guanFACINE (gwahn-fa-seen) Intuniv, Intuniv XR, Tenex

 Indications

Hypertension (with thiazide-type diuretics) (immediate-

release). Treatment of attention-deficit hyperactivity

disorder (ADHD) as monotherapy or as adjunctive

therapy to stimulants (extended-release).

Action

Stimulates CNS alpha2-adrenergic receptors, producing

a decrease in sympathetic outflow to heart, kidneys,

and blood vessels. Result is decreased BP and peripheral

resistance, a slight decrease in heart rate, and no

change in cardiac output. Mechanism of action in

ADHD is unknown. Therapeutic Effects: Lowering

of BP in hypertension. Increased attention span in

ADHD.

Pharmacokinetics

Absorption: Immediate-release is well absorbed

(80%); extended-release has lower rate and extent of

absorption (qabsorption with high-fat meals).

Distribution: Appears to be widely distributed.

Metabolism and Excretion: 50% metabolized by

the liver, 50% excreted unchanged by the kidneys.

Half-life: 17 hr.

TIME/ACTION PROFILE (antihypertensive

effect)

ROUTE ONSET PEAK DURATION

PO (single

dose)

unknown 8–12 hr 24 hr

PO (multiple

doses)

within 1 wk 1–3 mo unknown

Contraindications/Precautions

Contraindicated in: Hypersensitivity.

Use Cautiously in: Severe coronary artery disease

or recent myocardial infarction; Geri: May haveqsensitivity, especially those with hepatic, cardiac, or renal

dysfunction; Cerebrovascular disease; Severe renal or

liver disease; History of hypotension, heart block,

bradycardia, or cardiovascular disease; OB, Lactation,

Pedi: Pregnancy, lactation, or children 6 yr (safety not

established).

Adverse Reactions/Side Effects

CNS: drowsiness, headache, weakness, depression,

dizziness, fatigue, insomnia, irritability. EENT: tinnitus.

Resp: dyspnea. CV: bradycardia, chest pain, hypotension,

palpitations, rebound hypertension, syncope.

GI: constipation, dry mouth, abdominal pain,

nausea. GU: erectile dysfunction.

Interactions

Drug-Drug:qhypotension with other antihypertensives,

nitrates, and acute ingestion of alcohol.

qCNS depression may occur with other CNS depressants,

including alcohol, antihistamines,

opioid analgesics, tricyclic antidepressants, and

sedative/hypnotics. NSAIDs maypeffectiveness. Adrenergics

maypeffectiveness.qrisk of hypotension

and bradycardia with strong and moderate CYP3A4

inhibitors, including ketoconazole and fluconazole

(apin dose of guanfacine may be needed).

Strong and moderate CYP3A4 inducers, including rifampin,

efavirenz, and carbamazepine maypeffects

(anqin dose of guanfacine may be needed). Mayqlevels

of valproic acid.

Route/Dosage

Immediate-release and extended-release tablets should

not be interchanged.

Hypertension

PO (Adults): 1 mg daily given at bedtime, may beqif

necessary at 3–4 wk intervals up to 2 mg/day; may also

be given in 2 divided doses.

ADHD

PO (Adults and Children 6 yr): 1 mg once daily in

morning or evening; may beqby 1 mg/day at weekly

intervals to achieve dose of 1–4 mg/day (6–12 yr) or

1–7 mg-day (13–17 yr) when used as monotherapy

or 1–4 mg/day when used as adjunctive therapy. Concurrent

strong or moderate CYP3A4 inhibitor—p

initial and maintenance dose by 50%; Concurrent

strong or moderate CYP3A4 inducer—Considerq

initial and maintenance dose up to double the recommended

level (maintenance dose can beqover period

of 1–2 wk).

Availability (generic available)

Immediate-release tablets (Tenex): 1 mg, 2 mg.

Cost: Generic—1 mg $10.34/100, 2 mg $25.67/100.

Extended-release tablets (Intuniv): 1 mg, 2 mg, 3

mg, 4 mg. Cost: All strengths $884.11/100.