Verapamil

Serious adverse reactions are uncommon when verapamil therapy is initiated with upward dose titration within the recommended single and total daily dose. See WARNINGS for discussion of heart failure, hypotension, elevated liver enzymes, AV block, and rapid ventricular response. Reversible (upon discontinuation of verapamil) non-obstructive, paralytic ileus has been infrequently reported in association with the use of verapamil. The following reactions to orally administered COVERA-HS occurred at rates greater than 2.0% or occurred at lower rates but appeared drug-related in clinical trials in hypertension and angina:

In previous experience with other formulations of verapamil, the following reactions occurred at rates greater than 1.0% or occurred at lower rates but appeared clearly drug related in clinical trials in 4,954 patients.

The following reactions, reported with orally administered verapamil in 2% or less of patients, occurred under conditions (open trials, marketing experience) where a causal relationship is uncertain; they are listed to alert the physician to a possible relationship:

Cardiovascular: angina pectoris, AV block (2° & 3°), atrioventricular dissociation, CHF, pulmonary edema, chest pain, claudication, myocardial infarction, palpitations, purpura (vasculitis), syncope.

Digestive System: diarrhea, dry mouth, gastrointestinal distress, gingival hyperplasia.

Hemic And lymphatic: ecchymosis or bruising.

Nervous System: cerebrovascular accident, confusion, equilibrium disorders, insomnia, muscle cramps, psychotic symptoms, shakiness, somnolence, extrapyramidal symptoms.

Skin : arthralgia and rash, exanthema, hair loss, hyperkeratosis, macules, sweating, urticaria, Stevens-Johnson syndrome, erythema multiforme.

Special Senses: blurred vision, tinnitus.

Urogenital: gynecomastia, galactorrhea/hyperprolactinemia, increased urination, spotty menstruation, impotence.

Other :allergy aggravated, dyspnea.

Treatment Of Acute Cardiovascular Adverse Reactions

The frequency of cardiovascular adverse reactions that require therapy is rare; hence, experience with their treatment is limited. Whenever severe hypotension or complete AV block occurs following oral administration of verapamil, the appropriate emergency measures should be applied immediately; e.g., intravenously administered norepinephrine bitartrate, atropine sulfate, isoproterenol HCl (all in usual doses), or calcium gluconate (10% solution). In patients with hypertrophic cardiomyopathy (IHSS), alpha-adrenergic agents (phenylephrine HCl, metaraminol bitartrate, or methoxamine HCl) should be used to maintain blood pressure, and isoproterenol and norepinephrine should be avoided. If further support is necessary, dopamine HCl or dobutamine HCl may be administered. Actual treatment and dosage should depend on the severity of the clinical situation and the judgement and experience of the treating physician.

Read the entire FDA prescribing information for Covera-HS (Verapamil)

Verapamil is a prescription medication used to treat chest pain, an irregular heartbeat, and high blood pressure. The extended- and sustained-release forms are used to treat high blood pressure. Verapamil belongs to a group of drugs called calcium channel blockers, which work by relaxing the blood vessels, making it easier for the heart to pump blood.

Verapamil comes in an immediate release tablet form and is taken 3 to 4 times a day, with or without food. The extended-release tablet and capsule forms are usually taken once day with or without food. The sustained-release tablet form is usually taken once or twice a day with food.

This medication is available in an injectable form to be given directly into a vein (IV) by a healthcare professional.

Common side effects of verapamil include constipation, nausea, low blood pressure, and headache. This medication can also cause dizziness. Do not drive or operate heavy machinery until you know how verapamil affects you.

• Take verapamil exactly as prescribed.

Oral:

• Verapamil comes in an immediate-release tablet form and is taken 3 to 4 times a day, with or without food. The extended-release tablet and capsule forms are usually taken once day with or without food. The sustained-release tablet form is usually taken once a day with food.
• Verapamil capsules may also be taken by carefully opening the capsule and sprinkling the beads on a spoonful of applesauce. The applesauce should be swallowed immediately without chewing and followed with a glass of cool water to ensure complete swallowing of the beads. The applesauce used should not be hot, and it should be soft enough to be swallowed without chewing.
  • Any bead/applesauce mixture should be used immediately and not stored for future use.

Injectable:

• This medication is available in an injectable form to be given directly into a vein (IV) by a healthcare professional.
• If you miss a dose, take the missed dose as soon as you remember. If it is almost time for the next dose, skip the missed dose and take your next dose at the regular time. Do not take two doses of Calan at the same time.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Blue lips and fingernails
• blurred vision
• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
• chest pain
• confusion
• coughing that sometimes produces a pink frothy sputum
• difficult, fast, noisy breathing, sometimes with wheezing
• dizziness, faintness, or lightheadedness when getting up from a lying or sitting position suddenly
• increased sweating
• lightheadedness, dizziness, or fainting
• pale skin
• shortness of breath
• slow or irregular heartbeat
• sore throat
• sweating
• swelling in legs and ankles
• unusual tiredness or weakness

• Chills
• cold sweats
• feeling of warmth
• redness of the face, neck, arms and occasionally, upper chest

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Difficulty having a bowel movement (stool)
• headache

• Acid or sour stomach
• belching
• difficulty in moving
• heartburn
• indigestion
• joint pain
• muscle aching or cramping
• muscle pains or stiffness
• nausea
• rash
• stomach discomfort, upset, or pain
• trouble sleeping
• unusual drowsiness, dullness, tiredness, weakness, or feeling of sluggishness
• swollen joints

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Serious adverse reactions are uncommon when Verapamil hydrochloride therapy is initiated with upward dose titration within the recommended single and total daily dose. See WARNINGS for discussion of heart failure, hypotension, elevated liver enzymes, AV block, and rapid ventricular response. Reversible (upon discontinuation of Verapamil) non-obstructive, paralytic ileus has been infrequently reported in association with the use of Verapamil. The following reactions to orally administered Verapamil occurred at rates greater than 1.0% or occurred at lower rates but appeared clearly drug-related in clinical trials in 4,954 patients:

In clinical trials related to the control of ventricular response in digitalized patients who had atrial fibrillation or flutter, ventricular rates below 50 at rest occurred in 15% of patients and asymptomatic hypotension occurred in 5% of patients.

The following reactions, reported in 1.0% or less of patients, occurred under conditions (open trials, marketing experience) where a causal relationship is uncertain; they are listed to alert the physician to a possible relationship:

Cardiovascular: angina pectoris, atrioventricular dissociation, chest pain, claudication, myocardial infarction, palpitations, purpura (vasculitis), syncope.

Digestive system : diarrhea, dry mouth, gastrointestinal distress, gingival hyperplasia.

Hemic and lymphatic: ecchymosis or bruising.

Nervous system: cerebrovascular accident, confusion, equilibrium disorders, insomnia, muscle cramps, paresthesia, psychotic symptoms, shakiness, somnolence, extrapyramidal symptoms.

Skin: arthralgia and rash, exanthema, hair loss, hyperkeratosis, macules, sweating, urticaria, Stevens-Johnson syndrome, erythema multiforme.

Special senses: blurred vision, tinnitus.

Urogenital: gynecomastia, galactorrhea/hyperprolactinemia, increased urination, spotty menstruation, impotence.

Treatment of acute cardiovascular adverse reactions: The frequency of cardiovascular adverse reactions that require therapy is rare; hence, experience with their treatment is limited. Whenever severe hypotension or complete AV block occurs following oral administration of Verapamil, the appropriate emergency measures should be applied immediately; e.g., intravenously administered norepinephrine bitartrate, atropine sulfate, isoproterenol HCl (all in the usual doses), or calcium gluconate (10% solution). In patients with hypertrophic cardiomyopathy (IHSS), alpha¬;;;adrenergic agents (phenylephrine HCl, metaraminol bitartrate, or methoxamine HCl) should be used to maintain blood pressure, and isoproterenol and norepinephrine should be avoided. If further support is necessary, dopamine HCl or dobutamine HCl may be administered. Actual treatment and dosage should depend on the severity of the clinical situation and the judgment and experience of the treating physician.

Verapamil Hydrochloride Tablets, USP 120 mg tablets are round, standard concave, white film-coated, scored, debossed "HP" above and "27" below on one side and plain on the reverse side, supplied as:

Verapamil Hydrochloride Tablets, USP 40 mg tablets are round, white film-coated, debossed "HP59" on one side and plain on the reverse side, supplied as:

Store at 20° to 25°C (68° to 77°F) [See USP controlled room temperature] and protect from light. Dispense in a tight, light-resistant container using a child-resistant closure.

MANUFACTURED FOR:

Heritage Pharmaceuticals Inc.

Eatontown, NJ 07724

1.866.901.DRUG (3784)

51U000000252US04

Issued: 09/16

Inhibits calcium ion from entering the “slow channels” or select voltage-sensitive areas of vascular smooth muscle and myocardium during depolarization; produces relaxation of coronary vascular smooth muscle and coronary vasodilation; increases myocardial oxygen delivery in patients with vasospastic angina; slows automaticity and conduction of AV node.

Absorption

Oral: Well absorbed (>90%)

Distribution

Vd: 3.89 L/kg (Storstein 1984)

Metabolism

Hepatic (extensive first-pass effect) via multiple CYP isoenzymes; primary metabolite is norverapamil (~20% pharmacologic activity of verapamil)

Excretion

Urine (~70% as metabolites, 3% to 4% as unchanged drug); feces (≥16%)

Oral: Immediate release tablets: 6 to 8 hours; IV: 0.5 to 6 hours (Marik 2011)

Half-Life Elimination

Injection: Terminal: 2 to 5 hours.

Oral:

Immediate release: Single dose: 2.8 to 7.4 hours; Multiple doses: 4.5 to 12 hours

Extended release: ~12 hours

Severe hepatic impairment: 14 to 16 hours

Protein Binding

~90%

Hypertrophic cardiomyopathy

Based on the American College of Cardiology Foundation/American Heart Association (ACCF/AHA) guideline for the Diagnosis and Treatment of Hypertrophic Cardiomyopathy, verapamil is an effective and recommended alternative agent for the treatment of symptoms (eg, angina or dyspnea) in patients with obstructive or nonobstructive hypertrophic cardiomyopathy who do not tolerate beta-blockers or are unresponsive to beta-blockers.

Angina: Oral: Note: When switching from immediate-release to extended-release formulations, the total daily dose remains the same unless formulation strength does not allow for equal conversion.

Immediate release:

Manufacturer’s labeling: 80 to 120 mg 3 times daily; in patients with increased response to verapamil (eg, small stature): 40 mg 3 times daily; may titrate at daily (patients with unstable angina) or weekly intervals based on patient response; maximum: 480 mg/day

Alternate recommendations: Usual dose range (ACC/AHA [Gibbons 2003]): 80 to 160 mg 3 times daily

Atrial fibrillation (rate control):

IV: Initial bolus: 0.075 to 0.15 mg/kg (usual dose: 5 to 10 mg) over at least 2 minutes; if no response, may give an additional 10 mg bolus after 15 to 30 minutes; if patient responds to the initial or repeat bolus dose, then may begin a continuous infusion (AHA/ACC/HRS [January 2014]; Phillips 1997)

Continuous infusion: Initial: 5 mg/hour; titrate to goal heart rate (Barbarash, 1986; Phillips, 1997)

Oral:

Extended release (off-label use): Usual maintenance dose: 180 to 480 mg once daily (AHA/ACC/HRS [January 2014])

Immediate release: 240 to 480 mg daily in 3 to 4 divided doses (maximum: 480 mg/day)

Hypertension: Oral: Note: When switching from immediate-release to extended-release formulations, the total daily dose remains the same unless formulation strength does not allow for equal conversion.

Immediate release: Initial: 80 mg 3 times daily; in patients with increased response to verapamil (eg, small stature): 40 mg 3 times daily; maximum: 480 mg/day; usual dose range (ASH/ISH [Weber 2014]): 240 to 480 mg daily

Extended release: Usual dose range (ASH/ISH [Weber 2014]): 240 to 480 mg daily; Note: There is no evidence of additional benefit with doses >360 mg daily.

Calan SR, Isoptin SR (Canadian product): Initial: 180 mg once daily in the morning; in patients with increased response to verapamil (eg, small stature): 120 mg once daily; if inadequate response to 180 mg once daily, may increase dose at weekly intervals to 240 mg once daily, then 180 mg twice daily (or 240 mg in the morning followed by 120 mg in the evening), up to 240 mg twice daily; maximum: 480 mg/day.

Verelan: Usual dosage: 240 mg once daily in the morning; in patients with increased response to verapamil (eg, small stature): 120 mg once daily; if inadequate response to 120 mg once daily, may increase dose at weekly intervals in the following manner: 180 mg once daily; 240 mg once daily; 360 mg once daily; 480 mg once daily; maximum: 480 mg/day

Verelan PM: Usual dosage: 200 mg once daily at bedtime; in patients with increased response to verapamil (eg, small stature): 100 mg once daily; if inadequate response to 200 mg once daily, may increase to 300 mg once daily, then 400 mg once daily; maximum dose: 400 mg daily

PSVT prophylaxis: Oral: Note: When switching from immediate-release to extended release formulations, the total daily dose remains the same unless formulation strength does not allow for equal conversion.

Manufacturer’s labeling: Immediate release: 240 to 480 mg daily in 3 to 4 divided doses (maximum: 480 mg/day)

Alternate recommendations: Supraventricular tachycardia (ongoing management): Initial: 120 mg daily in divided doses (immediate release) or once daily (extended release); maximum maintenance dose: 480 mg/day in divided doses (immediate release) or once daily (extended release) (ACC/AHA/HRS [Page 2015])

Supraventricular tachycardia (SVT), acute treatment (off-label dose): IV:

ACLS guidelines: 2.5 to 5 mg over 2 minutes (over 3 minutes in older patients); second dose of 5 to 10 mg (~0.15 mg/kg) may be given 15 to 30 minutes after the initial dose if patient tolerates, but does not respond to initial dose; maximum total dose: 20 to 30 mg (ACLS [Neumar 2010])

ACC/AHA/HRS SVT guidelines: 5 to 10 mg (0.075 to 0.15 mg/kg) over 2 minutes; if no response, a second dose of 10 mg (0.15 mg/kg) may be given 30 minutes after the initial dose; followed by an infusion at 0.005 mg/kg/minute (ACC/AHA/HRS [Page 2015])

Monitor blood pressure and heart rate; periodic liver function tests; ECG, especially with renal and/or hepatic impairment

Consult individual institutional policies and procedures.

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience constipation or headache. Have patient report immediately to prescriber signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes), bradycardia, arrhythmia, severe dizziness, passing out, shortness of breath, excessive weight gain, or swelling of arms or legs (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

Take verapamil exactly as prescribed by your doctor. Follow all directions on your prescription label. Your doctor may occasionally change your dose. Do not use this medicine in larger or smaller amounts or for longer than recommended.

Do not crush, chew, or break an extended-release tablet or capsule. Swallow it whole.

If you have trouble swallowing an extended-release capsule whole, ask your doctor or pharmacist if it is safe for you to open the capsule and sprinkle the medicine into a spoonful of applesauce to make swallowing easier. Swallow this mixture right away without chewing. Do not save the mixture for later use. Discard the empty capsule.

Your blood pressure will need to be checked often. Your kidney or liver function may also need to be checked.

If you need surgery, tell the surgeon ahead of time that you are using this medicine.

You should not stop using verapamil suddenly. Stopping suddenly may make your condition worse.

If you are being treated for high blood pressure, keep using this medication even if you feel well. High blood pressure often has no symptoms. You may need to use blood pressure medication for the rest of your life.

Verapamil may be only part of a complete program of treatment that also includes diet, exercise, and other medications. Follow your doctor's instructions very closely.

Store at room temperature away from moisture, heat, and light.

Oral:
Extended release tablets (Covera HS (R)):
-Initial dose: 180 mg orally once a day at bedtime; if adequate response is not obtained with 180 mg, the dose may be titrated upward.
-Maximum dose: 480 mg/day

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 (e.g., renal/hepatic impairment, elderly)
-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.
-Maximum dose: 480 mg/day

Uses:
-Management of angina
-Treatment of angina at rest, including vasospastic (Prinzmetal's variant) and unstable (crescendo, pre-infarction) angina
-Treatment of chronic stable (classic effort-associated) angina

• Do not crush, break or chew extended or sustained-release verapamil tablets or capsules; swallow whole. Some extended-release capsules may be able to be opened and the contents sprinkled on applesauce then swallowed straight away. Ask your doctor about this if you have difficulty swallowing capsules.
• The dosage of verapamil varies among individuals depending on age, the condition being treated and the presence of other medical conditions. Your doctor will tailor your dosage to suit you.
• Avoid grapefruit and grapefruit juice products.
• People taking verapamil to lower high blood pressure should also make lifestyle changes including managing high blood pressure and high cholesterol, losing weight if they are overweight, stopping smoking if they smoke and partaking in exercise as per a doctor's recommendations.
• If verapamil makes you dizzy this may affect your ability to drive or operate machinery. Avoid doing these activities if verapamil has this effect on you.
• Verapamil may make you feel dizzy when going from a lying or sitting position to standing, increasing your risk of falls. Stand slowly and remove any fall hazards from your home such as loose rugs.
• Avoid or limit alcohol intake while taking verapamil because it may further lower your blood pressure or increase the likelihood of dizziness.
• Call your doctor if you experience shortness of breath, a change in your heartbeat, light-headedness, anxiety-like feelings, loss of appetite, yellowing of the skin or eyes, or flu symptoms while taking verapamil.
• Although verapamil works on calcium ions, it does not alter calcium levels in your blood; although high levels of blood calcium could possibly affect the way verapamil works.
• Your doctor will need to monitor your blood pressure, liver and kidney function regularly while you are taking verapamil.
• Do not take any other medication, including that brought over-the-counter, without first checking with your doctor or pharmacist that it is compatible with verapamil.