INDICATIONS AND USAGE
INTUNIV® is a central alpha2A-adrenergic receptor agonist indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) as monotherapy and as adjunctive therapy to stimulant medications (1, 14).
DOSAGE AND ADMINISTRATION
- Recommended dose: 1 mg to 7 mg (0.05-0.12 mg/kg target weight based dose range) once daily in the morning or evening based on clinical response and tolerability (2.2).
- Begin at a dose of 1 mg once daily and adjust in increments of no more than 1 mg/week (2.2).
- Do not crush, chew or break tablets before swallowing (2.1).
- Do not administer with high-fat meals, because of increased exposure (2.1).
- Do not substitute for immediate-release guanfacine tablets on a mg-per-mg basis, because of differing pharmacokinetic profiles (2.3).
- If switching from immediate-release guanfacine, discontinue that treatment and titrate with INTUNIV® as directed (2.3).
- When discontinuing, taper the dose in decrements of no more than 1 mg every 3 to 7 days to avoid rebound hypertension (2.5).
——————— DOSAGE FORMS AND STRENGTHS ——————–
Extended-release tablets: 1 mg, 2 mg, 3 mg and 4 mg (3)
ADVERSE REACTIONS
Most common adverse reactions (≥5% and at least twice placebo rate) in fixed-dose monotherapy ADHD trials in children and adolescents (6 to 17 years): hypotension, somnolence, fatigue, nausea, and lethargy (6.1) Flexible dose-optimization ADHD trials in children (6 to 12 years) and adolescents (13 to 17 years): somnolence, hypotension, abdominal pain, insomnia, fatigue, dizziness, dry mouth, irritability, nausea, vomiting, and bradycardia (6.1).
Adjunctive treatment to psychostimulant ADHD trial in children and adolescents (6 to 17 years): somnolence, fatigue, insomnia, dizziness, and abdominal pain (6.1). To report SUSPECTED ADVERSE REACTIONS, contact Shire US Inc. at 1-800-828-2088 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
CONTRAINDICATIONS
History of hypersensitivity to INTUNIV®, its inactive ingredients, or other products containing guanfacine (4).
WARNINGS AND PRECAUTIONS
- Hypotension, bradycardia, syncope: Titrate slowly and monitor vital signs frequently in patients at risk for hypotension, heart block, bradycardia, syncope, cardiovascular disease, vascular disease, cerebrovascular disease or chronic renal failure. Measure heart rate and blood pressure prior to initiation of therapy, following dose increases, and periodically while on therapy. Avoid concomitant use of drugs with additive effects unless clinically indicated. Advise patients to avoid becoming dehydrated or overheated (5.1).
- 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® (5.2).
- Cardiac Conduction Abnormalities: May worsen sinus node dysfunction and atrioventricular (AV) block, especially in patients taking other sympatholytic drugs. Titrate slowly and monitor vital signs frequently (5.3).
- Rebound Hypertension: Abrupt discontinuation of INTUNIV® can lead to clinically significant and persistent rebound hypertension. Subsequent hypertensive encephalopathy was also reported. To minimize the risk of rebound hypertension upon discontinuation, the total daily dose of INTUNIV® should be tapered in decrements of no more than 1 mg every 3 to 7 days (5.4).
DRUG INTERACTIONS
- Strong and moderate CYP3A4 inhibitors increase guanfacine exposure. Decrease INTUNIV® to 50% of target dosage when coadministered with strong and moderate CYP3A4 inhibitors (2.7).
- Strong and moderate CYP3A4 inducers decrease guanfacine exposure. Based on patient response, consider titrating INTUNIV dosage up to double the target dosage over 1 to 2 weeks (2.7).
OVERDOSAGE
Postmarketing reports of guanfacine overdosage indicate that hypotension, drowsiness, lethargy, and bradycardia have been observed following overdose. Initial hypertension may develop early and may be followed by hypotension. Similar symptoms have been described in voluntary reports to the American Association of Poison Control Center’s National Poison Data System. Miosis of the pupils may be noted on examination. No fatal overdoses of guanfacine have been reported in published literature.
Treatment: Consult a Certified Poison Control Center by calling 1-800-222-1222 for up-to-date guidance and advice.
Management of INTUNIV® overdose should include monitoring for and the treatment of initial hypertension, if that occurs, as well as hypotension, bradycardia, lethargy and respiratory depression. Children and adolescents who develop lethargy should be observed for the development of more serious toxicity including coma, bradycardia and hypotension for up to 24 hours, due to the possibility of delayed onset hypotension.
- Uses
-
INDICATIONS AND USAGE
INTUNIV® is a central alpha2A-adrenergic receptor agonist indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) as monotherapy and as adjunctive therapy to stimulant medications (1, 14).
DOSAGE AND ADMINISTRATION
- Recommended dose: 1 mg to 7 mg (0.05-0.12 mg/kg target weight based dose range) once daily in the morning or evening based on clinical response and tolerability (2.2).
- Begin at a dose of 1 mg once daily and adjust in increments of no more than 1 mg/week (2.2).
- Do not crush, chew or break tablets before swallowing (2.1).
- Do not administer with high-fat meals, because of increased exposure (2.1).
- Do not substitute for immediate-release guanfacine tablets on a mg-per-mg basis, because of differing pharmacokinetic profiles (2.3).
- If switching from immediate-release guanfacine, discontinue that treatment and titrate with INTUNIV® as directed (2.3).
- When discontinuing, taper the dose in decrements of no more than 1 mg every 3 to 7 days to avoid rebound hypertension (2.5).
——————— DOSAGE FORMS AND STRENGTHS ——————–
Extended-release tablets: 1 mg, 2 mg, 3 mg and 4 mg (3)
- Side Effects
-
ADVERSE REACTIONS
Most common adverse reactions (≥5% and at least twice placebo rate) in fixed-dose monotherapy ADHD trials in children and adolescents (6 to 17 years): hypotension, somnolence, fatigue, nausea, and lethargy (6.1) Flexible dose-optimization ADHD trials in children (6 to 12 years) and adolescents (13 to 17 years): somnolence, hypotension, abdominal pain, insomnia, fatigue, dizziness, dry mouth, irritability, nausea, vomiting, and bradycardia (6.1).
Adjunctive treatment to psychostimulant ADHD trial in children and adolescents (6 to 17 years): somnolence, fatigue, insomnia, dizziness, and abdominal pain (6.1). To report SUSPECTED ADVERSE REACTIONS, contact Shire US Inc. at 1-800-828-2088 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
- Precautions
-
CONTRAINDICATIONS
History of hypersensitivity to INTUNIV®, its inactive ingredients, or other products containing guanfacine (4).
WARNINGS AND PRECAUTIONS
- Hypotension, bradycardia, syncope: Titrate slowly and monitor vital signs frequently in patients at risk for hypotension, heart block, bradycardia, syncope, cardiovascular disease, vascular disease, cerebrovascular disease or chronic renal failure. Measure heart rate and blood pressure prior to initiation of therapy, following dose increases, and periodically while on therapy. Avoid concomitant use of drugs with additive effects unless clinically indicated. Advise patients to avoid becoming dehydrated or overheated (5.1).
- 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® (5.2).
- Cardiac Conduction Abnormalities: May worsen sinus node dysfunction and atrioventricular (AV) block, especially in patients taking other sympatholytic drugs. Titrate slowly and monitor vital signs frequently (5.3).
- Rebound Hypertension: Abrupt discontinuation of INTUNIV® can lead to clinically significant and persistent rebound hypertension. Subsequent hypertensive encephalopathy was also reported. To minimize the risk of rebound hypertension upon discontinuation, the total daily dose of INTUNIV® should be tapered in decrements of no more than 1 mg every 3 to 7 days (5.4).
- Interactions
-
DRUG INTERACTIONS
- Strong and moderate CYP3A4 inhibitors increase guanfacine exposure. Decrease INTUNIV® to 50% of target dosage when coadministered with strong and moderate CYP3A4 inhibitors (2.7).
- Strong and moderate CYP3A4 inducers decrease guanfacine exposure. Based on patient response, consider titrating INTUNIV dosage up to double the target dosage over 1 to 2 weeks (2.7).
- Overdose
-
OVERDOSAGE
Postmarketing reports of guanfacine overdosage indicate that hypotension, drowsiness, lethargy, and bradycardia have been observed following overdose. Initial hypertension may develop early and may be followed by hypotension. Similar symptoms have been described in voluntary reports to the American Association of Poison Control Center’s National Poison Data System. Miosis of the pupils may be noted on examination. No fatal overdoses of guanfacine have been reported in published literature.
Treatment: Consult a Certified Poison Control Center by calling 1-800-222-1222 for up-to-date guidance and advice.
Management of INTUNIV® overdose should include monitoring for and the treatment of initial hypertension, if that occurs, as well as hypotension, bradycardia, lethargy and respiratory depression. Children and adolescents who develop lethargy should be observed for the development of more serious toxicity including coma, bradycardia and hypotension for up to 24 hours, due to the possibility of delayed onset hypotension.