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Reserpine, Hydralazine, and Hydrochlorothiazide (Systemic)

Primary: CV408

Commonly used brand name(s): Cam-Ap-Es; Cherapas; Ser-A-Gen; Ser-Ap-Es; Seralazide; Serpazide; Tri-Hydroserpine; Unipres.

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





Hypertension (treatment)—This combination is indicated for treatment of hypertension . {01}
—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.


Reserpine—See Rauwolfia Alkaloids (Systemic).

Hydralazine—See Hydralazine (Systemic).

Hydrochlorothiazide—See Diuretics, Thiazide (Systemic).

Precautions to Consider

Reserpine—See Rauwolfia Alkaloids (Systemic).

Hydralazine—See Hydralazine (Systemic).

Hydrochlorothiazide—See Diuretics, Thiazide (Systemic) .

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

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 of serum electrolyte concentrations and renal function; the patient should be observed for at least 72 hours.

Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Reserpine, Hydralazine, and Hydrochlorothiazide (Systemic).

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

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

Pregnancy—Reserpine teratogenic in animals; hydralazine reported to cause blood problems in infants of mothers who took hydralazine and causes birth defects in animals; hydrochlorothiazide not recommended for routine use and may cause jaundice, thrombocytopenia, hypokalemia in infant

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

Use in the elderly—May be more sensitive to the CNS depressant, hypotensive, and electrolyte effects

Dental—May decrease or inhibit salivary flow
Other medications, especially monoamine oxidase (MAO) inhibitors, diazoxide, cholestyramine, colestipol, digitalis glycosides, or lithium
Other medical problems, especially gallstones, peptic ulcer, ulcerative colitis, mental depression, coronary artery disease, rheumatic heart disease, 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 medication 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

» Caution when driving or doing things requiring alertness because of possible headache, 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

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

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, angina pectoris, cutaneous vasculitis, lymphadenopathy, peripheral neuritis, SLE-like syndrome, cholecystitis, pancreatitis, hepatic function impairment, hyperuricemia, gout, thrombocytopenia, dizziness, arrhythmias, bradycardia, black tarry stools, bloody vomit, 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 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.

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. Patients with impaired renal function may require lower doses of hydralazine.

Incidence and severity of some of the side effects of hydralazine can be minimized if the dosage is increased slowly to its therapeutic level. Reserpine may reduce or prevent the tachycardia caused by hydralazine. In addition, if necessary, some side effects (especially tachycardia, headache, and dizziness) may be less pronounced if beta-adrenergic blocking agents are administered concurrently, although caution is necessary because of the possible interaction with reserpine.

All patients may be divided into 2 groups: slow and fast acetylators of hydralazine. Patients who are slow acetylators may be more prone to development of adverse effects and may require lower-than-usual doses. Eskimo, Oriental, and American Indian populations have the lowest prevalence of slow acetylators, while Egyptian, Israeli, Scandinavian, other Caucasian, and black populations have the highest prevalence of slow acetylators.

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.

Antihypertensive effects 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 this medication be taken with food or milk to minimize gastrointestinal upset. In addition, food may enhance the bioavailability of hydralazine by reducing first-pass metabolism in the gastrointestinal wall.

Tolerance to the antihypertensive effects of hydralazine may develop with chronic administration, as a result of fluid retention and expanded plasma volume and reflex activation of the sympathetic nervous system, which increases heart rate and cardiac output. Concurrent administration with a diuretic may decrease this likelihood and will enhance the antihypertensive effects.

To avoid a sudden increase in blood pressure, patients on hydralazine who have shown a significant decrease in blood pressure should have the medication withdrawn gradually at cessation of therapy.

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.

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 due to reserpine, although the tachycardia caused by hydralazine may also modify this effect somewhat. If a hypotensive episode occurs, use of a weak direct-acting sympathomimetic agent is recommended.

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

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

It is recommended that hydralazine therapy be discontinued if a systemic lupus erythematosus (SLE)-like syndrome occurs.

There is no substantial evidence that use of hydralazine in the treatment of hypertension in patients with systemic vasculitis or lupus erythematosus exacerbates the underlying disease process.

Peripheral neuritis has been observed in some patients on hydralazine therapy. Evidence suggests that this may be due to an antipyridoxine effect. Discontinuation of hydralazine or continuation of hydralazine with supplemental pyridoxine (vitamin B 6)—100 to 200 mg per day—usually results in remission of the neuritis over a period of 4 to 6 weeks.

Oral Dosage Forms


Usual adult dose
Oral, 1 or 2 tablets three times a day as determined by individual titration with the component agents. {01}

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

Usual pediatric dose
Safety and efficacy have not been established.

Strength(s) usually available

100 mcg (0.1 mg) of reserpine, 25 mg of hydralazine hydrochloride, and 15 mg of hydrochlorothiazide (Rx) [Cam-Ap-Es] [Cherapas] [Ser-A-Gen] [Seralazide] [Ser-Ap-Es] [Serpazide] [Tri-Hydroserpine] [Unipres][Generic]


100 mcg (0.1 mg) of reserpine, 25 mg of hydralazine hydrochloride, and 15 mg of hydrochlorothiazide (Rx) [Ser-Ap-Es]

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:
   • Avoid alcoholic beverages.
   • 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: 08/19/1998


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. Ser-Ap-Es package insert (CIBA—US), Rev 11/87, Rec 5/92.
  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.