HIGHLIGHTS OF PRESCRIBING INFORMATION
The highlights do not include all the information needed to u INTUNIV® safely and effectively. See full prescribing information for INTUNIV®.
INTUNIV® (guanfacine) extended-relea tablets, for oral u Initial U.S. Approval: 1986
------------------------RECENT MAJOR CHANGES----------------- Dosage and Administration (2) 02/2015 Contraindications (4) 11/2014 Warnings and Precautions (5) 11/2014
----------------------INDICATIONS AND USAGE------------------------- INTUNIV® is a central alpha2A-adrenergic receptor agonist
indicated for the treatment of Attention Deficit Hyperactivity
Disorder (ADHD) as monotherapy and as adjunctive therapy to stimulant medications (1, 14).
----------------------DOSAGE AND ADMINISTRATION---------------- •Recommended do: 1 mg to 7 mg (0.05-0.12 mg/kg target weight bad do range) once daily in the morning or
evening bad on clinical respon and tolerability (2.2).
•Begin at a do 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, becau of incread exposure (2.1).
•Do not substitute for immediate-relea guanfacine tablets on
a mg-per-mg basis, becau of differing pharmacokinetic
profiles (2.3).
五龙河旅游风景区•If switching from immediate-relea guanfacine, discontinue that treatment and titrate with INTUNIV® as directed (2.3). •When discontinuing, taper the do in decrements of no more than 1 mg every 3 to 7 days to avoid rebound hypertension
(2.5).
------------------DOSAGE FORMS AND STRENGTHS---------------- Extended-relea tablets: 1 mg, 2
mg, 3 mg and 4 mg (3)
装修风水禁忌>选美--------------------------CONTRAINDICATIONS---------------------------- History of hypernsitivity to INTUNIV®, its inactive ingredients, or other products containing guanfacine (4).
-----------------------WARNINGS AND PRECAUTIONS----------------------- •Hypotension, bradycardia, syncope: Titrate slowly and monitor vital signs frequently in patients at risk for hypotension, heart block, bradycardia, syncope, cardiovascular dia, vascular dia,
cerebrovascular dia or chronic renal failure. Measure heart rate and blood pressure prior to initiation of therapy, following do increas, and periodically while on therapy. Avoid concomitant u of drugs with additive effects unless clinically indicated. Advi patients to avoid becoming dehydrated or overheated (5.1).
•Sedation and somnolence: Occur commonly with INTUNIV®. Consider the potential for additive dative 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 worn sinus node dysfunction and atrioventricular (AV) blo
ck, especially in patients taking other sympatholytic drugs. Titrate slowly and monitor vital signs frequently (5.3).
--------------------------------ADVERSE REACTIONS-------------------------------- Most common adver reactions (≥5% and at least twice placebo rate) in fixed-do monotherapy ADHD trials in children and adolescents (6 to 17 years): hypotension, somnolence, fatigue, naua, and lethargy (6.1) Flexible do-optimization ADHD trials in children (6 to 12 years) and adolescents (13 to 17 years): somnolence, hypotension, abdominal pain, insomnia, fatigue, dizziness, dry mouth, irritability, naua, 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 Shire US Inc. at 1-800-828-2088 or FDA at 1-800-FDA-1088 or
v/medwatch.
-------------------------------- DRUG INTERACTIONS----------------------------- •Strong CYP3A4 inhibitors in
crea guanfacine exposure. Decrea INTUNIV® to 50% of target dosage when coadministered with strong CYP3A4 inhibitors (2.7).
•Strong CYP3A4 inducers decrea guanfacine exposure.Bad on patient respon, consider titrating INTUNIV dosage up to double the target dosage over 1 to 2 weeks (2.7).
See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.
Revid: 02/2015
FULL PRESCRIBING INFORMATION: CONTENTS*
1 INDICATIONS AND USAGE
2 DOSAGE AND ADMINISTRATION
2.1 General Instruction for U
2.2 Do Selection
2.3 Switching from Immediate-Relea
Guanfacine to INTUNIV
2.4 Maintenance Treatment
2.5 Discontinuation of Treatment
2.6 Misd Dos
2.7 Dosage Adjustment with Concomitant U
of Strong CYP3A4 Inhibitors or Inducers
3 DOSAGE FORMS AND STRENGTHS
4 CONTRAINDICATIONS
5 WARNINGS AND PRECAUTIONS
5.1 Hypotension, Bradycardia, and Syncope 5.2 Sedation and Somnolence
5.3 Cardiac Conduction Abnormalities
6 ADVERSE REACTIONS
6.1 Clinical Trials Experience
6.2 Post-marketing Experience
7 DRUG INTERACTIONS
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
8.3 Nursing Mothers
8.4 Pediatric U
8.5 Geriatric U
8.6 Renal Impairment
8.7 Hepatic Impairment
9 DRUG ABUSE AND DEPENDENCE
9.1 Controlled Substance 10 OVERDOSAGE
11 DESCRIPTION
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
12.2 Pharmacodynamics
12.3 Pharmacokinetics
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
14 CLINICAL STUDIES
16 HOW SUPPLIED/STORAGE AND
HANDLING雨丝
17 PATIENT COUNSELING INFORMATION
*Sections or subctions omitted from the full prescribing
information are not listed.
FULL PRESCRIBING INFORMATION
1 INDICATIONS AND USAGE
最霸气的微信名INTUNIV® is indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) as monotherapy and as adjunctive therapy to stimulant medications [e Clinical Studies (14)].
2 DOSAGE AND ADMINISTRATION
2.1 General Instruction for U
Swallow tablets whole. Do not crush, chew, or break tablets becau this will increa the rate of guanfacine relea.Do not administer with high fat meals, due to incread exposure.
2.2 Do Selection
Take INTUNIV orally once daily, either in the morning or evening, at approximately the same time each day. Begin at a do of 1 mg/day, and adjust in increments of no more than 1 mg/week.
In monotherapy clinical trials, there was do- and exposure-related clinical improvement as well as risks for veral clinically significant adver reactions (hypotension, bradycardia, dative events). To balance the exposure-related potential benefits and risks, the recommended target do range depending on clinical respon and tolerability for INTUNIV® is 0.05-0.12 mg/kg/day (total daily do between 1-7 mg) (See Table 1).
Table 1: Recommended Target Do Range for Therapy with INTUNIV®
Weight Target do range (0.05 - 0.12 mg/kg/day)
25-33.9 kg 2-3 mg/day
34-41.4 kg 2-4 mg/day
41.5-49.4 kg 3-5 mg/day
49.5-58.4 kg 3-6 mg/day
58.5-91 kg 4-7 mg/day
>91 kg 5-7 mg/day
Dos above 4 mg/day have not been evaluated in children (ages 6-12 years) and dos above
7 mg/day have not been evaluated in adolescents (ages 13-17 years)
In the adjunctive trial which evaluated INTUNIV® treatment with psychostimulants, the majority of patients reached optimal dos in the 0.05-0.12 mg/kg/day range. Dos above 4 mg/day have not been studied in adjunctive trials.
2.3 Switching from Immediate-Relea Guanfacine to INTUNIV®
If switching from immediate-relea guanfacine, discontinue that treatment, and titrate with INTUNIV® following above recommended schedule.
Do not substitute for immediate-relea guanfacine tablets on a milligram-per-milligram basis, becau
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 tho of the same do of immediate-relea guanfacine [e Clinical Pharmacology (12.3)].
2.4 Maintenance Treatment
Pharmacological treatment of ADHD may be needed for extended periods. Healthcare providers should periodically re-evaluate the long-term u of INTUNIV ®, and adjust weight-bad dosage as needed. The majority of children and adolescents reach optimal dos in the 0.05-0.12 mg/kg/day range. Dos above 4 mg/day have not been evaluated in children (ages 6-12 years) and above 7 mg/day have not been evaluated in adolescents (ages 13-17 years) [e Clinical Studies (14)]. 2.5
Discontinuation of Treatment
Following discontinuation of INTUNIV ®, patients may experience increas in blood pressure and heart rate [e Adver Reaction (6.1)]. Patients/caregivers should be instructed not to discontinue INTUNIV ® without consulting their health care provider. Monitor blood pressure and pul when reducing the do or discontinuing the drug. Taper the daily do in decrements of no more than 1 mg every 3 to 7 days to avoid rebound hypertension. 2.6
Misd Dos
月季花开花时间
When reinitiating patients to the previous maintenance do after two or more misd concutive dos, consider titration bad on patient tolerability. 2.7霜冷长河
Dosage Adjustment with Concomitant U of Strong CYP3A4 Inhibitors or Inducers
Dosage adjustments for INTUNIV ® are recommended with concomitant u of strong CYP3A4 inhibitors (e.g., ketoconazole), or CYP3A4 inducers (e.g., carbamazepine) (Table 2) [e Drug Interactions (7)].
Table 2: INTUNIV ® Dosage Adjustments for Patients Taking Concomitant CYP3A4 Inhibitors or Inducers
Clinical Scenarios
Starting INTUNIV ®
while currently on a CYP3A4 modulator Continuing
INTUNIV ®
黄钟大吕的意思
while adding a CYP3A4
modulator Continuing
INTUNIV ®
while
stopping a CYP3A4 modulator
CYP3A4
Strong Inhibitors Decrea INTUNIV ® dosage to half the recommended level. (e Table 1) Decrea INTUNIV ®
dosage to half the recommended level. (e Table 1) Increa INTUNIV ®
dosage to
recommended level. (e Table 1)
CYP3A4
Strong Inducers
Consider increasing INTUNIV ®
dosage up to double the
recommended level.
(e Table 1) Consider
increasing
INTUNIV ®
dosage up to double the recommended level over 1 to 2 weeks. (e Table 1)
Decrea INTUNIV ®
dosage to
recommended level over 1 to 2 weeks. (e Table 1)
3 DOSAGE FORMS AND STRENGTHS
1 mg,
2 mg,
3 mg and
4 mg extended-relea tablets 4
CONTRAINDICATIONS
INTUNIV is contraindicated in patients with a history of a hypernsitivity reaction to INTUNIV or its inactive ingredients, or other products containing guanfacine. Rash and pruritus have been reported.
5 WARNINGS AND PRECAUTIONS
5.1 Hypotension, Bradycardia, and Syncope
Treatment with INTUNIV® can cau do-dependent decreas in blood pressure and heart rate.
Decreas were less pronounced over time of treatment. Orthostatic hypotension and syncope have been reported [e Adver Reactions (6.1)].
Measure heart rate and blood pressure prior to initiation of therapy, following do increas, and periodically while on therapy. Titrate INTUNIV slowly in patients with a history of hypotension, and tho with underlying conditions that may be worned by hypotension and bradycardia; e.g., heart block, bradycardia, cardiovascular dia, vascular dia, cerebrovascular dia, or chronic renal failure. In patients who have a history of syncope or may have a condition that predispos them to syncope, such as hypotension, orthostatic hypotension, bradycardia, or dehydration, advi 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 increa the risk of syncope.
5.2 Sedation and Somnolence
Somnolence and dation were commonly reported adver reactions in clinical studies [e Adver Reactions (6.1)]. Before using INTUNIV®with other centrally active depressants, consider the potential for additive dative effects. Caution patients against operating heavy equipment or driv
ing until they know how they respond to treatment with INTUNIV®. Advi patients to avoid u with alcohol.
5.3 Cardiac Conduction Abnormalities
The sympatholytic action of INTUNIV®may worn 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.
6 ADVERSE REACTIONS
The following rious adver reactions are described elwhere in the labelling:
•Hypotension, bradycardia, and syncope [e Warnings and Precautions (5.1)]
•Sedation and somnolence [e Warnings and Precautions (5.2)]
•Cardiac conduction abnormalities [e Warnings and Precautions (5.3)]
6.1 Clinical Trials Experience
Becau clinical trials are conducted under widely varying conditions, adver reaction rates obrved 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 obrved 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.
Fixed Do Trials
