Data from FDA (Food and Drug Administration, USA) - Curated by EPG Health - Last updated 27 January 2017

Indication(s)

INDICATIONS AND USAGE Tenex (guanfacine hydrochloride) is indicated in the management of hypertension. Tenex may be given alone or in combination with other antihypertensive agents, especially thiazide-type diuretics.

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Advisory information

contraindications
CONTRAINDICATIONS Tenex is contraindicated in patients with known hypersensitivity to guanfacine hydrochloride.
Special warnings and precautions

PRECAUTIONS General Like other antihypertensive agents, Tenex (guanfacine hydrochloride) should be used with caution in patients with severe coronary insufficiency, recent myocardial infarction, cerebrovascular disease, or chronic renal or hepatic failure.

Sedation Tenex, like other orally active central ?2-adrenergic agonists, causes sedation or drowsiness, especially when beginning therapy.

These symptoms are dose-related (see ADVERSE REACTIONS).

When Tenex is used with other centrally active depressants (such as phenothiazines, barbiturates, or benzodiazepines), the potential for additive sedative effects should be considered.

Rebound Abrupt cessation of therapy with orally active central?

2-adrenergic agonists may be associated with increases (from depressed on-therapy levels) in plasma and urinary catecholamines, symptoms of " nervousness and anxiety " and, less commonly, increases in blood pressure to levels significantly greater than those prior to therapy.

Adverse reactions

ADVERSE REACTIONS Adverse reactions noted with Tenex (guanfacine hydrochloride) are similar to those of other drugs of the central ?2-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:

Adverse Reaction Placebo n=59 0.5 mg n=60 1 mg n=61 2 mg n=60 3 mg n=59 Dry Mouth 0 % 10 % 10 % 42 % 54 % Somnolence 8 % 5 % 10 % 13 % 39 % Asthenia 0 % 2 % 3 % 7 % 3 % Dizziness 8 % 12 % 2 % 8 % 15 %

Headache 8 % 13 % 7 % 5 % 3 % Impotence 0 % 0 % 0 % 7 % 3 % Constipation 0 % 2 % 0 % 5 % 15 % Fatigue 2 % 2 % 5 % 8 % 10 % 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 Percent dropouts 0 % 2.0 % 5.0 % 13 % 32 % 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:

Adverse Reaction Placebo n=73 0.5 mg n=72 1 mg n=72 2 mg n=72 3 mg n=72 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 Percent dropouts 6.9 % 4.2 % 3.2 % 6.9 % 8.3 % 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 Guanfacine (n=279) Clonidine (n=278) Dry Mouth 30 % 37 % Somnolence 21 % 35 % Dizziness 11 % 8 % Constipation 10 % 5 % Fatigue 9 % 8 % Headache 4 % 4 % Insomnia 4 % 3 % 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 Gastrointestinal - abdominal pain, diarrhea, dyspepsia, dysphagia, nausea CNS- amnesia, confusion, depression, insomnia, libido decrease ENT disorders - rhinitis, taste perversion, tinnitus Eye disorders - conjunctivitis, iritis, vision disturbance Musculoskeletal - leg cramps, hypokinesia Respiratory - dyspnea

Dermatologic - dermatitis, pruritus, purpura, sweating

Urogenital - testicular disorder, urinary incontinence Other - malaise, paresthesia, paresis 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 Incidence of adverse reactions at end of one year n = 580 n = 580 Dry Mouth 60 % 15 % Drowsiness 33 % 6 % Dizziness 15 % 1 % Constipation 14 % 3 % Weakness 5 % 1 % Headache 4 % 0.2 % Insomnia 5 % 0 % 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).

Postmarketing Experience 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: BODY AS A WHOLE asthenia, chest pain, edema, malaise, tremor 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 MUSCULO-SKELETAL SYSTEM arthralgia, leg cramps, leg pain, myalgia 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.

Usage information

Dosing and administration

DOSAGE AND ADMINISTRATION The recommended initial dose of Tenex (guanfacine hydrochloride) when given alone or in combination with another antihypertensive drug is 1 mg daily given at bedtime to minimize somnolence.

If after 3 to 4 weeks of therapy 1 mg does not give a satisfactory result, a dose of 2 mg may be given, although most of the effect of Tenex is seen at 1 mg (see CLINICAL PHARMACOLOGY).

Higher daily doses have been used, but adverse reactions increase significantly with doses above 3 mg/day.

The frequency of rebound hypertension is low, but it can occur.

When rebound occurs, it does so after 2 - 4 days, which is delayed compared with clonidine hydrochloride.

This is consistent with the longer half-life of guanfacine.

In most cases, after abrupt withdrawal of guanfacine, blood pressure returns to pretreatment levels slowly (within 2 - 4 days) without ill effects.

Use in special populations

Pediatric Use Safety and effectiveness in children under 12 years of age have not been demonstrated.

Therefore, the use of Tenex in this age group is not recommended.

There have been spontaneous postmarketing reports of mania and aggressive behavioral changes in pediatric patients with attention-deficit hyperactivity disorder (ADHD) receiving Tenex.

The reported cases were from a single center.

All patients had medical or family risk factors for bipolar disorder.

All patients recovered upon discontinuation of guanfacine HCl.

Hallucinations have been reported in pediatric patients receiving Tenex for treatment of attention-deficit hyperactivity disorder.

Geriatric Use Clinical studies of Tenex did not include sufficient numbers of subjects aged 65 and over to determine whether they responded 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 (see CLINICAL PHARMACOLOGY: Pharmacokinetics).

Pregnancy and lactation
Nursing Mothers It is not known whether Tenex (guanfacine hydrochloride) is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Tenex is administered to a nursing woman. Experiments with rats have shown that guanfacine is excreted in the milk.

Interactions

Drug Interactions 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 Rebound above).

Anticoagulants 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).

More information

Category Value
Authorisation number NDA019032
Orphan designation No
Product NDC 67857-706,67857-705
Date Last Revised 08-05-2013
Type HUMAN PRESCRIPTION DRUG
RXCUI 197746
Marketing authorisation holder Promius Pharma, LLC