HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use INTUNIV safely and effectively. See full prescribing information for INTUNIV . INTUNIV (guanfacine) extended-release tablets, for oral use Initial U.S. Approval: 1986 ®®
® RECENT MAJOR CHANGES
Dosage and Administration, Dose Selection ( ), 02/2013 2.2
INDICATIONS AND USAGE
INTUNIV is a central alpha -adrenergic receptor agonist indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) as monotherapy and as adjunctive therapy to stimulant medications ( ). ®2A1
DOSAGE AND ADMINISTRATION
Recommended dose: 1 to 4 mg once daily in the morning or evening ( ). 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
Consider dosing on a mg/kg basis. Improvements observed starting at doses of 0.05-0.08 mg/kg once daily. Doses up to 0.12 mg/kg once daily may provide additional benefit ( ). 2.2
When discontinuing, taper the dose in decrements of no more than 1 mg every 3 to 7 days ( ). 2.5
DOSAGE FORMS AND STRENGTHS
Extended-release tablets: 1 mg, 2 mg, 3 mg and 4 mg ( ) 3
CONTRAINDICATIONS
History of hypersensitivity to INTUNIV , its inactive ingredients, or other products containing guanfacine ( ). ®4
WARNINGS AND PRECAUTIONS
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 ( ). ®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
ADVERSE REACTIONS
Most common adverse reactions (≥5% and at least twice placebo rate) in the monotherapy trials: somnolence, fatigue, nausea, lethargy, and hypotension ( ). Most common adverse reactions (≥5% and at least twice placebo rate) in the adjunctive trial: somnolence, fatigue, insomnia, dizziness, and abdominal pain ( ). 66
To report SUSPECTED ADVERSE REACTIONS, contact Shire US Inc. at 1-800-828-2088 or FDA at 1-800-FDA-1088 orwww.fda.gov/medwatch.
DRUG INTERACTIONS
Strong CYP3A4 inhibitors (e.g., ketoconazole): Coadministration increases guanfacine exposure. Guanfacine dose should be limited to no more than 2 mg/day. When discontinuing CYP3A4 inhibitors, guanfacine dose should be doubled based on patient tolerability. The maximum dose should not exceed 4 mg/day ( and ). 2.77
Strong CYP3A4 inducers (e.g., rifampin): Coadministration decreases guanfacine exposure. Guanfacine dose may be titrated up to 8 mg/day. When discontinuing CYP3A4 inducers, guanfacine dose should be decreased by half in 1-2 weeks based on patient tolerab