CALCIUMCHANNEL BLOCKING AGENTS (Systemic)

Some commonly used brand names are:

In the U.S.?

• Adalat ⁸
• Adalat CC ⁸
• Calan ¹⁰
• Calan SR ¹⁰
• Cardene ⁷
• Cardizem ³
• Cardizem CD ³
• Cardizem LA ³
• Cardizem SR ³
• Dilacor-XR ³
• DynaCirc ⁶
• Isoptin ¹⁰
• Isoptin SR ¹⁰
• Nimotop ⁹
• Norvasc ¹
• Plendil ⁴
• Procardia ⁸
• Procardia XL ⁸
• Vascor ²
• Verelan ¹⁰
• Verelan PM ¹⁰

In Canada?

• Adalat ⁸
• Adalat PA ⁸
• Adalat XL ⁸
• Apo-Diltiaz ³
• Apo-Nifed ⁸
• Apo-Verap ¹⁰
• Cardizem ³
• Cardizem SR ³
• Isoptin ¹⁰
• Isoptin SR ¹⁰
• Nimotop ⁹
• Norvasc ¹
• Novo-Diltazem ³
• Novo-Nifedin ⁸
• Novo-Veramil ¹⁰
• Nu-Diltiaz ³
• Nu-Nifed ⁸
• Nu-Verap ¹⁰
• Plendil ⁴
• Renedil ⁴
• Sibelium ⁵
• Verelan ¹⁰

Category

• Antianginal?Amlodipine; Bepridil; Diltiazem; Felodipine; Isradipine; Nicardipine; Nifedipine; Verapamil
• Antiarrhythmic?Diltiazem; Verapamil
• Antihypertensive?Amlodipine; Diltiazem; Felodipine; Isradipine; Nicardipine; Nifedipine; Verapamil
• Hypertrophic cardiomyopathy therapyadjunct?Verapamil
• Subarachnoid hemorrhage therapy?Flunarizine; Nicardipine; Nimodipine
• Vascularheadache prophylactic?Flunarizine; Verapamil

Description

Amlodipine, bepridil, diltiazem, felodipine,flunarizine, isradipine, nicardipine, nifedipine, nimodipine, and verapamilbelong to the group of medicines called calcium channel blocking agents.

Calcium channel blocking agents affect the movement of calcium into thecells of the heart and blood vessels. As a result, they relax blood vesselsand increase the supply of blood and oxygen to the heart while reducing itsworkload.

Some of the calcium channel blocking agents are used to relieve and controlangina pectoris (chest pain).

Some are also used to treat high blood pressure (hypertension). High bloodpressure adds to the workload of the heart and arteries. If it continues fora long time, the heart and arteries may not function properly. This can damagethe blood vessels of the brain, heart, and kidneys, resulting in a stroke,heart failure, or kidney failure. High blood pressure may also increase therisk of heart attacks. These problems may be less likely to occur if bloodpressure is controlled.

Flunarizine is used to prevent migraine headaches.

Nimodipine is used to prevent and treat problems caused by a burst bloodvessel around the brain (also known as a ruptured aneurysm or subarachnoidhemorrhage).

Other calcium channel blocking agents may also be used for these and otherconditions as determined by your doctor.

These medicines are available only with your doctor's prescription, inthe following dosage forms:

Oral
• Amlodipine
  • Tablets (U.S. and Canada)
• Bepridil
  • Tablets (U.S.)
• Diltiazem
  • Extended-release capsules (U.S. and Canada)
  • Extended-release tablets (U.S.)
  • Tablets (U.S. and Canada)
• Felodipine
  • Extended-release tablets (U.S. and Canada)
• Flunarizine
  • Capsules (Canada)
• Isradipine
  • Capsules (U.S.)
• Nicardipine
  • Capsules (U.S.)
• Nifedipine
  • Capsules (U.S. and Canada)
  • Extended-release tablets (U.S. and Canada)
• Nimodipine
  • Capsules (U.S. and Canada)
• Verapamil
  • Extended-release capsules (U.S. and Canada)
  • Tablets (U.S. and Canada)
  • Extended-release tablets (U.S. and Canada)

Parenteral
• Diltiazem
  • Injection (U.S. and Canada)
• Verapamil
  • Injection (U.S. and Canada)

Before Using This Medicine

In deciding to use a medicine,the risks of taking the medicine must be weighed against the good it willdo. This is a decision you and your doctor will make. For the calcium channelblocking agents, the following should be considered:

Allergies?Tell your doctor if you have ever had any unusual orallergic reaction to amlodipine, bepridil, diltiazem, felodipine, flunarizine,isradipine, nicardipine, nifedipine, nimodipine, or verapamil. Also tell yourhealth care professional if you are allergic to any other substances, suchas foods, preservatives, or dyes.

Pregnancy?Calcium channel blocking agents have not been studiedin pregnant women. However, studies in animals have shown that large dosesof calcium channel blocking agents cause birth defects, prolonged pregnancy,poor bone development in the offspring, and stillbirth.

Breast-feeding?Although bepridil, diltiazem, nifedipine, verapamil,and possibly other calcium channel blocking agents, pass into breast milk,they have not been reported to cause problems in nursing babies.

Children?Although there is no specific information comparinguse of this medicine in children with use in other age groups, it is not expectedto cause different side effects or problems in children than it does in adults.

Older adults?Elderly people may be especially sensitive to theeffects of calcium channel blocking agents. This may increase the chance ofside effects during treatment. A lower starting dose may be required.

Other medicines?Although certain medicines should not be usedtogether at all, in other cases two different medicines may be used togethereven if an interaction might occur. In these cases, your doctor may want tochange the dose, or other precautions may be necessary. When taking calciumchannel blocking agents it is especially important that your health care professionalknow if you are taking any of the following:

• Acetazolamide (e.g., Diamox) or
• Amphotericin B by injection (e.g., Fungizone) or
• Corticosteroids (cortisone-like medicine) or
• Dichlorphenamide (e.g., Daranide) or
• Diuretics (water pills) or
• Methazolamide (e.g., Naptazane)?These medicines can cause hypokalemia(low levels of potassium in the body), which can increase the unwanted effectsof bepridil

• Beta-adrenergic blocking agents (acebutolol [e.g., Sectral], atenolol[e.g., Tenormin], betaxolol [e.g., Kerlone], carteolol [e.g., Cartrol], labetalol[e.g., Normodyne], metoprolol [e.g., Lopressor], nadolol [e.g., Corgard],oxprenolol [e.g., Trasicor], penbutolol [e.g., Levatol], pindolol [e.g., Visken],propranolol [e.g., Inderal], sotalol [e.g., Sotacor], timolol [e.g., Blocadren])?Effectsof both may be increased. In addition, unwanted effects may occur if a calciumchannel blocking agent or a beta-blocking agent is stopped suddenly afterboth have been used together

• Carbamazepine (e.g., Tegretol) or
• Cyclosporine (e.g., Sandimmune) or
• Procainamide (e.g., Pronestyl) or
• Quinidine (e.g., Quinidex)?Effects of these medicines may beincreased if they are used with some calcium channel blocking agents

• Digitalis glycosides (heart medicine)?Effects of these medicinesmay be increased if they are used with some calcium channel blocking agents

• Disopyramide (e.g., Norpace)?Effects of some calcium channelblocking agents on the heart may be increased

• Erythromycin (e.g., Ery-Tab)?Should not be used together withcalcium channel blocking agents, especially diltiazem or verapamil; severeheart problems may result.

• Grapefruit juice?Effects of felodipine may be increased. Noeffects on amlodipine.

Also, tell your health care professional if you are using any of the followingmedicines in the eye:

• Betaxolol (e.g., Betoptic) or
• Levobunolol (e.g., Betagan) or
• Metipranolol (e.g., OptiPranolol) or
• Timolol (e.g., Timoptic)?Effects on the heart and blood pressuremay be increased

Other medical problems?The presence of other medicalproblems may affect the use of the calcium channel blocking agents. Make sureyou tell your doctor if you have any other medical problems, especially:

• Congestive heart failure?Calcium channel blocking agents maymake this condition worse. Do not take diltiazem if you have a history ofheart attacks.
• Heart rhythm problems (history of)?Bepridil can cause seriousheart rhythm problems

• Kidney disease or
• Liver disease?Effects of the calcium channel blocking agentmay be increased

• Mental depression (history of)?Flunarizine may cause mentaldepression

• Parkinson's disease or similar problems?Flunarizine can causeparkinsonian-like effects

• Other heart or blood vessel disorders?Calcium channel blockingagents may make some heart conditions worse

Proper Use of This Medicine

Take this medicine exactly as directed even if you feel well and donot notice any signs of chest pain. Do not take more of this medicine anddo not take it more often than your doctor ordered. Do not miss any doses.

For patients taking amlodipine:

• Your doctor may suggest that you change your diet and eat foods thatare low in salt and fat. Losing weight will help your blood pressure alongwith your medicine. Talk to your doctor about the best diet for you.

For patients taking bepridil:

• If this medicine causes upset stomach, it can be taken with mealsor at bedtime.

For patients taking diltiazem extended-release capsulesor tablets:

• Swallow the capsule or tablet whole, without crushing or chewingit.
• Do not change to another brand without checkingwith your physician. Different brands have different doses. If yourefill your medicine and it looks different, check with your pharmacist.
• You should take Cardizem LA at about thesame time once each day either in the morning or at bedtime. If you have questionsabout when to take your medicine, ask your doctor.

For patients taking felodipine:

• Do not take this medicine with grapefruit juice.

For patients taking verapamil extended-release capsules:

• Swallow the capsule whole, without crushing or chewing it.
• If you have trouble swallowing capsules, you may open the verapamilcapsule and mix the medicine with applesauce. Mix only one dose at a timejust before taking it. Do not mix any doses to save forlater, because the medicine may change over time and may not work properly.

For patients taking felodipine or nifedipine extended-release tablets:

• Swallow the tablet whole, without breaking, crushing, or chewingit.
• If you are taking Adalat XL or Procardia XL, you may sometimes notice what looks like a tablet inyour stool. That is just the empty shell that is left after the medicine hasbeen absorbed into your body.
• If you are taking Adalat CC, take themedicine on an empty stomach

For patients taking verapamil extended-release tablets:

• Swallow the tablet whole, without crushing or chewing it. However,if your doctor tells you to, you may break the tablet in half.
• Take the medicine with food or milk.

For patients taking this medicine for high blood pressure:

• In addition to the use of the medicine your doctor has prescribed,appropriate treatment for your high blood pressure may include weight controland care in the types of food you eat, especially foods high in sodium (salt).Your doctor will tell you which factors are most important for you. You shouldcheck with your doctor before changing your diet.
• Many patients who have high blood pressure will not notice any signsof the problem. In fact, many may feel normal. It is very important that you take your medicine exactly as directed and thatyou keep your appointments with your doctor even if you feel well.
• Remember that this medicine will not cure your high blood pressurebut it does help control it. Therefore, you must continue to take it as directedif you expect to lower your blood pressure and keep it down. You may have to take high blood pressure medicine for the rest of your life. If high blood pressure is not treated, it can cause serious problemssuch as heart failure, blood vessel disease, stroke, or kidney disease.

Dosing?The dose of these medicines will be differentfor different patients. Follow your doctor's orders orthe directions on the label. The following information includes onlythe average doses of these medicines. If your dose isdifferent, do not change it unless your doctor tells you to do so.

The number of capsules or tablets that you take depends on the strengthof the medicine. Also, the number of doses you take eachday, the time allowed between doses, and the length of time you take the medicinedepend on the medical problem for which you are taking calcium channel blockingagents.

For amlodipine
• For oral dosage form (tablets):
  • For angina (chest pain):
    • Adults?5 to 10 milligrams (mg) once a day.
    • Children 6 years of age and older?2.5 to 5 mg once a day.
    • Children younger than 6 years of age?Use must be determinedby your doctor.

Note:

Elderly patients or patients determined by your health care professionalmay be started on a lower dose.

• For high blood pressure:
  • Adults?5 to 10 mg once a day.
  • Children?Use must be determined by your doctor.

Note:

Elderly patients or patients determined by your health care professionalmay be started on 2.5 mg once a day.

For bepridil
• For oral dosage form (tablets):
  • For angina (chest pain):
    • Adults?200 to 300 milligrams (mg) once a day.
    • Children?Use and dose must be determined by your doctor.

For diltiazem
• For long-acting oral dosage form (extended-releasecapsules and tablets):
  • For angina (chest pain):
    • Adults and teenagers:
      • For Cardizem LA: 180 mg once a day inthe morning or at bedtime.
    • Children?Dose must be determined by your doctor.
  • For high blood pressure:
    • Adults and teenagers:
      • For Cardizem CD or Cardizem LA or Dilacor-XR: 180to 240 milligrams (mg) once a day.
      • For Cardizem SR: 60 to 120 mg two timesa day.
    • Children?Dose must be determined by your doctor.
• For regular (short-acting) oral dosageform (tablets):
  • For angina (chest pain):
    • Adults and teenagers?30 mg three or four times a day. Yourdoctor may gradually increase your dose as needed.
    • Children?Dose must be determined by your doctor.
• For injection dosage form:
  • For arrhythmias (irregular heartbeat):
    • Adults and teenagers?Dose is based on body weight and mustbe determined by your doctor.
    • Children?Use and dose must be determined by your doctor.

For felodipine
• For long-acting oral dosage form (extended-releasetablets):
  • For high blood pressure:
    • Adults?5 to 10 milligrams (mg) once a day.
    • Children?Use and dose must be determined by your doctor.
  • For angina (chest pain):
    • Adults?10 mg once a day.
    • Children?Use and dose must be determined by your doctor.

For flunarizine
• For oral dosage form (capsules):
  • To prevent headaches:
    • Adults?10 milligrams (mg) once a day in the evening.
    • Children?Dose must be determined by your doctor.

For isradipine
• For oral dosage form (capsules):
  • For high blood pressure:
    • Adults?2.5 milligrams (mg) two times a day. Your doctor mayincrease your dose as needed.
    • Children?Use and dose must be determined by your doctor.

For nicardipine
• For oral dosage form (capsules):
  • For high blood pressure or angina (chest pain):
    • Adults and teenagers?20 milligrams (mg) three times a day.
    • Children?Dose must be determined by your doctor.

For nifedipine
• For regular (short-acting) oral dosageform (capsules):
  • For high blood pressure or angina (chest pain):
    • Adults and teenagers?10 milligrams (mg) three times a day.Your doctor may increase your dose as needed.
    • Children?Dose must be determined by your doctor.
• For long-acting oral dosage form (extended-releasetablets):
  • For high blood pressure or angina (chest pain):
    • Adults and teenagers:
      • For Adalat CC, AdalatXL or Procardia XL: 30 or 60 mg once a day.Your doctor may increase your dose as needed.
      • For Adalat PA: 10 or 20 mg two times aday. Your doctor may increase your dose as needed.
    • Children?Dose must be determined by your doctor.

For nimodipine
• For oral dosage form (capsules):
  • To treat a burst blood vessel around the brain:
    • Adults?60 milligrams (mg) every four hours.
    • Children?Dose must be determined by your doctor.

For verapamil
• For regular (short-acting) oral dosageform (tablets):
  • For angina (chest pain), arrhythmias (irregular heartbeat), or highblood pressure:
    • Adults and teenagers?40 to 120 milligrams (mg) three timesa day. Your doctor may increase your dose as needed.
    • Children?Dose is based on body weight and must be determinedby your doctor. The usual dose is 4 to 8 mg per kilogram (kg) (1.82 to 3.64mg per pound) of body weight a day. This is divided into smaller doses.
• For long-acting oral dosage form (extended-releasecapsules):
  • For high blood pressure:
    • Adults and teenagers
      • For Verelan: 240 to 480 mg once a day
      • For Verelan PM: 200 mg once a day at bedtime
      .
    • Children?Dose must be determined by your doctor.
• For long-acting oral dosage form (extended-releasetablets):
  • For high blood pressure:
    • Adults and teenagers?120 mg once a day to 240 mg every twelvehours.
    • Children?Dose must be determined by your doctor.
• For injection dosage form:
  • For arrhythmias (irregular heartbeat):
    • Adults?5 to 10 mg slowly injected into a vein. The dose maybe repeated after thirty minutes.
    • Children?Dose is based on body weight and must be determinedby your doctor.
      • Infants up to 1 year of age: 100 to 200 micrograms (mcg) per kg (45.5to 90.9 mcg per pound) of body weight injected slowly into a vein. The dosemay be repeated after thirty minutes.
      • Children 1 to 15 years of age: 100 to 300 mcg per kg (45.5 to 136.4mcg per pound) of body weight injected slowly into a vein. The dose may berepeated after thirty minutes.

Missed dose?If you miss a dose of this medicine, take it assoon as possible. However, if it is almost time for your next dose, skip themissed dose and go back to your regular dosing schedule. Do not double doses.

Storage?To store this medicine:

• Keep out of the reach of children.
• Store away from heat and direct light.
• Do not store in the bathroom, near the kitchen sink, or in otherdamp places. Heat or moisture may cause the medicine to break down.
• Do not keep outdated medicine or medicine no longer needed. Be surethat any discarded medicine is out of the reach of children.

Precautions While Using This Medicine

It isimportant that your doctor check your progress at regular visits. This willallow your doctor to make sure the medicine is working properly and to changethe dosage if needed.

If you have been using this medicine regularly for several weeks, do notsuddenly stop using it. Stopping suddenly may bring on your previous problem.Check with your doctor for the best way to reduce gradually the amount youare taking before stopping completely.

Chest pain resulting from exercise or physical exertion is usually reducedor prevented by this medicine. This may tempt you to be overly active. Make sure you discuss with your doctor a safe amount of exercisefor your medical problem.

After taking a dose of this medicine you may get a headache that lastsfor a short time. This effect is more common if you are taking felodipine,isradipine, or nifedipine. This should become less noticeable after you havetaken this medicine for a while. If this effect continues or if the headachesare severe, check with your doctor.

In some patients, tenderness, swelling, or bleeding of the gums may appearsoon after treatment with this medicine is started. Brushing and flossingyour teeth carefully and regularly and massaging your gums may help preventthis. See your dentist regularly to have your teeth cleaned.Check with your medical doctor or dentist if you have any questions abouthow to take care of your teeth and gums, or if you notice any tenderness,swelling, or bleeding of your gums.

For patients taking bepridil, diltiazem, or verapamil:

• Ask your doctor how to count your pulse rate.Then, while you are taking this medicine, check your pulse regularly.If it is much slower than your usual rate, or less than 50 beats per minute,check with your doctor. A pulse rate that is too slow may cause circulationproblems.

For patients taking flunarizine:

• This medicine may cause some people to become drowsy or less alertthan they are normally. This is more likely to happen when you begin to takeit or when you increase the amount of medicine you are taking. Make sure you know how you react to this medicine before you drive, use machines,or do anything else that could be dangerous if you are not alert.

For patients taking this medicine for high blood pressure:

• Do not take other medicines unless they havebeen discussed with your doctor. This especially includes over-the-counter(nonprescription) medicines for appetite control, asthma, colds, cough, hayfever, or sinus problems, since they may tend to increase your blood pressure.

Side Effects of This Medicine

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

Not all of the side effects listed below have been reported for each ofthese medicines, but they have been reported for at least one of them. Sincemany of the effects of calcium channel blocking agents are similar, some ofthese side effects may occur with any of these medicines. However, they maybe more common with some of these medicines than with others.

Check with your doctor as soon as possibleif any of the following side effects occur:

Less common

Breathing difficulty, coughing, or wheezing; irregular or fast, pounding heartbeat; skin rash; slow heartbeat (less than 50 beats per minute?bepridil,diltiazem, and verapamil only); swelling of ankles,feet, or lower legs (more common with amlodipine, felodipine and nifedipine)

For flunarizine only?less common

Lossof balance control; mask-like face; mental depression; shuffling walk; stiffness of arms or legs; tremblingand shaking of hands and fingers; trouble in speakingor swallowing

Rare

Bleeding, tender, or swollen gums; chest pain (may appear about 30 minutes after medicine is taken); fainting; painful, swollen joints (fornifedipine only); trouble in seeing (for nifedipineonly)

For flunarizine and verapamil only?rare

Unusual secretionof milk

Other side effects may occur that usually do not need medicalattention. These side effects may go away during treatment as your body adjuststo the medicine. However, check with your doctor if any of the following sideeffects continue or are bothersome:

More common

Drowsiness (for flunarizine only); increased appetite and/or weight gain (for flunarizine only)

Less common

Constipation; diarrhea; dizziness or lightheadedness (more common with bepridil and nifedipine); dryness of mouth (for amlodipine and flunarizineonly); flushing and feeling of warmth (more commonwith nicardipine and nifedipine); headache (morecommon with amlodipine, felodipine, isradipine, and nifedipine); nausea (more common with bepridil and nifedipine); unusual tiredness or weakness

Other side effects not listed above may also occur insome patients. If you notice any other effects, check with your doctor.

Additional Information

Once a medicine has been approvedfor marketing for a certain use, experience may show that it is also usefulfor other medical problems. Although these uses are not included in productlabeling, calcium channel blocking agents are used in certain patients withthe following medical conditions:

• Hypertrophic cardiomyopathy (a heart condition) (verapamil)
• Raynaud's phenomenon (circulation problems) (nicardipine and nifedipine)

Other than the above information, there is no additional information relatingto proper use, precautions, or side effects for these uses.