Intuniv

(guanfacine ER)
Intuniv (guanfacine); not controlled
Full Prescribing Information
DailyMed Drug Information
Summary
Intuniv is extended-release guanfacine, a central alpha-2A adrenergic agonist approved for ADHD in patients 6 to 17 years, as monotherapy or added to a stimulant. It is a once-daily tablet dosed by body weight rather than by age, and its selectivity for the alpha-2A subtype makes it less sedating than clonidine. It is the alpha-2 agonist to reach for when a stimulant is insufficient or poorly tolerated and daytime sedation is the limiting concern. Not controlled; brand and generic.
Forms & Strengths
Tablets, extended release: 1 mg, 2 mg, 3 mg, 4 mg; unscored
These are tablets, not capsules. No guanfacine capsule exists in any form
Separate label: immediate-release guanfacine tablets 1 mg and 2 mg (formerly Tenex), not interchangeable mg-for-mg
Dosing
Age: 6-17 y/o; not established below 6 years
Onset: sedation same day; ADHD benefit over weeks, trial endpoints at 5 to 8 weeks
Duration: once daily, morning or evening, same time each day; half-life about 18 hours
Release Profile: extended release from a matrix tablet; Cmax about 60% lower and AUC about 43% lower than immediate-release guanfacine, Tmax about 3 hours later, relative bioavailability 58%
Initial Dose: 1 mg once daily
Titration: no more than 1 mg every 7 days
Max Dose: target 0.05 to 0.12 mg/kg/day, total 1 mg to 7 mg/day. Two age ceilings sit above the weight bands and both apply:
6-12 y/o: do not exceed 4 mg/day
13-17 y/o: do not exceed 7 mg/day
As adjunct to a stimulant: do not exceed 4 mg/day at any age
Under 25 kg: no weight band; dose from 0.05 to 0.12 mg/kg/day, starting at 1 mg
25 to 33.9 kg: 2 to 3 mg/day
34 to 41.4 kg: 2 to 4 mg/day
41.5 to 49.4 kg: 3 to 5 mg/day
49.5 to 58.4 kg: 3 to 6 mg/day
58.5 to 91 kg: 4 to 7 mg/day
Over 91 kg: 5 to 7 mg/day
Considerations: Swallow whole and do not give with a high-fat meal, which raises Cmax about 75%. Halve the dose with strong or moderate CYP3A4 inhibitors, and re-check the weight band as the child grows.
Pharmacology
Mechanism: Central alpha-2 adrenergic agonist; reduces sympathetic outflow from the locus coeruleus and enhances prefrontal noradrenergic signalling. Alpha-2A selective, 15 to 20 fold. Mechanism in ADHD unknown.
Delivery / Release: Matrix tablet; a high-fat breakfast raises Cmax about 75% and AUC about 40%.
Metabolism: Primarily CYP3A4; neither inhibits nor induces major P450s. About 70% protein bound. Inhibits MATE1 and OCT1, which may raise OCT1 substrate exposure.
Pediatric exposure: higher in 6-12 year olds than in adolescents at the same dose (4 mg: Cmax 10 vs 7 ng/mL, AUC 162 vs 116 ng.h/mL). Plasma level falls as weight rises, hence weight banding.
Cardiac: a thorough QT study at 2 to 4 times maximum Intuniv concentrations showed no clinical QTc prolongation.
Class Positioning: Less sedating than non-selective clonidine; once daily against twice-daily Kapvay, weight-banded, with a CYP3A4 profile clonidine lacks. Alpha-2 effect size about 0.7 against 1.0 for stimulants. (AAP 2019)
Indications
ADHD, as monotherapy (ICD-10: F90.0, F90.1, F90.2, F90.8, F90.9): patients 6-17 y/o
ADHD, as adjunctive therapy to stimulants (ICD-10: F90.0, F90.1, F90.2, F90.8, F90.9): patients 6-17 y/o
Off-Label Uses
Tic disorders and Tourette syndrome (ICD-10: F95.1, F95.2): a positive double-blind trial for tic severity, the better tic evidence of the two alpha-2 agonists. (AACAP 2013)
Oppositional defiant disorder, irritability and aggression (ICD-10: F91.3): no eligible controlled pediatric evidence identified; insufficient
Irritability in autism spectrum disorder (ICD-10: F84.0): limited data
Where the evidence does not support use:
Anxiety disorders (ICD-10: F41.x): insufficient; no graded pediatric evidence identified
Children under 6 (ICD-10: F90.x): insufficient (AHRQ 2018), and exposure rises as weight falls
Contraindications & Warnings
Warning, rebound hypertension: abrupt discontinuation has caused persistent rebound hypertension above baseline, with hypertensive encephalopathy reported
Contraindicated: hypersensitivity to Intuniv, its excipients, or other guanfacine products; rash and pruritus reported
Use with caution:
Hypotension, heart block, bradycardia, cardiovascular or cerebrovascular disease; titrate slowly
Syncope, orthostatic hypotension, or a tendency to dehydration; avoid overheating
Conduction abnormality, concurrent sympatholytics or CNS depressants; risk of AV block and additive sedation
Significant renal or hepatic impairment; reduce the dose
Any child prone to vomiting illness; missed doses are a labeled rebound risk
Screen before starting:
Heart rate and blood pressure, supine and standing; the label makes this mandatory
Accurate weight, since the dose ladder is banded by it; renal and hepatic function
Medication list, screened for CYP3A4 inhibitors and inducers, sedating and sympatholytic agents, and any syncope or conduction history
Drug Interactions
Strong and moderate CYP3A4 inhibitors (ketoconazole, fluconazole, itraconazole, clarithromycin, erythromycin, grapefruit juice): exposure rises. Halve the dose; restore it when the inhibitor stops
Strong and moderate CYP3A4 inducers (rifampin, efavirenz, carbamazepine): exposure falls. Consider up to double the dose over 1 to 2 weeks, and reverse when the inducer stops
CNS depressants and alcohol (benzodiazepines, antihistamines, opioids): additive sedation; advise avoiding alcohol
Antihypertensives and rate-lowering drugs: additive hypotension and syncope; check orthostatic vitals after any dose change
Sympatholytics (beta-blockers, calcium channel blockers, digitalis): may worsen sinus node dysfunction and AV block; titrate slowly
Stimulants: the labeled combination, but featured in the rebound hypertension cases; taper the guanfacine even when the stimulant continues
Administration
Once daily, morning or evening, at about the same time each day
Swallow whole. Do not crush, chew or break; the tablet is unscored, so 1 mg is the smallest deliverable dose
Do not give with a high-fat meal. A prohibition, not a consistency instruction
Missed doses: after two or more in a row, consider re-titrating rather than resuming maintenance
Switching from immediate-release guanfacine: stop it and titrate from 1 mg; relative bioavailability is 58%, so never convert mg-for-mg
Re-check the weight band at every visit in a growing child
No liquid guanfacine exists; Onyda XR is the only liquid alpha-2 agonist, and it is clonidine
Do not stop abruptly; see Discontinuation & Taper
Side Effects
Common (fixed-dose monotherapy trials, all doses and the 4 mg column against placebo):
Somnolence 38%, 51% at 4 mg, vs 11% placebo; fatigue 14 / 15 vs 3%
Hypotension 7 / 8 vs 3%; dizziness 6 / 10 vs 4%; dry mouth 4 / 7 vs 1%; lethargy 6 vs 3%; nausea 6 vs 2%
Stopped for adverse effects: 3% at 1 mg, 7% at 2 mg, 10% at 3 mg, 18% at 4 mg, vs 3% placebo
Serious:
Persistent rebound hypertension on abrupt discontinuation, with hypertensive encephalopathy reported; taper
Dose-dependent hypotension, bradycardia and syncope; hold or reduce, and any syncope stops titration
Conduction abnormality including first-degree AV block; obtain an ECG and stop
Convulsion; discontinue and evaluate
Rash, pruritus, dermatitis and exfoliative dermatitis; discontinue
Hallucinations and confusion; discontinue and reassess
Raised ALT; check liver enzymes if hepatic injury is suspected
Monitoring & Labs
Heart rate and blood pressure, supine and standing: baseline, 1 to 2 weeks after each 1 mg increment, then every 3 months; hold titration for bradycardia by age or any syncope
Blood pressure and pulse during any dose reduction: at each step down and after the last dose
Sedation: ask about school-day sleepiness at each titration visit and every visit for 3 months
Weight: at every visit, to keep the dose in the right band
ADHD response: rated scale at 5 to 8 weeks, matching the trial endpoints
CYP3A4 co-medication: review at every visit and refill; starting or stopping one requires a dose change
ECG: not routine; baseline if conduction disease, syncope history or sympatholytics, and promptly for new syncope
Renal and hepatic function: baseline and annually
Laboratory: none routine; check ALT if hepatic injury is suspected
Discontinuation & Taper
Never stop abruptly. Reduce by no more than 1 mg every 3 to 7 days; from 7 mg/day that is 3 to 6 weeks
Abrupt cessation has caused persistent rebound hypertension with raised heart rate, and hypertensive encephalopathy has been reported
Cases involved higher doses and concomitant stimulants; taper even when the stimulant continues
Monitor blood pressure and pulse at every taper step and after the final dose
A vomiting illness is de facto abrupt discontinuation; families should call, not let doses lapse
After two or more consecutive missed doses, consider re-titrating
Drug holidays are not appropriate for this class; weekend and summer breaks are a rebound hypertension risk here
Pregnancy & Lactation
Pregnancy: no drug-associated risk identified, but pregnancy use has been infrequent. No fetal harm in rabbits and rats at 3 to 4 times the maximum human dose; reduced fetal survival at 13.5 times.
Lactation: no human data; guanfacine has not been measured in human milk. Present in rat milk at blood-comparable levels. Monitor an exposed infant for sedation, lethargy and poor feeding. (LactMed 2024)
Lactation, milk supply: no published information; guanfacine lowers basal prolactin in men and non-nursing women. Other agents may be preferred while nursing a newborn. (LactMed 2024)
Exposure Registry: National Pregnancy Registry for ADHD Medications, 1-866-961-2388
Counseling Points
Counsel the family on:
Sleepiness early and dose related, half the children on 4 mg, while the ADHD benefit takes 5 to 8 weeks
Not taking it with a high-fat breakfast, and swallowing the unscored tablet whole
The dose being set by weight, so it is revisited as the child grows
Never stopping on their own: stopping suddenly can push blood pressure above where it started
Telling other prescribers before an antifungal, clarithromycin, or a seizure medicine
Calling if a stomach bug stops the medicine going down, or after two days of missed doses
Advise them to call for:
Fainting, dizziness on standing that does not settle, or any seizure
A pulse that feels very slow or irregular, or heavy daytime sleepiness
Severe headache with blurred vision, especially after missed doses
A widespread rash, peeling skin, facial swelling, or new confusion or hallucinations
Any vomiting illness that stops the medicine going down
References
DailyMed. Intuniv (guanfacine) extended-release tablets prescribing information. Takeda Pharmaceuticals America, Inc. 2025. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b972af81-3a37-40be-9fe1-3ddf59852528
LactMed. Guanfacine. Drugs and Lactation Database, National Institute of Child Health and Human Development. 2024. https://www.ncbi.nlm.nih.gov/books/NBK501522/
American Academy of Pediatrics. Clinical practice guideline for the diagnosis, evaluation, and treatment of attention-deficit/hyperactivity disorder in children and adolescents. Pediatrics. 2019. https://publications.aap.org/pediatrics/article/144/4/e20192528/81590/
AACAP. Practice parameter for the assessment and treatment of children and adolescents with tic disorders. Journal of the American Academy of Child and Adolescent Psychiatry. 2013. https://www.jaacap.org/article/S0890-8567(13)00695-3/fulltext
AHRQ. Attention deficit hyperactivity disorder: diagnosis and treatment in children and adolescents. Comparative Effectiveness Review No. 203. 2018. https://www.ncbi.nlm.nih.gov/books/NBK487764/
FDA. openFDA National Drug Code Directory, guanfacine, queried by generic name across all labelers. 2026. https://api.fda.gov/drug/ndc.json?search=generic_name:%22guanfacine%22&limit=1000