RESERPINE,HYDRALAZINE, AND HYDROCHLOROTHIAZIDE (Systemic)

Some commonly used brand names are:

In the U.S.?

• Cam-Ap-Es
• Cherapas
• Ser-A-Gen
• Seralazide
• Ser-Ap-Es
• Serpazide
• Tri-Hydroserpine
• Unipres

In Canada?

• Ser-Ap-Es

Generic name product may be available in the U.S.

Category

• Antihypertensive

Description

Reserpine, hydralazine,and hydrochlorothiazide (re-SER-peen,hye-DRAL-a-zeen, and hye-droe-KLOR-oh-THYE-a-zide) combinationsare used to treat high blood pressure (hypertension).

High blood pressure adds to the workload 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.

Reserpine works by controlling nerve impulses along certain nerve pathways.As a result, it acts on the heart and blood vessels to lower blood pressure.Hydralazine works by relaxing blood vessels and increasing the supply of bloodto the heart while reducing its work load. Hydrochlorothiazide is a thiazidediuretic (water pill) that helps to reduce the amount of water in the bodyby increasing the flow of urine. This also helps to lower blood pressure.

This medicine is available only with your doctor's prescription, in thefollowing dosage form:

Oral
• 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 reserpine, hydralazine,and hydrochlorothiazide, the following should be considered:

Allergies?Tell your doctor if you have ever had any unusual orallergic reaction to hydralazine, sulfonamides (sulfa drugs), thiazide diuretics(water pills), or rauwolfia alkaloids. Also tell your health care professionalif you are allergic to any other substances, such as foods, preservatives,or dyes.

Pregnancy?Too much use of reserpine and hydrochlorothiazideduring pregnancy may cause unwanted effects (jaundice, blood problems, lowpotassium, difficult breathing, low temperatures, and loss of appetite) inthe baby. In rats, rauwolfia alkaloids (like reserpine) decrease newborn survivalrates.

Studies with hydralazine have not been done in humans. However, studiesin mice have shown that hydralazine causes birth defects (cleft palate, defectsin head and face bones); these birth defects may also occur in rabbits, butdo not occur in rats. Be sure that you have discussed this with your doctorbefore taking this medicine.

Breast-feeding?Reserpine passes into breast milk and may causeunwanted effects (difficult breathing, low temperature, loss of appetite)in infants of mothers taking large doses of it. Hydrochlorothiazide also passesinto breast milk. Be sure you have discussed this with your doctor beforetaking this medicine.

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

Older adults?Many medicines have not been studied specificallyin older people. Therefore, it may not be known whether they work exactlythe same way they do in younger adults. Although there is no specific informationcomparing use of reserpine, hydralazine, and hydrochlorothiazide combinationin the elderly with use in other age groups, this medicine is not expectedto cause different side effects or problems in older people than it does inyounger adults. However, drowsiness, dizziness, or faintness, or symptomsof too much potassium loss may be more likely to occur in the elderly, whoare usually more sensitive to the effects of this medicine. Also, this medicinemay reduce tolerance to cold temperatures in elderly patients.

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 you are takingthis medicine, it is especially important that your health care professionalknow if you are taking any of the following:

• Cholestyramine or
• Colestipol?Use with thiazide diuretics may prevent the diureticfrom working properly; take the diuretic at least 1 hour before or 4 hoursafter cholestyramine or colestipol

• Diazoxide (e.g., Proglycem)?Effect on blood pressure may beincreased

• Digitalis glycosides (heart medicine)?Hydrochlorothiazide maycause low potassium in the blood, which can lead to symptoms of digitalistoxicity

• Lithium (e.g., Lithane)?Risk of lithium overdose, even at usualdoses, may be increased

• Monoamine oxidase (MAO) inhibitor activity (isocarboxazid [e.g.,Marplan], phenelzine [e.g., Nardil], procarbazine [e.g., Matulane], selegiline[e.g., Eldepryl], tranylcypromine [e.g., Parnate])?Taking a rauwolfiaalkaloid while you are taking or within 2 weeks of taking MAO inhibitors mayincrease the risk of central nervous system depression or may cause a severehigh blood pressure reaction

Other medical problems?The presence of other medicalproblems may affect the use of this medicine. Make sure you tell your doctorif you have any other medical problems, especially:

• Allergies or other breathing problems such as asthma?Reserpinecan cause breathing problems

• Type 2 diabetes mellitus?Hydrochlorothiazide maychange the amount of diabetes medicine needed

• Epilepsy

• Gallstones or
• Stomach ulcer or
• Ulcerative colitis?Reserpine increases activity of the stomach,which may make the condition worse

• Gout (history of)?Hydrochlorothiazide may increase the amountof uric acid in the blood, which can lead to gout

• Heart disease?Reserpine can cause heart rhythm problems orslow heartbeat. Lowering blood pressure may worsen some conditions

• Kidney disease?Some patients may not do well when blood pressureis lowered by this medicine. Effects of hydralazine may be increased becauseof slower removal from the body. If kidney disease is severe, hydrochlorothiazidemay not work

• Liver disease?If hydrochlorothiazide causes loss of too muchwater from the body, liver disease can become much worse

• Lupus erythematosus (history of)?Hydrochlorothiazide may worsenthe condition

• Mental depression (or history of)?Reserpine causes mental depression

• Pancreatitis (inflammation of pancreas)

• Parkinson's disease?Reserpine can cause parkinsonism-like effects

• Pheochromocytoma

• Stroke (recent)?Lowering blood pressure may make problems resultingfrom this condition worse

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.

This medicine may cause you to have an unusual feeling of tiredness whenyou begin to take it. You may also notice an increase in the amount of urineor in your frequency of urination. After you have taken the medicine for awhile, these effects should lessen. In general, to keep the increase in urinefrom 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.

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

If this medicine upsets your stomach, it may be taken with meals or milk.If stomach upset (nausea, vomiting, stomach pain or cramps) continues, checkwith your doctor.

Dosing?The dose of reserpine, hydralazine, and hydrochlorothiazidecombination 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 reserpine, hydralazine, andhydrochlorothiazide combination. If your dose is different,do not change it unless your doctor tells you to do so.

• For oral dosage form (tablets):
  • For high blood pressure:
    • Adults?1 or 2 tablets three times a day.
    • Children?Use and 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 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 to make surethat this medicine is working properly.

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 tend to increase your blood pressure.

Before having any kind of surgery (including dental surgery), or emergencytreatment, make sure the medical doctor or dentist incharge knows that you are taking this medicine.

This medicine may cause some people to have headaches or to feel dizzyor drowsy. Make sure you know how you react to this medicinebefore you drive, use machines, or do anything else that could be dangerousif you are dizzy or are not alert.

Dizziness, lightheadedness, or fainting may occur,especially when you get up from a lying or sitting position. This ismore likely to occur in the morning. Getting up slowlymay help. When you get up from lying down, sit on the edge of the bedwith your feet dangling for 1 or 2 minutes. Then stand up slowly. If the problemcontinues or gets worse, check with your doctor.

The dizziness, lightheadedness, or fainting is also more likely to occurif you drink alcohol, stand for a long time, exercise, or if the weather ishot. While you are taking this medicine, be careful tolimit the amount of alcohol you drink. Also, use extra care during exerciseor hot weather or if you must stand for a long time.

In some patients, this medicine may cause mental depression. Tell your doctor right away:

• if you or anyone else notices unusual changes in your mood.
• if you start having early-morning sleeplessness or unusually vividdreams or nightmares.

This medicine will add to the effects of alcohol and other CNS depressants(medicines that slow down the nervous system, possibly causing drowsiness).Some examples of CNS depressants are antihistamines or medicine for hay fever,other allergies, or colds; sedatives, tranquilizers, or sleeping medicine;prescription pain medicine or narcotics; barbiturates; medicine for seizures;muscle relaxants; or anesthetics, including dental anesthetics. Check with your doctor before taking any of the above while you are takingthis medicine.

This medicine may cause 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 potassium supplementor a medicine to reduce potassium loss. Extra potassium may not be necessaryand, in some cases, too much potassium could be harmful.

Check with your doctor if you become sick and have severe or continuingnausea, vomiting, or diarrhea. These problems may cause you to lose additionalwater and potassium.

For diabetic patients:

• This medicine may raise blood sugar levels. While you are using thismedicine, be especially careful in testing for sugar in your urine. If youhave any questions about this, check with your doctor.

Some people who take this medicine may become more sensitive to sunlightthan they are normally. Exposure to sunlight, even for brief periods of time,may cause severe sunburn; skin rash, redness, itching, or discoloration; orvision changes. 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 and 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.
• Do not use a sunlamp or tanning bed or booth.

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

This medicine often causes stuffiness in the nose. However, do not usenasal decongestant medicines without first checking with your health careprofessional.

This medicine may cause dryness of the mouth. For temporary relief, usesugarless candy or gum, melt bits of ice in your mouth, or use a saliva substitute.However, if dry mouth continues for more than 2 weeks, check with your medicaldoctor or dentist. Continuing dryness of the mouth may increase the chanceof dental disease, including tooth decay, gum disease, and fungus infections.

Side Effects of This Medicine

Suggestions that rauwolfia alkaloids may increase the risk of breast canceroccurring later have not been proven. However, rats and mice given 100 to300 times the human dose had an increased number of tumors.

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

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

More common

General feeling of discomfort or illness or weakness

Less common

Drowsiness or faintness; impotence ordecreased sexual interest; lack of energy or weakness; mental depression or inability to concentrate; nervousness or anxiety; vivid dreamsor nightmares or early-morning sleeplessness

Check with your doctor assoon as possible if any of the following side effects occur:

Signs and symptoms of too much potassium loss

Dryness of mouth; increased thirst; irregular heartbeat; mood or mentalchanges; muscle cramps or pain; weak pulse

Signs and symptoms of too much sodium loss

Confusion; convulsions; decreased mental activity; irritability; muscle cramps; unusualtiredness or weakness

Less common

Black, tarry stools; blisters on skin; bloody vomit; chest pain; fever and sore throat; headache; irregular heartbeat; joint pain; numbness, tingling, pain, or weaknessin hands or feet; shortness of breath; skin rash or itching; slow heartbeat; stomach cramps or pain; swelling of lymph glands

Rare

Lower back or side pain; painful ordifficult urination; stiffness; stomach pain (severe) with nausea and vomiting; trembling and shaking of hands and fingers; unusualbleeding or bruising; yellow eyes or skin

Signs and symptoms of overdose

Dizziness or drowsiness (severe); drynessof mouth; flushing of skin; increased thirst; muscle cramps or pain; nausea or vomiting (severe); pinpointpupils of eyes; slow pulse

Other side effects may occur that usually do not need medical attention.These side effects may go away during treatment as your body adjusts to themedicine. However, check with your doctor if any of the following side effectscontinue or are bothersome:

More common

Diarrhea; dizziness, especially whengetting up from a lying or sitting position; lossof appetite; nausea or vomiting; stuffy nose

Less common

Constipation; flushing or redness ofskin; increased sensitivity of skin to sunlight; swelling of feet and lower legs; wateringor irritated eyes

After you stop using this medicine, it may still produce someside effects that need attention. During this period of time check with your doctor immediately if you notice any of the followingside effects:

Drowsiness or faintness; general feelingof discomfort or illness or weakness; impotence ordecreased sexual interest; irregular heartbeat; mental depression or inability to concentrate; nervousness or anxiety; vivid dreams or nightmaresor early-morning sleeplessness

Other sideeffects not listed above may also occur in some patients. If you notice anyother effects, check with your doctor.