EXTENDED-RELEASE- guanfacine tablet, extended release
TWi Pharmaceuticals, Inc.
1 INDICATIONS AND USAGE
Guanfacine extended-release tablets are indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) as monotherapy and as adjunctive therapy to stimulant medications [ see CLINICAL STUDIES ( 14) ].
2 DOSAGE AND ADMINISTRATION
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
Take guanfacine extended-release tablets orally once daily, either in the morning or evening, at approximately the same time each day. Begin at a dose of 1 mg/day, and adjust in increments of no more than 1 mg/week.
In monotherapy clinical trials, there was dose- and exposure-related clinical improvement as well as risks for several clinically significant adverse reactions (hypotension, bradycardia, sedative events). To balance the exposure-related potential benefits and risks, the recommended target dose range depending on clinical response and tolerability for guanfacine extended-release tablets is 0.05 to 0.12 mg/kg/day (total daily dose between 1 to 7 mg) (See Table 1 ).
|Doses above 4 mg/day have not been evaluated in children (ages 6 to 12 years) and doses above 7 mg/day have not been evaluated in adolescents (ages 13 to 17 years)|
|Weight||Target dose range (0.05 to 0.12 mg/kg/day)|
|25 to 33.9 kg||2 to 3 mg/day|
|34 to 41.4 kg||2 to 4 mg/day|
|41.5 to 49.4 kg||3 to 5 mg/day|
|49.5 to 58.4 kg||3 to 6 mg/day|
|58.5 to 91 kg||4 to 7 mg/day|
|>91 kg||5 to 7 mg/day|
In the adjunctive trial which evaluated guanfacine extended-release tablets treatment with psychostimulants, the majority of patients reached optimal doses in the 0.05 to 0.12 mg/kg/day range. Doses above 4 mg/day have not been studied in adjunctive trials.
2.3 Switching from Immediate-Release Guanfacine to Guanfacine Extended-Release Tablets
If switching from immediate-release guanfacine, discontinue that treatment, and titrate with guanfacine extended-release tablets 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 tablets have significantly reduced C max (60% lower), bioavailability (43% lower), and a delayed T max (3 hours later) compared to those of the same dose of immediate-release guanfacine [see Clinical Pharmacology ( 12.3) ] .
2.4 Maintenance Treatment
Pharmacological treatment of ADHD may be needed for extended periods. Healthcare providers should periodically re-evaluate the long-term use of guanfacine extended-release tablets, and adjust weight-based dosage as needed. The majority of children and adolescents reach optimal doses in the 0.05 to 0.12 mg/kg/day range. Doses above 4 mg/day have not been evaluated in children (ages 6 to 12 years) and above 7 mg/day have not been evaluated in adolescents (ages 13 to 17 years) [see CLINICAL STUDIES ( 14) ] .
2.5 Discontinuation of Treatment
Following discontinuation of guanfacine extended-release tablets, patients may experience increases in blood pressure and heart rate [see Warnings and Precautions ( 5.4) and Adverse Reactions ( 6.1) ]. Patients/caregivers should be instructed not to discontinue guanfacine extended-release tablets without consulting their health care provider. Monitor blood pressure and pulse when reducing the dose or discontinuing the drug. Taper the daily dose in decrements of no more than 1 mg every 3 to 7 days to minimize the risk of rebound hypertension.
2.6 Missed Doses
When reinitiating patients to the previous maintenance dose after two or more missed consecutive doses, consider titration based on patient tolerability.
2.7 Dosage Adjustment with Concomitant Use of Strong and Moderate CYP3A4 Inhibitors or Inducers
Dosage adjustments for guanfacine extended-release tablets are recommended with concomitant use of strong and moderate CYP3A4 inhibitors (e.g., ketoconazole), or CYP3A4 inducers (e.g., carbamazepine) ( Table 2 ) [see DRUG INTERACTIONS ( 7) ] .
|Starting guanfacine extended-release tablets while currently on a CYP3A4 modulator||Continuing guanfacine extended-release tablets while adding a CYP3A4 modulator||Continuing guanfacine extended-release tablets while stopping a CYP3A4 modulator|
|CYP3A4 Strong and moderate Inhibitors||Decrease guanfacine extended-release tablets dosage to half the recommended level. (see Table 1 )||Decrease guanfacine extended-release tablets dosage to half the recommended level. (see Table 1 )||Increase guanfacine extended-release tablets dosage to recommended level. (see Table 1 )|
|CYP3A4 Strong and moderate Inducers||Consider increasing guanfacine extended-release tablets dosage up to double the recommended level. (see Table 1 )||Consider increasing guanfacine extended-release tablets dosage up to double the recommended level over 1 to 2 weeks. (see Table 1 )||Decrease guanfacine extended-release tablets dosage to recommended level over 1 to 2 weeks. (see Table 1 )|
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