Guanfacine extended release for ADHD
Once-daily formulation may improve adherence and control symptoms across a full day
Figure: Incidence of somnolence, sedation, and fatigue in study patients receiving GXR
with or without psychostimulants
In an open-label continuation study of 259 patients treated with guanfacine extended release (GXR), somnolence, sedation, or fatigue was reported by 49% of subjects overall, 59% of those who received GXR monotherapy, and 11% of those given GXR with a psychostimulant.
GXR: guanfacine extended release
Source: Reprinted with permission from Sallee FR, Lyne A, Wigal T, et al. Long-term safety and efficacy of guanfacine extended release in children and adolescents with attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol. 2009;19(3):215-226 Safety warnings relating to the likelihood of hypotension, bradycardia, and possible syncope when prescribing GXR should be understood in the context of its pharmacologic action to lower heart rate and blood pressure. In the short-term (8 to 9 weeks) controlled trials, the maximum mean changes from baseline in systolic blood pressure, diastolic blood pressure, and pulse were -5 mm Hg, -3 mm Hg, and -6 bpm, respectively, for all dose groups combined. These changes, which generally occurred 1 week after reaching target doses of 1 to 4 mg/d, were dose-dependent but usually modest and did not cause other symptoms; however, hypotension and bradycardia can occur.
In the longer-term, open-label safety study,10 maximum decreases in systolic and diastolic blood pressure occurred in the first month of treatment; decreases were less pronounced over time. Syncope occurred in 1% of pediatric subjects but was not dose-dependent. Guanfacine IR can increase QT interval but not in a dose-dependent fashion.
Dosing
The approved dose range for GXR is 1 to 4 mg once daily in the morning. Initiate treatment at 1 mg/d, and adjust the dose in increments of no more than 1 mg/week, evaluating the patient weekly. GXR maintenance therapy is frequently in the range of 2 to 4 mg/d.
Because adverse events such as hypotension, bradycardia, and sedation are dose-related, evaluate benefit and risk using mg/kg range approximation. GXR efficacy on a weight-adjusted (mg/kg) basis is consistent across a dosage range of 0.01 to 0.17 mg/kg/d. Clinically relevant improvements are usually observed beginning at doses of 0.05 to 0.08 mg/kg/d. In clinical trials, efficacy increased with increasing weight-adjusted dose (mg/kg), so if GXR is well-tolerated, doses up to 0.12 mg/kg once daily may provide additional benefit up to the maximum of 4 mg/d.
Instruct patients to swallow GXR whole because crushing, chewing, or otherwise breaking the tablet’s enteric coating will markedly enhance guanfacine release.
Abruptly discontinuing GXR is associated with infrequent, transient elevations in blood pressure above the patient’s baseline (ie, rebound). To minimize these effects, GXR should be gradually tapered in decrements of no more than 1 mg every 3 to 7 days. Isolated missed doses of GXR generally are not a problem, but ≥2 consecutive missed doses may warrant reinitiation of the titration schedule.
Related resource
- Guanfacine extended release (Intuniv) prescribing information. www.intuniv.com/documents/INTUNIV_Full_Prescribing_Information.pdf.
Drug brand names
- Atomoxetine • Strattera
- Guanfacine extended release • Intuniv
- Guanfacine immediate release • Tenex
- Ketoconazole • Nizoral
- Rifampin • Rifadin, Rimactane
- Valproic acid • Depakene, Depakote
Disclosure
Dr. Sallee receives grant/research support from the National Institutes of Health. He is a consultant to Otsuka, Nextwave, and Sepracor and a consultant to and speaker for Shire. Dr. Sallee is a consultant to, shareholder of, and member of the board of directors of P2D Inc. and a principal in Satiety Solutions.
