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guanfacine 4 mg Tablet, Extended Release, 100-count — NDC 42291-0327-01 package photo
Label image from the product's FDA listing (DailyMed) — may show a different pack size or an older label revision.

guanfacine 4 mg Tablet, Extended Release, 100-count — NDC 42291-327-01 (Billing 42291-0327-01)

by AvKARE · 100 TABLET, EXTENDED RELEASE in 1 BOTTLE

This is a package of 100 tablets of guanfacine 4 mg Tablet, Extended Release from AvKARE, no longer marketed (first marketed Jul 2015), no longer in the FDA NDC Directory. It is this product's only package size.

NDC 42291-0327-01
🏷️ FDA NDC (as labeled) 42291-327-01 billing pads the product segment with a zero
Rx only Generic Discontinued Non-controlled ⚠ Inactivated by FDA ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 1, 2026 · this listing last changed Jul 24, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

This page is curated, coded, and maintained by

Compiled from public FDA, CMS, DailyMed, NADAC, and related drug data sources. Editorial policy

⚠️
Excluded from the active FDA NDC Directory. FDA inactivated this product’s listing record, so it is excluded from the active NDC Directory. The listing was last certified through Dec 2026. A label may still appear on DailyMed, but the NDC is no longer in the current FDA NDC Directory. Search the FDA NDC Directory ↗

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 42291-327-01
Product NDC 42291-327
11-digit billing NDC 42291032701
NCPDP billing unit EA — each (per item)
RxCUI 862006, 862013, 862019, 862025
UNII PML56A160O
UPC 0342291327016, 0342291325012
Application # ANDA200881
SPL Set ID 301f01a7-2b0a-cfba-9c3d-a1dd831785a3
Established class (EPC) Central alpha-2 Adrenergic Agonist
Mechanism of action Adrenergic alpha2-Agonists
DEA schedule Non-controlled
Marketing category ANDA
Marketing status Discontinued
FDA listing status Inactivated by FDA (certified through Dec 2026)
Marketing start 2015-07-09
Route ORAL
Dosage form TABLET, EXTENDED RELEASE
Substance GUANFACINE HYDROCHLORIDE
TE code (Orange Book) AB · RLD · RS

Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification

GPI-14 61353030107550
GPI class guanFACINE HCl ER
GCN Seq No 065574
GCN 27582
HICL code 000120
Ingredient (HICL) Guanfacine Hcl
HIC1 code H
Therapeutic class — broad (HIC1) Nervous System (Except Autonomic)
HIC2 code H8
Therapeutic class — intermediate (HIC2) Psychoactive Drugs (Continued 2)
HIC3 code H8M
Therapeutic class — specific (HIC3) Tx For Adhd - Selective Alpha-2 Receptor Agonist
AHFS code 24:24.00.00
AHFS class Central Alpha-Agonists
FDB label name GUANFACINE HCL ER 4 MG TABLET
FDB brand name Guanfacine Hcl Er
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 065574
  • GCN: 27582
  • GPI-14 (Medi-Span): 61353030107550
  • HICL (First Databank): 000120
  • AHFS class code: 24:24.00.00
  • RxCUI (RxNorm): 862006
Why two NDCs? The FDA registers this code as 42291-327-01 — a 5-3-2 layout, and that's what's printed on the package and shown on DailyMed. For insurance claims, every NDC is standardized to a uniform 11-digit 5-4-2 format by adding a zero to the product segment → 42291-0327-01. Same drug, same package — only the format differs.
Where does this data come from?
Identifiers from the FDA openFDA NDC Directory and Structured Product Labeling; RxCUI from RxNorm (NLM); GPI from Medi-Span; GCN / HIC / AHFS / legend from First Databank.

RxNorm drug class

This medicine belongs to the Central alpha-2 Adrenergic Agonist class.

Pharmacologic class Central alpha-2 Adrenergic Agonist
Drug family (ATC) Imidazoline receptor agonists
How it works Adrenergic alpha2-Agonists
Where does this data come from?
Therapeutic classes from RxNorm RxClass (U.S. National Library of Medicine) — Established Pharmacologic Class (FDA), ATC drug family (WHO) and mechanism of action, matched by this product’s RxCUI.

Clinical

Label name GUANFACINE HCL ER 4 MG TABLET Ingredient Guanfacine Hcl
📗 Our plain-language guide HelloPharmacist
  • It's used for both, depending on which form you have. The regular (immediate-release) tablet is prescribed for high blood pressure. The extended-release version — brand name Intuni...
  • What is guanfacine actually used for — is it for ADHD or blood pressure?
  • No, Intuniv is not a stimulant at all. It works on a different part of the brain than medications like Adderall or Ritalin. That's actually one reason it's sometimes used alongside...
  • My child takes Intuniv for ADHD — is it a stimulant?
📖 Read our full Guanfacine guide →
1
Nutrient depletion considerations

Guanfacine may be associated with lower levels of 1 nutrient — worth a chat with your pharmacist, not a cause for alarm.

🧪 Full Guanfacine nutrient depletion report →
An association is not a deficiency. Educational only — don't start or stop anything without professional guidance.
Where does this data come from?
Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

Pricing

A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.

Price systemPer eachPer package
Retail pharmacies payNADAC · weekly Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data.
Medicare drug plans payPart D · Q2 2026 $0.4957 $49.57 / 100 tablets
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

Packaging — all sizes for this product

Package NDCDescription Marketing startMarketing endStatus
42291-0327-01 You're viewing this Main listing 100 TABLET, EXTENDED RELEASE in 1 BOTTLE 2015-07-09 — Inactivated by FDA

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
guanfacine 4 mg 00228-2855-11 Actavis 100 tablets $0.176 AB Availability likely —
Guanfacine Extended-Release 4 mg 24979-0538-01 Upsher-Smith 100 tablets $0.176 AB Availability likely —
Guanfacine 4 mg 29300-0463-01 Unichem 100 tablets $0.176 AB Availability likely —
Guanfacine extended-release 4 mg 60505-3930-01 Apotex 100 tablets $0.176 AB Availability likely —
Guanfacine 4 mg 62332-0748-31 Alembic 100 tablets $0.176 AB Availability likely —
Guanfacine 4 mg 70436-0042-01 Slate 100 tablets $0.176 AB Availability likely —
Guanfacine 4 mg 72266-0258-55 Fosun 100 tablets $0.176 AB Availability likely —
Guanfacine 4 mg 63304-0927-01 Sun 100 tablets $0.192 — FDA listed —
Guanfacine 4 mg 16714-0193-01 NORTHSTAR 100 tablets $0.233 — FDA listed —
Intuniv 4 mg 54092-0519-02 Takeda 100 tablets $9.270 AB Availability likely —
guanfacine 4 mgthis 42291-0327-01 AvKARE 100 tablets — AB Discontinued —
Guanfacine 4 mg 46708-0748-31 Alembic 100 tablets — AB FDA listed —
Guanfacine 4 mg 51407-0955-01 Golden 100 tablets — AB FDA listed —
Guanfacine Extended-Release 4 mg 60429-0963-01 Golden 100 tablets — AB FDA listed —
Guanfacine Extended-Release 4 mg 71205-0947-00 Proficient 100 tablets — AB FDA listed —
Guanfacine extended-release 4 mg 71335-3005-01 Bryant 100 tablets — AB FDA listed —
Guanfacine 4 mg 72162-1801-01 Bryant 100 tablets — — FDA listed —
Guanfacine 4 mg 72888-0227-00 Advagen 1000 tablets — AB FDA listed —
About this product: this is a generic version of the medicine. FDA equivalence ratings are shown when available, and other versions are listed above, least expensive first.
Where does this data come from?
Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

Availability & generic status

🏛️
2015
On the market since
Jul 2015
📍
2026
Currently FDA-listed
11 years listed
🔓
·
Generic on the market
this product is a generic
✅This is a generic drug

This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.

Where does this data come from?
Patents and exclusivity from the FDA Orange Book (small-molecule drugs), refreshed from public FDA data. Generic launch timing is an estimate, not a guarantee.

What it looks like

Color orange / yellow
ShapeOval
Imprint855
Size12 mm
ScoringNot scored
One label can cover several strengths, so colors may be combined — always confirm a loose pill against the dispensed prescription label or a pharmacist.
Where does this data come from?
Physical description (imprint, shape, color, scoring, coating) from this product’s FDA Structured Product Labeling (SPL), mirrored from DailyMed / openFDA.

Inactive Ingredients / Excipients

Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.

💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.

  • UNII OP1R32D61U
    Microcrystalline cellulose is a purified form of cellulose, a natural fiber from plant sources. It acts as a binder and filler in tablets and capsules, helping hold ingredients together and give the medicine its shape and size.
  • UNII 2S7830E561
    Crospovidone is a synthetic polymer derived from povidone. It acts as a disintegrant, helping the tablet or capsule break apart quickly in the stomach so the active ingredient can be absorbed.
  • UNII 35SW5USQ3G
    A synthetic yellow dye used to color medicines. It helps make tablets, capsules, and liquids visually distinct so patients can easily identify their medication.
  • UNII 88XHZ13131
    Fumaric acid is an organic acid used in medications as a buffer and pH regulator. It helps maintain the proper acidity level in the medicine and may aid in tablet disintegration.
  • UNII 73CJJ317SR
    A waxy substance derived from plant oils, used as a binder and lubricant to help hold tablet ingredients together and improve how the medicine flows during manufacturing.
  • UNII U3JF91U133
    Hydroxypropyl cellulose is a plant-derived polymer that acts as a binder, thickener, and film-former in medications. It helps hold tablet ingredients together, control how quickly the drug dissolves, and create protective coatings on pills.
  • UNII 3NXW29V3WO
    Hypromellose is a plant-based thickener made from cellulose. It's used in medicines as a binder to hold ingredients together, a coating for tablets, and a thickener for liquids.
  • UNII EWQ57Q8I5X
    Lactose monohydrate is a natural sugar derived from milk. It serves as a filler and binder in tablets and capsules, helping create the proper size, texture, and consistency of the medicine.
  • UNII FZ989GH94E
    Povidone is a synthetic polymer made from a plastic-like material. It acts as a binder to hold tablet ingredients together and as a disintegrant to help the tablet break apart in your stomach so the medicine can be absorbed.
  • UNII ETJ7Z6XBU4
    Silicon dioxide is a naturally occurring mineral used as a glidant and anti-caking agent. It helps powder ingredients flow smoothly and prevents clumping during manufacturing and storage.

10 inactive ingredients listed in the exact product block matched to this NDC.

Where does this data come from?
Data sourced from official FDA Structured Product Labeling (SPL) via DailyMed — ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.

Inactive ingredient FAQ

Are inactive ingredients the same for every manufacturer?
No. Inactive ingredients can differ by manufacturer, dosage form, strength, and package / product version.
Why might an inactive ingredient be missing?
Some SPLs do not provide a complete structured inactive-ingredient list, and older or unusual labels may only include the information in narrative text.
Can inactive ingredients matter?
Yes. They can matter for allergies, intolerances, dyes, gluten / lactose concerns, preservatives, and formulation differences — but confirm with a pharmacist or the manufacturer when it’s clinically important.

Manufacturer & labeler

LabelerAvKARE
Application holderACTAVIS ELIZABETH LLC
FDA applicationANDA200881 (ANDA)
Labeler code42291
First marketedJul 2015
Product typeHuman Prescription Drug
Portfolio384 products on file
The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Very long sections are excerpted here and marked; the full text is on DailyMed (linked in the sources below). Jump with a chip, search within the label, or expand everything.
🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications ⚠️ Warnings and Cautions 🤒 Adverse Reactions 🔄 Drug Interactions 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📋 Description 💬 Information for Patients 🍼 Nursing Mothers 🧬 Pharmacokinetics 🧬 Pharmacodynamics 🔬 Clinical Studies 🔒 Drug Abuse and Dependence 🔒 Controlled Substance 🧪 Nonclinical Toxicology 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📄 Patient Package Insert 📄 Recent Major Changes 📄 Package Label / Principal Display Panel
🎯 Indications and Usage 68 words ▾

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 )] . Guanfacine extended-release is 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 ~3 min read ▾

2 DOSAGE AND ADMINISTRATION Recommended dose: 1 mg to 4 mg (0.05 mg/kg 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 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 ).

2.1General 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.

2.2Dose 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 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) In the adjunctive trial which evaluated guanfacine extended-release 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. 1

2.3Switching from Immediate-Release Guanfacine to Guanfacine E xtended- R elease If switching from immediate-release guanfacine, discontinue that treatment, and titrate with guanfacine extended-release 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 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 )].

2.4Maintenance 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, 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)].

2.5Discontinuation of Treatment Following discontinuation of guanfacine extended-release, patients may experience increases in blood pressure and heart rate [see Warnings and Precautions (5.4) and Adverse Reaction s (6) ] . Patients/caregivers should be instructed not to discontinue guanfacine extended-release 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 avoid rebound hypertension.

2.6Missed Doses When reinitiating patients to the previous maintenance dose after two or more missed consecutive doses, consi… [Excerpted — this section continues on DailyMed.]

💊 Dosage Forms and Strengths 30 words ▾

3 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 50 words ▾

4 CONTRAINDICATIONS Guanfacine extended-release is contraindicated in patients with a history of a hypersensitivity reaction to guanfacine extended-release or its inactive ingredients, or other products containing guanfacine. Rash and pruritus have been reported. History of hypersensitivity to guanfacine extended-release, its inactive ingredients, or other products containing guanfacine ( 4 ).

⚠️ Warnings and Cautions ~2 min read ▾

5 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 extended-release. 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 extended-release ( 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 extended-release tablets 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 extended-release tablets should be tapered in decrements of no more than 1 mg every 3 to 7 days ( 5.4 ).

5.1Hypotension, Bradycardia, and Syncope Treatment with guanfacine extended-release 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 extended-release 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.

5.2Sedation and Somnolence Somnolence and sedation were commonly reported adverse reactions in clinical studies [see Adverse Reactions ( 6.1 )] . Before using guanfacine extended-release 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.

Advise patients to avoid use with alcohol.

5.3Cardiac Conduction Abnormalities The sympatholytic action of guanfacine extended-release may worsen sinus node dysfunction and atrioventricular (AV) block, especially in patients taking other sympatholytic drugs. Titrate guanfacine extended-release slowly and monitor vital signs frequently in patients with cardiac conduction abnormalities or patients concomitantly treated with other sympatholytic drugs.

5.4Rebound 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 tablets and immediate release guanfacine [see Adverse Reactions ( 6.2 )] . In th… [Excerpted — this section continues on DailyMed.]

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS 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 (greater than or equal to 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): 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 AvKARE, Inc. at 1-855-361-3993 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical 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 extended-release in 2,028 patients. This includes 1,533 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 G uanfacine E xtended- R elease (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 G uanfacine E xtended- R elease (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 Extended-Release and > rate in placebo) in Fixed Dose Studies 1 and 2 G uanfacine E xtended- R elease (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 G uanfacine E xtended- R elease (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 Extended-Release and > rate than in placebo) in Fixed Dose Studies 1 and 2 G uanfacine E xtended- R elease (mg) Adverse Reaction Term Placebo (N=… [Excerpted — this section continues on DailyMed.]

🔄 Drug Interactions ~1 min read ▾

7 DRUG INTERACTIONS Table 14 contains clinically important drug interactions with guanfacine extended-release [see Clinical Pharmacology ( 12.3 )] . Table 14: Clinically Important Drug Interactions: Effect of other Drugs on Guanfacine Extended-Release 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 extended-release 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 extended-release dosage up to double the target dosage over 1 to 2 weeks ( 2.7 ).

Additional pediatric use information for patients ages 6 to 17 years is approved for Shire US Inc.’s INTUNIV ® (guanfacine) extended- release tablet product. However, due to Shire US Inc.'s marketing exclusivity rights, this drug product is not labeled with that pediatric information.

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS

8.1Pregnancy 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/m2 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.

8.3Lactation 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 extended-release tablets and any potential adverse effects on the breastfed child from guanfacine extended-release tablets 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.

8.4Pediatric Use Safety and efficacy of guanfacine extended-release in pediatric patients less than 6 years of age have not been established. The efficacy of guanfacine extended-release was studied for the treatment of ADHD in three controlled monotherapy clinical trials (up to 8 weeks in duration), 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 s… [Excerpted — this section continues on DailyMed.]

🤰 Pregnancy ~1 min read ▾

8.1Pregnancy 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/m2 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 ~2 min read ▾

8.4Pediatric Use Safety and efficacy of guanfacine extended-release in pediatric patients less than 6 years of age have not been established. The efficacy of guanfacine extended-release was studied for the treatment of ADHD in three controlled monotherapy clinical trials (up to 8 weeks in duration), 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 17 words ▾

8.5Geriatric Use The safety and efficacy of guanfacine extended-release in geriatric patients have not been established.

🆘 Overdosage 147 words ▾

10 OVERDOSAGE Symptoms Postmarketing reports of guanfacine 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 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 extended-release 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.

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism 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.

12.2Pharmacodynamics Guanfacine is a selective central alpha 2A -adrenergic receptor agonist in that it has a 15 to 20 times higher affinity for this receptor subtype than for the alpha 2B or alpha 2C subtypes. Guanfacine is a known antihypertensive agent. By stimulating central alpha 2A -adrenergic receptors, guanfacine reduces sympathetic nerve impulses from the vasomotor center to the heart and blood vessels.

This results in a decrease in peripheral vascular resistance and a reduction in heart rate. In a thorough QT study, the administration of two dose levels of immediate-release guanfacine (4 mg and 8 mg) produced concentrations approximately 2 to 4 times the concentrations observed with the maximum recommended dose of guanfacine extended-release of 0.12 mg/kg. Guanfacine was not shown to prolong the QTc interval to any clinically relevant extent.

12.3Pharmacokinetics Absorption and Distribution Guanfacine is readily absorbed and approximately 70% bound to plasma proteins independent of drug concentration. After oral administration of guanfacine extended-release the time to peak plasma concentration is approximately 5 hours in children and adolescents with ADHD. Immediate-release guanfacine and guanfacine extended-release have different pharmacokinetic characteristics; dose substitution on a milligram per milligram basis will result in differences in exposure.

A comparison across studies suggests that the C max is 60% lower and AUC 0- ∞ 43% lower, respectively, for guanfacine extended-release compared to immediate-release guanfacine. Therefore, the relative bioavailability of guanfacine extended-release to immediate-release guanfacine is 58%. The mean pharmacokinetic parameters in adults following the administration of guanfacine extended-release 1 mg once daily and immediate-release guanfacine 1 mg once daily are summarized in Table 15.

Table 15: Comparison of Pharmacokinetics: Guanfacine Extended-Release vs. Immediate release Guanfacine in Adults Parameter G uanfacine E xtended- R elease 1 mg once daily (n=52) Immediate- r elease g uanfacine 1 mg once daily (n=12) C max (ng/mL) 1.0 ± 0.3 2.5 ±

0.6AUC 0- ∞ (ng.h/mL) 32 ± 9 56 ± 15 t max (h) 6.0 (4.0 – 8.0) 3.0 (1.5-4.0) t ½ (h) 18 ± 4 16 ± 3 Note: Values are mean +/- SD, except for t max which is median (range) Figure 1: Comparison of Pharmacokinetics: Guanfacine Extended-Release vs. Immediate-release Guanfacine in Adults Exposure to guanfacine was higher in children (ages 6 to 12) compared to adolescents (ages 13 to 17) and adults. After oral administration of multiple doses of guanfacine extended-release 4 mg, the C max was 10 ng/mL compared to 7 ng/mL and the AUC was 162 ng•h/mL compared to 116 ng•h/mL in children (ages 6 to 12) and adolescents (ages 13 to 17), respectively.

These differences are probably attributable to the lower body weight of children compared to adolescents and adults. The pharmacokinetics were affected by intake of food when a single dose of guanfacine extended-release 4 mg was administered with a high-fat breakfast. The mean exposure increased (C max ~75% and AUC ~40%) compared to dosing in a fasted state.

Dose Proportionality Following administration of guanfacine extended-release in single doses of 1 mg, 2 mg, 3 mg, and 4 mg to adults, C max and AUC 0- ∞ of guanfacine were proportional to dose. Metabolism and Elimination In vitro studies with human liver microsomes and recombinant CYP’s demonstrated that guanfacine was primarily metabolized by CYP3A4. In pooled human hepatic microsomes, guanfacine did not inhibit the activities of the major cytochrome P450 isoenzymes (CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6 or CYP3A4/5).

Guanfacine is a substrate of CYP3A4/5 and exposure is affected by CYP3A4/5 inducers/inhibito… [Excerpted — this section continues on DailyMed.]

🧬 Mechanism of Action 33 words ▾

12.1Mechanism 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 / Storage and Handling 209 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING Guanfacine extended-release tablets are available as follows: 1 mg - Each orange, round tablet debossed with on one side and 850 on the other side contains guanfacine hydrochloride, USP equivalent to 1 mg of guanfacine base. Tablets are supplied in bottles of 100 (NDC 42291-324-01). 2 mg - Each orange, oval tablet debossed with on one side and 851 on the other side contains guanfacine hydrochloride, USP equivalent to 2 mg of guanfacine base.

Tablets are supplied in bottles of 100 (NDC 42291-325-01). 3 mg - Each yellow, round tablet debossed with on one side and 853 on the other side contains guanfacine hydrochloride, USP equivalent to 3 mg of guanfacine base. Tablets are supplied in bottles of 100 (NDC 42291-326-01).

4 mg - Each yellow, oval tablet debossed with on one side and 855 on the other side contains guanfacine hydrochloride, USP equivalent to 4 mg of guanfacine base. Tablets are supplied in bottles of 100 (NDC 42291-327-01). Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature].

Dispense in a tight, light-resistant container as defined in the USP. round tablet debossed round tablet debossed round tablet debossed round tablet debossed

📋 Description 185 words ▾

11 DESCRIPTION Guanfacine extended-release is a once-daily, extended-release formulation of guanfacine hydrochloride (HCl), in a matrix tablet formulation for oral administration only. The chemical designation is N-amidino-2-(2, 6-dichlorophenyl) acetamide monohydrochloride. The chemical structure is: C 9 H 9 Cl 2 N 3 O•HCl M.W.

282.55 Guanfacine hydrochloride, USP is a white to off-white crystalline powder, sparingly soluble in water (approximately 1 mg/mL) and alcohol and slightly soluble in acetone. The only organic solvent in which it has relatively high solubility is methanol (greater than 30 mg/mL). Each tablet contains guanfacine hydrochloride, USP equivalent to 1 mg, 2 mg, 3 mg, or 4 mg of guanfacine base.

The tablets also contain colloidal silicon dioxide, crospovidone, fumaric acid, glyceryl behenate, hydroxypropyl cellulose, hypromellose, lactose monohydrate, microcrystalline cellulose, and povidone. In addition, the 1 mg and 2 mg tablets contain FD&C Yellow #6 Aluminum Lake and the 3 mg and 4 mg tablets contain D&C Yellow #10 Aluminum Lake. The following chemical structure of Guanfacine hydrochloride, USP is a white to off-white crystalline powder, sparingly soluble in water (approximately 1 mg/mL) and alcohol and slightly soluble in ace

💬 Information for Patients ~2 min read ▾

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. 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 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)]. Brands listed are the trademarks of their respective owners. Manufactured for: AvKARE Pulaski, TN 38478 Mfg.

Rev. 01/20 AV Rev. 11/20 (P)

🍼 Nursing Mothers 198 words ▾

8.3Lactation 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 extended-release tablets and any potential adverse effects on the breastfed child from guanfacine extended-release tablets 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.

🧬 Pharmacokinetics ~3 min read ▾

12.3Pharmacokinetics Absorption and Distribution Guanfacine is readily absorbed and approximately 70% bound to plasma proteins independent of drug concentration. After oral administration of guanfacine extended-release the time to peak plasma concentration is approximately 5 hours in children and adolescents with ADHD. Immediate-release guanfacine and guanfacine extended-release have different pharmacokinetic characteristics; dose substitution on a milligram per milligram basis will result in differences in exposure.

A comparison across studies suggests that the C max is 60% lower and AUC 0- ∞ 43% lower, respectively, for guanfacine extended-release compared to immediate-release guanfacine. Therefore, the relative bioavailability of guanfacine extended-release to immediate-release guanfacine is 58%. The mean pharmacokinetic parameters in adults following the administration of guanfacine extended-release 1 mg once daily and immediate-release guanfacine 1 mg once daily are summarized in Table 15.

Table 15: Comparison of Pharmacokinetics: Guanfacine Extended-Release vs. Immediate release Guanfacine in Adults Parameter G uanfacine E xtended- R elease 1 mg once daily (n=52) Immediate- r elease g uanfacine 1 mg once daily (n=12) C max (ng/mL) 1.0 ± 0.3 2.5 ±

0.6AUC 0- ∞ (ng.h/mL) 32 ± 9 56 ± 15 t max (h) 6.0 (4.0 – 8.0) 3.0 (1.5-4.0) t ½ (h) 18 ± 4 16 ± 3 Note: Values are mean +/- SD, except for t max which is median (range) Figure 1: Comparison of Pharmacokinetics: Guanfacine Extended-Release vs. Immediate-release Guanfacine in Adults Exposure to guanfacine was higher in children (ages 6 to 12) compared to adolescents (ages 13 to 17) and adults. After oral administration of multiple doses of guanfacine extended-release 4 mg, the C max was 10 ng/mL compared to 7 ng/mL and the AUC was 162 ng•h/mL compared to 116 ng•h/mL in children (ages 6 to 12) and adolescents (ages 13 to 17), respectively.

These differences are probably attributable to the lower body weight of children compared to adolescents and adults. The pharmacokinetics were affected by intake of food when a single dose of guanfacine extended-release 4 mg was administered with a high-fat breakfast. The mean exposure increased (C max ~75% and AUC ~40%) compared to dosing in a fasted state.

Dose Proportionality Following administration of guanfacine extended-release in single doses of 1 mg, 2 mg, 3 mg, and 4 mg to adults, C max and AUC 0- ∞ of guanfacine were proportional to dose. Metabolism and Elimination In vitro studies with human liver microsomes and recombinant CYP’s demonstrated that guanfacine was primarily metabolized by CYP3A4. In pooled human hepatic microsomes, guanfacine did not inhibit the activities of the major cytochrome P450 isoenzymes (CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6 or CYP3A4/5).

Guanfacine is a substrate of CYP3A4/5 and exposure is affected by CYP3A4/5 inducers/inhibitors. Studies in Specific Populations Renal Impairment The impact of renal impairment on the pharmacokinetics of guanfacine in children 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.

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. Hepatic Impairment The impact of hepatic impairment on PK of guanfacine in children was not assessed.

Guanfacine in adults is cleared both by the liver and the kidney, and approximately 50% of the clearance of guanfacine is hepatic [see Hepatic Impairment ( 8.7 )]. Drug Interaction Studies Guanfacine is primarily metabolized by CYP3A4 and its plasma concentrations can be affected significantly by CYP3A4 inhibitors or inducers (Figure 2). Guanfacine does not significantly affect exposures of methylphenidate and lisdexamfetamine when coadministered (Figure 3). correct-figure F… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacodynamics 133 words ▾

12.2Pharmacodynamics Guanfacine is a selective central alpha 2A -adrenergic receptor agonist in that it has a 15 to 20 times higher affinity for this receptor subtype than for the alpha 2B or alpha 2C subtypes. Guanfacine is a known antihypertensive agent. By stimulating central alpha 2A -adrenergic receptors, guanfacine reduces sympathetic nerve impulses from the vasomotor center to the heart and blood vessels.

This results in a decrease in peripheral vascular resistance and a reduction in heart rate. In a thorough QT study, the administration of two dose levels of immediate-release guanfacine (4 mg and 8 mg) produced concentrations approximately 2 to 4 times the concentrations observed with the maximum recommended dose of guanfacine extended-release of 0.12 mg/kg. Guanfacine was not shown to prolong the QTc interval to any clinically relevant extent.

🔬 Clinical Studies ~3 min read ▾

6.1Clinical 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 extended-release in 2,028 patients. This includes 1,533 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 G uanfacine E xtended- R elease (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 G uanfacine E xtended- R elease (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 Extended-Release and > rate in placebo) in Fixed Dose Studies 1 and 2 G uanfacine E xtended- R elease (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 G uanfacine E xtended- R elease (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 Extended-Release and > rate than in placebo) in Fixed Dose Studies 1 and 2 G uanfacine E xtended- R elease (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 G uanfacine E xtended- R elease (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 extended-release 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 do… [Excerpted — this section continues on DailyMed.]

🔒 Drug Abuse and Dependence 24 words ▾

9 DRUG ABUSE AND DEPENDENCE

9.1Controlled Substance Guanfacine extended-release is not a controlled substance and has no known potential for abuse or dependence.

🔒 Controlled Substance 19 words ▾

9.1Controlled Substance Guanfacine extended-release is not a controlled substance and has no known potential for abuse or dependence.

🧪 Nonclinical Toxicology 116 words ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, 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/m 2 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/m 2 basis.

📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 113 words ▾

13.1Carcinogenesis, 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/m 2 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/m 2 basis.

📄 Patient Package Insert ~3 min read ▾

Patient Information G uanfacine ( gwahn' fa seen ) Extended-Release Tablets Rx Only Read the Patient Information that comes with guanfacine extended-release before you start taking it and each time you get a refill. There may be new information. This leaflet does not take the place of talking with your doctor about your medical condition or your treatment.

What are g uanfacine e xtended- r elease t ablets ? Guanfacine extended-release tablets are a prescription medicine used to treat the symptoms of attention deficit hyperactivity disorder (ADHD). Guanfacine extended-release tablets may be used alone or with ADHD stimulant medicines.

Guanfacine extended-release is not a central nervous system (CNS) stimulant. It is not known if guanfacine extended-release tablets are safe and effective in children younger than 6 years of age. Who should not take g uanfacine e xtended- r elease t ablets ?

Do not take guanfacine extended-release tablets if you are allergic to guanfacine or any of the ingredients in guanfacine extended-release tablets. See the end of this leaflet for a complete list of ingredients in guanfacine extended-release tablets. What should I tell my doctor before taking g uanfacine e xtended- r elease t ablets ?

Before you take g uanfacine e xtended- r elease t ablets , tell your doctor if you: have heart problems or a low heart rate have fainted have low or high blood pressure have liver or kidney problems have any other medical conditions are pregnant or plan to become pregnant. It is not known if guanfacine extended-release tablets will harm your unborn baby. Talk to your doctor if you are pregnant or plan to become pregnant. are breastfeeding or plan to breastfeed.

It is not known if guanfacine passes into your breast milk. Talk to your doctor about the best way to feed your baby while taking guanfacine extended-release. Tell your doctor about all of the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Guanfacine extended-release tablets may affect the way other medicines work, and other medicines may affect how guanfacine extended-release tablets work. Especially tell your doctor if you take: ketoconazole medicines that can affect enzyme metabolism high blood pressure medicine sedatives benzodiazepines barbiturates antipsychotics Ask your doctor or pharmacist for a list of these medicines, if you are not sure. Know the medicines you take.

Keep a list of them and show it to your doctor and pharmacist when you get a new medicine. How should I take g uanfacine e xtended- r elease t ablets ? Take guanfacine extended-release tablets exactly as your doctor tells you.

Your doctor may change your dose. Do not change your dose of guanfacine extended-release tablets without talking to your doctor. Try not to miss your dose of guanfacine extended-release tablets.

If you miss a dose of guanfacine extended-release tablets, take the next dose at your regular time. If you miss 2 or more doses, talk to your doctor, as you may need to restart guanfacine extended-release tablets with a lower dose. Do not take a double dose to make up for a missed dose.

Do not stop taking guanfacine extended-release tablets without talking to your doctor. Guanfacine extended-release tablets should be taken 1 time a day in the morning or in the evening, either alone or in combination with an ADHD stimulant medicine that your doctor may prescribe. Your doctor will tell you when to take guanfacine extended-release tablets and when to take your ADHD stimulant medication.

Guanfacine extended-release tablets should be swallowed whole with a small amount of water, milk, or other liquid. Do not crush, chew, or break guanfacine extended-release tablets. Tell your doctor if you cannot swallow guanfacine extended-release tablets whole.

Do not take guanfacine extended-release tablets with a high-fat meal. Your doctor will check your blood pressure and heart rate while you take guanfacine extended-release… [Excerpted — this section continues on DailyMed.]

📄 Recent Major Changes 17 words ▾

RECENT MAJOR CHANGES Dosage and Administration ( 2.5 ) 11/2017 Warnings and Precautions ( 5.4 ) 11/2017

📄 Package Label / Principal Display Panel 8 words ▾

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL 1 1 1 1

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗

About this NDC listing & data coverage

Finished prescription product No longer marketed (per FDA listing data)
What data is (and isn’t) available for this NDC — tap to expand
NDC identity (package / product / labeler codes) ✓ Available
Labeler ✓ Available
Product & package description ✓ Available
Marketing category & status ✓ Available
Active ingredient / dosage form / route ✓ Available
FDA label (SPL via DailyMed) ✓ Available
Package photos ✓ Available
Inactive ingredients (structured) ✓ Available
NADAC pharmacy acquisition price (CMS) — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey.
Orange Book / therapeutic-equivalence data ✓ Available
HCPCS J-code billing crosswalk — Not published for this NDC Most self-administered / retail products have no J-code — that is normal.
Medicaid utilization (CMS SDUD) — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold.
“Not published” reflects what the public FDA / CMS / NLM sources provide for this exact package code — it is a property of the data feeds, not a judgment about the product.

Questions about this listing

Why is there no price listed?
The pricing shown on our NDC pages comes from CMS NADAC, a voluntary survey of retail community pharmacy invoices. CMS does not publish a NADAC for every NDC — packages outside the retail survey (institutional and hospital products, bulk packages, discontinued items, and many OTC items) may never receive one. A missing price reflects the survey's scope, not this product's actual cost, and does not mean the product is free or unavailable.
What does the discontinued status mean for this NDC?
The labeler reported a marketing end date (or the listing was delisted), so this specific package is no longer actively marketed. Remaining stock may still be dispensed for a time, and the NDC stays valid for historical records and claims — but data feeds (pricing, labeling) typically stop updating for it. Other package sizes or other manufacturers' versions of the same medication may still be marketed — see the equivalents section where available.
Is the NDC printed on the package the same as the 11-digit billing NDC?
Yes, they identify this exact package in different formats. The form printed on the packaging and shown on DailyMed is the one the FDA registered. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero and the dashes are dropped. The Identity section at the top of this page lists each form of this code.
Who lists this product with the FDA?
AvKARE is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.
Do I need a prescription for this product?
This NDC is listed with FDA as a prescription product, so it is dispensed under a prescriber's order. Your pharmacist can tell you whether any over-the-counter forms of the same medication exist.
This page identifies an FDA-listed package (the NDC) and reports public regulatory and pricing data about the listing. It is reference information, not a medical recommendation — talk to your pharmacist or prescriber about your own medication.
Where does this data come from?
Listing facts (marketing category, packager status, marketing dates) from the FDA openFDA NDC Directory; label availability from DailyMed; pricing coverage from CMS NADAC; equivalence scope from the FDA Orange Book.
← 42291-0326-01 · AvKARE 42291-0366-01 · AvKARE →
For educational and professional reference only — not medical advice. Pricing reflects published NADAC and CMS ASP (free public data) and may differ from your acquisition cost; always verify before billing or dispensing.