridine calcium channel blocker indicated for the reduction of blood pressure when oral therapy is not feasible or not desirable.
USE IN SPECIFIC POPULATIONS
DOSAGE AND ADMINISTRATION
Monitoring: Monitor blood pressure and heart rate during infusion, and until vital signs stabilize.
Initial dose: Initiate intravenous infusion of Cleviprex at 1-2 mg/hour.
Dose titration: Double the dose at short (90 second) intervals initially. As the blood pressure approaches goal, increase the dose by less than doubling and lengthen the time between dose adjustments to every 5-10 minutes. An approximately 1-2 mg/hour increase will generally produce an additional 2-4 mmHg decrease in systolic pressure.
Maintenance dose: Most patients will achieve the desired therapeutic response at approximately 4-6 mg/hour. Severe hypertension is likely to require higher doses.
Maximum dose: Most patients have received maximum doses of 16 mg/hour or less. There is limited experience with short-term dosing as high as 32 mg/hour. Because of lipid load restrictions, no more than 1000 mL or an average of 21 mg/hour of Cleviprex infusion is recommended per 24-hour period. There is little experience beyond 72 hours at any dose.
Transition to an oral antihypertensive agent: Discontinue Cleviprex or titrate downward while appropriate oral therapy is established. When an oral antihypertensive agent is being instituted, consider the lag time of onset of the oral agent’s effect. Continue blood pressure monitoring until desired effect is achieved.
Special populations: Special populations were not specifically studied. In clinical trials, 78 patients with abnormal hepatic function (one or more of the following: elevated serum bilirubin, AST/SGOT, ALT/SGPT) and 121 patients with moderate to severe renal impairment were treated with Cleviprex. An initial Cleviprex infusion rate of 1-2 mg/hour is appropriate in these patients.
Table 1 is a guideline for dosing conversion from mg/hour to mL/hour.
Instructions for Administration
Cleviprex is supplied in sterile, pre-mixed, ready-to-use 50 mL or 100 mL vials. Invert vial gently several times before use to ensure uniformity of the emulsion prior to administration. Inspect parenteral drug products for particulate matter and discoloration prior to administration whenever solution and container permit. Administer Cleviprex using an infusion device allowing calibrated infusion rates. Commercially available standard plastic cannulae may be used to administer the infusion. Administer Cleviprex by a central line or a peripheral line.
Cleviprex should not be administered in the same line as other medications.
Cleviprex should not be diluted, but it can be administered with the following
50 mL single-use vial with 0.5 mg/mL clevidipine
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.
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.
[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) ]
| CLINICAL PHARMACOLOGY - Mechanism of Action
Felodipine is a member of the dihydropyridine class of calcium channel antagonists (calcium channel blockers). It reversibly competes with nitrendipine and/or other calcium channel blockers for dihydropyridine binding sites, blocks voltage-dependent Ca++ currents in vascular smooth muscle and cultured rabbit atrial cells, and blocks potassium-induced contracture of the rat portal vein.
In vitro studies show that the effects of felodipine on contractile processes are selective, with greater effects on vascular smooth muscle than cardiac muscle. Negative inotropic effects can be detected in vitro, but such effects have not been seen in intact animals.
The effect of felodipine on blood pressure is principally a consequence of a dose-related decrease of peripheral vascular resistance in man, with a modest reflex increase in heart rate. With the exception of a mild diuretic effect seen in several animal species and man, the effects of felodipine are accounted for by its effects on peripheral vascular resistance.
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.
[Supplied 2.5 mg, 5 mg, 10 mg ER tab]
| CLINICAL PHARMACOLOGY
Mechanism of Action
Isradipine is a dihydropyridine calcium channel blocker. It binds to calcium channels with high affinity and specificity and inhibits calcium flux into cardiac and smooth muscle. The effects observed in mechanistic experiments in vitro and studied in intact animals and man are compatible with this mechanism of action and are typical of the class.
Except for diuretic activity, the mechanism of which is not clearly understood, the pharmacodynamic effects of isradipine observed in whole animals can also be explained by calcium channel blocking activity, especially dilating effects in arterioles which reduce systemic resistance and lower blood pressure, with a small increase in resting heart rate. Although like other dihydropyridine calcium channel blockers, isradipine has negative inotropic effects in vitro, studies conducted in intact anesthetized animals have shown that the vasodilating effect occurs at doses lower than those which affect contractility. In patients with normal ventricular function, isradipine’s afterload reducing properties lead to some increase in cardiac output.
Effects in patients with impaired ventricular function have not been fully studied.
DynaCirc® (isradipine) has been shown in controlled, double-blind clinical trials to be an effective antihypertensive agent when used as monotherapy, or when added to therapy with thiazide-type diuretics. During chronic administration, divided doses (b.i.d.) in the range of 5-20 mg daily have been shown to be effective, with response at trough (prior to next dose) over 50% of the peak blood pressure effect. The response is dose-related between 5-10 mg daily. DynaCirc® (isradipine) is equally effective in reducing supine, sitting, and standing blood pressure.
On chronic administration, increases in resting pulse rate averaged about 3-5 beats/min. These increases were not dose-related.
| Clinical Pharmacology- MECHANISM OF ACTION
Nicardipine inhibits the transmembrane influx of calcium ions into cardiac muscle and smooth muscle without changing serum calcium concentrations. The contractile processes of cardiac muscle and vascular smooth muscle are dependent upon the movement of extracellular calcium ions into these cells through specific ion channels. The effects of nicardipine are more selective to vascular smooth muscle than cardiac muscle. In animal models, nicardipine produced relaxation of coronary vascular smooth muscle at drug levels which cause little or no negative inotropic effect
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):
Substitution for oral therapy (approximate equivalents):
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.
Mechanism of Action:
Nifedipine is a peripheral arterial vasodilator which acts directly on vascular smooth muscle. The binding of nifedipine to voltage-dependent and possibly receptor-operated channels in vascular smooth muscle results in an inhibition of calcium influx through these channels. Stores of intracellular calcium in vascular smooth muscle are limited and thus dependent upon the influx of extracellular calcium for contraction to occur. The reduction in calcium influx by nifedipine causes arterial vasodilation and decreased peripheral vascular resistance which results in reduced arterial blood pressure.
Initial: 30 mg once daily as sustained release formulation, or if indicated, 10 mg 3 times/day as capsules
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.
| Drug UPDATES: Nimodipine capsule
[Drug information / PDF]
Dosing: Click (+) next to Dosage and Administration section (drug info link)
Initial U.S. Approval: 2013
Mechanism of Action:
The precise mechanism of action of nimodipine in humans is unknown. Although the clinical studies described below demonstrate a favorable effect of nimodipine on the severity of neurological deficits caused by cerebral vasospasm following SAH, there is no arteriographic evidence that the drug either prevents or relieves the spasm of these arteries. However, whether or not the arteriographic methodology utilized was adequate to detect a clinically meaningful effect, if any, on vasospasm is unknown.
INDICATIONS AND USAGE: Nimodipine is indicated for the improvement of neurological outcome by reducing the incidence and severity of ischemic deficits in patients with subarachnoid hemorrhage from ruptured intracranial berry aneurysms regardless of their post-ictus neurological condition (i.e., Hunt and Hess Grades I-V).
HOW SUPPLIED: Nimodipine capsules 30 mg are clear yellow solution filled in oblong opaque light yellow softgel capsules, imprinted “135” in black ink. The capsules are available as follows:
NDC 57664-135-64 Unit Dose Blisters of 30 (6 x 5)
Storage: The capsules should be stored in manufacturer's original foil package at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].
Capsules should be protected from light and freezing.
Initial U.S. Approval: 2013
INDICATIONS AND USAGE: NYMALIZE is a dihydropyridine calcium channel blocker indicated for the improvement of neurological outcome by reducing the incidence and severity of ischemic deficits in adult patients with subarachnoid hemorrhage (SAH) from ruptured intracranial berry aneurysms regardless of their post-ictus neurological condition (i.e., Hunt and Hess Grades I-V).
DOSAGE AND ADMINISTRATION
2.2 Administration by Oral Route
2.3 Administration Via Nasogastric or Gastric Tube
2.4 Dosage Adjustments in Patients with Cirrhosis
HOW SUPPLIED:Oral Solution: 60 mg per 20 mL (3 mg/mL), pale yellow solution
| CLINICAL PHARMACOLOGY
Mechanism of Action
Nisoldipine is a member of the dihydropyridine class of calcium channel antagonists (calcium ion antagonists or slow channel blockers) that inhibit the transmembrane influx of calcium into vascular smooth muscle and cardiac muscle. It reversibly competes with other dihydropyridines for binding to the calcium channel. Because the contractile process of vascular smooth muscle is dependent upon the movement of extracellular calcium into the muscle through specific ion channels, inhibition of the calcium channel results in dilation of the arterioles. In vitro studies show that the effects of nisoldipine on contractile processes are selective, with greater potency on vascular smooth muscle than on cardiac muscle. Although, like other dihydropyridine calcium channel blockers, nisoldipine has negative inotropic effects in vitro, studies conducted in intact anesthetized animals have shown that the vasodilating effect occurs as doses lower than those that affect cardiac contractility.
The effect of nisoldipine on blood pressure is principally a consequence of a dose-related decrease of peripheral vascular resistance. While nisoldipine, like other dihydropyridines, exhibits a mild diuretic effect, most of the antihypertensive activity is attributed to its effect on peripheral vascular resistance.
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.
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.
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
National Institutes of Health, U.S. National Library of Medicine, DailyMed Database.
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