Guanabenz Acetate Information
Guanabenz acetate (Guanabenz acetate)
Guanabenz acetate (Guanabenz acetate) Description
Guanabenz acetate (Guanabenz acetate) USP, an antihypertensive agent for oral administration, is an aminoguanidine derivative. The chemical name for Guanabenz acetate (Guanabenz acetate) USP is [(2,6-Dichlorobenzylidene)amino] guanidine monoacetate, and its structural formula is:
CHClN•CHO M.W. 291.14
It is an odorless, white to off-white, crystalline substance, sparingly soluble in water and soluble in alcohol. Each tablet of guanabenz USP acetate is equivalent to 4 mg or 8 mg of free guanabenz base. Guanabenz acetate (Guanabenz acetate) USP, available as 4 mg or 8 mg tablets for oral administration, contains the following inactive ingredients: FD&C Blue #2 Aluminum Lake (8 mg only), lactose monohydrate, magnesium stearate, microcrystalline cellulose, and ferric oxide.
Guanabenz acetate (Guanabenz acetate) Clinical Pharmacology
Guanabenz acetate (Guanabenz acetate) is an orally active central alpha-2 adrenergic agonist. Its antihypertensive action appears to be mediated via stimulation of central alpha adrenergic receptors, resulting in a decrease of sympathetic outflow from the brain at the bulbar level to the peripheral circulatory system.
The onset of the antihypertensive action of guanabenz begins within 60 minutes after a single oral dose and reaches a peak effect within two to four hours. The effect of an acute single dose is reduced appreciably six to eight hours after administration, and blood pressure approaches baseline values within 12 hours of administration.
The acute antihypertensive effect of guanabenz occurs without major changes in peripheral resistance, but its chronic effect appears to be a decrease in peripheral resistance. A decrease in blood pressure is seen in both the supine and standing positions without alterations of normal postural mechanisms, so that postural hypotension has not been observed. Guanabenz decreases pulse rate by about 5 beats per minute. Cardiac output and left ventricular ejection fraction are unchanged during long-term therapy.
In clinical trials, Guanabenz acetate (Guanabenz acetate) , given orally to hypertensive patients, effectively controlled blood pressure without any significant effect on glomerular filtration rate, renal blood flow, body fluid volume or body weight. Guanabenz given parenterally to dogs has produced a natriuresis. Similarly, hypertensive subjects, 24 hours after salt loading, have shown a decrease in blood pressure and a natriuresis (5% to 240% increase in sodium excretion) following a single oral dose of Guanabenz acetate (Guanabenz acetate) . After seven consecutive days of administration and effective blood-pressure control, no significant change on glomerular filtration rate, renal blood flow, or body weight was observed. However, in clinical trials of six to thirty months duration, hypertensive patients with effective blood-pressure control by guanabenz lost one to four pounds of body weight. The mechanism of this weight loss has not been established. Tolerance to the antihypertensive effect of guanabenz has not been observed.
During long-term administration of guanabenz, there is a small decrease in serum cholesterol and total triglycerides without any change in the high-density lipoprotein fraction. Plasma norepinephrine, serum dopamine beta-hydroxylase and plasma renin activity are decreased during chronic administration of guanabenz. No changes in serum electrolytes, uric acid, bloodurea nitrogen, calcium, or glucose have been observed.
Guanabenz and hydrochlorothiazide have been shown to have at least partially additive effects in patients not responding adequately to either drug alone.
Guanabenz acetate (Guanabenz acetate) Indications And Usage
Guanabenz acetate (Guanabenz acetate) tablets are indicated in the treatment of hypertension. It may be employed alone or in combination with a thiazide diuretic.
Guanabenz acetate (Guanabenz acetate) Contraindications
Guanabenz acetate (Guanabenz acetate) is contraindicated in patients with a known sensitivity to the drug or any of the tablet ingredients.
Guanabenz acetate (Guanabenz acetate) Precautions
1. Sedation: Guanabenz causes sedation or drowsiness in a large fraction of patients. When guanabenz is used with centrally active depressants, such as phenothiazines, barbiturates, and benzodiazepines, the potential for additive sedative effects should be considered.
2. Patients with vascular insufficiency: Guanabenz, like other antihypertensive agents, should be used with caution in patients with severe coronary insufficiency, recent myocardial infarction, cerebrovascular disease, or severe hepatic or renal failure.
3. Rebound: Sudden cessation of therapy with central alpha agonists like guanabenz may rarely result in “overshoot” hypertension and more commonly produces an increase in serum catecholamines and subjective symptomatology.
4. Patients with hepatic impairment: The disposition of orally administered Guanabenz acetate (Guanabenz acetate) is altered in patients with alcohol-induced liver disease. Mean plasma concentrations of guanabenz were higher in these patients than in healthy subjects. The clinical significance of this finding is unknown. However, careful monitoring of blood pressure is suggested when guanabenz is administered to patients with hypertension and coexisting chronic hepatic dysfunction.
5. Patients with renal impairment: The disposition of orally administered Guanabenz acetate (Guanabenz acetate) is altered modestly in patients with renal impairment. Guanabenz’s half-life is prolonged and clearance decreased, more so in patients on hemodialysis. The clinical significance of these findings is unknown. Careful monitoring of blood pressure during guanabenz dose titration is suggested in patients with coexisting hypertension and renal impairment.
Clinical studies of guanabenz did not include sufficient number of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.
In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
Guanabenz acetate (Guanabenz acetate) Adverse Reactions
The incidence of adverse effects has been ascertained from controlled clinical studies conducted in the United States and is based on data from 859 patients who received guanabenz for up to 3 years. There is some evidence that the side effects are dose-related.
The following table shows the incidence of adverse effects occurring in at least 5% of patients in a study comparing Guanabenz acetate (Guanabenz acetate) to placebo, at a starting dose of 8 mg b.i.d.
In other controlled clinical trials at the starting dose of 16 mg/day in 476 patients, the incidence of dry mouth was slightly higher (38%) and that of dizziness was slightly lower (12%), but the incidence of the most frequent adverse effects was similar to the placebo-controlled trial. Although these side effects were not serious, they led to discontinuation of treatment about 15% of the time. In more recent studies using an initial dose of 8 mg/day in 274 patients, the incidence of drowsiness or sedation was lower, about 20%.
Other adverse effects were reported during clinical trials with guanabenz but are not clearly distinguishable from placebo effects and occurred with a frequency of 3% or less:
Cardiovascular-chest pain, edema, arrhythmias, palpitations.
Gastrointestinal-nausea, epigastric pain, diarrhea, vomiting, constipation, abdominal discomfort.
Central nervous system-anxiety, ataxia, depression, sleep disturbances.
ENT disorders-nasal congestion.
Eye disorders-blurring of vision.
Musculoskeletal-aches in extremities, muscle aches.
Respiratory-dyspnea.
Dermatologic-rash, pruritus.
Urogenital-urinary frequency, disturbances of sexual function (decreased libido, impotence).
Other-gynecomastia, taste disorders.
In very rare instances atrioventricular dysfunction, up to and including complete AV block, has been caused by guanabenz.
Guanabenz acetate (Guanabenz acetate) Drug Abuse And Dependence
No reported dependence or abuse has been associated with the administration of guanabenz.
Guanabenz acetate (Guanabenz acetate) Overdosage
Accidental ingestion of guanabenz caused hypotension, somnolence, lethargy, irritability, miosis, and bradycardia in two pediatric patients aged one and three years. Gastric lavage and administration of pressor substances, fluids, and oral activated charcoal resulted in complete and uneventful recovery within 12 hours in both patients.
Since experience with accidental overdosage is limited, the suggested treatment is mainly supportive while the drug is being eliminated from the body and until the patient is no longer symptomatic. Vital signs and fluid balance should be carefully monitored. An adequate airway should be maintained and, if indicated, assisted respiration instituted. There are no data available on the dialyzability of guanabenz.
Guanabenz acetate (Guanabenz acetate) Dosage And Administration
Dosage with Guanabenz acetate (Guanabenz acetate) tablets should be individualized. A starting dose of 4 mg twice a day is recommended, whether Guanabenz acetate (Guanabenz acetate) tablets are used alone or with a thiazide diuretic. Dosage may be increased in increments of 4 to 8 mg per day every one to two weeks, depending on the patient’s response. The maximum dose studied to date has been 32 mg twice daily, but doses as high as this are rarely needed.
Guanabenz acetate (Guanabenz acetate) How Supplied
Guanabenz acetate (Guanabenz acetate) Tablets USP are available as peach, round, compressed tablets, debossed with company logo on one side and “4226” on the other side, containing Guanabenz acetate (Guanabenz acetate) USP equivalent to 4 mg guanabenz packaged in bottles of 100 tablets; and as grey, round, bisected compressed tablets, debossed with company logo on one side and “4227” on the other side, containing Guanabenz acetate (Guanabenz acetate) USP equivalent to 8 mg guanabenz packaged in bottles of 100 tablets.
PHARMACIST: Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required).
Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].
Manufactured In Ireland By: 0172
IVAX PHARMACEUTICALS IRELAND 01/08
Waterford, Ireland B7
Manufactured For:
IVAX PHARMACEUTICALS, INC.
Miami, FL 33137
Distributed By:
TEVA PHARMACEUTICALS USA
Sellersville, PA 18960
Guanabenz acetate (Guanabenz acetate) Principal Display Panel
Guanabenz acetate (Guanabenz acetate)
Tablets USP
4 mg
*Each tablet contains Guanabenz acetate (Guanabenz acetate) , USP equivalent to 4 mg guanabenz
Rx only
100 TABLETS
TEVA
Guanabenz acetate (Guanabenz acetate) Principal Display Panel
Guanabenz acetate (Guanabenz acetate)
Tablets USP
8 mg
*Each tablet contains Guanabenz acetate (Guanabenz acetate) , USP equivalent to 8 mg guanabenz
Rx only
100 TABLETS
TEVA
