Professional Information
Guanabenz (Systemic)
VA CLASSIFICATION
Primary: CV409
Commonly used brand name(s): Wytensin.
Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).
†Not commercially available in Canada.
Category:
Antihypertensive—
Indications
Accepted
Hypertension (treatment)—Guanabenz is indicated for treatment of hypertension {02} {03} {04} {05}. Because it usually does not cause postural hypotension, guanabenz may be useful as a substitute for other central adrenergic blockers in patients who cannot tolerate these agents because of severe orthostatic hypotension.
—For additional information on initial therapeutic guidelines related to the treatment of hypertension, see Appendix III.
Pharmacology/Pharmacokinetics
Physicochemical characteristics:
Molecular weight—
Guanabenz acetate: 291.14 {07}
Mechanism of action/Effect:
Guanabenz is a centrally acting alpha-2 adrenergic agonist {03}. The antihypertensive effect is thought to be due to central alpha-adrenergic stimulation, which results in a decreased sympathetic outflow to the heart, kidneys, and peripheral vasculature; decreased systolic and diastolic blood pressure; and slight slowing of pulse rate. Chronic administration of guanabenz also causes a decrease in peripheral vascular resistance.
Absorption:
Approximately 75% absorbed from gastrointestinal tract; however, bioavailability is very low because of extensive first-pass metabolism {03}.
Protein binding:
Very high (90%). {06}
Biotransformation:
Hepatic. {06}
Half-life:
Average, 6 hours. {03}
Onset of action:
Within 60 minutes (after a single dose). {03}
Time to peak plasma concentration
2 to 5 hours. {06}
Time to peak effect
2 to 4 hours. {03}
Duration of action:
12 hours (after a single dose). {03}
Elimination:
Renal (less than 1% unchanged); fecal, about 16%. {06}
Precautions to Consider
Carcinogenicity
Studies in rats at doses up to 10 times the maximum recommended human dose have not shown that guanabenz causes carcinogenic effects. {03}
Mutagenicity
Dose-related increases in the number of mutants occurred in one (TA 1537) of five Salmonella typhimurium strains in the Ames test at doses of 200 to 500 mcg per plate or 30 to 50 mcg per mL in suspension {03}. No mutagenic activity was seen in other assays {03}.
Pregnancy/Reproduction
Fertility—
Guanabenz has been found to impair fertility in both male and female rats given high doses (9.6 mg per kg of body weight [mg/kg]). {03}
Pregnancy—
Studies have not been done in humans {03}.
Animal studies suggest that guanabenz crosses the placenta. Studies in mice have shown that guanabenz at doses of 3 to 6 times the maximum recommended human dose of 1 mg/kg causes an increase in skeletal abnormalities; these did not occur in rabbits or rats {03}. Other studies have found increased fetal loss in rats and rabbits given 14 to 20 mg/kg. Slightly decreased live-birth indexes, decreased fetal survival rate, and decreased pup body weight occurred in rats given 6.4 to 9.6 mg/kg. {01} {03}
FDA Pregnancy Category C {03}.
Breast-feeding
It is not known whether guanabenz is distributed into breast milk {03}. However, problems in humans have not been documented.
Pediatrics
Appropriate studies on the relationship of age to the effects of guanabenz have not been performed in the pediatric population {03}. Safety and efficacy have not been established {03}.
Geriatrics
Although appropriate studies on the relationship of age to the effects of guanabenz have not been performed in the geriatric population, no geriatrics-specific problems have been documented to date. However, elderly patients are more likely to have age-related renal function impairment, which may require caution in patients receiving guanabenz. In addition, elderly patients may be more sensitive to the hypotensive and sedative effects of guanabenz.
Dental
Use of guanabenz may decrease or inhibit salivary flow, thus contributing to the development of caries, periodontal disease, oral candidiasis, and discomfort.
Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):
Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.
Alcohol or
Central nervous system (CNS) depression–producing medications (See Appendix II ) (concurrent use may enhance the CNS depressant effects of either these medications or guanabenz {03})
Anti-inflammatory drugs, nonsteroidal (NSAIDs), especially indomethacin (concurrent use may reduce antihypertensive effects of guanabenz; indomethacin, and possibly other NSAIDs, may antagonize the antihypertensive effect by inhibiting renal prostaglandin synthesis and/or by causing sodium and fluid retention; the patient should be carefully monitored to confirm that the desired effect is being obtained)
Beta-adrenergic blocking agents, ophthalmic (if significant systemic absorption of ophthalmic beta-adrenergic blocking agents occurs, concurrent use may increase the hypotensive effect of guanabenz)
» Beta-adrenergic blocking agents, systemic or
Hypotension-producing medications, other (See Appendix II ) (antihypertensive effects may be potentiated when these medications are used concurrently with guanabenz; although some antihypertensive and/or diuretic combinations are frequently used for therapeutic advantage, dosage adjustments may be necessary during concurrent use)
(when therapy is discontinued in patients receiving a systemic beta-adrenergic blocking agent and guanabenz concurrently, the beta-adrenergic blocking agent should be gradually discontinued in order to avoid beta-adrenergic blocking agent–withdrawal hypertensive crisis; blood pressure control may also be impaired when the two are combined)
Sympathomimetics (concurrent use may reduce the antihypertensive effects of guanabenz; the patient should be carefully monitored to confirm that the desired effect is being obtained)
Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):
With physiology/laboratory test values
Cholesterol and total triglyceride (serum values may be reduced with chronic administration {03})
Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).
Risk-benefit should be considered when the following medical problems exist
Cerebrovascular disease or
Coronary insufficiency or
Myocardial infarction, recent (may be aggravated by reduced blood pressure {03})
Hepatic function impairment (plasma concentrations of guanabenz may increase; careful monitoring of blood pressure during dosage titration is recommended {01} {03})
Renal function impairment (half-life of guanabenz is increased and clearance is decreased; careful monitoring of blood pressure during dosage titration is recommended {01} {02} {03})
Sensitivity to guanabenz{01}
Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):
» Blood pressure measurements (recommended at periodic intervals in patients being treated for hypertension; selected patients may be trained to perform blood pressure measurements at home and report the results at regular physician visits)
Side/Adverse Effects
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:
Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
Dizziness
drowsiness
dryness of mouth
weakness
Note: Incidence of drowsiness is dose-related and usually declines with continued administration.
Incidence less frequent or rare
Decreased sexual ability
headache
nausea
Those indicating possible withdrawal and the need for medical attention if they occur after medication is abruptly discontinued
Anxiety or tenseness
chest pain
fast or irregular heartbeat
headache
increased salivation
increase in sweating
nausea or vomiting
nervousness or restlessness
shaking or trembling of hands or fingers
stomach cramps
trouble in sleeping {08}
Note: The above are symptoms of sympathetic overactivity {08}; elevation of blood pressure above baseline levels occurs rarely {03}. The risk appears to be increased in patients receiving doses of greater than 32 mg of guanabenz per day {08}.
Overdose
For specific information on the agents used in the management of guanabenz overdose, see: • Atropine in Anticholinergics/Antispasmodics (Systemic) monograph;
• Charcoal (Oral-Local) monograph; and/or
• Dopamine in Sympathomimetic Agents—Cardiovascular Use (Systemic) monograph.
For more information on the management of overdose or unintentional ingestion, contact a Poison Control Center (see Poison Control Center Listing ).
Clinical effects of overdose
The following effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:
Bradycardia{03}{09} (slow heartbeat)
hypotension{03}{09} (dizziness, severe)
irritability{03}
lethargy{03}{09} (unusual tiredness or weakness)
miosis{03} (pinpoint pupils)
somnolence{03}
Treatment of overdose
To decrease absorption:
Gastric lavage and administration of activated charcoal.
Specific treatment:
Treatment is mainly supportive. Maintaining adequate airway and fluid balance is recommended {03}.
For bradycardia: Atropine has been used successfully {09}.
For hypotension: Vasopressor agents, such as dopamine, have been used successfully {03} {09}.
Monitoring:
Carefully monitor vital signs and fluid balance {03}.
Supportive care:
Patients in whom intentional overdose is known or suspected should be referred for psychiatric evaluation.
Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Guanabenz (Systemic) .
In providing consultation, consider emphasizing the following selected information (» = major clinical significance):
Before using this medication
» Conditions affecting use, especially:
Sensitivity to guanabenz
Pregnancy—High doses in animals cause decreased fertility, birth defects, and fetal death
Use in the elderly—Increased sensitivity to hypotensive and sedative effects
Dental—May decrease or inhibit salivary flow
Other medications, especially systemic beta-adrenergic blocking agents
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
Compliance with therapy; taking medication at the same time(s) each day to maintain the therapeutic effect
» Proper dosing
Missed dose: Taking as soon as possible; not taking if almost time for next dose; checking with physician if two or more doses in a row are missed; possible unpleasant effects if stopped abruptly
» Proper storage
Precautions while using this medication
Making regular visits to physician to check progress
Checking with physician before discontinuing medication; possible need for gradual dosage reduction
Caution if any kind of surgery (including dental surgery) or emergency treatment is required
» Not taking other medications, especially nonprescription sympathomimetics, unless discussed with physician
» Caution in taking alcohol or other CNS depressants
» Caution when driving or doing things requiring alertness because of possible dizziness or drowsiness
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 of potential side effects, especially signs and symptoms of overdose or withdrawal reaction
General Dosing Information
It is recommended that the last daily dose be taken at bedtime to ensure overnight control of blood pressure and reduce daytime drowsiness.
Recent evidence suggests that withdrawal of antihypertensive therapy prior to surgery is not necessary, but that the anesthesiologist must be aware of such therapy.
The possibility of withdrawal syndrome should be kept in mind if guanabenz is discontinued abruptly, since rebound hypertension occurs rarely.
Oral Dosage Forms
GUANABENZ ACETATE TABLETS USP
Usual adult dose
Antihypertensive
Oral, 4 mg two times a day initially, the dosage being increased if necessary in increments of 4 to 8 mg per day every one to two weeks up to the minimum effective dose {02} {03}.
Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.
Usual adult prescribing limits
32 mg per day {03}.
Usual pediatric dose
Safety and efficacy have not been established. {03}
Strength(s) usually available
U.S.—
4 mg (Rx) [Wytensin (lactose)]
8 mg (Rx) [Wytensin (lactose)]
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:
• Do not take other medicines without your doctor's advice.
• May cause dizziness.
• May cause drowsiness.
Revised: 08/19/1998
References
- Wytensin package insert (Wyeth—US), 8/8/88.
- Wytensin package insert (Wyeth—US), Rev 11/89, Rec 6/92.
- Wytensin package insert (Wyeth—US), Rev 1/94, Rec 10/95.
- McMahon FG, Ryan JR, Jain AK, Vargas R, Vanov SK. Guanabenz in essential hypertension. Clin Pharmacol Ther 1977; 21(3): 272-7.
- Walker BR, Schneider BE, Gold JA. A two-year evaluation of guanabenz in the treatment of hypertension. Curr Ther Res 1980; 27(6): 784-96.
- Meacham RH, Emmett M, Kyriakopoulos AA, Chiang ST, et al. Disposition of C-guanabenz in patients with essential hypertension. Clin Pharmacol Ther 1980; 27(1): 44-52.
- Canada JR, editor. USP dictionary of USAN and international drug names 1998. Rockville, MD: The United States Pharmacopeial Convention Inc; 1997.
- Ram CV, Holland OB, Fairchild C, Gomez-Sanchez CE. Withdrawal syndrome following cessation of guanabenz therapy. J Clin Pharmacol 1979; 19: 148-50.
- Hall AH, Smolinske SC, Kulig KW, Rumack BH. Guanabenz overdose. Ann Intern Med 1985; 102: 787-8.
- 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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