Rauwolfia Alkaloids and Thiazide Diuretics (Systemic)

This monograph includes information on the following:

1) Deserpidine and Hydrochlorothiazide 
2) Deserpidine and Methyclothiazide
3) Rauwolfia Serpentina and Bendroflumethiazide 
4) Reserpine and Chlorothiazide 
5) Reserpine and Chlorthalidone  
6) Reserpine and Hydrochlorothiazide  *
7) Reserpine and Methyclothiazide  

VA CLASSIFICATION
Primary: CV408

Commonly used brand name(s): Demi-Regroton5; Diupres4; Diurigen with Reserpine4; Diutensen-R7; Dureticyl2; Enduronyl2; Enduronyl Forte2; Hydropres6; Oreticyl1; Oreticyl Forte1; Rauzide3; Regroton5.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).

*Not commercially available in the U.S.

Not commercially available in Canada.



Category:


Antihypertensive—

Indications

Accepted

Hypertension (treatment)—This combination is indicated for treatment of hypertension .
—Fixed-dosage combinations are generally not recommended for initial therapy and are useful for subsequent therapy only when the proportion of the component agents corresponds to the dose of the individual agents, as determined by titration.
—For additional information on initial therapeutic guidelines related to the treatment of hypertension, see Appendix III.


Pharmacology/Pharmacokinetics

Rauwolfia Alkaloids—See Rauwolfia Alkaloids (Systemic).

Thiazide Diuretics—See Diuretics, Thiazide (Systemic).


Precautions to Consider

Rauwolfia Alkaloids—See Rauwolfia Alkaloids (Systemic).

Thiazide Diuretics—See Diuretics, Thiazide (Systemic).


Side/Adverse Effects
Rauwolfia Alkaloids—See Rauwolfia Alkaloids (Systemic).
Thiazide Diuretics—See Diuretics, Thiazide (Systemic).



Overdose
For more information on the management of overdose or unintentional ingestion, contact a Poison Control Center (see Poison Control Center Listing ).

Treatment of overdose
Rauwolfia alkaloid overdose should be treated by: Immediate evacuation of the stomach and instillation of an activated charcoal slurry; supportive, symptomatic treatment; if treatment with a vasopressor is necessary, one with a direct action on smooth muscle (phenylephrine, norepinephrine, metaraminol) should be used; monitoring serum electrolyte concentrations and renal function.


Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Rauwolfia Alkaloids and Thiazide Diuretics (Systemic).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to rauwolfia alkaloids, thiazide diuretics, other sulfonamide-type medications, bumetanide, furosemide, or carbonic anhydrase inhibitors

Pregnancy—Reserpine is teratogenic in animals; thiazide diuretics are not recommended for routine use and may cause jaundice, thrombocytopenia, hypokalemia in infant





Breast-feeding—Reserpine and thiazide diuretics are distributed into breast milk; recommended that nursing mothers avoid thiazide diuretics during first month of breast-feeding because of reports of suppression of lactation





Use in the elderly—May be more sensitive to the hypotensive and electrolyte effects
Other medications, especially monoamine oxidase (MAO) inhibitors, cholestyramine, colestipol, digitalis glycosides, or lithium
Other medical problems, especially gallstones, peptic ulcer, ulcerative colitis, mental depression, or anuria or severe renal function impairment

Proper use of this medication
Possible need for control of weight and diet, especially sodium intake

» Patient may not experience symptoms of hypertension; importance of taking medication even if feeling well

» Does not cure, but helps control hypertension; possible need for lifelong therapy; serious consequences of untreated hypertension

Diuretic effects of medications and timing of doses to minimize inconvenience of diuresis

Compliance with therapy; taking medication at the same time(s) each day to maintain the therapeutic effect

Taking with meals or milk to reduce gastrointestinal irritation

» Proper dosing
Missed dose: Taking as soon as possible; not taking if almost time for next dose; not doubling doses

» Proper storage

Precautions while using this medication
Making regular visits to physician to check progress

» Not taking other medications, especially nonprescription sympathomimetics, unless discussed with physician

» Caution if any kind of surgery (including dental surgery) or emergency treatment is required

Possibility of hypokalemia; possible need for additional potassium in diet; not changing diet without first checking with physician

To prevent dehydration, checking with physician if severe nausea, vomiting, or diarrhea occurs and continues

» Caution when driving or doing things requiring alertness because of possible drowsiness or dizziness

» Caution if orthostatic hypotension occurs

» Caution if depression or changes in sleep pattern occur

» Caution in taking alcohol or other central nervous system (CNS) depressants

Diabetics: May increase blood sugar levels

Possible photosensitivity; avoiding unprotected exposure to sun; using protective clothing and sun block product; avoiding use of sunlamp, tanning bed, or tanning booth

Nasal stuffiness may occur; nasal decongestants or other OTC preparations containing sympathomimetics should not be used without first consulting physician or pharmacist

Possible dryness of mouth; using sugarless candy or gum, ice, or saliva substitute for relief; checking with physician or dentist if dry mouth continues for more than 2 weeks


Side/adverse effects
Signs and symptoms of potential side effects, especially electrolyte imbalance, agranulocytosis, allergic reaction, cholecystitis, pancreatitis, hepatic function impairment, hyperuricemia, gout, thrombocytopenia, dizziness, arrhythmias, bradycardia, black tarry stools, bloody vomit, chest pain, drowsiness or faintness, headache, impotence or decreased sexual interest, lack of energy or weakness, mental depression or inability to concentrate, nervousness or anxiety, vivid dreams or nightmares or early-morning sleeplessness, and shortness of breath


General Dosing Information
Dosage must be adjusted to meet the individual requirements of each patient, on the basis of clinical response. The lowest effective dose should be utilized in order to minimize problems with electrolyte imbalance and mental depression.

Fixed-dosage combinations are generally not recommended for initial therapy and are useful for subsequent therapy only when the proportion of the component agents corresponds to the dose of the individual agents, as determined by titration.

If a single daily dose is indicated, it is preferably taken on arising in order to minimize the effect of increased frequency of urination on sleep.

Concurrent administration of potassium supplements may be indicated in patients considered to be at higher risk for developing hypokalemia. Caution in administering potassium supplements is recommended, however, since loss of potassium is not clinically significant in most patients, and supplementation leads to a risk of development of hyperkalemia.

Doses higher than the recommended dose should be used with caution because of the risk of severe mental depression.

A lower dose is recommended in the elderly or severely debilitated.

Antihypertensive effects of rauwolfia alkaloids may not be observed for a few days to several weeks after oral administration and may persist for 1 to 6 weeks after withdrawal of the medication. It is recommended that adjustments in dosage be made every 7 to 14 days to allow the full effects of the preceding dose to occur.

It is recommended that these medications be withdrawn at the first sign of despondency, early-morning insomnia, loss of appetite, impotence, or self-deprecation.

Recent evidence suggests that withdrawal of catecholamine-depleting antihypertensive therapy prior to surgery is not necessary, but that the anesthesiologist must be aware of such therapy. Administration of atropine prior to induction may prevent excessive bradycardia. If a hypotensive episode occurs, use of a weak direct-acting sympathomimetic agent is recommended.

It is recommended that rauwolfia alkaloids be withdrawn 2 weeks before electroconvulsive therapy is employed.

Diet/Nutrition
It is recommended that these medications be taken with food or milk to minimize gastrointestinal upset.

DESERPIDINE AND HYDROCHLOROTHIAZIDE


Oral Dosage Forms

DESERPIDINE AND HYDROCHLOROTHIAZIDE TABLETS

Usual adult dose
Antihypertensive
Oral, 1 tablet two times a day as determined by individual titration with the component agents.


Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.


Usual pediatric dose
Dosage has not been established.

Strength(s) usually available
U.S.—


125 mcg (0.125 mg) of deserpidine and 25 mg of hydrochlorothiazide (Rx) [Oreticyl]


125 mcg (0.125 mg) of deserpidine and 50 mg of hydrochlorothiazide (Rx) [Oreticyl]


250 mcg (0.25 mg) of deserpidine and 25 mg of hydrochlorothiazide (Rx) [Oreticyl Forte]

Canada—
Not commercially available.

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container. Protect from light.

Auxiliary labeling:
   • Take with meals or milk.
   • Do not take other medicines without your doctor's advice.

Note: Check refill frequency to determine compliance in hypertensive patients.



DESERPIDINE AND METHYCLOTHIAZIDE


Oral Dosage Forms

DESERPIDINE AND METHYCLOTHIAZIDE TABLETS

Usual adult dose
Antihypertensive
Oral, 1/2 to 1 tablet a day as determined by individual titration with the component agents.


Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.


Usual pediatric dose
Dosage has not been established.

Strength(s) usually available
U.S.—


250 mcg (0.25 mg) of deserpidine and 5 mg of methyclothiazide (Rx) [Enduronyl]


500 mcg (0.5 mg) of deserpidine and 5 mg of methyclothiazide (Rx) [Enduronyl Forte][Generic]

Canada—


250 mcg (0.25 mg) of deserpidine and 5 mg of methyclothiazide (Rx) [Dureticyl]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container. Protect from light.

Auxiliary labeling:
   • Take with meals or milk.
   • Do not take other medicines without your doctor's advice.

Note: Check refill frequency to determine compliance in hypertensive patients.



RAUWOLFIA SERPENTINA AND BENDROFLUMETHIAZIDE


Oral Dosage Forms

RAUWOLFIA SERPENTINA AND BENDROFLUMETHIAZIDE TABLETS

Usual adult dose
Antihypertensive
Oral, 1 to 4 tablets a day as determined by individual titration with the component agents.


Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.


Usual pediatric dose
Dosage has not been established.

Strength(s) usually available
U.S.—


50 mg of rauwolfia serpentina and 4 mg of bendroflumethiazide (Rx) [Rauzide]

Canada—
Not commercially available.

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container. Protect from light.

Auxiliary labeling:
   • Take with meals or milk.
   • Do not take other medicines without your doctor's advice.

Note: Check refill frequency to determine compliance in hypertensive patients.



RESERPINE AND CHLOROTHIAZIDE


Oral Dosage Forms

RESERPINE AND CHLOROTHIAZIDE TABLETS USP

Usual adult dose
Antihypertensive
Oral, 1 or 2 tablets one or two times a day as determined by individual titration with the component agents.


Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.


Usual pediatric dose
Dosage has not been established.

Strength(s) usually available
U.S.—


125 mcg (0.125 mg) of reserpine and 250 mg of chlorothiazide (Rx) [Diupres] [Diurigen with Reserpine][Generic]


125 mcg (0.125 mg) of reserpine and 500 mg of chlorothiazide (Rx) [Diupres][Generic]

Canada—
Not commercially available.

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight, light-resistant container.

Auxiliary labeling:
   • Take with meals or milk.
   • Do not take other medicines without your doctor's advice.

Note: Check refill frequency to determine compliance in hypertensive patients.



RESERPINE AND CHLORTHALIDONE

Summary of Differences
Pharmacology/pharmacokinetics: Although not chemically the same, chlorthalidone has the same action as the thiazide diuretics.

Protein binding: 90% of chlorthalidone protein binding is to or in red blood cells.


Oral Dosage Forms

RESERPINE AND CHLORTHALIDONE TABLETS

Usual adult dose
Antihypertensive
Oral, 1 or 2 tablets once a day as determined by individual titration with the component agents.


Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.


Usual pediatric dose
Dosage has not been established.

Strength(s) usually available
U.S.—


125 mcg (0.125 mg) of reserpine and 25 mg of chlorthalidone (Rx) [Demi-Regroton]


250 mcg (0.25 mg) of reserpine and 50 mg of chlorthalidone (Rx) [Regroton]

Canada—
Not commercially available.

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container. Protect from light.

Auxiliary labeling:
   • Take with meals or milk.
   • Do not take other medicines without your doctor's advice.

Note: Check refill frequency to determine compliance in hypertensive patients.



RESERPINE AND HYDROCHLOROTHIAZIDE


Oral Dosage Forms

RESERPINE AND HYDROCHLOROTHIAZIDE TABLETS USP

Usual adult dose
Antihypertensive
Oral, 1 tablet one to four times a day as determined by individual titration with the component agents.


Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.


Usual pediatric dose
Dosage has not been established.

Strength(s) usually available
U.S.—
Not commercially available.

Canada—


125 mcg (0.125 mg) of reserpine and 50 mg of hydrochlorothiazide (Rx) [Hydropres]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight, light-resistant container.

Auxiliary labeling:
   • Take with meals or milk.
   • Do not take other medicines without your doctor's advice.

Note: Check refill frequency to determine compliance in hypertensive patients.



RESERPINE AND METHYCLOTHIAZIDE


Oral Dosage Forms

RESERPINE AND METHYCLOTHIAZIDE TABLETS

Usual adult dose
Antihypertensive
Oral, 1 to 4 tablets a day as determined by individual titration with the component agents.


Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.


Usual pediatric dose
Dosage has not been established.

Strength(s) usually available
U.S.—


100 mcg (0.1 mg) of reserpine and 2.5 mg of methyclothiazide (Rx) [Diutensen-R]

Canada—
Not commercially available.

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container. Protect from light.

Auxiliary labeling:
   • Take with meals or milk.
   • Do not take other medicines without your doctor's advice.

Note: Check refill frequency to determine compliance in hypertensive patients.




Revised: 9/08/2000



References

Note: All references used in the development and earlier revisions of this monograph have not yet been incorporated into the computer database and, therefore, are not listed below. Citations for information not yet referenced in the monograph will be provided upon request.

  1. Renese-R package insert (Pfizer—US), Rev 7/90, Rec 6/92.
  1. The fifth report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC V). Arch Intern Med 1993; 153(2): 154-83.
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