veral clinically significant adverse reactions (hypotension, bradycardia, sedative events). Thus, consideration should be given to dosing INTUNIV on a mg/kg basis, in order to balance the exposure-related potential benefits and risks of treatment. ®
2.3 Switching from Immediate-Release Guanfacine to INTUNIV
If switching from immediate-release guanfacine, discontinue that treatment, and titrate with INTUNIV following above recommended schedule. ®
Do not substitute for immediate-release guanfacine tablets on a milligram-per-milligram basis, because of differing pharmacokinetic profiles. INTUNIV has a delayed T , reduced C and lower bioavailability compared to those of the same dose of immediate-release guanfacine . ®maxmax[ ] SEE CLINICAL PHARMACOLOGY (12.3)
2.4 Maintenance Treatment
It is generally agreed that pharmacological treatment of ADHD may be needed for an extended period. The effectiveness of INTUNIV for longer-term use (more than 9 weeks) has not been systematically eva luated in controlled trials. Therefore the physician electing to use INTUNIV for extended periods should periodically re-eva luate the long-term usefulness of the drug for the individual patient. ®®
2.5 Discontinuation
Infrequent, transient elevations in blood pressure above original baseline (i.e., rebound) have been reported to occur upon abrupt discontinuation of guanfacine. To minimize these effects, the dose should generally be tapered in decrements of no more than 1 mg every 3 to 7 days.
2.6 Missed Doses
When reinitiating patients to the previous maintenance dose after two or more missed consecutive doses, physicians should consider titration based on patient tolerability.
2.7 Dose Adjustment with Concomitant Use of Strong CYP3A4 Inhibitors or Inducers
Dosage adjustments for INTUNIV are recommended with concomitant use of strong CYP3A4 inhibitors (e.g., boceprevir, clarithromycin, conivaptan, grapefruit juice, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, mibefradil, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, and voriconazole), or CYP3A4 inducers (e.g., avasimibe, carbamazepine, phenytoin, rifampin, and St.John’s wort) (Table 1) . ®[] SEE DRUG INTERACTIONS (7)
Table 1: Dose Adjustments in Patients Taking Concomitant CYP3A4 Inhibitors or Inducers
Comedications Scenarios
Initiate INTUNIV when taking comedications ®
Continue INTUNIV when adding a comedication ®
Stop a comedication when continuing INTUNIV
®
Strong CYP3A4 Inhibitors
INTUNIV dose should be limited to 2 mg/day ®
INTUNIV dose should be decreased by half. ®
INTUNIV dose should be doubled based on patient tolerability. The maximum dose should not exceed 4 mg/day ®
Strong CYP3A4 Inducers
INTUNIV dose may be titrated up to 8 mg/day. Consider faster titration (e.g. in increments of 2 mg/week) ®
Consider increase INTUNIV dose gradually in 1-2 weeks to 2 fold of the original dose based on patient tolerability.
®
INTUNIV dose should be decreased by half in 1-2 weeks based on patient tolerability. The maximum dose should not exceed 4 mg/day ®
3 DOSAGE FORMS AND STRENGTHS
1 mg, 2 mg, 3 mg and 4 mg extended-release tablets
4 CONTRAINDICATIONS
Patients with a history of hypersensitivity to |
