Verapamil Dosage

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Usual Adult Dose for Hypertension

Oral: The antihypertensive effects of verapamil are evident within the first week of therapy.

Immediate release tablets (Calan (R)):
Initial dose: 80 mg orally 3 times a day; alternatively, 40 mg orally 3 times a day may be considered in patients who might respond to lower doses (e.g., small stature)

Maintenance dose: Upward titration should be based on therapeutic efficacy, assessed at the end of the dosing interval. Daily dosages of 360 and 480 mg have been used but there is no evidence that dosages beyond 360 mg provided added effect.

Sustained release tablets (Calan SR (R), Isoptin SR (R)):
Initial dose: 180 mg orally once a day in the morning with food: alternatively, 120 mg orally once a day in the morning with food may be warranted in patients who may have an increased response to verapamil (e.g., small stature)

Maintenance dose: Upward titration should be based on therapeutic efficacy and safety evaluated weekly, about 24 hours after the previous dose. If adequate response is not obtained with the initial dose, it may be titrated upward.

Sustained release capsules (Verelan (R)):
Initial dose: 240 mg orally once a day in the morning (usual dose in clinical trials); alternatively, 120 mg orally once a day in the morning may be warranted in patients who may have an increased response to verapamil (e.g., small stature)

Maintenance dose: Upward titration should be based on therapeutic efficacy and safety evaluated about 24 hours after dosing. If adequate response is not obtained with the initial dose, it may be titrated upward.

Extended release tablets (Covera HS (R)):
Initial dose: 180 mg orally once a day at bedtime
Maintenance dose: If adequate response is not obtained with the initial dose, it may be titrated upward.

Extended release capsules (Verelan PM (R)):
Initial dose: 200 mg orally once a day at bedtime (usual dose in clinical trials); in rare cases, initial doses of 100 mg orally once a day at bedtime may be warranted in patients who have an increased response to verapamil (e.g., low-weight patients)

Maintenance dose: Upward titration should be based on therapeutic efficacy and safety evaluated about 24 hours after dosing. If adequate response is not obtained with the initial dose, it may be titrated upward.

Usual Adult Dose for Supraventricular Tachycardia

IV:
Manufacturer:
Initial dose: 5 to 10 mg (0.075 to 0.15 mg/kg) given as an IV bolus over at least 2 minutes
Repeat dose: 10 mg (0.15 mg/kg) 30 minutes after the first dose if the initial response is not adequate

An optimal interval for subsequent doses has not been determined and must be individualized for each patient.

ACLS guidelines:
Initial dose: 2.5 to 5 mg
If no response in 15 to 30 minutes and no side effects seen: 5 to 10 mg every 15 to 30 minutes to a maximum total dose of 20 mg

Alternative ACLS dosing regimen:
Initial dose: 5 mg
If no response in 15 minutes and no side effects seen: 5 mg every 15 minutes up to a total dose of 30 mg

Usual Adult Dose for Angina Pectoris

Oral:
Immediate release tablets:
Initial dose: 80 to 120 mg orally 3 times a day; alternatively, 40 mg orally 3 times a day may be warranted in patients who may have an increased response to verapamil

Maintenance dose: Upward titration should be based on therapeutic efficacy and safety evaluated about 8 hours after dosing. Dosage may be increased daily (e.g., patients with unstable angina) or weekly until optimum clinical response is obtained.

Extended release tablets (Covera HS (R)):
Initial dose: 180 mg orally once a day at bedtime
Maintenance dose: If adequate response is not obtained with 180 mg, the dose may be titrated upward.

Usual Adult Dose for Arrhythmias

Oral:
Immediate release tablets:
Chronic atrial fibrillation in digitalized patients: 240 to 320 mg/day orally in 3 or 4 divided doses
Prophylaxis of PSVT (non-digitalized patients): 240 to 480 mg/day orally in 3 or 4 divided doses

In general, maximum effects for any given dosage will be apparent during the first 48 hours of therapy.

Usual Adult Dose for Cluster Headache

Oral:
Initial dose:
Immediate release tablets: 80 mg orally 3 to 4 times a day
Sustained release tablets or capsules: 240 mg orally once a day at bedtime
Extended release tablets (Covera HS (R)): 180 mg orally once a day

Maintenance dose: Dosage may be adjusted at weekly intervals until optimum clinical response is obtained.

Usual Adult Dose for Migraine Prophylaxis

Oral:
Initial dose:
Immediate release tablets: 80 mg orally 3 to 4 times a day
Sustained release tablets or capsules: 240 mg orally once a day at bedtime
Extended release tablets (Covera HS (R)): 180 mg orally once a day

Maintenance dose: Dosage may be adjusted at weekly intervals until optimum clinical response is obtained.

Usual Adult Dose for Bipolar Disorder

Oral:
Initial dose:
Immediate release tablets: 80 mg orally 3 to 4 times a day
Sustained release tablets or capsules: 240 mg orally once a day at bedtime
Extended release tablets (Covera HS (R)): 180 mg orally once a day

Maintenance dose: Dosage may be adjusted at weekly intervals until optimum clinical response is obtained.

Usual Adult Dose for Idiopathic Hypertrophic Subaortic Stenosis

Oral:
Initial dose:
Immediate release tablets: 80 mg orally 3 to 4 times a day
Sustained release tablets or capsules: 240 mg orally once a day at bedtime
Extended release tablets (Covera HS (R)): 180 mg orally once a day

Maintenance dose: Dosage may be adjusted at weekly intervals until optimum clinical response is obtained.

Usual Geriatric Dose for Hypertension

Oral: The antihypertensive effects of verapamil are evident within the first week of therapy.

Immediate release tablets (Calan (R)):
Initial dose: 40 mg orally 3 times a day; this reduced dosage may be considered in patients who might respond to lower doses

Maintenance dose: Upward titration should be based on therapeutic efficacy, assessed at the end of the dosing interval. Daily dosages of 360 and 480 mg have been used but there is no evidence that dosages beyond 360 mg provided added effect.

Sustained release tablets (Calan SR (R), Isoptin SR (R)):
Initial dose: 120 mg orally once a day in the morning with food; this reduced dosage may be warranted in patients who may have an increased response to verapamil

Maintenance dose: Upward titration should be based on therapeutic efficacy and safety evaluated weekly, about 24 hours after the previous dose. If adequate response is not obtained with the initial dose, it may be titrated upward.

Sustained release capsules (Verelan (R)):
Initial dose: 120 mg orally once a day in the morning; this reduced dosage may be warranted in patients who may have an increased response to verapamil

Maintenance dose: Upward titration should be based on therapeutic efficacy and safety evaluated about 24 hours after dosing. If adequate response is not obtained with the initial dose, it may be titrated upward.

Extended release tablets (Covera HS (R)):
Initial dose: 180 mg orally once a day at bedtime
Maintenance dose: If adequate response is not obtained with the initial dose, it may be titrated upward.

Extended release capsules (Verelan PM (R)):
Initial dose: 100 mg orally once a day at bedtime; in rare cases, this reduced initial dosage may be warranted in patients who have an increased response to verapamil

Maintenance dose: Upward titration should be based on therapeutic efficacy and safety evaluated about 24 hours after dosing. If adequate response is not obtained with the initial dose, it may be titrated upward.

Usual Geriatric Dose for Angina Pectoris

Oral:
Immediate release tablets:
Initial dose: 40 mg orally 3 times a day; this reduced dosage may be warranted in patients who may have an increased response to verapamil

Maintenance dose: Upward titration should be based on therapeutic efficacy and safety evaluated about 8 hours after dosing. Dosage may be increased daily (e.g., patients with unstable angina) or weekly until optimum clinical response is obtained.

Extended release tablets (Covera HS (R)):
Initial dose: 180 mg orally once a day at bedtime
Maintenance dose: If adequate response is not obtained with 180 mg, the dose may be titrated upward.

Usual Pediatric Dose for Supraventricular Tachycardia

IV:
Less than 1 year: Generally not recommended due to potential risk of severe apnea, bradycardia, hypotensive reactions, and cardiac arrest; IV calcium should be available at bedside

Initial dose: 0.1 to 0.2 mg/kg/dose (usual single dose range: 0.75 to 2 mg/dose) should be administered as an IV bolus over at least 2 minutes under continuous ECG monitoring

Repeat dose: 0.1 to 0.2 mg/kg/dose (usual single dose range: 0.75 to 2 mg/dose) 30 minutes after the first dose if the initial response is not adequate (under continuous ECG monitoring)

An optimal interval for subsequent doses has not been determined and must be individualized for each patient.

1 to 15 years:
Initial dose: 0.1 to 0.3 mg/kg/dose (usual single dose range: 2 to 5 mg/dose) should be administered as an IV bolus over at least 2 minutes; doses of 5 mg should not be exceeded

Repeat dose: 0.1 to 0.3 mg/kg/dose (usual single dose range: 2 to 5 mg/dose) 30 minutes after the first dose if the initial response is not adequate; doses of 10 mg should not be exceeded

An optimal interval for subsequent doses has not been determined and must be individualized for each patient.

Renal Dose Adjustments

IV: In general, multiple doses in patients with renal failure should be avoided. If repeated injections are essential, smaller repeat doses are recommended.

Oral: The manufacturers recommend caution when administering this drug to patients with renal dysfunction.

Extended release capsules (Verelan PM (R)): 100 mg orally once a day at bedtime; in rare cases, this reduced initial dosage may be warranted in patients who have an increased response to verapamil (e.g., patients with impaired renal function)

Liver Dose Adjustments

IV: In general, multiple doses in patients with hepatic failure should be avoided. If repeated injections are essential, smaller repeat doses are recommended.

Oral: The manufacturers recommend caution when administering this drug to patients with liver dysfunction.

Immediate release tablets: 40 mg orally 3 times a day; this reduced initial dosage may be warranted in patients who may have an increased response to verapamil (e.g., patients with decreased hepatic function)

Immediate release tablets, sustained release tablets and capsules, extended release tablets:
Severe liver dysfunction: Approximately 30% of the usual dose

Extended release capsules (Verelan PM (R)): 100 mg orally once a day at bedtime; in rare cases, this reduced initial dosage may be warranted in patients who have an increased response to verapamil (e.g., patients with impaired hepatic function)

Dose Adjustments

Sustained release tablets (Calan SR (R), Isoptin SR (R)): If adequate response is not obtained with 120 mg, the dose may be titrated upward in the following manner:
a) 180 mg each morning
b) 240 mg each morning
c) 180 mg every 12 hours or 240 mg each morning plus 120 mg each evening
d) 240 mg every 12 hours

Sustained release capsules (Verelan (R)): If adequate response is not obtained with 120 mg, the dose may be titrated upward in the following manner:
a) 180 mg in the morning
b) 240 mg in the morning
c) 360 mg in the morning
d) 480 mg in the morning

Extended release tablets (Covera HS (R)): If adequate response is not obtained with 180 mg, the dose may be titrated upward in the following manner:
a) 240 mg each evening
b) 360 mg each evening
c) 480 mg each evening

Extended release capsules (Verelan PM (R)): If adequate response is not obtained with 100 mg, the dose may be titrated upward in the following manner:
a) 200 mg each evening
b) 300 mg each evening
c) 400 mg each evening

Precautions

Verapamil is contraindicated in hypotension (systolic pressure less than 90 mm Hg) or cardiogenic shock, in sick sinus syndrome or second- or third-degree AV block in patients without a functioning artificial ventricular pacemaker, and in patients with atrial flutter or atrial fibrillation and an accessory bypass tract (e.g., Wolff-Parkinson-White, Lown-Ganong-Levine syndromes). In addition, oral verapamil is contraindicated in severe left ventricular dysfunction and IV verapamil is contraindicated in severe congestive heart failure (unless secondary to a supraventricular tachycardia amenable to verapamil therapy), in patients receiving IV beta-adrenergic blocking drugs, and in ventricular tachycardia.

Verapamil should be avoided in patients with severe left ventricular dysfunction (e.g., ejection fraction less than 30%) or moderate to severe symptoms of heart failure and in patients with any degree of ventricular dysfunction if they are receiving beta-blockers. Patients with milder ventricular dysfunction should, if possible, be controlled with digitalis and/or diuretics prior to initiation of verapamil.

Asymptomatic first-degree AV block and transient bradycardia (sometimes accompanied by nodal escape rhythms) may occur due to the effect of verapamil on AV conduction and the SA node. Prolonged PR interval correlates with verapamil plasma levels, especially during the early titration phase of treatment. Infrequently, higher degrees of AV block were observed. Marked first-degree or progression to second- or third-degree AV block requires a dosage reduction or, rarely, verapamil discontinuation and initiation of appropriate therapy.

In 120 patients with hypertrophic cardiomyopathy, idiopathic hypertrophic subaortic stenosis (most refractory or intolerant to propranolol) who received verapamil therapy at doses up to 720 mg/day, a variety of serious side effects were seen. Most side effects responded well to dose reduction and only rarely required discontinuation of verapamil.

Elevated transaminases with and without elevated alkaline phosphatase and bilirubin have been reported. Such elevations have sometimes been transient and may disappear with continued verapamil therapy. Several cases of hepatocellular injury related to verapamil have been proven by rechallenge; half of these had clinical symptoms in addition to elevated SGOT, SGPT, and alkaline phosphatase. Periodic monitoring of liver function is recommended in patients receiving verapamil.

Since verapamil is highly metabolized by the liver, it should be administered cautiously to patients with impaired hepatic function. When using the extended release capsule formulation (Verelan PM) in such patients, lower dosages should be considered and responses to the drug should be closely monitored. Careful monitoring for abnormal prolongation of the PR interval or other signs of excessive pharmacologic effects is recommended.

Patients with impaired renal function should be carefully monitored for abnormal prolongation of the PR interval or other signs of overdosage.

Significant hepatic and renal failure should not increase the effects of a single IV dose of verapamil but may prolong its duration. Repeated injections of IV verapamil in patients with significant hepatic and renal failure may lead to accumulation and an excessive pharmacologic effect of the drug. In general, multiple doses should be avoided in such patients. If repeated injections are essential, blood pressure and PR interval should be closely monitored and smaller repeat doses are recommended.

IV verapamil should be used with caution in patients with Duchenne's muscular dystrophy since it can precipitate respiratory muscle failure in these patients.

Patients with attenuated neuromuscular transmission may require a decreased dosage of verapamil.

Increased intracranial pressure in patients with supratentorial tumors at the time of anesthesia induction has been reported with IV verapamil. Caution and appropriate monitoring are recommended.

As with any other nondeformable dosage form, the extended release tablet formulation (Covera-HS (R)) should be used with caution in patients with preexisting severe gastrointestinal narrowing (pathologic or iatrogenic). In patients with extremely short gastrointestinal transit time (less than 7 hours), pharmacokinetic data are not available and dosage adjustment may be necessary.

Safety and effectiveness of oral verapamil have not been established in pediatric patients (less than 18 years of age).

Dialysis

Verapamil is not removed by hemodialysis.

Other Comments

IV verapamil should be administered as a slow IV injection over at least 2 minutes under continuous ECG and blood pressure monitoring. IV doses in older patients should be administered over at least 3 minutes to minimize the risk of untoward drug effects.

The dose of oral verapamil should be individualized by titration. The maximum recommended daily dose is 480 mg.

Calan SR (R) and Isoptin SR (R) should be administered in the morning initially. Both should be administered with food.

Covera HS (R) should be administered at bedtime. Covera-HS (R) tablets should be swallowed whole and should not be broken, crushed, or chewed. Since the outer shell of Covera-HS (R) does not dissolve, patients may notice it in their stools.

Verelan (R) capsules should be administered in the morning. Verelan PM (R) capsules should be administered at bedtime. Verelan (R) and Verelan PM (R) capsules may be opened and the pellets sprinkled on a spoonful of applesauce. The applesauce should be swallowed at once without chewing and followed with a glass of cool water to ensure complete swallowing of the pellets.

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