WYTENSIN Tablet Ref.[51002] Active ingredients: Guanabenz

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 Wytensin for up to 3 years. There is some evidence that the side effects are doserelated.

The following table shows the incidence of adverse effects, occurring in at least 5% of patients in a study comparing Wytensin 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 Wytensin 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 Wytensin.

1. Sedation:

Wytensin causes sedation or drowsiness in a large fraction of patients. When Wytensin 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:

Wytensin, 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 Wytensin 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 Wytensin is altered in patients with alcohol-induced liver disease. Mean plasma concentrations of Wytensin 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 Wytensin is administered to patients with hypertension and coexisting chronic hepatic dysfunction.

5. Patients with renal impairment:

The disposition of orally administered Wytensin is altered modestly in patients with renal impairment. Wytensin’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 Wytensin dose titration is suggested in patients with coexisting hypertension and renal impairment.

Patients who receive Wytensin should be advised to exercise caution when operating dangerous machinery or driving motor vehicles until it is determined that they do not become drowsy or dizzy from the medication. Patients should be warned that their tolerance for alcohol and other CNS depressants may be diminished. Patients should be advised not to discontinue therapy abruptly.

In clinical trials, no clinically significant laboratory-test abnormalities were identified during either acute or chronic therapy with Wytensin. Tests carried out included CBC, urinalysis, electrolytes, SGOT, bilirubin, alkaline phosphatase, uric acid, BUN, creatinine, glucose, calcium, phosphorus, total protein, and Coombs' test. During long-term administration of Wytensin, there was a small decrease in serum cholesterol and total triglycerides without any change in the high-density lipoprotein fraction. In rare instances an occasional nonprogressive increase in liver enzymes has been observed. However, no clinical evidence of hepatic disease has been found.

Wytensin has not been demonstrated to cause any drug interactions when administered with other drugs, such as digitalis, diuretics, analgesics, anxiolytics, and anti-inflammatory or antiinfective agents, in clinical trials. However, the potential for increased sedation when Wytensin is administered concomitantly with CNS-depressant drugs should be noted.

Pregnancy Category C.

WYTENSIN MAY HAVE ADVERSE EFFECTS ON THE FETUS WHEN ADMINISTERED TO PREGNANT WOMEN. A teratology study in mice has indicated a possible increase in skeletal abnormalities when Wytensin is given orally at doses of 3 to 6 times the maximum recommended human dose of 1.0 mg/kg. These abnormalities, principally costal and vertebral, were not noted in similar studies in rats and rabbits. However, increased fetal loss has been observed after oral Wytensin administration to pregnant rats (14 mg/kg) and rabbits (20 mg/kg). Reproductive studies of Wytensin in rats have shown slightly decreased live-birth indices, decreased fetal survival rate, and decreased pup body weight at oral doses of 6.4 and 9.6 mg/kg. There are no adequate, well-controlled studies in pregnant women. Wytensin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Wytensin is administered to a nursing woman.

The safety and effectiveness of Wytensin in pediatric patients have not been established.

No laboratory-test abnormalities were identified with the use of Wytensin.

No reported dependence or abuse has been associated with the administration of Wytensin.