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AG-GUANFACINE XR is a brand name for Guanfacine, supplied as a tablet (extended-release). The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: Pediatrics (6 -17 years of age) AG-Guanfacine XR (guanfacine hydrochloride extended-release tablets) is indicated as monotherapy for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in children and adolescents aged 6 to 17 years. AG-Guanfacine XR is also indicated as adjunctive therapy to…
Verbatim from this product's HC label. Tap a section to expand.
1 Dosing Considerations The tablets should not be administered with high-fat meals, due to increased exposure (see ACTION AND CLINICAL PHARMACOLOGY, Pharmacokinetics). Do not substitute for immediate-release guanfacine tablets on a milligram for milligram basis, because of differing pharmacokinetic profiles.
Guanfacine hydrochloride extended-release tablets has a delayed Tmax, reduced Cmax and lower bioavailability compared to those of the same dose of immediate-release guanfacine. The safety and efficacy of guanfacine hydrochloride extended-release tablets in pediatric patients less than 25 kg/55 lbs in weight have not been studied.
Heart rate and blood pressure should be monitored at baseline, after dose adjustments, periodically during treatment and following drug discontinuation (see WARNINGS AND PRECAUTIONS, Cardiovascular, and WARNINGS AND PRECAUTIONS, Monitoring and Laboratory Tests).
Advise patients that sedation can occur, particularly early in treatment or with dose increases. If sedation is judged to be clinically concerning or persistent, a dose decrease or discontinuation should be considered (see WARNINGS AND PRECAUTIONS, Cardiovascular, and DOSAGE AND ADMINISTRATION, Recommended Dose and Dosage Adjustment, Discontinuation).
1 Children (6-17 years old) The recommended starting dose for both AG-Guanfacine XR monotherapy and adjunct therapy to psychostimulants is 1 mg, taken orally once a day (morning or evening). The dose should be adjusted, depending on clinical response and tolerability, in increments of no more than 1 mg per week up to a maximum daily dose of 4 mg (6-12 years) or 7 mg (13-17 years), for monotherapy and up to a maximum daily dose of 4 mg for adjunctive therapy to psychostimulants.
In monotherapy clinical trials, there were dose-related and exposure-related risks for several clinically significant adverse reactions (hypotension, bradycardia, sedative events). 12 mg/kg/day (total daily dose 1-7 mg) (Table 1). 12 mg/kg/day range.
Doses above 4 mg/day have not been studied in adjunctive trials. 2 Renal Impairment The impact of renal impairment on the pharmacokinetics of guanfacine in children and adolescents, 6-17 years old, was not assessed. In adult patients with impaired renal function, the cumulative urinary excretion of guanfacine and the renal clearance diminished as renal function decreased.
1 Adverse Reaction Overview Short-Term Monotherapy Trials (children/adolescents aged 6-17 years) The two forced-dose clinical trials (Studies 1 and 2) with guanfacine hydrochloride extended- release tablet alone, one 8-week and one 9-week, were randomized, multi-center, double-blind, parallel-group, placebo-controlled studies in 664 children/adolescents aged 6-17 years with ADHD.
8%) and somnolence/sedation (38%) (see Table 3). Short-Term Monotherapy Trial (adolescents aged 13-17 years) This clinical trial (Study 3) was a 15-week, double-blind, placebo-controlled study conducted in adolescents aged 13-17 years with ADHD.
9%) (see Table 4). Short-Term Adjunctive Trial (children/adolescents aged 6-17 years) This clinical trial (Study 4) was a 9-week, placebo controlled, double-blind study conducted in children and adolescents aged 6-17 years treated with psychostimulants who were identified as having a sub optimal response to psychostimulants.
Guanfacine hydrochloride extended- release tablets was evaluated as adjunct therapy to their psychostimulant treatment. AG-Guanfacine XR (guanfacine extended-release tablets) Page 15 of 45 Treatment-Emergent Adverse Events with the highest subject incidence rates were headache and somnolence (see Table 5).
Adverse Events Leading to Discontinuation of Treatment Twelve percent (12%) of patients (6-17 years) receiving guanfacine hydrochloride extended- release tablets discontinued from the two pediatric monotherapy clinical studies (Studies 1 and 2) due to adverse events, compared to 4% in the placebo group.
The most common adverse reactions leading to discontinuation of guanfacine hydrochloride extended-release tablets- treated patients from the studies were somnolence/sedation (6%) and fatigue (2%). Less common adverse reactions leading to discontinuation (occurring in approximately 1% of patients) included: hypotension/decreased blood pressure, headache, dizziness.
General Somnolence and Sedation Sedative events, especially during initial use, were commonly reported adverse reactions in clinical trials. In two 8-and 9-week monotherapy trial (Studies 1 and 2) in 6-17 year olds, sedative events reported as adverse reactions were 38% for guanfacine hydrochloride extended-release tablets vs.
23% for placebo. In an adjunctive trial (Study 4) in 6-17 year olds, sedative events reported as adverse events were 18% for guanfacine hydrochloride extended-release tablets vs. 7% for placebo. Guanfacine hydrochloride extended-release tablets should be dosed based on clinical response and tolerability.
Advise patients that sedation can occur, particularly early in treatment or with dose increases. If sedation is judged to be clinically concerning or persistent, a dose decrease or discontinuation should be considered. Before AG-Guanfacine XR is used with other centrally active depressants (such as phenothiazines, barbiturates, or benzodiazepines), the potential for additive sedative effects should be considered.
Patients should avoid use with alcohol (see DRUG INTERACTIONS, Drug-Drug Interactions - CNS Depressant Drugs and DOSAGE AND ADMINISTRATION, Dosing Considerations). Cardiovascular Hypotension, Bradycardia and Syncope Guanfacine hydrochloride extended-release tablets can cause syncope and dose-dependent decreases in heart rate and blood pressure (systolic and diastolic) (see ADVERSE REACTIONS, Clinical Trial Adverse Reactions, Effects on Blood Pressure and Heart Rate and ACTION AND CLINCIAL PHARMACOLOGY, Cardiovascular Safety: Effects on Heart Rate and QT Interval).
In pediatric (6-17 year olds), short-term (8-9 weeks), controlled monotherapy trials (Studies 1 and 2), the maximum mean changes from baseline in systolic blood pressure, diastolic blood pressure, and heart rate were decreases of 5 mmHg, 3 mmHg, and 6 bpm, respectively, for all dose groups combined (generally one week after reaching AG-Guanfacine XR (guanfacine extended-release tablets) Page 10 of 45 target doses of 1 mg/day, 2 mg/day, 3 mg/day or 4 mg/day).
AG-Guanfacine XR is contraindicated in patients with a history of hypersensitivity to this drug, to any ingredient in the formulation, to any other product containing guanfacine, or component of the container. For a complete listing, see Dosage Forms, Strengths, Composition and Packaging.
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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In patients on hemodialysis, the dialysis clearance was about 15% of the total clearance. The low dialysis clearance suggests that the hepatic elimination (metabolism) increases as renal function decreases. It may be necessary to adjust the dose in patients with significant impairment of renal function (see WARNINGS AND PRECAUTIONS, Renal).
3 Hepatic Impairment The impact of hepatic impairment on the pharmacokinetics of guanfacine in children and adolescents, 6-17 years old, was not assessed. Guanfacine in adults is cleared both by the liver AG-Guanfacine XR (guanfacine extended-release tablets) Page 7 of 45 and the kidney, and approximately 50% of the clearance of guanfacine is hepatic.
It may be necessary to adjust the dose in patients with significant impairment of hepatic function (see WARNINGS AND PRECAUTIONS, Hepatic/Biliary/Pancreatic). 4 Patients treated with CYP3A4/5 inhibitors /inducers CYP3A4/5 inhibitors and inducers have been shown to have a significant effect on the pharmacokinetics of guanfacine when co-administered (see DRUG INTERACTIONS, Drug-Drug Interactions).
g. g. carbamazepine). In the case of concomitant use of strong and moderate CYP3A inhibitors, an initial 50% reduction of the guanfacine dose is recommended. Further individualized dose titration may then be needed. If guanfacine is combined with strong enzyme inducers, a retitration to increase the dose up to a maximum daily dose 7 mg, may be considered if needed.
If the inducing treatment is ended, retitration to reduce the guanfacine dose is recommended during the following weeks. 5 Discontinuation Patients/caregivers should be instructed not to discontinue AG-Guanfacine XR without consulting their physician.
The total daily dose should be tapered in decrements of no more than 1 mg every 3 to 7 days to minimize the risk of an increase in blood pressure upon discontinuation (see WARNINGS AND PRECAUTIONS, Cardiovascular, Elevated Blood Pressure and Heart Rate Upon Discontinuation and WARNINGS AND PRECAUTIONS, Monitoring and Laboratory Tests).
, rebound) have been reported to occur upon discontinuation of guanfacine hydrochloride extended-release tablets monotherapy. Patients should be monitored during dose downward titration and following AG- Guanfacine XR discontinuation until blood pressure and heart rate have returned to baseline (see WARNINGS AND PRECAUTIONS, […]
9% in the placebo group. 3%). Three percent (3%) of patients receiving guanfacine hydrochloride extended-release tablets discontinued from the adjunctive clinical study (Study 4) due to adverse events, compared to 1% in the placebo group.
No adverse event to guanfacine hydrochloride extended-release tablets causing discontinuation was reported more than once. 2 Clinical Trial Adverse Reactions Because clinical trials are conducted under very specific conditions, the adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.
Adverse reaction information from clinical trials is useful for identifying drug-related adverse events and for approximating rates. The developmental program for guanfacine hydrochloride extended-release tablets included exposures in a total of 2411 participants in clinical trials (1718 children aged 6-12 years, 693 adolescent patients aged 13-17 years).
The information included in this section is based on data from 2 monotherapy forced-dose clinical trials in children and adolescents aged 6-17 years (Studies 1 and 2), 1 dose-optimized monotherapy trial in adolescents aged 13-17 years (Study 3) and 1 dose-optimized adjunctive trial in children and adolescents aged 6-17 years (Study 4).
The stated frequencies of the listed treatment-emergent adverse events represent the proportion of individuals who experienced, at least once, a treatment-emergent adverse event of the kind listed. 7 0 Other common treatment-emergent adverse events (1% to 5%) included Diarrhea, Vomiting, and Insomnia.
Treatment-Emergent Adverse Events (reported by ≥1% of pediatric patients taking guanfacine hydrochloride extended-release tablets in other Phase 2/3 clinical trials: Cardiac Disorders: Bradycardia Gastrointestinal Disorders: Abdominal pain, stomach discomfort Investigations: Blood pressure increased Nervous System Disorders: Syncope/syncope vasovagal/loss of consciousness Psychiatric Disorders: Anxiety, […]
In the adolescent controlled monotherapy trial (Study 3), the maximum mean change from baseline in systolic blood pressure, diastolic blood pressure and heart rate were decreases of 5 mmHg, 4 mmHg, and 6 bpm for all dose groups combined.
Decreases in blood pressure and heart rate were usually asymptomatic; however, hypotension and bradycardia can occur. In long-term, open-label studies (mean exposure of approximately 10 months), maximum decreases in systolic and diastolic blood pressure occurred in the first month of therapy.
Decreases were less pronounced over time. The majority of syncope cases occurred in the long term, open-label studies. In a 9-week controlled adjunctive trial, the maximum mean changes from baseline in supine systolic blood pressure, diastolic blood pressure, and heart rate were decreases of 4 mmHg, 3 mmHg, and 9 bpm, respectively, between weeks 3 and 5 of the study.
Decreases in blood pressure and heart rate were usually asymptomatic; however, hypotension and bradycardia can occur. Measurements of heart rate and blood pressure should be performed prior to initiating therapy, following dose adjustments, periodically during treatment and following drug discontinuation.
, arrhythmia, sick sinus syndrome, ischemic heart disease, congestive heart failure, or congenital long QT syndrome), as AG-Guanfacine XR can decrease blood pressure and heart rate. Caution is advised when treating patients with AG-Guanfacine XR who have a history of syncope or a condition that may predispose them to syncope, such as hypotension, orthostatic hypotension, bradycardia, or dehydration.
Given the effect on blood pressure and heart rate, caution is advised when treating patients with AG-Guanfacine XR who are being treated concomitantly with antihypertensives or other drugs that reduce blood pressure or heart rate, QT prolonging drugs, and drugs that increase the risk of syncope (see DRUG INTERACTIONS, Drug-Drug Interactions - Heart Rate Lowering Drugs, and DRUG INTERACTIONS, Overview - QT Prolonging Drugs, and ADVERSE REACTIONS, Clinical Trial Adverse Reactions, Effects on Heart Rate and QT Interval).
Patients/caregivers should be advised that patients should avoid becoming dehydrated or overheated. , rebound) have been reported. In post-marketing experience, hypertensive encephalopathy has been very rarely reported upon abrupt discontinuation of guanfacinehydrochloride extended-release tablets.
To minimize the risk of an increase in blood pressure upon discontinuation, the total daily dose of guanfacine hydrochloride extended-release tablets should be tapered in decrements of no more than 1 mg every 3 to 7 days. Patients should be monitored during dose downward titration and following AG-Guanfacine XR discontinuation until blood pressure and heart rate have returned to baseline (see WARNINGS AND PRECAUTIONS, Monitoring and Laboratory Tests and DOSAGE AND ADMINISTRATION, Recommended Dose and Dosage Adjustment, Discontinuation).
g. headaches, feeling confused, nervousness, agitation, and tremors) and to seek immediate medical care. In randomized controlled monotherapy trials, increases of up to 10 […]