2.1 General Instruction for Use
Swallow tablets whole. Do not crush, chew, or break tablets because this will increase the rate of guanfacine release. Do not administer with high fat meals, due to increased exposure.
2.2 Dose Selection
Guanfacine extended-release tablets should be taken once daily, either in the morning or evening, at approximately same time each day. Begin at a dose of 1 mg/day, and adjust in increments of no more than 1 mg/week. Maintain the dose within the range of 1 mg to 4 mg once daily, depending on clinical response and tolerability, for both monotherapy and adjunctive therapy to a psychostimulant. Doses above 4 mg/day have not been systematically studied in controlled clinical studies [see Clinical Studies (14.1)].
Clinically relevant improvements were observed beginning at doses in the range 0.05 to 0.08 mg/kg once daily in both mono- and adjunctive therapy. Efficacy increased with increasing weight-adjusted dose (mg/kg). If well tolerated, doses up to 0.12 mg/kg once daily may provide additional benefit.
In clinical trials, there were dose-related and exposure-related risks for several clinically significant adverse reactions (hypotension, bradycardia, sedative events). Thus, consideration should be given to dosing guanfacine extended-release 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 Guanfacine Extended-Release
If switching from immediate-release guanfacine, discontinue that treatment, and titrate with guanfacine extended-release following above recommended schedule.
Do not substitute for immediate-release guanfacine tablets on a milligram-per-milligram basis, because of differing pharmacokinetic profiles. Guanfacine extended-release has a delayed Tmax, reduced Cmax and lower bioavailability compared to those of the same dose of immediate-release guanfacine [see Clinical Pharmacology (12.3)].
2.4 Maintenance Treatment
It is generally agreed that pharmacological treatment of ADHD may be needed for extended period. The effectiveness of guanfacine extended-release for longer-term use (more than 9 weeks) has not been systematically evaluated in controlled trials. Therefore the physician electing to use guanfacine extended-release for extended periods should periodically re-evaluate 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 guanfacine extended-release 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
Scenarios
Comedications
Initiate guanfacine extended-release when taking comedications
Continue guanfacine extended-release when adding a comedication
Stop a comedication when continuing guanfacine extended-release
Strong CYP3A4 Inhibitors
Guanfacine extended-release dose should be limited to 2 mg/day
Guanfacine extended-release dose should be decreased by half.
Guanfacine extended-release dose should be doubled based on patient tolerability. The maximum dose should not exceed 4 mg/day
Strong CYP3A4 Inducers
Guanfacine extended-release dose may be titrated up to 8 mg/day. Consider faster titration (e.g. in increments of 2 mg/week)
Consider increase guanfacine extended-release dose gradually in 1 to 2 weeks to 2 fold of the original dose based on patient tolerability.
Guanfacine extended-release dose should be decreased by half in 1 to 2 weeks based on patient tolerability. The maximum dose should not exceed 4 mg/day
