guanfacine

guanfacine

 [gwahn´fah-sēn]

an α₂-adrenergic agonist used in the form of the hydrochloride salt as an antihypertensive.

guanfacine

Intuniv

Pharmacologic class: Centrally acting antiadrenergic

Therapeutic class: Antiadrenergic-sympatholytic, antihypertensive

Pregnancy risk category B

Action

Stimulates central alpha₂-adrenergic receptors, reducing sympathetic nerve impulses from vasomotor center to heart and blood vessels

Availability

Tablets: 1 mg, 2 mg

Tablets (extended-release): 1 mg, 2 mg, 3 mg, 4 mg

Indications and dosages

➣ Management of hypertension (used alone or in combination with other agents, especially thiazide diuretics)

Adults: 1 mg (immediate-release) P.O. at bedtime. If response unsatisfactory after 3 to 4 weeks, increase to 2 mg (immediate-release) P.O. at bedtime.

➣ Attention deficit hyperactivity disorder (ADHD) as monotherapy and as adjunctive therapy to stimulants

Adults and children age 6 and older: 1 mg (extended-release) P.O. daily; adjust in increments of no more than 1 mg/week. Maintain dosage within 1 to 4 mg/day, depending on clinical response and tolerability. Consider dosing on a mg/kg basis. Improvements have been observed starting at dosages of 0.05 to 0.08 mg/kg once daily. Dosages up to 0.12 mg/kg once daily may provide additional benefit. Dosages above 4 mg/day haven't been studied. If switching from immediate-release guanfacine, discontinue immediate-release treatment and titrate with extended-release, as directed.

Dosage adjustment

• Hepatic or renal impairment (immediate-release form)

• Concurrent use of CYP3A4 inducers such as rifampin (immediate-release form)

Off-label uses

• Attention deficit hyperactivity disorder (immediate-release form)

• Treatment of heroin withdrawal

• Hypertension in pregnancy

Contraindications

• Hypersensitivity to drug, its components, or other products containing guanfacine

Precautions

Use cautiously in:

• hepatic or renal impairment

• severe coronary insufficiency, cardiovascular or cerebovascular disease

• history of syncope, patients at risk for hypotension, bradycardia, heart block, or syncope, such as those taking antihypertensives (immediate-release form)

• concurrent use of CNS depressants

• concurrent use of antihypertensives, other products containing guanfacine, or CYP3A4/5 inhibitors such as ketoconazole (immediate-release form)

• elderly patients

• sedated patients (especially when given with centrally acting depressants)

• pregnant or breastfeeding patients

• children younger than age 6 (extended-release form) or 12 (immediate-release form).

Administration

• Measure heart rate and blood pressure before starting drug and after dosage increases.

• Give at bedtime to reduce daytime sleepiness (immediate-release form).

• Don't administer with high-fat meals (extended-release form).

• Know that therapy shouldn't be stopped abruptly, because this may cause rebound plasma and urinary catecholamines, anxiety, hypertension, and increase in blood pressure. When discontinuing, taper dosage in decrements of no more than 1 mg every 3 to 7 days.

• Be aware that drug may be used alone or with other agents, especially thiazide diuretics (immediate-release form).

• Be aware that for adolescents and children age 6 and older, efficacy beyond 9 weeks and safety beyond 2 years of treatment haven't been established.

• Don't substitute extended-release tablet for immediate-release tablet on a milligram-per-milligram basis, because of differing pharmacokinetic profiles.

Adverse reactions

CNS: somnolence, insomnia, dizziness, postural dizziness, lethargy, irritability, agitation, anxiety, nightmares, headache, fatigue, amnesia, confusion, depression, hypokinesia, asthenia, malaise, paresthesia, paresis, seizures

CV: hypertension, hypotension, syncope, bradycardia, palpitations, substernal pain, AV block, sinus arrhythmia

EENT: conjunctivitis, iritis, vision disturbance, tinnitus, rhinitis

GI: nausea, vomiting, diarrhea, constipation, abdominal pain, dyspepsia, dysphagia, dry mouth

GU: erectile dysfunction, decreased libido, increased urinary frequency, enuresis

Musculoskeletal: leg cramps

Respiratory: dyspnea, asthma

Skin: dermatitis, pruritus, purpura, sweating, pallor, rash

Other: taste perversion, decreased appetite, weight gain, chest pain, hypersensitivity

Interactions

Drug-drug. Antihypertensives: increased risk of additive pharmacodynamic effects, such as hypotension and syncope

CNS depressants: (such as antipsychotics, barbiturates, benzodiazepines, sedative-hypnotics): additive sedation

CYP3A4 inducers (such as rifampin): decreased guanfacine plasma concentration

CYP3A4/5 inhibitors (such as ketoconazole), valproic acid: increased guanfacine plasma concentration

Phenobarbital, phenytoin: decreased elimination half-life and blood level of guanfacine

Valproic acid: increased serum valproic acid concentration

Drug-diagnostic tests. Alanine aminotransferase: increased level

Drug-food. High-fat meal: increased guanfacine C_max and area under the curve

Drug-behaviors. Alcohol use: additive sedation

Patient monitoring

• Monitor patient for evidence of drug efficacy.

• Monitor patient closely during drug withdrawal.

☞ Continue to monitor heart rate and blood pressure periodically during therapy. Watch for hypotension, bradycardia, syncope, and heart block, especially in patients taking antihypertensives.

☞ Be aware that rash with exfoliation has occurred in a few patients. Should rash occur, discontinue drug and monitor patient appropriately.

Patient teaching

• Tell patient to take immediate-release tablets at bedtime to reduce daytime sleepiness.

• Tell patient to take extended-release tablets whole with water, milk, or other liquid but not to take with high-fat meals.

• Tell patient not to crush, chew, or break extended-release tablets before swallowing.

• Caution patient not to stop taking drug abruptly.

☞ Instruct patient how to recognize and immediately report signs and symptoms of serious cardiovascular disorders.

☞ Instruct patient to immediately report development of a rash.

• Advise patient to avoid driving and other hazardous activities until he knows how drug affects concentration and alertness.

• Tell patient to avoid alcohol during therapy.

• Advise patient to avoid dehydration or overheating.

• As appropriate, review all other significant adverse reactions and interactions, especially those related to the drugs, tests, foods, and behaviors mentioned above.

h

guanFACINE

(gwahn-fa-seen) ,

Intuniv

(trade name),

Tenex

(trade name)

Classification

Therapeutic: antihypertensives
Pharmacologic: centrally acting antiadrenergics

Pregnancy Category: B

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 (↑ absorption 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; Geriatric: May have ↑ sensitivity, especially those with hepatic, cardiac, or renal dysfunction;Cerebrovascular disease;Severe renal or liver disease;History of hypotension, heart block, bradycardia, or cardiovascular disease; Obstetric / Lactation / Pediatric: Pregnancy, lactation, or children <6 yr (safety not established).

Adverse Reactions/Side Effects

Central nervous system

• drowsiness (most frequent)
• headache (most frequent)
• weakness (most frequent)
• depression
• dizziness
• fatigue
• insomnia
• irritability

Ear, Eye, Nose, Throat

• tinnitus

Respiratory

• dyspnea

Cardiovascular

• bradycardia
• chest pain
• hypotension
• palpitations
• rebound hypertension
• syncope

Gastrointestinal

• constipation (most frequent)
• dry mouth (most frequent)
• abdominal pain
• nausea

Genitourinary

• erectile dysfunction (most frequent)

Interactions

Drug-Drug interaction

↑ hypotension with other antihypertensives, nitrates, and acute ingestion of alcohol.↑ CNS depression may occur with other CNS depressants, including alcohol, antihistamines, opioid analgesics, tricyclicantidepressants, and sedative/hypnotics.NSAIDs may ↓ effectiveness.Adrenergics may ↓ effectiveness.↑ risk of hypotension and bradycardia with strong CYP3A4 inhibitors, including ketoconazole.Strong CYP3A4 inducers, including rifampin may ↓ effects (an ↑ in dose of guanfacine may be needed).May ↑ levels of valproic acid.

Route/Dosage

Immediate-release and extended-release tablets should not be interchanged

Hypertension

Oral (Adults) 1 mg daily given at bedtime, may be ↑ if necessary at 3–4 wk intervals up to 2 mg/day; may also be given in 2 divided doses.

ADHD

Oral (Adults and Children ≥6 yr) 1 mg daily in morning; may be ↑ by 1 mg/day at weekly intervals to achieve dose of 1–4 mg/day.

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

Nursing implications

Nursing assessment

• Hypertension: Monitor BP (lying and standing) and pulse frequently during initial dose adjustment and periodically during therapy. Report significant changes.
  • Monitor frequency of prescription refills to determine adherence.
• ADHD: Assess attention span, impulse control, and interactions with others.
• Lab Test Considerations: May cause temporary, clinically insignificant ↑ in plasma growth hormone levels.
  • May cause ↓ in urinary catecholamines and vanillylmandelic acid levels.

Potential Nursing Diagnoses

Risk for injury (Side Effects)
Noncompliance (Patient/Family Teaching)

Implementation

• Do not confuse guanfacine with guaifenesin.
• Do not substitute extended-release tablets for immediate-release tablets on a mg-mg basis. Doses are not the same.
• Oral: For hypertension: Administer daily dose at bedtime to minimize daytime sedation.
  • For ADHD: Administer once daily. Swallow extended-release tablets whole; do not crush, break, or chew. Do not administer with high fat meals, due to increased exposure.

Patient/Family Teaching

• Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications, especially cough, cold, or allergy remedies.
• Caution patient to avoid alcohol and other CNS depressants while taking guanfacine.
• Advise patient to notify health care professional if dry mouth or constipation persists. Frequent mouth rinses, good oral hygiene, and sugarless gum or candy may minimize dry mouth. Increase in fluid and fiber intake and exercise may decrease constipation.
• Instruct patient to notify health care professional of medication regimen prior to treatment or surgery.
• Advise patient to notify health care professional if dizziness, prolonged drowsiness, fatigue, weakness, depression, headache, sexual dysfunction, mental depression, or sleep pattern disturbance occurs. Discontinuation may be required if drug-related mental depression occurs.
• Advise female patients to notify health care professional if pregnancy is planned or suspected or if breast feeding.
• Emphasize the importance of follow-up exams to evaluate effectiveness of medication.
• Hypertension: Emphasize the importance of continuing to take medication as directed, even if feeling well. Medication controls but does not cure hypertension. Instruct patient to take medication at the same time each day. Take missed doses as soon as remembered; do not double doses. If 2 or more doses are missed, consult health care professional. Do not discontinue abruptly; may cause sympathetic overstimulation (nervousness, anxiety, rebound hypertension, chest pain, tachycardia, increased salivation, nausea, trembling, stomach cramps, sweating, difficulty sleeping). These effects may occur 2–7 days after discontinuation, although rebound hypertension is rare and more likely to occur with high doses.
• Advise patient to make sure enough medication is available for weekends, holidays, and vacations. A written prescription may be kept in wallet in case of emergency.
• Encourage patient to comply with additional interventions for hypertension (weight reduction, low-sodium diet, smoking cessation, moderation of alcohol consumption, regular exercise, and stress management).
• Instruct patient and family on proper technique for BP monitoring. Advise them to check BP at least weekly and to report significant changes.
• May cause drowsiness or dizziness. Advise patient to avoid driving or other activities requiring alertness until response to the medication is known.
• ADHD: Instruct patient to take medication as directed. Take missed doses as soon as possible, but should not take more than the total daily amount in any 24-hr period. Do not stop taking abruptly; discontinue gradually at no more than 1 mg/3–7 days. Advise patient and parents to read the Medication Guide prior to starting therapy and with each Rx refill.
• Inform patient that sharing this medication may be dangerous.
• Pediatric: Advise parents to notify school nurse of medication regimen.

Evaluation/Desired Outcomes

• Decrease in BP without excessive side effects.
• Improved attention span and social interactions in ADHD. Re-evaluate use if used for >9 wk.