Guanfacine
These highlights do not include all the information needed to use GUANFACINE EXTENDED-RELEASE TABLETS safely and effectively. See full prescribing information for GUANFACINE EXTENDED-RELEASE TABLETS. GUANFACINE extended-release tablets, for oral useInitial U.S. Approval: 1986
6e16cf54-c0d7-47ea-b502-c2146fd87f23
HUMAN PRESCRIPTION DRUG LABEL
Aug 31, 2023
Bryant Ranch Prepack
DUNS: 171714327
Products 1
Detailed information about drug products covered under this FDA approval, including NDC codes, dosage forms, ingredients, and administration routes.
Guanfacine
Product Details
FDA regulatory identification and product classification information
FDA Identifiers
Product Classification
Product Specifications
INGREDIENTS (9)
Drug Labeling Information
WARNINGS AND PRECAUTIONS SECTION
5 WARNINGS AND PRECAUTIONS
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.
- 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).
DRUG INTERACTIONS SECTION
7 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. ** (7)
NONCLINICAL TOXICOLOGY SECTION
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenesis
No carcinogenic effect of guanfacine was observed in studies of 78 weeks in mice or 102 weeks in rats at doses up to 6.8 times the maximum recommended human dose of 0.12 mg/kg/day on a mg/m2 basis.
Mutagenesis
Guanfacine was not genotoxic in a variety of test models, including the Ames test and an in vitro chromosomal aberration test; however, a marginal increase in numerical aberrations (polyploidy) was observed in the latter study.
Impairment of Fertility
No adverse effects were observed in fertility studies in male and female rats at doses up to 22 times the maximum recommended human dose on a mg/m2 basis.
HOW SUPPLIED SECTION
16 HOW SUPPLIED/STORAGE AND HANDLING
Guanfacine extended-release tablets are supplied in 2 mg strength.
Guanfacine extended-release tablets 2 mg are white to off-white, oval-shaped tablets with**“RJ71”** debossed on one side and plain on the other side.
- NDC 72162-1799-1: 100 Tablets in a BOTTLE
Storage - Store at 20° - 25° C (68° - 77° F) [See USP Controlled Room Temperature].
Repackaged/Relabeled by:
Bryant Ranch Prepack, Inc.
Burbank, CA 91504
INFORMATION FOR PATIENTS SECTION
17 PATIENT COUNSELING 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
January 2020 FDA-08