"The European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) has recommended the marketing of selexipag (Uptravi, Actelion Registration Ltd) for the treatment of adults with pulmonary arterial hypertension (PAH)./"...
Adverse reactions noted with Tenex (guanfacine hydrochloride) are similar to those of other drugs of the central α2-adrenoreceptor agonist class: dry mouth, sedation (somnolence), weakness (asthenia), dizziness, constipation, and impotence. While the reactions are common, most are mild and tend to disappear on continued dosing.
Skin rash with exfoliation has been reported in a few cases; although clear cause and effect relationships to Tenex could not be established, should a rash occur, Tenex should be discontinued and the patient monitored appropriately.
In the dose-response monotherapy study described under CLINICAL PHARMACOLOGY, the frequency of the most commonly observed adverse reactions showed a dose relationship from 0.5 to 3 mg as follows:
The percent of patients who dropped out because of adverse reactions are shown below for each dosage group.
|Placebo||0.5 mg||1 mg||2 mg||3 mg|
The most common reasons for dropouts among patients who received guanfacine were dry mouth, somnolence, dizziness, fatigue, weakness, and constipation.
In the 12-week, placebo-controlled, dose-response study of guanfacine administered with 25 mg chlorthalidone at bedtime, the frequency of the most commonly observed adverse reactions showed a clear dose relationship from 0.5 to 3 mg as follows:
|Dry Mouth||5 (7%)||4 (5%)||6 (8%)||8 (11%)||20 (28%)|
|Somnolence||1 (1%)||3 (4%)||0 (0%)||1 (1%)||10 (14%)|
|Asthenia||0 (0%)||2 (3%)||0 (0%)||2 (2%)||7 (10%)|
|Dizziness||2 (2%)||1 (1%)||3 (4%)||6 (8%)||3 (4%)|
|Headache||3 (4%)||4 (3%)||3 (4%)||1 (1%)||2 (2%)|
|Impotence||1 (1%)||1 (0%)||0 (0%)||1 (1%)||3 (4%)|
|Constipation||0 (0%)||0 (0%)||0 (0%)||1 (1%)||1 (1%)|
|Fatigue||3 (3%)||2 (3%)||2 (3%)||5 (6%)||3 (4%)|
There were 41 premature terminations because of adverse reactions in this study. The percent of patients who dropped out and the dose at which the dropout occurred were as follows:
|Dose||Placebo||0.5 mg||1 mg||2 mg||3 mg|
Reasons for dropouts among patients who received guanfacine were: somnolence, headache, weakness, dry mouth, dizziness, impotence, insomnia, constipation, syncope, urinary incontinence, conjunctivitis, paresthesia, and dermatitis.
In a second 12-week placebo-controlled combination therapy study in which the dose could be adjusted upward to 3 mg per day in 1-mg increments at 3-week intervals, i.e., a setting more similar to ordinary clinical use, the most commonly recorded reactions were: dry mouth, 47%; constipation, 16%; fatigue, 12%; somnolence, 10%; asthenia, 6%; dizziness, 6%; headache, 4%; and insomnia, 4%.
Reasons for dropouts among patients who received guanfacine were: somnolence, dry mouth, dizziness, impotence, constipation, confusion, depression, and palpitations.
In the clonidine/guanfacine comparison described in CLINICAL PHARMACOLOGY, the most common adverse reactions noted were as follows:
Adverse reactions occurring in 3% or less of patients in the three controlled trials of Tenex (guanfacine hydrochloride) with a diuretic were:
Cardiovascular- bradycardia, palpitations, substernal pain
Eye disorders- conjunctivitis, iritis, vision disturbance
Musculoskeletal- leg cramps, hypokinesia
Urogenital- testicular disorder, urinary incontinence
Adverse reaction reports tend to decrease over time. In an open-label trial of one year's duration, 580 hypertensive subjects were given guanfacine, titrated to achieve goal blood pressure, alone (51%), with diuretic (38%), with beta blocker (3%), with diuretic plus beta blocker (6%), or with diuretic plus vasodilator (2%). The mean daily dose of guanfacine reached was 4.7 mg.
|Adverse Reaction||Incidence of adverse reactions at any time during the study
n = 580
|Incidence of adverse reactions at end of one year
n = 580
There were 52 (8.9%) dropouts due to adverse effects in this 1-year trial. The causes were: dry mouth (n = 20), weakness (n = 12), constipation (n = 7), somnolence (n = 3), nausea (n = 3), orthostatic hypotension (n = 2), insomnia (n = 1), rash (n = 1), nightmares (n = 1), headache (n = 1), and depression (n = 1).
An open-label postmarketing study involving 21,718 patients was conducted to assess the safety of Tenex (guanfacine hydrochloride) 1 mg/day given at bedtime for 28 days. Tenex was administered with or without other antihypertensive agents. Adverse events reported in the postmarketing study at an incidence greater than 1% included dry mouth, dizziness, somnolence, fatigue, headache and nausea. The most commonly reported adverse events in this study were the same as those observed in controlled clinical trials.
Less frequent, possibly Tenex-related events observed in the postmarketing study and/or reported spontaneously include:
Cardiovascular: bradycardia, palpitations, syncope, tachycardia
Central Nervous System: paresthesias, vertigo
Eye Disorders: blurred vision
Gastrointestinal System: abdominal pain, constipation, diarrhea, dyspepsia
Liver And Billiary System: abnormal liver function tests
Psychiatric: agitation, anxiety, confusion, depression, insomnia, nervousness
Rreproductive System: Male- impotence
Respiratory System: dyspnea
Skin And Appendages: alopecia, dermatitis, exfoliative dermatitis, pruritus, rash
Special Senses: alterations in taste
Urinary System: nocturia, urinary frequency
Rare, serious disorders with no definitive cause and effect relationship to Tenex have been reported spontaneously and/or in the postmarketing study. These events include acute renal failure, cardiac fibrillation, cerebrovascular accident, congestive heart failure, heart block, and myocardial infarction.
Drug Abuse And Dependence
No reported abuse or dependence has been associated with the administration of Tenex (guanfacine hdyrochloride).
Read the Tenex (guanfacine hydrochloride tablets) Side Effects Center for a complete guide to possible side effects
The potential for increased sedation when Tenex is given with other CNS-depressant drugs should be appreciated.
The administration of guanfacine concomitantly with a known microsomal enzyme inducer (phenobarbital or phenytoin) to two patients with renal impairment reportedly resulted in significant reductions in elimination half-life and plasma concentration. In such cases, therefore, more frequent dosing may be required to achieve or maintain the desired hypotensive response. Further, if guanfacine is to be discontinued in such patients, careful tapering of the dosage may be necessary in order to avoid rebound phenomena (see section on Rebound under PRECAUTIONS).
Ten patients who were stabilized on oral anticoagulants were given guanfacine, 1 - 2 mg/day, for 4 weeks. No changes were observed in the degree of anticoagulation.
In several well-controlled studies, guanfacine was administered together with diuretics with no drug interactions reported. In the long-term safety studies, Tenex was given concomitantly with many drugs without evidence of any interactions. The principal drugs given (number of patients in parentheses) were: cardiac glycosides (115), sedatives and hypnotics (103), coronary vasodilators (52), oral hypoglycemics (45), cough and cold preparations (45), NSAIDs (38), antihyperlipidemics (29), antigout drugs (24), oral contraceptives (18), bronchodilators (13), insulin (10), and beta blockers (10).
Drug/Laboratory Test Interactions
No laboratory test abnormalities related to the use of Tenex (guanfacine hydrochloride) have been identified.This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 7/18/2013
Additional Tenex Information
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