BETA-ADRENERGICBLOCKING AGENTS AND THIAZIDE DIURETICS (Systemic)

Some commonly used brand names are:

In the U.S.?

• Corzide 40/5 ⁴
• Corzide 80/5 ⁴
• Inderide ⁶
• Inderide LA ⁶
• Lopressor HCT ³
• Tenoretic 50 ¹
• Tenoretic 100 ¹
• Timolide 10-25 ⁷
• Ziac ²

In Canada?

• Corzide ⁴
• Inderide ⁶
• Tenoretic ¹
• Timolide ⁷
• Viskazide ⁵

Category

• Antihypertensive?Atenolol and Chlorthalidone; Bisprolol and Hydrochlorothiazide; Metoprololand Hydrochlorothiazide; Nadolol and Bendroflumethiazide; Pindolol and Hydrochlorothiazide; Propranolol and Hydrochlorothiazide; Timolol and Hydrochlorothiazide

Description

Beta-adrenergic blocking agent (more commonly,beta-blockers) and thiazide diuretic combinations belong to the group of medicinesknown as antihypertensives (high blood pressure medicine). Both ingredientsof the combination control high blood pressure, but they work in differentways. Beta-blockers (atenolol, bisoprolol, metoprolol, nadolol, pindolol,propranolol, and timolol) reduce the work load on the heart as well as havingother effects. Thiazide diuretics (bendroflumethiazide, chlorthalidone, andhydrochlorothiazide) reduce the amount of fluid pressure in the body by increasingthe flow of urine.

High blood pressure adds to the work load of the heart and arteries. Ifit continues for a long time, the heart and arteries may not function properly.This can damage the blood vessels of the brain, heart, and kidneys, resultingin a stroke, heart failure, or kidney failure. High blood pressure may alsoincrease the risk of heart attacks. These problems may be less likely to occurif blood pressure is controlled.

Beta-blocker and thiazide diuretic combinations are available only withyour doctor's prescription, in the following dosage forms:

Oral
• Atenolol and chlorthalidone
  • Tablets (U.S. and Canada)
• Bisoprolol and hydrochlorothiazide
  • Tablets (U.S.)
• Metoprolol and hydrochlorothiazide
  • Tablets (U.S.)
• Nadolol and bendroflumethiazide
  • Tablets (U.S. and Canada)
• Pindolol and hydrochlorothiazide
  • Tablets (Canada)
• Propranolol and hydrochlorothiazide
  • Extended-release capsules (U.S.)
  • Tablets (U.S. and Canada)
• Timolol and hydrochlorothiazide
  • Tablets (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 beta-blockerand thiazide diuretic combinations, the following should be considered:

Allergies?Tell your doctor if you have ever had any unusual orallergic reaction to beta-blockers, sulfonamides (sulfa drugs), bumetanide,furosemide, acetazolamide, dichlorphenamide, methazolamide, or any of thethiazide diuretics. Also tell your health care professional if you are allergicto any other substances, such as foods, preservatives, or dyes.

Pregnancy?Use of some beta-blockers during pregnancy has beenassociated with low blood sugar, breathing problems, a slower heart rate,and low blood pressure in the newborn infant. Other reports have not shownunwanted effects in the newborn infant. Animal studies have shown some beta-blockersto cause problems in pregnancy when used in doses many times the usual humandose.

Studies with thiazide diuretics have not been done in pregnant women. However,use of thiazide diuretics during pregnancy may cause side effects such asjaundice, blood problems, and low potassium in the newborn infant. Animalstudies have not shown thiazide diuretic medicines to cause birth defectseven when used in doses several times the usual human dose.

Before taking a beta-blocker and thiazide diuretic combination, make sureyour doctor knows if you are pregnant or if you may become pregnant.

Breast-feeding?Atenolol, metoprolol, nadolol, propranolol, pindolol,timolol, and thiazide diuretics pass into breast milk. It is not known whetherbisoprolol passes into breast milk. Thiazide diuretics may decrease the flowof breast milk.

Children?Although there is no specific information comparinguse of this combination medicine in children with use in other age groups,this medicine is not expected to cause different side effects or problemsin children than it does in adults. However, extra caution may be necessaryin infants with jaundice, because these medicines can make the condition worse.

Older adults?Some side effects, especially dizziness or lightheadednessand signs and symptoms of too much potassium loss, may be more likely to occurin the elderly, who are usually more sensitive to the effects of this medicine.Also, beta-blockers may reduce tolerance to cold temperatures in elderly patients.

Other medicines?Although certain medicines should not be usedtogether at all, in other cases 2 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 you are takingbeta-blocker and thiazide diuretic combinations, it is especially importantthat your health care professional know if you are taking any of the following:

• Allergy shots or
• Allergy skin tests?The beta-blocker contained in this medicinemay increase the risk of a serious allergic reaction to these medicines

• Aminophylline (e.g., Somophyllin) or
• Caffeine (e.g., NoDoz) or
• Dyphylline (e.g., Lufylline) or
• Oxtriphylline (e.g., Choledyl) or
• Theophylline (e.g., Somophyllin-T)?The effects of these medicinesand beta-blockers may be blocked; in addition, theophylline levels in thebody may be increased, especially in patients who smoke

• Antidiabetics, oral (diabetes medicine you take by mouth) or
• Insulin?There is an increased risk of hyperglycemia (high bloodsugar); the beta-blocker contained in this medicine may also cover up certainsymptoms of hypoglycemia (low blood sugar), such as increases in pulse rateand blood pressure, and may make the hypoglycemia last longer

• Calcium channel blockers (amlodipine [e.g., Norvasc], bepridil [e.g.,Bepadin], diltiazem [e.g., Cardizem], felodipine [e.g., Plendil], flunarizine[e.g., Sibelium], isradipine [e.g., DynaCirc], nicardipine [e.g., Cardene],nifedipine [e.g., Procardia], nimodipine [e.g., Nimotop], verapamil [e.g.,Calan]) or
• Clonidine (e.g., Catapres) or
• Guanabenz (e.g., Wytensin)?Effects on blood pressure may beincreased. In addition, unwanted effects may occur if clonidine, guanabenz,or a beta-blocker are stopped suddenly after use together. Unwanted effectson the heart may occur when beta-blocker and thiazide diuretic combinationsare used with calcium channel blockers

• Cocaine?Cocaine may block the effects of beta-blockers; inaddition, there is an increased risk of high blood pressure, fast heartbeat,and possibly heart problems if you use cocaine while taking a beta-blockerand thiazide diuretic combination

• Digitalis glycosides (heart medicine)?Use with beta-blockerand thiazide diuretic combinations may cause high blood levels of digoxin,which may increase the chance of side effects

• Lithium?The thiazide diuretic contained in this combinationmay cause high blood levels of lithium, which may increase the chance of sideeffects

• Monoamine oxidase (MAO) inhibitors (furazolidone [e.g., Furoxone],isocarboxazid [e.g., Marplan], phenelzine [e.g., Nardil], procarbazine [e.g.,Matulane], selegiline [e.g., Eldepryl], tranylcypromine [e.g., Parnate])?Takinga beta-blocker and thiazide diuretic combination while you are taking or within2 weeks of taking monoamine oxidase (MAO) inhibitors may cause severe highblood pressure

Other medical problems?The presence of other medicalproblems may affect the use of the beta-blockers and thiazide diuretics. Makesure you tell your doctor if you have any other medical problems, especially:

• Allergy, history of (asthma, eczema, hay fever, hives), or
• Bronchitis or
• Emphysema?This combination medicine may make allergic reactionsto other substances more severe or make the reaction last longer; in addition,the beta-blocker contained in this combination can increase trouble in breathing

• Bradycardia (unusually slow heartbeat) or
• Heart or blood vessel disease?This combination medicine maymake these heart problems worse; also, if treatment is stopped suddenly, unwantedeffects may occur

• Type 2 diabetes mellitus?The beta-blocker contained in thismedicine may cause hyperglycemia (high blood sugar) and circulation problems;in addition, if your diabetes medicine causes your blood sugar to be too low,beta-blockers may cover up some of the symptoms (fast heartbeat), althoughthey will not cover up other symptoms such as dizziness or sweating; the thiazidediuretic contained in this medicine may increase the amount of sugar in theblood

• Gout (history of) or
• Lupus erythematosus (history of) or
• Pancreatitis (inflammation of the pancreas)?The thiazide diureticcontained in this medicine may make these conditions worse

• Kidney disease or
• Liver disease?Effects of this medicine may be increased becauseof slower removal from the body

• Mental depression (or history of) or
• Myasthenia gravis or
• Pheochromocytoma or
• Psoriasis or
• Raynaud's syndrome?The beta-blocker contained in this medicinemay make these conditions worse

• Overactive thyroid?Stopping this medicine suddenly may increasesymptoms of overactive thyroid; the beta-blocker contained in this medicinemay cover up fast heartbeat, which is a sign of overactive thyroid

Proper Use of This Medicine

In additionto the use of the medicine your doctor has prescribed, treatment for yourhigh blood pressure may include weight control and care in the types of foodsyou eat, especially foods high in sodium. Your doctor will tell you whichof these are most important for you. You should check with your doctor beforechanging your diet.

Many patients who have high blood pressure will not notice any signs ofthe 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 pressure butit 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.

For patients taking the extended-release tabletform of this medicine:

• Swallow the tablet whole.
• Do not crush, break, or chew before swallowing.

To help you remember to take your medicine, try to get into the habit oftaking it at the same time each day.

Ask your doctor about checking your pulse rate before and after takingbeta-blocking agents. Then, while you are taking this medicine, check yourpulse regularly. If it is much slower than your usual rate (or less than 50beats per minute), check with your doctor. A pulse rate that is too slow maycause circulation problems.

The thiazide diuretic (e.g., bendroflumethiazide, chlorthalidone, or hydrochlorothiazide)contained in this combination medicine may cause you to have an unusual feelingof tiredness when you begin to take it. You may also notice an increase inthe amount of urine or in your frequency of urination. After you take themedicine for a while, these effects should lessen. To keep the increase inurine from affecting your sleep:

• If you are to take a single dose a day, take it in the morning afterbreakfast.
• If you are to take more than one dose a day, take the last dose nolater than 6 p.m., unless otherwise directed by your doctor.

However, it is best to plan your dose or doses according to a schedulethat will least affect your personal activities and sleep. Ask your healthcare professional to help you plan the best time to take this medicine.

Do not miss any doses. This is especially importantwhen you are taking only one dose per day. Some conditions may become worsewhen this medicine is not taken regularly.

Dosing?The dose of beta-blocker and thiazide diureticcombinations will be different for different patients. Follow your doctor's orders or the directions on the label. The followinginformation includes only the average doses of beta-blocker and thiazide diureticcombinations. If your dose is different, do not changeit unless your doctor tells you to do so.

The number of capsules or tablets that you take depends on the strengthof the medicine.

For atenolol and chlorthalidone combination
• For oral dosage form (tablets):
  • For high blood pressure:
    • Adults?1 or 2 tablets once a day.
    • Children?Dose must be determined by your doctor.

For bisoprolol and hydrochlorothiazide combination
• For oral dosage form (tablets):
  • For high blood pressure:
    • Adults?1 or 2 tablets once a day.
    • Children?Dose must be determined by your doctor.

For metoprolol and hydrochlorothiazide combination
• For oral dosage form (tablets):
  • For high blood pressure:
    • Adults?1 or 2 tablets a day.
    • Children?Dose must be determined by your doctor.

For nadolol and bendroflumethiazide combination
• For oral dosage form (tablets):
  • For high blood pressure:
    • Adults?1 tablet once a day.
    • Children?Dose must be determined by your doctor.

For pindolol and hydrochlorothiazide combination
• For oral dosage form (tablets):
  • For high blood pressure:
    • Adults?1 or 2 tablets once a day.
    • Children?Dose must be determined by your doctor.

For propranolol and hydrochlorothiazide combination
• For regular (short-acting) oral dosageform (tablets):
  • For high blood pressure:
    • Adults?1 or 2 tablets two times a day.
    • Children?Dose must be determined by your doctor.
• For long-acting oral dosage form (capsules):
  • For high blood pressure:
    • Adults?1 capsule a day.
    • Children?Dose must be determined by your doctor.

For timolol and hydrochlorothiazide combination
• For oral dosage form (tablets):
  • For high blood pressure:
    • Adults?1 tablet two times a day or 2 tablets once a day.
    • Children?Dose must be determined by your doctor.

Missed dose?If you miss a dose of this medicine, take it assoon as possible. However, if it is within 4 hours of your next dose (8 hoursif you are using atenolol and chlorthalidone, bisoprolol and hydrochlorothiazide,nadolol and bendroflumethiazide, or extended-release propranolol and hydrochlorothiazide),skip the missed dose and go back to your regular dosing schedule. Do not doubledoses.

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 isto make sure the medicine is properly controlling your blood pressure andto allow the dosage to be changed if needed.

Do not stop taking this medicine without first checkingwith your doctor. Your doctor may want you to reduce gradually theamount you are taking before stopping completely. Some conditions may becomeworse when the medicine is stopped suddenly, and the risk of heart attackis increased in some patients.

Make sure that you have enough medicine on hand to last through weekends,holidays, or vacations. You may want to carry an extra written prescriptionin your billfold or purse in case of an emergency. You can then have it filledif you run out of medicine while you are away from home.

Your doctor may want you to carry medical identification stating that youare taking this medicine.

Do not take other medicines unless they have been discussedwith your doctor. This especially includes over-the-counter (nonprescription)medicines for appetite control, asthma, colds, cough, hay fever, or sinusproblems since they may increase your blood pressure.

Before having any kind of surgery (including dentalsurgery) or emergency treatment, tell the medical doctor or dentist in chargethat you are taking this medicine.

For diabetic patients:

• This medicine may increase your blood sugar levels. Also, this medicine may cover up signs of hypoglycemia(low blood sugar), such as change in pulse rate. While you are takingthis medicine, be especially careful in testing for sugar in your urine. Ifyou have any questions about this, check with your doctor.

The thiazide diuretic contained in this medicine maycause a loss of potassium from your body.

• To help prevent this, your doctor may want you to:
  • eat or drink foods that have a high potassium content (for example,orange or other citrus fruit juices), or
  • take a potassium supplement, or
  • take another medicine to help prevent the loss of the potassium inthe first place.
• It is very important to follow these directions. Also, it is importantnot to change your diet on your own. This is more important if you are alreadyon a special diet (as for diabetes), or if you are taking a potassiumsupplement or a medicine to reduce potassium loss. Extra potassium may notbe necessary and, in some cases, too much potassium could be harmful.

Check with your doctor if you become sick and have severe or continuingvomiting or diarrhea. These problems may cause you to lose additional waterand potassium.

This medicine may cause some people to become dizzy, drowsy, lightheaded,or less alert than they are normally. Make sure you knowhow you react to this medicine before you drive, use machines, or do anythingelse that could be dangerous if you are dizzy or are not alert. Ifthe problem continues or gets worse, check with your doctor.

The beta-blocker (atenolol, bisoprolol, metoprolol, nadolol, pindolol,propranolol, or timolol) contained in this medicine may make you more sensitiveto cold temperatures, especially if you have blood circulation problems. Beta-blockerstend to decrease blood circulation in the skin, fingers, and toes. Dress warmlyduring cold weather and be careful during prolonged exposure to cold, suchas in winter sports.

This medicine may cause your skin to be more sensitive to sunlight thanit is normally. Exposure to sunlight, even for brief periods of time, maycause a skin rash, itching, redness or other discoloration of the skin, ora severe sunburn. When you begin taking this medicine:

• Stay out of direct sunlight, especially between the hours of 10:00a.m. and 3:00 p.m., if possible.
• Wear protective clothing, including a hat. Also, wear sunglasses.
• Apply a sun block product that has a skin protection factor (SPF)of at least 15. Some patients may require a product with a higher SPF number,especially if they have a fair complexion. If you have any questions aboutthis, check with your health care professional.
• Apply a sun block lipstick that has an SPF of at least 15 to protectyour lips.
• Do not use a sunlamp or tanning bed or booth.

If you have a severe reaction from the sun, check withyour doctor.

Before you have any medical tests, tell the doctor in charge that you aretaking this medicine. The results of some tests may be affected by this medicine.

For patients with allergies to foods, medicines, or insect stings:

• There is a chance that this medicine will make allergic reactionsworse and harder to treat. If you have a severe allergic reaction while youare being treated with this medicine, check with a doctor right away so thatit can be treated.

Side Effects of This Medicine

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 mayneed medical attention.

Check with your doctor as soon as possible if any of the following sideeffects occur:

Less common

Breathing difficulty and/or wheezing; cold hands and feet; mental depression; slow heartbeat (especially less than 50 beats per minute); swelling of ankles, feet, and/or lower legs

Rare

Black, tarry stools; blood in urineor stools; chest pain; dark urine; fever, chills, cough, or sore throat; hallucinations (seeing, hearing, or feeling thingsthat are not there); joint pain; lower back or side pain; pinpoint red spots on skin; red, scaling, or crusted skin; skin rash or hives; stomach pain (severe) with nauseaand vomiting; unusual bleeding or bruising; or yellow eyes or skin

Signs and symptoms of too much potassium or sodium loss

Confusion; convulsions (seizures); dryness of mouth; increased thirst; irregular heartbeats; irritability,mood or mental changes; muscle cramps or pain; nausea or vomiting, unusual tiredness or weakness; weak pulse

Signs and symptoms of overdose (in the order in which they may occur)

Slow heartbeat; dizziness (severe) orfainting; difficulty in breathing; bluish-colored fingernails or palms of hands; convulsions(seizures)

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

Decreased sexual ability; dizzinessor lightheadedness; drowsiness (mild); trouble in sleeping

Less common

Anxiety or nervousness; constipation; diarrhea; increased sensitivityof skin to sunlight (skin rash, itching, redness or other discoloration ofskin, or severe sunburn); loss of appetite; numbness or tingling of fingers and toes; stomach discomfort or upset; stuffy nose

Rare

Changes in taste; dry, sore eyes; itching of skin; nightmares and vividdreams

Although not all of the above sideeffects have been reported for all of these medicines, they have been reportedfor at least one of the beta-blockers or thiazide diuretics. Since all ofthe beta-blockers are very similar and the thiazide diuretics are also verysimilar, any of the above side effects may occur with any of these medicines.However, they may be more common with some combinations than with others.

After you have been takingthis medicine for a while, it may cause unpleasant or even harmful effectsif you stop taking it too suddenly. After you stop taking this medicine orwhile you are gradually reducing the amount you are taking, check with yourdoctor right away if any of the following occur:

Chest pain; fast or irregular heartbeat; general feeling of discomfort, illness, or weakness; headache; shortness ofbreath (sudden); sweating; trembling

Other side effects not listedabove may also occur in some patients. If you notice any other effects, checkwith your doctor.