RAUWOLFIAALKALOIDS AND THIAZIDE DIURETICS (Systemic)

Some commonly used brand names are:

In the U.S.?

• Demi-Regroton ⁵
• Diupres ⁴
• Diurigen with Reserpine ⁴
• Diutensen-R ⁷
• Enduronyl ²
• Enduronyl Forte ²
• Oreticyl ¹
• Oreticyl Forte ¹
• Rauzide ³
• Regroton ⁵

In Canada?

• Dureticyl ²
• Hydropres-50 ⁶

Category

• Antihypertensive?Deserpidine and Hydrochlorothiazide; Deserpidine and Methyclothiazide; RauwolfiaSerpentina and Bendroflumethiazide; Reserpineand Chlorothiazide; Reserpine and Chlorthalidone; Reserpine and Hydrochlorothiazide; Reserpine and Methyclothiazide

Description

Rauwolfia alkaloid and thiazidediuretic combinations are used in the treatment of 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.

Rauwolfia alkaloids work by controlling nerve impulses along certain nervepathways. As a result, they act on the heart and blood vessels to lower bloodpressure. Thiazide diuretics help to reduce the amount of water in the bodyby increasing the flow of urine. This also helps to lower blood pressure.

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

Oral
• Deserpidine and Hydrochlorothiazide
  • Tablets (U.S.)
• Deserpidine and Methyclothiazide
  • Tablets (U.S. and Canada)
• Rauwolfia Serpentina and Bendroflumethiazide
  • Tablets (U.S.)
• Reserpine and Chlorothiazide
  • Tablets (U.S.)
• Reserpine and Chlorthalidone
  • Tablets (U.S.)
• Reserpine and Hydrochlorothiazide
  • Tablets (Canada)
• Reserpine and Methyclothiazide
  • Tablets (U.S.)

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 rauwolfia alkaloidsand thiazide diuretics, the following should be considered:

Allergies?Tell your doctor if you have ever had any unusual orallergic reaction to sulfonamides (sulfa drugs), thiazide diuretics (waterpills), or rauwolfia alkaloids. Also tell your health care professional ifyou are allergic to any other substance, such as foods, preservatives, ordyes.

Pregnancy?Too much use of thiazide diuretics (contained inthis combination medicine) during pregnancy may cause unwanted effects includingjaundice, blood problems, and low potassium in the baby. Too much use of rauwolfiaalkaloids may cause difficult breathing, low temperature, and loss of appetitein the baby. This medicine has not been shown to cause birth defects in humans.In rats, use of rauwolfia alkaloids during pregnancy decreases newborn survivalrates. Be sure that you have discussed this with your doctor before takingthis medicine.

Breast-feeding?Rauwolfia alkaloids pass into breast milk and maycause unwanted effects (difficult breathing, low temperature, loss of appetite)in infants of mothers taking it in large doses. Thiazide diuretics also passinto breast milk. Be sure you have discussed this with your doctor beforetaking this medicine.

Children?Although there is no specific information comparinguse of these medicines in children with use in other age groups, these medicinesare not expected to cause different side effects or problems in children thanthey do 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 rauwolfia alkaloid and thiazide diuretic combinations inthe elderly with use in other age groups, this medicine is not expected tocause different side effects or problems in older people than it does in youngeradults. However, drowsiness, dizziness, or faintness or symptoms of too muchpotassium loss may be more likely to occur in the elderly, who are more sensitiveto the effects of rauwolfia alkaloids and thiazide diuretics.

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 takingrauwolfia alkaloids and thiazide diuretics, it is especially important thatyour health care professional know 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

• Digitalis glycosides (heart medicine)?Thiazide diuretics 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 rauwolfia alkaloids and thiazide diuretics.Make sure you tell your doctor if you have any other medical problems, especially:

• Allergies or other breathing problems such as asthma?Rauwolfiaalkaloids can cause breathing problems

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

• Epilepsy

• Gallstones or
• Stomach ulcer or
• Ulcerative colitis?Rauwolfia alkaloids increase activity ofthe stomach, which may make the condition worse

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

• Heart disease?Rauwolfia alkaloids can cause heart rhythm problemsor slow heartbeat

• Kidney disease?Some patients may not do well when blood pressureis lowered by this medicine. If kidney disease is severe, thiazide diureticsmay not work

• Liver disease?If thiazide diuretics cause loss of too muchwater from the body, liver disease can become much worse

• Lupus erythematosus (history of)?Thiazide diuretics may worsenthe condition

• Mental depression (or history of)?Rauwolfia alkaloids causemental depression

• Pancreatitis (inflammation of pancreas)

• Parkinson's disease?Rauwolfia alkaloids can cause parkinsonism-likeeffects

• Pheochromocytoma

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 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.

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

For deserpidine and methyclothiazide combination
• For oral dosage form (tablets):
  • For high blood pressure:
    • Adults?One-half to 1 tablet a day.
    • Children?Dose must be determined by your doctor.

For rauwolfia serpentina and bendroflumethiazide combination
• For oral dosage form (tablets):
  • For high blood pressure:
    • Adults?1 to 4 tablets a day.
    • Children?Dose must be determined by your doctor.

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

For reserpine 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 reserpine and hydrochlorothiazide combination
• For oral dosage form (tablets):
  • For high blood pressure:
    • Adults?1 tablet one to four times a day.
    • Children?Dose must be determined by your doctor.

For reserpine and methyclothiazide combination
• For oral dosage form (tablets):
  • For high blood pressure:
    • Adults?1 to 4 tablets 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 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, tell the medical doctor or dentist in chargethat you are taking this 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 continuingvomiting or diarrhea. These problems may cause you to lose additional waterand potassium.

This medicine may cause some people to become drowsy or less alert thanthey are normally. This is more likely to happen when you begin to take itor 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.

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 slowly may help. When youget up from lying down, sit on the edge of the bed with your feet danglingfor 1 or 2 minutes. Then stand up slowly. If the problem continues or getsworse, 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 moods.
• 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.

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 rauwolfiaalkaloids may increase the risk of breast cancer occurring later have notbeen proven. However, rats and mice given 100 to 300 times the human dosehad an increased risk 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:

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:

Less common

Black, tarry stools; bloody vomit; chest pain; headache; irregular or slow heartbeat; joint pain; shortness of breath

Rare

Painful or difficult urination; skinrash or itching; sore throat and fever; stiffness; stomach pain (severe) withnausea and vomiting; trembling and shaking of handsand fingers; unusual bleeding or bruising; yellow eyes or skin

Symptoms of too much potassium loss or overdose

Dry mouth; increased thirst; muscle cramps or pain; nausea or vomiting

Other signs and symptoms of overdose

Dizziness or drowsiness, severe; flushingof skin; pinpoint pupils of eyes; slow pulse

Other side effects may occur that usually donot need medical attention. These side effects may go away during treatmentas your body adjusts to the medicine. However, check with your doctor if anyof the following side effects continue or are bothersome:

More common

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

After you stop using thismedicine, it may still produce some side effects that need attention. Duringthis period of time check with your doctor immediately if you notice any of the following side effects:

Drowsiness or faintness; impotence ordecreased sexual interest; irregular or slow heartbeat; lack of energy or weakness; mental depression or inability to concentrate; nervousnessor anxiety; vivid dreams or nightmares or early-morningsleeplessness

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