Side Effects of Tenex (guanfacine)

Tenex (guanfacine) is a centrally-acting alpha 2A adrenergic receptor agonist used alone or in combination with other medications to treat hypertension (high blood pressure). 

Tenex reduces blood pressure by reducing the resistance of blood flow in the blood vessels, and by decreasing heart rate. Intuniv is the extended release form of guanfacine.

Common side effects of Tenex include

• tiredness,
• sleepiness,
• trouble sleeping,
• nausea,
• low blood pressure,
• stomach pain, and
• dizziness.

Serious side effects of Tenex include

• hair loss,
• memory impairment,
• heart failure,
• depression,
• seizures,
• skin problems,
• difficulty swallowing,
• edema,
• hallucinations,
• hypersensitivity or allergic reactions,
• mania,
• heart attack,
• rebound hypertension,
• kidney failure,
• rapid heartbeat, and
• visual disturbance.

Drug interactions of Tenex include rifampin and St. John's wort, which may reduce blood levels of Tenex by increasing its metabolism (breakdown) in the intestine; doses of Tenex may need to be increased when combined with drugs that reduce its blood levels. 

Other drugs that also may reduce blood levels of Tenex include

• carbamazepine,
• phenytoin,
• phenobarbital,
• oxcarbazepine,
• rifabutin,
• rifampin,
• rifapentine,
• bosentan, and
• tipranavir/ritonavir. 

Ketoconazole, itraconazole, and simeprevir may increase blood levels of Tenex by decreasing its metabolism in the intestine; the dose of Tenex may need to be decreased when combined with drugs that increase its blood levels. 

There are no adequate and well-controlled studies of Tenex in pregnant women. Tenex should be used during pregnancy only if clearly needed. 

It is unknown if Tenex is excreted in breast milk. Due to the lack of safety data, Tenex should be used cautiously in nursing mothers. Consult your doctor before breastfeeding. 

WARNING

Hypotension, bradycardia, and syncope

Use Intuniv with caution in patients at risk for hypotension, bradycardia, heart block, or syncope (e.g., those taking antihypertensives). Measure heart rate and blood pressure prior to initiation of therapy, following dose increases, and periodically while on therapy. Advise patients to avoid becoming dehydrated or overheated.

Sedation and somnolence occur commonly with Intuniv

Consider the potential for additive sedative effects with CNS depressant drugs. Caution patients against operating heavy equipment or driving until they know how they respond to Intuniv.

Common side effects

The most common side effects associated with guanfacine treatment are

• tiredness,
• sleepiness,
• trouble sleeping,
• nausea,
• low blood pressure,
• stomach pain, and
• dizziness.

Other important side effects that are rare, but serious, are:

• hair loss,
• memory impairment,
• heart failure,
• depression,
• seizures,
• skin problems,
• difficulty swallowing,
• edema,
• hallucinations,
• hypersensitivity or
• allergic
• reactions,
• mania,
• heart attack,
• rebound hypertension,
• kidney failure,
• rapid heartbeat, and
• visual disturbance.

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 in the prescribing information, 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.

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:

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:

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 the prescribing information, 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
• 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.

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
• Musculoskeletal 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.

Drug Abuse And Dependence

No reported abuse or dependence has been associated with the administration of Tenex (guanfacine hdyrochloride).

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.

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).

Drug/Laboratory Test Interactions

No laboratory test abnormalities related to the use of Tenex (guanfacine hydrochloride) have been identified.