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Guanfacine

Pronunciation

Pronunciation: GWAHN-fa-seen
Class: Antiadrenergic, centrally acting

Trade Names

Guanfacine Hydrochloride
- Tablets 1 mg
- Tablets 2 mg

Intuniv
- Tablets, ER 1 mg
- Tablets, ER 2 mg
- Tablets, ER 3 mg
- Tablets, ER 4 mg

Tenex
- Tablets 1 mg
- Tablets 2 mg

Pharmacology

Appears to stimulate central alpha-2 adrenergic receptors, with decreased sympathetic outflow causing a decrease in peripheral vascular resistance and reduction in heart rate. The mechanism of action in the treatment of attention deficit hyperactivity disorder (ADHD) is unknown.

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Pharmacokinetics

Absorption

Absolute bioavailability is approximately 80%. T max is 1 to 4 h for immediate-release (IR) and 4 to 8 h for ER.

Distribution

Protein binding is approximately 70%. Mean Vd is 6.3 L/kg.

Elimination

Half-life is 10 to 30 h for IR and 18 h for ER. Approximately 50% is excreted unchanged in the urine, the remainder as metabolites.

Special Populations

Renal Function Impairment

Cl is reduced; plasma levels are only slightly increased.

Children

Exposure to guanfacine was higher in children (6 to 12 yr of age) compared with adolescents (13 to 17 yr of age).

Indications and Usage

Treatment of hypertension (IR only); treatment of ADHD (ER only).

Unlabeled Uses

Amelioration of heroin withdrawal symptoms; Tourette syndrome.

Contraindications

Standard considerations.

Dosage and Administration

Attention Deficit Hyperactivity Disorder (ER only)
Children (6 to 17 yr of age)

PO 1 mg daily initially. Adjust in increments of no more than 1 mg/wk. Maintenance dosage of 1 to 4 mg/day. Max, 4 mg/day.

Hypertension (IR only)
Adults (12 yr of age and older)

PO 1 mg daily at bedtime alone or in combination with another antihypertensive drug; may increase gradually up to 3 mg daily.

General Advice

  • Administer guanfacine IR at bedtime to decrease daytime sedation.
  • Administer guanfacine ER once daily in the morning. Tablets should not be crushed, chewed, or broken.
  • Do not administer guanfacine ER with a high-fat meal.
  • Do not substitute guanfacine ER for guanfacine IR on a mg-per-mg basis because of differing pharmacokinetic profiles.

Storage/Stability

Store at 68° to 77°F in a tightly closed container and protect from light.

Drug Interactions

Alcohol, CNS depressants (eg, antipsychotics, benzodiazepines [eg, diazepam], sedative/hypnotics [eg, phenobarbital])

Increased CNS depression (eg, sedation, somnolence). Avoid use.

Alpha-2 adrenergic agonists (eg, tizanidine)

Additive hypotension effects may occur. Avoid coadministration. If concurrent use cannot be avoided, closely monitor for signs of hypotension.

Antihypertensive agents or other drugs that can reduce blood pressure, decrease heart rate, or increase risk of syncope

Pharmacodynamic effects may be additive (eg, hypotension, syncope).

CYP3A4 inducers (eg, rifampin)

Guanfacine plasma concentrations may be reduced, decreasing the efficacy. Monitor the response of the patient. Consider increasing the guanfacine dose within the recommended dose range.

CYP3A4/5 strong inhibitors (eg, ketoconazole)

Guanfacine plasma concentrations may be elevated, increasing the pharmacologic effects and risk of adverse reactions. Monitor the response of the patient and adjust the guanfacine dose as needed.

Tricyclic antidepressants (eg. amitriptyline)

The antihypertensive effect of guanfacine may be decreased. Carefully monitor BP during coadministration and when stopping tricyclic antidepressants. Adjust the guanfacine dose as needed.

Valproic acid

Valproic acid plasma concentrations may be elevated. Consider monitoring valproic acid concentrations and observing the patient for additive CNS effects (eg, sedation). Adjust the valproic acid dose as needed.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Hypotension (10%); syncope (2%); blood pressure increased (2% to less than 5%); AV block, bradycardia, orthostatic hypotension, sinus arrhythmia (less than 2%); tachycardia (postmarketing).

CNS

Somnolence (45%); headache (26%); dizziness, fatigue (15%); asthenia (7%); irritability, lethargy (6%); insomnia (4%); agitation, anxiety, depression, emotional lability, interrupted sleep, nightmares, postural dizziness (less than 2%).

Dermatologic

Exfoliative dermatitis, rash (postmarketing).

EENT

Blurred vision (postmarketing).

GI

Dry mouth (60%); constipation (15%); upper abdominal pain (11%); vomiting (9%); nausea (7%); decreased appetite (5%); diarrhea, stomach discomfort (2% to less than 5%); dyspepsia (less than 2%).

Genitourinary

Impotence (7%); enuresis, increased urinary frequency (less than 2%).

Hepatic

ALT increased (less than 2%).

Respiratory

Asthma (less than 2%); dyspnea (postmarketing).

Miscellaneous

Weight increased (7%); chest pain, pallor (less than 2%); paresthesias (postmarketing).

Precautions

Monitor

Monitor heart rate and blood pressure prior to initiation of therapy, following dose increases, and periodically while on therapy for ADHD.


Pregnancy

Category B .

Lactation

Undetermined.

Children

Safety and efficacy of guanfacine IR in children younger than 12 yr of age not established. Safety and efficacy of guanfacine ER in children younger than 6 yr of age not established.

Renal Function

It may be necessary to adjust the dose in patients with significant renal impairment.

Hepatic Function

It may be necessary to adjust the dose in patients with significant hepatic impairment.

Special Risk Patients

Use with caution in patients with severe coronary insufficiency, recent MI, cerebrovascular or cardiovascular disease, history of syncope, or chronic renal or hepatic function impairment.

CV effects

Bradycardia, hypotension, and syncope may occur in children treated with guanfacine for ADHD.

Sedation

Occurs in a large percentage of patients.

Withdrawal

Do not discontinue therapy without consulting health care provider; drug must be withdrawn gradually to avoid rapid rise in BP (rebound hypertension).

Overdosage

Symptoms

Bradycardia, dizziness, hypotension, lethargy, severe drowsiness.

Patient Information

  • Instruct patients taking guanfacine IR to take medication at bedtime.
  • Instruct patients taking guanfacine ER to take medication in the morning. Advise patient not to crush, chew, or break the tablets.
  • Instruct patients to avoid taking guanfacine ER with a high-fat meal.
  • Teach patient proper technique for taking BP. Advise patient to check BP weekly.
  • Instruct patient not to discontinue drug abruptly.
  • In hypertension, advise patient on benefits of weight loss, exercise, reduction of alcohol and sodium intake, and cessation of smoking.
  • Instruct patient to lie down if dizziness or blurred vision occurs.
  • Explain that impotence may occur but is reversible. Tell patient to report impotence to health care provider.
  • Instruct patient to report these symptoms to health care provider: constipation, dizziness, headache, insomnia, nausea, sweating, or weakness.
  • Advise patient to take sips of water frequently, suck on ice chips or sugarless hard candy, or chew sugarless gum if dry mouth occurs.
  • Advise patients to avoid becoming dehydrated or overheated.
  • Caution patient to avoid sudden position changes to avoid orthostatic hypotension.
  • Instruct patient to avoid intake of alcoholic beverages or other CNS depressants.
  • Advise patient that drug may cause drowsiness and to use caution while driving or performing other tasks requiring mental alertness.
  • Advise patients that Intuniv and Tenex contain the same active ingredient (guanfacine) and not to take the two in combination.

Copyright © 2009 Wolters Kluwer Health.

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