These Highlights Do Not Include All The Information Needed To Use Intuniv®

INTUNIV^® (in-TOO-niv)

(guanfacine)

Extended-Release Tablets

Read the Patient Information that comes with INTUNIV 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 is INTUNIV ?

INTUNIV is a prescription medicine used to treat the symptoms of attention deficit hyperactivity disorder (ADHD). INTUNIV may be used alone or with ADHD stimulant medicines.

INTUNIV is not a central nervous system (CNS) stimulant.

It is not known if INTUNIV is safe and effective in children younger than 6 years of age.

Who should not take INTUNIV ?

Do not take INTUNIV if you are allergic to guanfacine or any of the ingredients in INTUNIV. See the end of this leaflet for a complete list of ingredients in INTUNIV.

What should I tell my doctor before taking INTUNIV ?

Before you take INTUNIV , 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 INTUNIV will harm your unborn baby. Talk to your doctor if you are pregnant or plan to become pregnant.
  • There is a pregnancy registry for females who are exposed to ADHD medications, including INTUNIV, during pregnancy. The purpose of the registry is to collect information about the health of females exposed to INTUNIV and their baby. If you or your child becomes pregnant during treatment with INTUNIV, talk to your healthcare provider about registering with the National Pregnancy Registry of ADHD medications at 1-866-961-2388.
• are breastfeeding or plan to breastfeed. It is not known if INTUNIV passes into your breast milk. Talk to your doctor about the best way to feed your baby while taking INTUNIV.

Tell your doctor about all of the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

INTUNIV may affect the way other medicines work, and other medicines may affect how INTUNIV works.

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 INTUNIV ?

• Take INTUNIV exactly as your doctor tells you.
• Your doctor may change your dose. Do not change your dose of INTUNIV without talking to your doctor.
• Do not stop taking INTUNIV without talking to your doctor.
• Try not to miss your dose of INTUNIV. If you miss a dose of INTUNIV, 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 INTUNIV with a lower dose.
• Do not take a double dose to make up for a missed dose.
• INTUNIV 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 INTUNIV and when to take your ADHD stimulant medication.
• INTUNIV should be swallowed whole with a small amount of water, milk, or other liquid.
• Do not crush, chew, or break INTUNIV. Tell your doctor if you cannot swallow INTUNIV whole.
• Do not take INTUNIV with a high-fat meal.
• Your doctor will check your blood pressure and heart rate while you take INTUNIV.
• If you take too much INTUNIV, call your local Poison Control Center at 1-800-222-1222 or go to the nearest emergency room right away.

What should I avoid while taking INTUNIV ?

• Do not drive, operate heavy machinery, or do other dangerous activities until you know how INTUNIV affects you. INTUNIV can slow your thinking and motor skills.
• Do not drink alcohol or take other medicines that make you sleepy or dizzy while taking INTUNIV until you talk with your doctor. INTUNIV taken with alcohol or medicines that cause sleepiness or dizziness may make your sleepiness or dizziness worse.
• Do not become dehydrated or overheated. This may increase your chance of having low blood pressure or fainting while taking INTUNIV.
• Do not suddenly stop INTUNIV. Tell your healthcare provider if you have been vomiting and cannot take INTUNIV, you may be at risk for rebound hypertension.

What are the possible side effects of INTUNIV ?

INTUNIV may cause serious side effects including:

• low blood pressure
• low heart rate
• fainting
• sleepiness
• increased blood pressure and heart rate after suddenly stopping INTUNIV (rebound hypertension). Suddenly stopping INTUNIV can cause increased blood pressure and heart rate and other withdrawal symptoms such as headache, confusion, nervousness, agitation, and tremors. If these symptoms continue to get worse and are left untreated, it could lead to a very serious condition including very high blood pressure, feeling very sleepy or tired, severe headache, vomiting, vision problems, seizures.

Get medical help right away, if you have any of the symptoms listed above.

The most common side effects of INTUNIV include:

• sleepiness
• tiredness
• trouble sleeping
• low blood pressure
• nausea
• stomach pain
• dizziness
• dry mouth
• irritability
• vomiting
• slow heart rate

Tell the doctor if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of INTUNIV. For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store INTUNIV ?

• Store INTUNIV between 68°F to 77°F (20°C to 25°C)

Keep INTUNIV and all medicines out of the reach of children.

General Information about the safe and effective use INTUNIV

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information Leaflet. Do not use INTUNIV for a condition for which it was not prescribed. Do not give INTUNIV to other people, even if they have the same symptoms that you have. It may harm them.

This leaflet summarizes the most important information about INTUNIV. If you would like more information, talk with your doctor. You can ask your pharmacist or doctor for information about INTUNIV that is written for health professionals.

For more information, go to www.INTUNIV.com or call 1-877-825-3327.

What are the ingredients in INTUNIV ?

Active ingredient: guanfacine hydrochloride

Inactive ingredients: hypromellose, methacrylic acid copolymer, lactose, povidone, crospovidone, microcrystalline cellulose, fumaric acid, and glycerol behenate. In addition, the 3 mg and 4 mg tablets also contain green pigment blend PB-1763.

This Patient Information has been approved by the U.S. Food and Drug Administration.

Distributed by:

Takeda Pharmaceuticals America, Inc.

Cambridge, MA 02142

INTUNIV is a registered trademark of Takeda Pharmaceuticals U.S.A., Inc.

© 2025 Takeda Pharmaceuticals U.S.A., Inc. All rights reserved.

Patented: see www.takeda.com/en-us/patents.

Revised: 6/2025

Fixed Dose Trials

Storage - 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.

INTUNIV 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 molecular formula is C₉H₉Cl₂ N₃O∙HCl corresponding to a molecular weight of 282.55 g/mol. The chemical structure is:

Guanfacine HCl 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 (>30 mg/mL). Each tablet contains guanfacine HCl equivalent to 1 mg, 2 mg, 3 mg, or 4 mg of guanfacine base. The tablets also contain hypromellose, methacrylic acid copolymer, lactose, povidone, crospovidone, microcrystalline cellulose, fumaric acid, and glyceryl behenate. In addition, the 3-mg and 4-mg tablets also contain green pigment blend PB-1763.

When reinitiating patients to the previous maintenance dose after two or more missed consecutive doses, consider titration based on patient tolerability.

Safety and efficacy of INTUNIV in pediatric patients less than 6 years of age have not been established. The efficacy of INTUNIV 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)].

The safety and efficacy of INTUNIV in geriatric patients have not been established.

Take INTUNIV 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 INTUNIV is 0.05 to 0.12 mg/kg/day (total daily dose between 1 to 7 mg) (See Table 1).

In the adjunctive trial which evaluated INTUNIV 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.

Efficacy of INTUNIV in the treatment of ADHD was established in children and adolescents (6 to 17 years) in:

• Five short-term, placebo-controlled monotherapy trials (Studies 1, 2, 4, 5, and 6).
• One short-term, placebo-controlled adjunctive trial with psychostimulants (Study 3).
• One long-term, placebo-controlled monotherapy maintenance trial (Study 7).

INTUNIV is contraindicated in patients with a history of a hypersensitivity reaction to INTUNIV or its inactive ingredients, or other products containing guanfacine. Rash and pruritus have been reported.

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)]

Table 14 contains clinically important drug interactions with INTUNIV [see Clinical Pharmacology (12.3)].

It may be necessary to reduce the dosage in patients with significant impairment of renal function [see Clinical Pharmacology (12.3)].

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 INTUNIV of 0.12 mg/kg. Guanfacine was not shown to prolong the QTc interval to any clinically relevant extent.

It may be necessary to reduce the dosage in patients with significant impairment of hepatic function [see Clinical Pharmacology (12.3)].

INTUNIV^® is indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) as monotherapy and as adjunctive therapy to stimulant medications [see Clinical Studies (14)].

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.

In post marketing experience, abrupt discontinuation of INTUNIV 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 INTUNIV 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. 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 INTUNIV 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 INTUNIV. If abrupt discontinuation occurs (especially with concomitant stimulant use), patients should be closely followed for rebound hypertension.

INTUNIV is not a controlled substance and has no known potential for abuse or dependence.

Pharmacological treatment of ADHD may be needed for extended periods. Healthcare providers should periodically re-evaluate the long-term use of INTUNIV, 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)].

• 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 INTUNIV. 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 INTUNIV (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 INTUNIV 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 INTUNIV should be tapered in decrements of no more than 1 mg every 3 to 7 days (5.4).

• 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 INTUNIV 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).

Somnolence and sedation were commonly reported adverse reactions in clinical studies [see Adverse Reactions (6.1)]. Before using INTUNIV 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 INTUNIV. Advise patients to avoid use with alcohol.

1 mg, 2 mg, 3 mg, and 4 mg extended-release tablets

The following adverse reactions have been identified during post-approval use of guanfacine. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Less frequent, possibly guanfacine-related events observed in the post-marketing study and/or reported spontaneously, not included in section 6.1, include:

General: edema, malaise, tremor

Cardiovascular: palpitations, tachycardia, rebound hypertension, hypertensive encephalopathy

Central Nervous System: paresthesias, vertigo

Eye Disorders: blurred vision

Musculo-Skeletal System: arthralgia, leg cramps, leg pain, myalgia

Psychiatric: confusion, hallucinations

Reproductive System, Male: erectile dysfunction

Respiratory System: dyspnea

Skin and Appendages: alopecia, dermatitis, exfoliative dermatitis, pruritus, rash

Special Senses: alterations in taste

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 INTUNIV 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.

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.

Following discontinuation of INTUNIV, 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 INTUNIV 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.

Advise the patient to read the FDA-approved patient labeling (Patient Information).

INTUNIV is supplied in 1 mg, 2 mg, 3 mg, and 4 mg strength extended-release tablets in 100 count bottles.

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

Treatment with INTUNIV 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 INTUNIV 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.

Image not Available

NDC 54092-513-02

intuniv^®

(guanfacine)

Extended-Release Tablets

100 Tablets

1 mg

Rx only

Each tablet contains: 1 mg of guanfacine, as guanfacine HCl

Tablets should not be crushed,

chewed or broken before swallowing.

Distributed by:

Takeda Pharmaceuticals

America, Inc.

Cambridge, MA 02142

Takeda

Product of Spain

NDC 54092-515-02

intuniv^®

(guanfacine)

Extended-Release Tablets

100 Tablets

2 mg

Rx only

Each tablet contains: 2 mg of guanfacine, as guanfacine HCl

Tablets should not be crushed,

chewed or broken before swallowing.

Distributed by:

Takeda Pharmaceuticals

America, Inc.

Cambridge, MA 02142

Takeda

Product of Spain

NDC 54092-517-02

intuniv^®

(guanfacine)

Extended-Release Tablets

100 Tablets

3 mg

Rx only

Each tablet contains: 3 mg of guanfacine, as guanfacine HCl

Tablets should not be crushed,

chewed or broken before swallowing.

Distributed by:

Takeda Pharmaceuticals

America, Inc.

Cambridge, MA 02142

Takeda

Product of Spain

NDC 54092-519-02

intuniv^®

(guanfacine)

Extended-Release Tablets

100 Tablets

4 mg

Rx only

Each tablet contains: 4 mg of guanfacine, as guanfacine HCl

Tablets should not be crushed,

chewed or broken before swallowing.

Distributed by:

Takeda Pharmaceuticals

America, Inc.

Cambridge, MA 02142

Takeda

Product of Spain

If switching from immediate-release guanfacine, discontinue that treatment, and titrate with INTUNIV following above recommended schedule.

Do not substitute for immediate-release guanfacine tablets on a milligram-per-milligram basis, because of differing pharmacokinetic profiles. INTUNIV 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)].

Dosage adjustments for INTUNIV 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)].

Fixed Dose Trials

Storage - 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.

INTUNIV 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 molecular formula is C₉H₉Cl₂ N₃O∙HCl corresponding to a molecular weight of 282.55 g/mol. The chemical structure is:

Guanfacine HCl 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 (>30 mg/mL). Each tablet contains guanfacine HCl equivalent to 1 mg, 2 mg, 3 mg, or 4 mg of guanfacine base. The tablets also contain hypromellose, methacrylic acid copolymer, lactose, povidone, crospovidone, microcrystalline cellulose, fumaric acid, and glyceryl behenate. In addition, the 3-mg and 4-mg tablets also contain green pigment blend PB-1763.

When reinitiating patients to the previous maintenance dose after two or more missed consecutive doses, consider titration based on patient tolerability.

Safety and efficacy of INTUNIV in pediatric patients less than 6 years of age have not been established. The efficacy of INTUNIV 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)].

The safety and efficacy of INTUNIV in geriatric patients have not been established.

Take INTUNIV 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 INTUNIV is 0.05 to 0.12 mg/kg/day (total daily dose between 1 to 7 mg) (See Table 1).

In the adjunctive trial which evaluated INTUNIV 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.

Efficacy of INTUNIV in the treatment of ADHD was established in children and adolescents (6 to 17 years) in:

• Five short-term, placebo-controlled monotherapy trials (Studies 1, 2, 4, 5, and 6).
• One short-term, placebo-controlled adjunctive trial with psychostimulants (Study 3).
• One long-term, placebo-controlled monotherapy maintenance trial (Study 7).

INTUNIV is contraindicated in patients with a history of a hypersensitivity reaction to INTUNIV or its inactive ingredients, or other products containing guanfacine. Rash and pruritus have been reported.

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)]

Table 14 contains clinically important drug interactions with INTUNIV [see Clinical Pharmacology (12.3)].

INTUNIV^® (in-TOO-niv)

(guanfacine)

Extended-Release Tablets

Read the Patient Information that comes with INTUNIV 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 is INTUNIV ?

INTUNIV is a prescription medicine used to treat the symptoms of attention deficit hyperactivity disorder (ADHD). INTUNIV may be used alone or with ADHD stimulant medicines.

INTUNIV is not a central nervous system (CNS) stimulant.

It is not known if INTUNIV is safe and effective in children younger than 6 years of age.

Who should not take INTUNIV ?

Do not take INTUNIV if you are allergic to guanfacine or any of the ingredients in INTUNIV. See the end of this leaflet for a complete list of ingredients in INTUNIV.

What should I tell my doctor before taking INTUNIV ?

Before you take INTUNIV , 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 INTUNIV will harm your unborn baby. Talk to your doctor if you are pregnant or plan to become pregnant.
  • There is a pregnancy registry for females who are exposed to ADHD medications, including INTUNIV, during pregnancy. The purpose of the registry is to collect information about the health of females exposed to INTUNIV and their baby. If you or your child becomes pregnant during treatment with INTUNIV, talk to your healthcare provider about registering with the National Pregnancy Registry of ADHD medications at 1-866-961-2388.
• are breastfeeding or plan to breastfeed. It is not known if INTUNIV passes into your breast milk. Talk to your doctor about the best way to feed your baby while taking INTUNIV.

Tell your doctor about all of the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

INTUNIV may affect the way other medicines work, and other medicines may affect how INTUNIV works.

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 INTUNIV ?

• Take INTUNIV exactly as your doctor tells you.
• Your doctor may change your dose. Do not change your dose of INTUNIV without talking to your doctor.
• Do not stop taking INTUNIV without talking to your doctor.
• Try not to miss your dose of INTUNIV. If you miss a dose of INTUNIV, 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 INTUNIV with a lower dose.
• Do not take a double dose to make up for a missed dose.
• INTUNIV 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 INTUNIV and when to take your ADHD stimulant medication.
• INTUNIV should be swallowed whole with a small amount of water, milk, or other liquid.
• Do not crush, chew, or break INTUNIV. Tell your doctor if you cannot swallow INTUNIV whole.
• Do not take INTUNIV with a high-fat meal.
• Your doctor will check your blood pressure and heart rate while you take INTUNIV.
• If you take too much INTUNIV, call your local Poison Control Center at 1-800-222-1222 or go to the nearest emergency room right away.

What should I avoid while taking INTUNIV ?

• Do not drive, operate heavy machinery, or do other dangerous activities until you know how INTUNIV affects you. INTUNIV can slow your thinking and motor skills.
• Do not drink alcohol or take other medicines that make you sleepy or dizzy while taking INTUNIV until you talk with your doctor. INTUNIV taken with alcohol or medicines that cause sleepiness or dizziness may make your sleepiness or dizziness worse.
• Do not become dehydrated or overheated. This may increase your chance of having low blood pressure or fainting while taking INTUNIV.
• Do not suddenly stop INTUNIV. Tell your healthcare provider if you have been vomiting and cannot take INTUNIV, you may be at risk for rebound hypertension.

What are the possible side effects of INTUNIV ?

INTUNIV may cause serious side effects including:

• low blood pressure
• low heart rate
• fainting
• sleepiness
• increased blood pressure and heart rate after suddenly stopping INTUNIV (rebound hypertension). Suddenly stopping INTUNIV can cause increased blood pressure and heart rate and other withdrawal symptoms such as headache, confusion, nervousness, agitation, and tremors. If these symptoms continue to get worse and are left untreated, it could lead to a very serious condition including very high blood pressure, feeling very sleepy or tired, severe headache, vomiting, vision problems, seizures.

Get medical help right away, if you have any of the symptoms listed above.

The most common side effects of INTUNIV include:

• sleepiness
• tiredness
• trouble sleeping
• low blood pressure
• nausea
• stomach pain
• dizziness
• dry mouth
• irritability
• vomiting
• slow heart rate

Tell the doctor if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of INTUNIV. For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store INTUNIV ?

• Store INTUNIV between 68°F to 77°F (20°C to 25°C)

Keep INTUNIV and all medicines out of the reach of children.

General Information about the safe and effective use INTUNIV

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information Leaflet. Do not use INTUNIV for a condition for which it was not prescribed. Do not give INTUNIV to other people, even if they have the same symptoms that you have. It may harm them.

This leaflet summarizes the most important information about INTUNIV. If you would like more information, talk with your doctor. You can ask your pharmacist or doctor for information about INTUNIV that is written for health professionals.

For more information, go to www.INTUNIV.com or call 1-877-825-3327.

What are the ingredients in INTUNIV ?

Active ingredient: guanfacine hydrochloride

Inactive ingredients: hypromellose, methacrylic acid copolymer, lactose, povidone, crospovidone, microcrystalline cellulose, fumaric acid, and glycerol behenate. In addition, the 3 mg and 4 mg tablets also contain green pigment blend PB-1763.

This Patient Information has been approved by the U.S. Food and Drug Administration.

Distributed by:

Takeda Pharmaceuticals America, Inc.

Cambridge, MA 02142

INTUNIV is a registered trademark of Takeda Pharmaceuticals U.S.A., Inc.

© 2025 Takeda Pharmaceuticals U.S.A., Inc. All rights reserved.

Patented: see www.takeda.com/en-us/patents.

Revised: 6/2025

It may be necessary to reduce the dosage in patients with significant impairment of renal function [see Clinical Pharmacology (12.3)].

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 INTUNIV of 0.12 mg/kg. Guanfacine was not shown to prolong the QTc interval to any clinically relevant extent.

It may be necessary to reduce the dosage in patients with significant impairment of hepatic function [see Clinical Pharmacology (12.3)].

INTUNIV^® is indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) as monotherapy and as adjunctive therapy to stimulant medications [see Clinical Studies (14)].

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.

In post marketing experience, abrupt discontinuation of INTUNIV 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 INTUNIV 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. 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 INTUNIV 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 INTUNIV. If abrupt discontinuation occurs (especially with concomitant stimulant use), patients should be closely followed for rebound hypertension.

INTUNIV is not a controlled substance and has no known potential for abuse or dependence.

Pharmacological treatment of ADHD may be needed for extended periods. Healthcare providers should periodically re-evaluate the long-term use of INTUNIV, 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)].

• 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 INTUNIV. 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 INTUNIV (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 INTUNIV 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 INTUNIV should be tapered in decrements of no more than 1 mg every 3 to 7 days (5.4).

• 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 INTUNIV 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).

Somnolence and sedation were commonly reported adverse reactions in clinical studies [see Adverse Reactions (6.1)]. Before using INTUNIV 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 INTUNIV. Advise patients to avoid use with alcohol.

1 mg, 2 mg, 3 mg, and 4 mg extended-release tablets

The following adverse reactions have been identified during post-approval use of guanfacine. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Less frequent, possibly guanfacine-related events observed in the post-marketing study and/or reported spontaneously, not included in section 6.1, include:

General: edema, malaise, tremor

Cardiovascular: palpitations, tachycardia, rebound hypertension, hypertensive encephalopathy

Central Nervous System: paresthesias, vertigo

Eye Disorders: blurred vision

Musculo-Skeletal System: arthralgia, leg cramps, leg pain, myalgia

Psychiatric: confusion, hallucinations

Reproductive System, Male: erectile dysfunction

Respiratory System: dyspnea

Skin and Appendages: alopecia, dermatitis, exfoliative dermatitis, pruritus, rash

Special Senses: alterations in taste

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 INTUNIV 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.

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.

Following discontinuation of INTUNIV, 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 INTUNIV 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.

Advise the patient to read the FDA-approved patient labeling (Patient Information).

INTUNIV is supplied in 1 mg, 2 mg, 3 mg, and 4 mg strength extended-release tablets in 100 count bottles.

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

Treatment with INTUNIV 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 INTUNIV 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.

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NDC 54092-513-02

intuniv^®

(guanfacine)

Extended-Release Tablets

100 Tablets

1 mg

Rx only

Each tablet contains: 1 mg of guanfacine, as guanfacine HCl

Tablets should not be crushed,

chewed or broken before swallowing.

Distributed by:

Takeda Pharmaceuticals

America, Inc.

Cambridge, MA 02142

Takeda

Product of Spain

NDC 54092-515-02

intuniv^®

(guanfacine)

Extended-Release Tablets

100 Tablets

2 mg

Rx only

Each tablet contains: 2 mg of guanfacine, as guanfacine HCl

Tablets should not be crushed,

chewed or broken before swallowing.

Distributed by:

Takeda Pharmaceuticals

America, Inc.

Cambridge, MA 02142

Takeda

Product of Spain

NDC 54092-517-02

intuniv^®

(guanfacine)

Extended-Release Tablets

100 Tablets

3 mg

Rx only

Each tablet contains: 3 mg of guanfacine, as guanfacine HCl

Tablets should not be crushed,

chewed or broken before swallowing.

Distributed by:

Takeda Pharmaceuticals

America, Inc.

Cambridge, MA 02142

Takeda

Product of Spain

NDC 54092-519-02

intuniv^®

(guanfacine)

Extended-Release Tablets

100 Tablets

4 mg

Rx only

Each tablet contains: 4 mg of guanfacine, as guanfacine HCl

Tablets should not be crushed,

chewed or broken before swallowing.

Distributed by:

Takeda Pharmaceuticals

America, Inc.

Cambridge, MA 02142

Takeda

Product of Spain

If switching from immediate-release guanfacine, discontinue that treatment, and titrate with INTUNIV following above recommended schedule.

Do not substitute for immediate-release guanfacine tablets on a milligram-per-milligram basis, because of differing pharmacokinetic profiles. INTUNIV 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)].

Dosage adjustments for INTUNIV 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)].