Guanfacine
Tablet, Extended Release · Oral
Uses
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)] . Guanfacine extended-release tablets are a central alpha 2A -adrenergic receptor agonist indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) as monotherapy and as adjunctive therapy to stimulant medications (1, 14).
Dosage and administration
Recommended dose: 1 mg to 7 mg (0.05 to 0.12 mg/kg target weight based dose range) once daily in the morning or evening based on clinical response and tolerability (2.2). Begin at a dose of 1 mg once daily and adjust in increments of no more than 1 mg/week (2.2). Do not crush, chew or break tablets before swallowing (2.1). Do not administer with high-fat meals, because of increased exposure (2.1). Do not substitute for immediate-release guanfacine tablets on a mg-per-mg basis, because of differing pharmacokinetic profiles (2.3). If switching from immediate-release guanfacine, discontinue that treatment and titrate with guanfacine extended-release tablets as directed (2.3). When discontinuing, taper the dose in decrements of no more than 1 mg every 3 to 7 days to avoid rebound hypertension (2.5). 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). Table 1: Recommended Target Dose Range for Therapy with guanfacine extended-release tablets 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 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) 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 has 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 6-12 years) and above 7 mg/day have not been evaluated in adolescents (ages 13-17 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)] . 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)] . Table 2: Guanfacine Extended-Release Tablets Dosage Adjustments for Patients Taking Concomitant CYP3A4 Inhibitors or Inducers Clinical Scenarios 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)
Dosage forms and strengths
1 mg, 2 mg, 3 mg and 4 mg extended-release tablets Extended-release tablets: 1 mg, 2 mg, 3 mg and 4 mg (3)
Contraindications
Guanfacine is contraindicated in patients with a history of a hypersensitivity reaction to guanfacine extended-release tablets or its inactive ingredients, or other products containing guanfacine. Rash and pruritus have been reported. History of hypersensitivity to guanfacine, its inactive ingredients, or other products containing guanfacine (4).
Warnings and precautions
Hypotension, bradycardia, syncope: Titrate slowly and monitor vital signs frequently in patients at risk for hypotension, heart block, bradycardia, syncope, cardiovascular disease, vascular disease, cerebrovascular disease or chronic renal failure. Measure heart rate and blood pressure prior to initiation of therapy, following dose increases, and periodically while on therapy. Avoid concomitant use of drugs with additive effects unless clinically indicated. Advise patients to avoid becoming dehydrated or overheated (5.1). Sedation and somnolence: Occur commonly with guanfacine. Consider the potential for additive sedative effects with CNS depressant drugs. Caution patients against operating heavy equipment or driving until they know how they respond to guanfacine (5.2). Cardiac Conduction Abnormalities: May worsen sinus node dysfunction and atrioventricular (AV) block, especially in patients taking other sympatholytic drugs. Titrate slowly and monitor vital signs frequently (5.3). Rebound Hypertension: Abrupt discontinuation of guanfacine can lead to clinically significant and persistent rebound hypertension. Subsequent hypertensive encephalopathy was also reported. To minimize the risk of rebound hypertension upon discontinuation, the total daily dose of guanfacine should be tapered in decrements of no more than 1 mg every 3 to 7 days (5.4). 5.1 Hypotension, Bradycardia, and Syncope Treatment with guanfacine extended-release tablets can cause dose-dependent decreases in blood pressure and heart rate. Decreases were less pronounced over time of treatment. Orthostatic hypotension and syncope have been reported [see Adverse Reactions (6.1)] . Measure heart rate and blood pressure prior to initiation of therapy, following dose increases, and periodically while on therapy. Titrate guanfacine slowly in patients with a history of hypotension, and those with underlying conditions that may be worsened by hypotension and bradycardia; e.g., heart block, bradycardia, cardiovascular disease, vascular disease, cerebrovascular disease, or chronic renal failure. In patients who have a history of syncope or may have a condition that predisposes them to syncope, such as hypotension, orthostatic hypotension, bradycardia, or dehydration, advise patients to avoid becoming dehydrated or overheated. Monitor blood pressure and heart rate, and adjust dosages accordingly in patients treated concomitantly with antihypertensives or other drugs that can reduce blood pressure or heart rate or increase the risk of syncope. 5.2 Sedation and Somnolence Somnolence and sedation were commonly reported adverse reactions in clinical studies [see Adverse Reactions (6.1)] . Before using guanfacine extended-release tablets with other centrally active depressants, consider the potential for additive sedative effects. Caution patients against operating heavy equipment or driving until they know how they respond to treatment with guanfacine extended-release tablets . Advise patients to avoid use with alcohol. 5.3 Cardiac Conduction Abnormalities The sympatholytic action of guanfacine may worsen sinus node dysfunction and atrioventricular (AV) block, especially in patients taking other sympatholytic drugs. Titrate guanfacine slowly and monitor vital signs frequently in patients with cardiac conduction abnormalities or patients concomitantly treated with other sympatholytic drugs. 5.4 Rebound Hypertension In post marketing experience, abrupt discontinuation of guanfacine extended-release tablets has resulted in clinically significant and persistent rebound hypertension above baseline levels and increases in heart rate. Hypertensive encephalopathy has also been reported in association with rebound hypertension with both guanfacine extended-release and immediate release guanfacine [see Adverse Reactions (6.2)] . In these cases, high-dosage guanfacine was discontinued; concomitant stimulant use was also reported, which may potentially increase hypertensive response upon abrupt discontinuation of guanfacine extended-release tablets. Children commonly have gastrointestinal illnesses that lead to vomiting, and a resulting inability to take medications, so they may be especially at risk for rebound hypertension. To minimize the risk of rebound hypertension upon discontinuation, the total daily dose of guanfacine should be tapered in decrements of no more than 1 mg every 3 to 7 days [see Dosage and Administration (2.5)] . Blood pressure and heart rate should be monitored when reducing the dose or discontinuing guanfacine extended-release tablets. If abrupt discontinuation occurs (especially with concomitant stimulant use), patients should be closely followed for rebound hypertension.
Side effects
The following serious adverse reactions are described elsewhere in the labeling: Hypotension, bradycardia, and syncope [see Warnings and Precautions (5.1)] Sedation and somnolence [see Warnings and Precautions (5.2)] Cardiac conduction abnormalities [see Warnings and Precautions (5.3)] Rebound Hypertension [see Warnings and Precautions (5.4)] Most common adverse reactions (≥ 5% and at least twice placebo rate) in fixed-dose monotherapy ADHD trials in children and adolescents (6 to 17 years): hypotension, somnolence, fatigue, nausea, and lethargy (6.1). Flexible dose-optimization ADHD trials in children (6 to 12 years) and adolescents (13 to 17 years): somnolence, hypotension, abdominal pain, insomnia, fatigue, dizziness, dry mouth, irritability, nausea, vomiting, and bradycardia (6.1). Adjunctive treatment to psychostimulant ADHD trial in children and adolescents (6 to 17 years): somnolence, fatigue, insomnia, dizziness, and abdominal pain (6.1). To report SUSPECTED ADVERSE REACTIONS, contact Sun Pharmaceutical Industries, Inc. at 1-800-406-7984 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data described below reflect clinical trial exposure to guanfacine in 2,825 patients. This includes 2,330 patients from completed studies in children and adolescents, ages 6 to 17 years and 495 patients in completed studies in adult healthy volunteers. The mean duration of exposure of 446 patients that previously participated in two 2-year, open-label long-term studies was approximately 10 months. Fixed Dose Trials Table 3: Percentage of Patients Experiencing Most Common (≥ 5% and at least twice the rate for placebo) Adverse Reactions in Fixed Dose Studies 1 and 2 GUANFACINE (mg) Adverse Reaction Term Placebo (N = 149) 1 mg* (N = 61) 2 mg (N = 150) 3 mg (N = 151) 4 mg (N = 151) All Doses of Guanfacine (N = 513) Somnolence a 11% 28% 30% 38% 51% 38% Fatigue 3% 10% 13% 17% 15% 14% Hypotension b 3% 8% 5% 7% 8% 7% Dizziness 4% 5% 3% 7% 10% 6% Lethargy 3% 2% 3% 8% 7% 6% Nausea 2% 7% 5% 5% 6% 6% Dry mouth 1% 0% 1% 6% 7% 4% *The lowest dose of 1 mg used in Study 2 was not randomized to patients weighing more than 50 kg. a: The somnolence term includes somnolence, sedation, and hypersomnia. b: The hypotension term includes hypotension, diastolic hypotension, orthostatic hypotension, blood pressure decreased, blood pressure diastolic decreased, blood pressure systolic decreased). Table 4: Adverse Reactions Leading to Discontinuation (≥ 2% for all doses of Guanfacine and > rate than in placebo) in Fixed Dose Studies 1 and 2 GUANFACINE (mg) Adverse Reaction Term Placebo (N = 149) 1 mg* (N = 61) 2 mg (N = 150) 3 mg (N = 151) 4 mg (N = 151) All Doses of Guanfacine (N = 513) n (%) n (%) n (%) n (%) n (%) n (%) Total patients 4 (3%) 2 (3%) 10 (7%) 15 (10%) 27 (18%) 54 (11%) Somnolence a 1 (1%) 2 (3%) 5 (3%) 6 (4%) 17 (11%) 30 (6%) Fatigue 0 (0%) 0 (0%) 2 (1%) 2 (1%) 4 (3%) 8 (2%) Adverse reactions leading to discontinuation in ≥ 2% in any dose group but did not meet this criteria in all doses combined: hypotension (hypotension, diastolic hypotension, orthostatic hypotension, blood pressure decreased, blood pressure diastolic decreased, blood pressure systolic decreased), headache, and dizziness. * The lowest dose of 1 mg used in Study 2 was not randomized to patients weighing more than 50 kg. a: The somnolence term includes somnolence, sedation, and hypersomnia. Table 5: Other Common Adverse Reactions (≥ 2% for all doses of Guanfacine and > rate than in placebo) in Fixed Dose Studies 1 and 2 GUANFACINE(mg) Adverse Reaction Term Placebo (N = 149) 1 mg* (N = 61) 2 mg (N = 150) 3 mg (N = 151) 4 mg (N = 151) All Doses of Guanfacine (N = 513) Headache 19% 26% 25% 16% 28% 23% Abdominal Pain a 9% 10% 7% 11% 15% 11% Decreased Appetite 4% 5% 4% 9% 6% 6% Irritability 4% 5% 8% 3% 7% 6% Constipation 1% 2% 2% 3% 4% 3% Nightmare b 0% 0% 0% 3% 4% 2% Enuresis c 1% 0% 1% 3% 2% 2% Affect Lability d 1% 2% 1% 3% 1% 2% Adverse reactions ≥ 2% for all doses of guanfacine and > rate in placebo in any dose group but did not meet this criteria in all doses combined: insomnia (insomnia, initial insomnia, middle insomnia, terminal insomnia, sleep disorder), vomiting, diarrhea, abdominal/stomach discomfort (abdominal discomfort, epigastric discomfort, stomach discomfort), rash (rash, rash generalized, rash papular), dyspepsia, increased weight, bradycardia (bradycardia, sinus bradycardia), asthma (asthma, bronchospasm, wheezing), agitation, anxiety (anxiety, nervousness), sinus arrhythmia, blood pressure increased (blood pressure increased, blood pressure diastolic increased), and first degree atrioventricular block. * The lowest dose of 1 mg used in Study 2 was not randomized to patients weighing more than 50 kg. a: The abdominal pain term includes abdominal pain, abdominal pain lower, abdominal pain upper, and abdominal tenderness. b: The nightmare term includes abnormal dreams, nightmare, and sleep terror. c: The enuresis term includes enuresis, nocturia, and urinary incontinence. d: The affect lability term includes affect lability and mood swings.
Drug interactions
Table 14 contains clinically important drug interactions with guanfacine [see Clinical Pharmacology (12.3)] . Table 14: Clinically Important Drug Interactions: Effect of other Drugs on Guanfacine Concomitant Drug Name or Drug Class Clinical Rationale and Magnitude of Drug Interaction Clinical Recommendation Strong and moderate CYP3A4 inhibitors, e.g., ketoconazole, fluconazole Guanfacine is primarily metabolized by CYP3A4 and its plasma concentrations can be significantly affected resulting in an increase in exposure Consider dose reduction [see Dosage and administration (2.7)] Strong and moderate CYP3A4 inducers, e.g., rifampin, efavirenz Guanfacine is primarily metabolized by CYP3A4 and its plasma concentrations can be significantly affected resulting in a decrease in exposure Consider dose increase [see Dosage and administration (2.7)] Strong and moderate CYP3A4 inhibitors increase guanfacine exposure. Decrease guanfacine to 50% of target dosage when coadministered with strong and moderate CYP3A4 inhibitors (2.7). Strong and moderate CYP3A4 inducers decrease guanfacine exposure. Based on patient response, consider titrating guanfacine dosage up to double the target dosage over 1 to 2 weeks (2.7). See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.
Use in specific populations
8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ADHD medications, including guanfacine extended-release tablets, during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for ADHD Medications at 1-866-961-2388. Risk Summary Available data with guanfacine over decades of use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. However, use of guanfacine in pregnant women over this time has been infrequent. In animal reproduction studies, rabbits and rats exposed to 3 and 4 times the maximum recommended human dose (MRHD), respectively, showed no adverse outcomes. However, higher doses were associated with reduced fetal survival and maternal toxicity ( see Data ). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data Reproduction studies conducted in rats have shown that guanfacine crosses the placenta. However, administration of guanfacine to rabbits and rats during organogenesis at 3 (rabbit) and 4 (rat) times the MRHD of 0.12 mg/kg/day on a mg/m 2 basis resulted in no evidence of harm to the fetus. Higher doses (13.5 times the MRHD in both rabbits and rats) were associated with reduced fetal survival and maternal toxicity. 8.2 Lactation Risk Summary There are no data on the presence of guanfacine in human milk or the effects on the breastfed infant. The effects on milk production are also unknown. Guanfacine is present in the milk of lactating rats (see Data) . If a drug is present in animal milk, it is likely that the drug will be present in human milk. If an infant is exposed to guanfacine through breastmilk, monitor for symptoms of hypotension and bradycardia such as sedation, lethargy and poor feeding (see Clinical Considerations). The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for guanfacine and any potential adverse effects on the breastfed child from guanfacine or from the underlying maternal condition. Clinical Considerations Monitor breastfeeding infants exposed to guanfacine through breastmilk for sedation, lethargy, and poor feeding. Data Guanfacine was excreted in breast milk of lactating rats at a concentration comparable to that observed in blood, but slightly less than the concentration in plasma when administered following a single oral dose of 5 mg/kg. The concentration of drug in animal milk does not necessarily predict the concentration of drug in human milk. 8.4 Pediatric Use Safety and efficacy of guanfacinein pediatric patients less than 6 years of age have not been established. The efficacy of guanfacine was studied for the treatment of ADHD in five controlled monotherapy clinical trials (up to 15 weeks in duration), one randomized withdrawal study and one controlled adjunctive trial with psychostimulants (8 weeks in duration) in children and adolescents ages 6 to 17 who met DSM-IV ® criteria for ADHD [see Adverse Reactions (6) and Clinical Studies (14)] . Animal Data In studies in juvenile rats, guanfacine alone produced a slight delay in sexual maturation in males and females at 2 to 3 times the maximum recommended human dose (MRHD). Guanfacine in combination with methylphenidate produced a slight delay in sexual maturation and decreased growth as measured by a decrease in bone length in males at a dose of guanfacine comparable to the MRHD and a dose of methylphenidate approximately 4 times the MRHD. In a study where juvenile rats were treated with guanfacine alone from 7 to 59 days of age, development was delayed as indicated by a slight delay in sexual maturation and decreased body weight gain in males at 2 mg/kg/day and in females at 3 mg/kg/day. The No Adverse Effect Level (NOAEL) for delayed sexual maturation was 1 mg/kg/day, which is equivalent to the MRHD of 4 mg/day, on a mg/m 2 basis. The effects on fertility were not evaluated in this study. In a study where juvenile rats were treated with guanfacine in combination with methylphenidate from 7 to 59 days of age, a decrease in ulna bone length and a slight delay in sexual maturation were observed in males given 1 mg/kg/day of guanfacine in combination with 50 mg/kg/day of methylphenidate. The NOAELs for these findings were 0.3 mg/kg of guanfacine in combination with 16 mg/kg/day of methylphenidate, which are equivalent to 0.3 and 1.4 times the MRHD of 4 mg/day and 54 mg/day for guanfacine and methylphenidate, respectively, on a mg/m 2 basis. These findings were not observed with guanfacine alone at 1 mg/kg/day or methylphenidate alone at 50 mg/kg/day. 8.5 Geriatric Use The safety and efficacy of guanfacine in geriatric patients have not been established. 8.6 Renal Impairment It may be necessary to reduce the dosage in patients with significant impairment of renal function [see Clinical Pharmacology (12.3)] . 8.7 Hepatic Impairment It may be necessary to reduce the dosage in patients with significant impairment of hepatic function [see Clinical Pharmacology (12.3)] .
Pregnancy
8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ADHD medications, including guanfacine extended-release tablets, during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for ADHD Medications at 1-866-961-2388. Risk Summary Available data with guanfacine over decades of use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. However, use of guanfacine in pregnant women over this time has been infrequent. In animal reproduction studies, rabbits and rats exposed to 3 and 4 times the maximum recommended human dose (MRHD), respectively, showed no adverse outcomes. However, higher doses were associated with reduced fetal survival and maternal toxicity ( see Data ). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data Reproduction studies conducted in rats have shown that guanfacine crosses the placenta. However, administration of guanfacine to rabbits and rats during organogenesis at 3 (rabbit) and 4 (rat) times the MRHD of 0.12 mg/kg/day on a mg/m 2 basis resulted in no evidence of harm to the fetus. Higher doses (13.5 times the MRHD in both rabbits and rats) were associated with reduced fetal survival and maternal toxicity.
Pediatric use
8.4 Pediatric Use Safety and efficacy of guanfacinein pediatric patients less than 6 years of age have not been established. The efficacy of guanfacine was studied for the treatment of ADHD in five controlled monotherapy clinical trials (up to 15 weeks in duration), one randomized withdrawal study and one controlled adjunctive trial with psychostimulants (8 weeks in duration) in children and adolescents ages 6 to 17 who met DSM-IV ® criteria for ADHD [see Adverse Reactions (6) and Clinical Studies (14)] . Animal Data In studies in juvenile rats, guanfacine alone produced a slight delay in sexual maturation in males and females at 2 to 3 times the maximum recommended human dose (MRHD). Guanfacine in combination with methylphenidate produced a slight delay in sexual maturation and decreased growth as measured by a decrease in bone length in males at a dose of guanfacine comparable to the MRHD and a dose of methylphenidate approximately 4 times the MRHD. In a study where juvenile rats were treated with guanfacine alone from 7 to 59 days of age, development was delayed as indicated by a slight delay in sexual maturation and decreased body weight gain in males at 2 mg/kg/day and in females at 3 mg/kg/day. The No Adverse Effect Level (NOAEL) for delayed sexual maturation was 1 mg/kg/day, which is equivalent to the MRHD of 4 mg/day, on a mg/m 2 basis. The effects on fertility were not evaluated in this study. In a study where juvenile rats were treated with guanfacine in combination with methylphenidate from 7 to 59 days of age, a decrease in ulna bone length and a slight delay in sexual maturation were observed in males given 1 mg/kg/day of guanfacine in combination with 50 mg/kg/day of methylphenidate. The NOAELs for these findings were 0.3 mg/kg of guanfacine in combination with 16 mg/kg/day of methylphenidate, which are equivalent to 0.3 and 1.4 times the MRHD of 4 mg/day and 54 mg/day for guanfacine and methylphenidate, respectively, on a mg/m 2 basis. These findings were not observed with guanfacine alone at 1 mg/kg/day or methylphenidate alone at 50 mg/kg/day.
Geriatric use
8.5 Geriatric Use The safety and efficacy of guanfacine in geriatric patients have not been established.
Overdosage
Symptoms Postmarketing reports of guanfacine extended-release tablets overdosage indicate that hypotension, drowsiness, lethargy, and bradycardia have been observed following overdose. Initial hypertension may develop early and may be followed by hypotension. Similar symptoms have been described in voluntary reports to the American Association of Poison Control Center’s National Poison Data System. Miosis of the pupils may be noted on examination. No fatal overdoses of guanfacine extended-release tablets have been reported in published literature. Treatment Consult a Certified Poison Control Center by calling 1-800-222-1222 for up-to-date guidance and advice. Management of guanfacine overdose should include monitoring for and the treatment of initial hypertension, if that occurs, as well as hypotension, bradycardia, lethargy and respiratory depression. Children and adolescents who develop lethargy should be observed for the development of more serious toxicity including coma, bradycardia and hypotension for up to 24 hours, due to the possibility of delayed onset hypotension.
Description
Guanfacine is a once-daily, extended-release formulation of guanfacine hydrochloride (HCl), USP in a matrix tablet formulation for oral administration only. The chemical designation is N-amidino-2-(2,6-dichlorophenyl) acetamide monohydrochloride. The molecular formula is C 9 H 9 Cl 2 N 3 O·HCl corresponding to a molecular weight of 282.55. The chemical structure is: Guanfacine hydrochloride, USP is a white or almost white crystalline powder, sparingly soluble in water, methanol and ethanol. Each tablet contains guanfacine HCl equivalent to 1 mg, 2 mg, 3 mg, or 4 mg of guanfacine base. The tablets also contain colloidal silicon dioxide, fumaric acid, glyceryl dibehenate, hypromellose, lactose monohydrate, methacrylic acid copolymer, microcrystalline cellulose, and povidone. In addition, the 3 mg and 4 mg tablets also contain FD&C blue #2/indigo carmine aluminum lake and ferric oxide yellow. Meets USP dissolution test 3 spl-structure
Mechanism of action
12.1 Mechanism of Action Guanfacine is a central alpha 2A -adrenergic receptor agonist. Guanfacine is not a central nervous system (CNS) stimulant. The mechanism of action of guanfacine in ADHD is not known.
How supplied
Guanfacine extended-release tablets, USP are supplied in 1 mg, 2 mg, 3 mg, and 4 mg strength as follows: Guanfacine extended-release tablets, USP 1 mg are white to off-white, round shaped tablets with “ RJ70 ” debossed on one side and plain on the other side. NDC 63304-924-30 Bottles of 30 NDC 63304-924-01 Bottles of 100 NDC 63304-924-05 Bottles of 500 Guanfacine extended-release tablets, USP 2 mg are white to off-white, oval-shaped tablets with “ RJ71 ” debossed on one side and plain on the other side. NDC 63304-925-30 Bottles of 30 NDC 63304-925-01 Bottles of 100 NDC 63304-925-05 Bottles of 500 Guanfacine extended-release tablets, USP 3 mg are green colored, round shaped tablets with “ RJ72 ” debossed on one side and plain on the other side. NDC 63304-926-30 Bottles of 30 NDC 63304-926-01 Bottles of 100 NDC 63304-926-05 Bottles of 500 Guanfacine extended-release tablets, USP 4 mg are green colored, oval-shaped tablets with “ RJ73 ” debossed on one side and plain on the other side. NDC 63304-927-30 Bottles of 30 NDC 63304-927-01 Bottles of 100 NDC 63304-927-05 Bottles of 500 Storage - Store at 20° - 25° C (68° - 77° F) [See USP Controlled Room Temperature].
Patient information
Advise the patient to read the FDA-approved patient labeling (Patient Information). Dosing and Administration Instruct patients to swallow guanfacine extended-release tablets whole with water, milk or other liquid. Tablets should not be crushed, chewed or broken prior to administration because this may increase the rate of release of the active drug . Patients should not take guanfacine extended-release tablets together with a high-fat meal, since this can raise blood levels of guanfacine extended-release tablets. Instruct the parent or caregiver to supervise the child or adolescent taking guanfacine extended-release tablets and to keep the bottle of tablets out of reach of children. Advise patients not to abruptly discontinue guanfacine extended-release tablets as abrupt discontinuation can result in clinically significant rebound hypertension. Concomitant stimulant use and abrupt discontinuation of guanfacine extended-release tablets may increase this hypertensive response. Instruct patients on how to properly taper the dose to minimize the risk of rebound hypertension [see Dosage and Administration (2.5) and Warnings and Precautions (5.4)]. Adverse Reactions Advise patients that sedation can occur, particularly early in treatment or with dose increases. Caution against operating heavy equipment or driving until they know how they respond to treatment with guanfacine extended-release tablets [see Warnings and Precautions (5.2)]. Headache and abdominal pain can also occur. If any of these symptoms persist, or other symptoms occur, the patient should be advised to discuss the symptoms with the health care provider. Advise patients to avoid becoming dehydrated or overheated, which may potentially increase the risks of hypotension and syncope [see Warnings and Precautions (5.1)] . Advise patients to avoid use with alcohol. Pregnancy Registry Advise patients that there is a pregnancy exposure registry that monitors pregnancy outcomes in patients exposed to guanfacine extended-release tablets during pregnancy [see Use in Specific Populations (8.1)] . Lactation Advise breastfeeding mothers to monitor infants exposed to guanfacine through breastmilk for sedation, lethargy and poor feeding [see Use in Specific Populations (8.2)]. All brand names listed are the registered trademarks of their respective owners. Manufactured by: Ohm Laboratories Inc. New Brunswick, NJ 08901 Distributed by: Sun Pharmaceutical Industries, Inc. Cranbury, NJ 08512 August 2023 FDA-12
Label text from the FDA structured product label by Sun Pharmaceutical Industries, Inc (revised Jun 4, 2026). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Guanfacine Hydrochloride in 73 products
- Guanfacine in 14 products
Guanfacine NDC products (87)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 50090-7644 | Guanfacine Hydrochloride 3 mg/1 Tablet, Extended Release | A-S Medication Solutions | ANDA |
| 50090-7129 | Guanfacine Hydrochloride 3 mg/1 Tablet, Extended Release | A-S Medication Solutions | ANDA |
| 73141-019 | Guanfacine Hydrochloride 2 mg/1 Tablet | A2A Integrated Pharmaceuticals | ANDA |
| 73141-018 | Guanfacine Hydrochloride 1 mg/1 Tablet | A2A Integrated Pharmaceuticals | ANDA |
| 0228-2851 | Guanfacine Hydrochloride 2 mg/1 Tablet, Extended Release | Actavis Pharma, Inc. | ANDA |
| 0591-0453 | Guanfacine Hydrochloride 2 mg/1 Tablet | Actavis Pharma, Inc. | ANDA |
| 0228-2855 | Guanfacine Hydrochloride 4 mg/1 Tablet, Extended Release | Actavis Pharma, Inc. | ANDA |
| 0591-0444 | Guanfacine Hydrochloride 1 mg/1 Tablet | Actavis Pharma, Inc. | ANDA |
| 0228-2853 | Guanfacine Hydrochloride 3 mg/1 Tablet, Extended Release | Actavis Pharma, Inc. | ANDA |
| 0228-2850 | Guanfacine Hydrochloride 1 mg/1 Tablet, Extended Release | Actavis Pharma, Inc. | ANDA |
| 72888-227 | Guanfacine Hydrochloride 4 mg/1 Tablet, Extended Release | Advagen Pharma Limited | ANDA |
| 72888-226 | Guanfacine Hydrochloride 3 mg/1 Tablet, Extended Release | Advagen Pharma Limited | ANDA |
| 72888-225 | Guanfacine Hydrochloride 2 mg/1 Tablet, Extended Release | Advagen Pharma Limited | ANDA |
| 72888-224 | Guanfacine Hydrochloride 1 mg/1 Tablet, Extended Release | Advagen Pharma Limited | ANDA |
| 72888-124 | Guanfacine Hydrochloride 2 mg/1 Tablet | Advagen Pharma Ltd | ANDA |
| 72888-123 | Guanfacine Hydrochloride 1 mg/1 Tablet | Advagen Pharma Ltd | ANDA |
| 27241-242 | Guanfacine Hydrochloride 1 mg/1 Tablet | Ajanta Pharma USA Inc. | ANDA |
| 27241-243 | Guanfacine Hydrochloride 2 mg/1 Tablet | Ajanta Pharma USA Inc. | ANDA |
| 62332-745 | Guanfacine Hydrochloride 1 mg/1 Tablet, Extended Release | Alembic Pharmaceuticals Inc. | ANDA |
| 62332-746 | Guanfacine Hydrochloride 2 mg/1 Tablet, Extended Release | Alembic Pharmaceuticals Inc. | ANDA |
| 62332-747 | Guanfacine Hydrochloride 3 mg/1 Tablet, Extended Release | Alembic Pharmaceuticals Inc. | ANDA |
| 62332-748 | Guanfacine Hydrochloride 4 mg/1 Tablet, Extended Release | Alembic Pharmaceuticals Inc. | ANDA |
| 46708-747 | Guanfacine Hydrochloride 3 mg/1 Tablet, Extended Release | Alembic Pharmaceuticals Limited | ANDA |
| 46708-748 | Guanfacine Hydrochloride 4 mg/1 Tablet, Extended Release | Alembic Pharmaceuticals Limited | ANDA |
| 46708-746 | Guanfacine Hydrochloride 2 mg/1 Tablet, Extended Release | Alembic Pharmaceuticals Limited | ANDA |
| 46708-745 | Guanfacine Hydrochloride 1 mg/1 Tablet, Extended Release | Alembic Pharmaceuticals Limited | ANDA |
| 59651-840 | Guanfacine Hydrochloride 1 mg/1 Tablet | Aurobindo Pharma Limited | ANDA |
| 59651-841 | Guanfacine Hydrochloride 2 mg/1 Tablet | Aurobindo Pharma Limited | ANDA |
| 72162-1799 | Guanfacine Hydrochloride 2 mg/1 Tablet, Extended Release | Bryant Ranch Prepack | ANDA |
| 72162-1801 | Guanfacine Hydrochloride 4 mg/1 Tablet, Extended Release | Bryant Ranch Prepack | ANDA |
| 72162-1798 | Guanfacine Hydrochloride 1 mg/1 Tablet, Extended Release | Bryant Ranch Prepack | ANDA |
| 71335-2379 | Guanfacine Hydrochloride 1 mg/1 Tablet, Extended Release | Bryant Ranch Prepack | ANDA |
| 63629-8161 | Guanfacine Hydrochloride 1 mg/1 Tablet, Extended Release | Bryant Ranch Prepack | ANDA |
| 63629-8203 | Guanfacine Hydrochloride 2 mg/1 Tablet, Extended Release | Bryant Ranch Prepack | ANDA |
| 67046-1655 | Guanfacine Hydrochloride 2 mg/1 Tablet | Coupler LLC | ANDA |
| 67046-1433 | Guanfacine Hydrochloride 1 mg/1 Tablet | Coupler LLC | ANDA |
| 42806-048 | Guanfacine Hydrochloride 1 mg/1 Tablet | Epic Pharma, LLC | ANDA |
| 42806-296 | Guanfacine Hydrochloride 2 mg/1 Tablet | Epic Pharma, LLC | ANDA |
| 72266-258 | Guanfacine Hydrochloride 4 mg/1 Tablet, Extended Release | Fosun Pharma USA, Inc | ANDA |
| 72266-257 | Guanfacine Hydrochloride 3 mg/1 Tablet, Extended Release | Fosun Pharma USA, Inc | ANDA |
| 72266-256 | Guanfacine Hydrochloride 2 mg/1 Tablet, Extended Release | Fosun Pharma USA, Inc | ANDA |
| 72266-255 | Guanfacine Hydrochloride 1 mg/1 Tablet, Extended Release | Fosun Pharma USA, Inc | ANDA |
| 60429-961 | Guanfacine 2 mg/1 Tablet, Extended Release | Golden State Medical Supply, Inc. | ANDA |
| 51407-952 | Guanfacine Hydrochloride 1 mg/1 Tablet, Extended Release | Golden State Medical Supply, Inc. | ANDA |
| 51407-953 | Guanfacine Hydrochloride 2 mg/1 Tablet, Extended Release | Golden State Medical Supply, Inc. | ANDA |
| 51407-954 | Guanfacine Hydrochloride 3 mg/1 Tablet, Extended Release | Golden State Medical Supply, Inc. | ANDA |
| 51407-955 | Guanfacine Hydrochloride 4 mg/1 Tablet, Extended Release | Golden State Medical Supply, Inc. | ANDA |
| 60429-963 | Guanfacine 4 mg/1 Tablet, Extended Release | Golden State Medical Supply, Inc. | ANDA |
| 60429-962 | Guanfacine 3 mg/1 Tablet, Extended Release | Golden State Medical Supply, Inc. | ANDA |
| 60429-960 | Guanfacine 1 mg/1 Tablet, Extended Release | Golden State Medical Supply, Inc. | ANDA |
| 72319-018 | Guanfacine Hydrochloride 1 mg/1 Tablet | i3 Pharmaceuticals, LLC | ANDA |
| 72319-019 | Guanfacine Hydrochloride 2 mg/1 Tablet | i3 Pharmaceuticals, LLC | ANDA |
| 0904-7140 | Guanfacine Hydrochloride 1 mg/1 Tablet | Major Pharmaceuticals | ANDA |
| 16714-190 | Guanfacine Hydrochloride 1 mg/1 Tablet, Extended Release | NORTHSTAR RXLLC | ANDA |
| 16714-191 | Guanfacine Hydrochloride 2 mg/1 Tablet, Extended Release | NORTHSTAR RXLLC | ANDA |
| 16714-192 | Guanfacine Hydrochloride 3 mg/1 Tablet, Extended Release | NORTHSTAR RXLLC | ANDA |
| 16714-193 | Guanfacine Hydrochloride 4 mg/1 Tablet, Extended Release | NORTHSTAR RXLLC | ANDA |
| 63187-302 | Guanfacine Hydrochloride 1 mg/1 Tablet | Proficient Rx LP | ANDA |
| 71205-947 | Guanfacine 4 mg/1 Tablet, Extended Release | Proficient Rx LP | ANDA |
| 71205-946 | Guanfacine 3 mg/1 Tablet, Extended Release | Proficient Rx LP | ANDA |
| 71205-945 | Guanfacine 2 mg/1 Tablet, Extended Release | Proficient Rx LP | ANDA |
| 71205-944 | Guanfacine 1 mg/1 Tablet, Extended Release | Proficient Rx LP | ANDA |
| 24658-730 | Guanfacine Hydrochloride 1 mg/1 Tablet | PuraCap Laboratories LLC dba Blu Pharmaceuticals | ANDA |
| 70518-4539 | Guanfacine Hydrochloride 1 mg/1 Tablet, Extended Release | REMEDYREPACK INC. | ANDA |
| 70518-4564 | Guanfacine Hydrochloride 2 mg/1 Tablet | REMEDYREPACK INC. | ANDA |
| 70518-4675 | Guanfacine Hydrochloride 2 mg/1 Tablet, Extended Release | REMEDYREPACK INC. | ANDA |
| 70518-4488 | Guanfacine Hydrochloride 2 mg/1 Tablet | REMEDYREPACK INC. | ANDA |
| 70518-4333 | Guanfacine Hydrochloride 1 mg/1 Tablet | REMEDYREPACK INC. | ANDA |
| 70518-3809 | Guanfacine 2 mg/1 Tablet, Extended Release | REMEDYREPACK INC. | ANDA |
| 70518-2771 | Guanfacine 1 mg/1 Tablet, Extended Release | REMEDYREPACK INC. | ANDA |
| 70436-039 | Guanfacine Hydrochloride 1 mg/1 Tablet, Extended Release | Slate Run Pharmaceuticals, LLC | ANDA |
| 70436-042 | Guanfacine Hydrochloride 4 mg/1 Tablet, Extended Release | Slate Run Pharmaceuticals, LLC | ANDA |
| 70436-041 | Guanfacine Hydrochloride 3 mg/1 Tablet, Extended Release | Slate Run Pharmaceuticals, LLC | ANDA |
| 70436-040 | Guanfacine Hydrochloride 2 mg/1 Tablet, Extended Release | Slate Run Pharmaceuticals, LLC | ANDA |
| 60760-863 | Guanfacine Hydrochloride 1 mg/1 Tablet, Extended Release | St. Mary's Medical Park Pharmacy | ANDA |
| 63304-924 | Guanfacine Hydrochloride 1 mg/1 Tablet, Extended Release | Sun Pharmaceutical Industries, Inc | ANDA |
| 63304-925 | Guanfacine Hydrochloride 2 mg/1 Tablet, Extended Release | Sun Pharmaceutical Industries, Inc | ANDA |
| 63304-926 | Guanfacine Hydrochloride 3 mg/1 Tablet, Extended Release | Sun Pharmaceutical Industries, Inc | ANDA |
| 63304-927 | Guanfacine Hydrochloride 4 mg/1 Tablet, Extended Release | Sun Pharmaceutical Industries, Inc | ANDA |
| 29300-463 | Guanfacine Hydrochloride 4 mg/1 Tablet, Extended Release | Unichem Pharmaceuticals (USA), Inc. | ANDA |
| 29300-462 | Guanfacine Hydrochloride 3 mg/1 Tablet, Extended Release | Unichem Pharmaceuticals (USA), Inc. | ANDA |
| 29300-461 | Guanfacine Hydrochloride 2 mg/1 Tablet, Extended Release | Unichem Pharmaceuticals (USA), Inc. | ANDA |
| 29300-460 | Guanfacine Hydrochloride 1 mg/1 Tablet, Extended Release | Unichem Pharmaceuticals (USA), Inc. | ANDA |
| 24979-538 | Guanfacine 4 mg/1 Tablet, Extended Release | Upsher-Smith Laboratories, LLC | ANDA |
| 24979-536 | Guanfacine 3 mg/1 Tablet, Extended Release | Upsher-Smith Laboratories, LLC | ANDA |
| 24979-534 | Guanfacine 2 mg/1 Tablet, Extended Release | Upsher-Smith Laboratories, LLC | ANDA |
| 24979-533 | Guanfacine 1 mg/1 Tablet, Extended Release | Upsher-Smith Laboratories, LLC | ANDA |
Frequently asked questions
What is Guanfacine used for?
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)] . Guanfacine extended-release tablets are a central alpha 2A -adrenergic receptor agonist indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) as monotherapy…
What are the side effects of Guanfacine?
The following serious adverse reactions are described elsewhere in the labeling: Hypotension, bradycardia, and syncope [see Warnings and Precautions (5.1)] Sedation and somnolence [see Warnings and Precautions (5.2)] Cardiac conduction abnormalities [see Warnings and Precautions (5.3)] Rebound Hypertension [see Warnings and Precautions (5.4)] Most common adverse reactions (≥ 5% and at least twice… See the full label for the complete list.
Who makes Guanfacine?
Guanfacine is listed by 25 labelers in the FDA NDC directory, including A-S Medication Solutions, A2A Integrated Pharmaceuticals, Actavis Pharma, Inc., Advagen Pharma Limited.