2.1 General Instruction for Use

Swallow tablets whole. Do not crush, chew, or break tablets because this will increase the rate of guanfacine release. Do not administer with high fat meals, due to increased exposure.

2.2 Dose Selection

 

Take guanfacine extended-release tablets orally once daily, either in the morning or evening, at approximately the same time each day. Begin at a dose of 1 mg/day, and adjust in increments of no more than 1 mg/week.

 

Doses above 4 mg/day have not been evaluated in children (ages 6 to 12 years) and doses above 7 mg/day have not been evaluated in adolescents (ages 13 to 17 years)

In the adjunctive trial which evaluated guanfacine extended-release tablets treatment with psychostimulants, the majority of patients reached optimal doses in the 0.05 to 0.12 mg/kg/day range. Doses above 4 mg/day have not been studied in adjunctive trials.

2.3 Switching from Immediate-Release Guanfacine to Guanfacine Extended-Release Tablets

 

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

2.4 Maintenance Treatment

 

Pharmacological treatment of ADHD may be needed for extended periods. Healthcare providers should periodically re-evaluate the long-term use of guanfacine extended-release tablets, and adjust weight-based dosage as needed. The majority of children and adolescents reach optimal doses in the 0.05 to 0.12 mg/kg/day range. Doses above 4 mg/day have not been evaluated in children (ages 6 to 12 years) and above 7 mg/day have not been evaluated in adolescents (ages 13 to 17 years) [see CLINICAL STUDIES ( 14 ) ] .

2.5 Discontinuation of Treatment

 

Following discontinuation of guanfacine extended-release tablets, patients may experience increases in blood pressure and heart rate [see Warnings and Precautions ( 5.4 ) and Adverse Reactions ( 6.1 ) ]. Patients/caregivers should be instructed not to discontinue guanfacine extended-release tablets without consulting their health care provider. Monitor blood pressure and pulse when reducing the dose or discontinuing the drug. Taper the daily dose in decrements of no more than 1 mg every 3 to 7 days to minimize the risk of rebound hypertension.

2.6 Missed Doses

 

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

2.7 Dosage Adjustment with Concomitant Use of Strong and Moderate CYP3A4 Inhibitors or Inducers

 

Dosage adjustments for guanfacine extended-release tablets are recommended with concomitant use of strong and moderate CYP3A4 inhibitors (e.g., ketoconazole), or CYP3A4 inducers (e.g., carbamazepine) ( Table 2 ) [see DRUG INTERACTIONS ( 7 ) ] .

5.1 Hypotension, Bradycardia, and Syncope

 

Treatment with guanfacine extended-release tablets can cause dose-dependent decreases in blood pressure and heart rate. Decreases were less pronounced over time of treatment. Orthostatic hypotension and syncope have been reported [see Adverse Reactions ( 6.1 ) ] .

5.2 Sedation and Somnolence

Somnolence and sedation were commonly reported adverse reactions in clinical studies [see Adverse Reactions (6.1)]. Before using guanfacine extended-release tablets with other centrally active depressants, consider the potential for additive sedative effects. Caution patients against operating heavy equipment or driving until they know how they respond to treatment with guanfacine extended-release tablets . Advise patients to avoid use with alcohol.

5.3 Cardiac Conduction Abnormalities

 

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

5.4 Rebound Hypertension

In post marketing experience, abrupt discontinuation of guanfacine extended-release tablets has resulted in clinically significant and persistent rebound hypertension above baseline levels and increases in heart rate. Hypertensive encephalopathy has also been reported in association with rebound hypertension with both guanfacine extended-release tablets 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 guanfacine extended-release tablets should be tapered in decrements of no more than 1 mg every 3 to 7 days [see Dosage and Administration (2.5)]. Blood pressure and heart rate should be monitored when reducing the dose or discontinuing guanfacine extended-release tablets. If abrupt discontinuation occurs (especially with concomitant stimulant use), patients should be closely followed for rebound hypertension.

6.1 Clinical Trials Experience

 

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Fixed Dose Trials

 

*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).

 

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.

 

Adverse reactions ≥ 2% for all doses of guanfacine extended-release tablets and > rate in placebo in any dose group but did not meet this criteria in all doses combined: insomnia (insomnia, initial insomnia, middle insomnia, terminal insomnia, sleep disorder), vomiting, diarrhea, abdominal/stomach discomfort (abdominal discomfort, epigastric discomfort, stomach discomfort), rash (rash, rash generalized, rash papular), dyspepsia, increased weight, bradycardia (bradycardia, sinus bradycardia), asthma (asthma, bronchospasm, wheezing), agitation, anxiety (anxiety, nervousness), sinus arrhythmia, blood pressure increased (blood pressure increased, blood pressure diastolic increased), and first degree atrioventricular block.

* The lowest dose of 1 mg used in Study 2 was not randomized to patients weighing more than 50 kg.

a: The abdominal pain term includes abdominal pain, abdominal pain lower, abdominal pain upper, and abdominal tenderness.

b: The nightmare term includes abnormal dreams, nightmare, and sleep terror.

c: The enuresis term includes enuresis, nocturia, and urinary incontinence.

d: The affect lability term includes affect lability and mood swings.

Monotherapy Flexible Dose Trials

 

a: The somnolence term includes somnolence, sedation, and hypersomnia.

b: The abdominal pain term includes abdominal pain, abdominal pain lower, abdominal pain upper, and abdominal tenderness

c: The hypotension term includes hypotension, diastolic hypotension, orthostatic hypotension, blood pressure decreased, blood pressure diastolic decreased, blood pressure systolic decreased).

d: The enuresis term includes enuresis, nocturia, and urinary incontinence.

 

Adverse reactions leading to discontinuation in ≥ 2% in any dose group but did not meet this criteria in all doses combined: fatigue

a: The somnolence term includes somnolence, sedation, and hypersomnia.

 

a: The somnolence term includes somnolence, sedation, and hypersomnia.

b: The insomnia term includes insomnia, initial insomnia, middle insomnia, terminal insomnia, and sleep disorder.

c: The hypotension term includes hypotension, diastolic hypotension, orthostatic hypotension, blood pressure decreased, blood pressure diastolic decreased, blood pressure systolic decreased).

d: The bradycardia term includes bradycardia and sinus bradycardia.

 

Adverse reactions ≥ 2% for all doses of guanfacine extended-release tablets and > rate in placebo in any dose group but did not meet this criteria in all doses combined: nausea, diarrhea, vomiting, and depression (depressed mood, depression, depressive symptom).

a: The abdominal pain term includes abdominal pain, abdominal pain lower, abdominal pain upper, and abdominal tenderness.

b: The anxiety term includes anxiety and nervousness.

c: The rash term includes rash, rash generalized, and rash papular.

d: The abdominal/stomach discomfort term includes abdominal discomfort, epigastric discomfort, and stomach discomfort.

Adjunctive Trial

 

a: The somnolence term includes somnolence, sedation, and hypersomnia.

b: The insomnia term includes insomnia, initial insomnia, middle insomnia, terminal insomnia, and sleep disorder.

c: The abdominal pain term includes abdominal pain, abdominal pain lower, abdominal pain upper, and abdominal tenderness.

There were no specific adverse reactions ≥ 2% in any treatment group that led to discontinuation in the short-term adjunctive study (Study 3).

 

Adverse reactions ≥ 2% for all doses of guanfacine extended-release tablets and > rate in placebo in any dose group but did not meet this criteria in all doses combined: irritability, vomiting, asthma (asthma, bronchospasm, wheezing), and enuresis (enuresis, nocturia, urinary incontinence).

a: The hypotension term includes hypotension, diastolic hypotension, orthostatic hypotension, blood pressure decreased, blood pressure diastolic decreased, blood pressure systolic decreased.

b: The affect lability term includes affect lability and mood swings.

c: The bradycardia term includes bradycardia and sinus bradycardia.

d: The rash term includes rash, rash generalized, and rash papular.

e: The nightmare term includes abnormal dreams, nightmare, and sleep terror.

f: The tachycardia term includes tachycardia and sinus tachycardia.

Effects on Blood Pressure and Heart Rate

 

In the monotherapy pediatric, short-term, controlled trials (Studies 1 and 2), the maximum mean changes from baseline in seated systolic blood pressure, diastolic blood pressure, and pulse were -5.4 mmHg, -3.4 mmHg, and -5.5 bpm, respectively, for all doses combined (generally one week after reaching target doses). For the respective fixed doses 1 mg/day, 2 mg/day, 3 mg/day or 4 mg/day the maximum mean changes in seated systolic blood pressure were -4.3 mmHg, -5.5 mmHg, -5.4 mmHg and -8.2 mmHg. For these respective fixed doses the maximum mean changes in seated diastolic blood pressure were -3.4 mmHg, -3.3 mmHg, -4.4 mmHg and -5.4 mmHg. For these respective fixed doses the maximum mean changes in seated pulse were -4.8bpm, -3.1 bpm, -6.5 bpm and -8.6 bpm. Decreases in blood pressure and heart rate were usually modest and asymptomatic; however, hypotension and bradycardia can occur. Hypotension was reported as an adverse reaction for 7% of the guanfacine extended-release tabletsgroup and 3% of the placebo group. This includes orthostatic hypotension, which was reported for 1% of the guanfacine extended-release tablets group and none in the placebo group. These findings were generally similar in the monotherapy flexible dose trials (Studies 4 and 5). In the adjunctive trial, hypotension (3%) and bradycardia (2%) were observed in patients treated with guanfacine extended-release tablets as compared to none in the placebo group. In long-term, open-label studies, (mean exposure of approximately 10 months), maximum decreases in systolic and diastolic blood pressure occurred in the first month of therapy. Decreases were less pronounced over time. Syncope occurred in 1% of pediatric patients in the clinical program. The majority of these cases occurred in the long-term, open-label studies.

Discontinuation of Treatment

Blood pressure and pulse may increase above baseline values following discontinuation of guanfacine extended-release tablets. In five studies of children and adolescents [see CLINICAL STUDIES (14)] , increases in mean systolic and diastolic blood pressure averaging approximately 3 mmHg and increases in heart rate averaging 5 beats per minute above original baseline were observed upon discontinuation with tapering of guanfacine extended-release tablets. In a maintenance of efficacy study, increases in blood pressure and heart rate above baseline slowly diminished over the follow up period, which ranged between 3 and 26 weeks post final dose; the estimated average time to return to baseline was between six and twelve months. In this study, the increases in blood pressure and pulse were not considered serious or associated with adverse events. However, individuals may have larger increases than reflected by the mean changes.

In postmarketing experience, following abrupt discontinuation of guanfacine extended-release tablets, rebound hypertension and hypertensive encephalopathy have been reported [see Warnings and Precautions (5.4) and Adverse Reactions (6.2]

Effects on Height, Weight, and Body Mass Index (BMI)

Patients taking guanfacine extended-release tablets demonstrated similar growth compared to normative data. Patients taking guanfacine extended-release tablets had a mean increase in weight of 0.5 kg compared to those receiving placebo over a comparable treatment period. Patients receiving guanfacine extended-release tablets for at least 12 months in open-label studies gained an average of 8 kg inweight and 8 cm (3 in) in height. The height, weight, and BMI percentile remained stable in patients at 12 months in the long-term studies compared to when they began receiving guanfacine extended-release tablets.

Other Adverse Reactions Observed in Clinical Studies

Table 13 includes additional adverse reactions observed in short-term, placebo-controlled and long-term, open-label clinical studies not included elsewhere in section 6.1, listed by organ system.

6.2 Postmarketing Experience

 

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.

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

8.1 Pregnancy

Pregnancy Category B

Risk Summary

There are no adequate and well-controlled studies of guanfacine extended-release tablets in pregnant women. No fetal harm was observed in rats and rabbits with administration of guanfacine at 4 and 2.7 times, respectively, the maximum recommended human dose. Because animal studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Animal data

Reproduction studies conducted in rats have shown that guanfacine crosses the placenta. However, administration of guanfacine to rats and rabbits at 4 and 2.7 times, respectively, the maximum recommended human dose of 0.12 mg/kg/day on a mg/m 2basis resulted in no evidence of harm to the fetus. Higher doses (13.5 times the maximum recommended human dose in both rabbits and rats) were associated with reduced fetal survival and maternal toxicity.

8.3 Nursing Mothers

 

It is not known whether guanfacine is excreted in human milk; however, guanfacine is excreted in rat milk. Because many drugs are excreted in human milk, caution should be exercised when guanfacine extended-release tablets are administered to a nursing woman. Observe human milk-fed infants for sedation and somnolence.

8.4 Pediatric Use

 

Safety and efficacy of guanfacine extended-release tabletsin pediatric patients less than 6 years of age have not been established. The efficacy of guanfacine extended-release tablets was studied for the treatment of ADHD in five controlled monotherapy clinical trials (up to 15 weeks in duration), one randomized withdrawal study and one controlled adjunctive trial with psychostimulants (8 weeks in duration) in children and adolescents ages 6 to 17 who met DSM-IV ® criteria for ADHD [see ADVERSE REACTIONS ( 6 ) and CLINICAL STUDIES ( 14 ) ] .

Animal Data

In studies in juvenile rats, guanfacine alone produced a slight delay in sexual maturation in males and females at 2 to 3 times the maximum recommended human dose (MRHD). Guanfacine in combination with methylphenidate produced a slight delay in sexual maturation and decreased growth as measured by a decrease in bone length in males at a dose of guanfacine comparable to the MRHD and a dose of methylphenidate approximately 4 times the MRHD.

 

In a study where juvenile rats were treated with guanfacine alone from 7 to 59 days of age, development was delayed as indicated by a slight delay in sexual maturation and decreased body weight gain in males at 2 mg/kg/day and in females at 3 mg/kg/day. The No Adverse Effect Level (NOAEL) for delayed sexual maturation was 1 mg/kg/day, which is equivalent to the MRHD of 4 mg/day, on a mg/m 2 basis. The effects on fertility were not evaluated in this study.

8.5 Geriatric Use

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

8.6 Renal Impairment

 

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

8.7 Hepatic Impairment

 

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

9.1 Controlled Substance

 

Guanfacine extended-release tablets are not controlled substance and have no known potential for abuse or dependence.

12.1 Mechanism of Action

 

Guanfacine is a central alpha 2A -adrenergic receptor agonist. Guanfacine is not a central nervous system (CNS) stimulant. The mechanism of action of guanfacine in ADHD is not known.

12.2 Pharmacodynamics

 

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.

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

12.3 Pharmacokinetics

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 tablets the time to peak plasma concentration is approximately 5 hours in children and adolescents with ADHD.

Immediate-release guanfacine and guanfacine extended-release tablets 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 tablets compared to immediate-release guanfacine. Therefore, the relative bioavailability of guanfacine extended-release tablets to immediate-release guanfacine is 58%. The mean pharmacokinetic parameters in adults following the administration of guanfacine extended-release tablets 1 mg once daily and immediate-release guanfacine 1 mg once daily are summarized in Table 15 .

 

Note: Values are mean +/- SD, except for t max which is median (range)

Figure 1: Comparison of Pharmacokinetics: Guanfacine Extended-Release Tablets 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 tablets 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 tablets 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 tablets 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,CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 or CYP3A4/5); guanfacine is also not an inducer of CYP3A, CYP1A2 and CYP2B6. Guanfacine is a substrate of CYP3A4/5 and exposure is affected by CYP3A4/5 inducers/inhibitors.

Guanfacine inhibits MATE1 and OCT1, but does not inhibit BSEP, MRP2, OATP1B1, OATP1B3, OAT1, OAT3, OCT2, or MATE2K. Guanfacine is a substrate of OCT1 and OCT2, but not BCRP, OATP1B1, OATP1B3, OAT1, OAT3, MATE1, or MATE2. Concomitant administration of guanfacine with OCT1 substrates might potentially increase the exposure of these OCT1 substrates.

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 ).

Figure 2: Effect of Other Drugs on the Pharmacokinetics (PK) of Guanfacine Extended-Release Tablets

 

Guanfacine does not significantly affect exposures of methylphenidate and lisdexamfetamine when coadministered ( Figure 3 ).

Figure 3: Effect of Guanfacine Extended-Release Tablets on the Pharmacokinetics (PK) of Other Drugs

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

 

Carcinogenesis

Patient Information

Guanfacine Extended-Release Tablets

(gwahn-fa-seen)

Read the Patient Information that comes with guanfacine extended-release tablets 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 guanfacine extended-release tablets?

Guanfacine extended-release tablets are 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 tablets are not 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 guanfacine extended-release tablets?

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 guanfacine extended-release tablets?

Before you take guanfacine extended-release tablets, 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 extended-release tablets pass into your breast milk. Talk to your doctor about the best way to feed your baby while taking guanfacine extended-release tablets.

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 guanfacine extended-release tablets?

•

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.

•

Do not stop taking 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.

•

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 tablets.

•

If you take too much guanfacine extended-release tablets, 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 guanfacine extended-release tablets?

•

Do not drive, operate heavy machinery, or do other dangerous activities until you know how guanfacine extended-release tablets affect you. Guanfacine extended-release tablets can slow your thinking and motor skills.

•

Do not drink alcohol or take other medicines that make you sleepy or dizzy while taking guanfacine extended-release tablets until you talk with your doctor. Guanfacine extended-release tablets 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 guanfacine extended-release tablets.

•

Do not suddenly stop guanfacine extended-release tablets. Tell your healthcare provider if you have been vomiting and cannot take guanfacine extended-release tablets, you may be at risk for rebound hypertension.

What are the possible side effects of guanfacine extended-release tablets?

Guanfacine extended-release tablets may cause serious side effects including:

•

low blood pressure

•

low heart rate

•

fainting

•

sleepiness

•

increased blood pressure and heart rate after suddenly stopping guanfacine extended-release tablets (rebound hypertension). Suddenly stopping guanfacine extended-release tablets 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 guanfacine extended-release tablets 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 guanfacine extended-release tablets. For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to TWi Pharmaceuticals, inc. 1-844-518-2989 or FDA at 1-800-FDA-1088 or www. fda.gov/medwatch.

How should I store guanfacine extended-release tablets?

•

Store guanfacine extended-release tablets at 20º to 25°C (68º to 77°F). [see USP Controlled Room Temperature].

Keep guanfacine extended-release tablets and all medicines out of the reach of children.

General Information about the safe and effective use guanfacine extended-release tablets

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information Leaflet. Do not use guanfacine extended-release tablets for a condition for which it was not prescribed. Do not give guanfacine extended-release tablets 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 guanfacine extended-release tablets. If you would like more information, talk with your doctor. You can ask your pharmacist or doctor for information about guanfacine extended-release tablets that is written for health professionals.

What are the ingredients in guanfacine extended-release tablets?

Active ingredient: guanfacine hydrochloride

Inactive ingredients: microcrystalline cellulose, hypromellose, polyvinyl acetate, povidone, lactose monohydrate, magnesium stearate, sodium lauryl sulfate and silica. In addition, the 3 mg and 4 mg tablets also contain FD&C Blue #1.

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

All other trademarks are the property of their respective owners.

Manufactured for:

TWi Pharmaceuticals USA, Inc.

Paramus, NJ 07652

Manufactured by:

TWi Pharmaceuticals, Inc.

Taoyuan City, 32063, Taiwan

Revised: 10/19

Repackaged and Relabeled by:

Proficient Rx LP

Thousand Oaks, CA 91320

OS24979533