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Included as part of the PRECAUTIONS section.

Hypotension, Bradycardia, and Syncope

Treatment with INTUNIV® can cause decreases in blood pressure and heart rate. In the monotherapy, pediatric, short-term (8-9 weeks), controlled trials, the maximum mean changes from baseline in systolic blood pressure, diastolic blood pressure, and pulse were -5 mm Hg, -3 mm Hg, and -6 bpm, respectively, for all dose groups combined (generally one week after reaching target doses of 1 mg/day, 2 mg/day, 3 mg/day or 4 mg/day). These changes were dose dependent. Decreases in blood pressure and heart rate were usually modest and asymptomatic; however, hypotension and bradycardia can occur. Hypotension was reported as an adverse event for 7% of the INTUNIV® group and 3% of the placebo group. This includes orthostatic hypotension, which was reported for 1% of the INTUNIV® group and none in the placebo group. In the adjunctive trial, hypotension (3%) and bradycardia (2%) were observed in patients treated with INTUNIV® 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 subjects in the clinical program. The majority of these cases occurred in the long-term, open-label studies.

Measure heart rate and blood pressure prior to initiation of therapy, following dose increases, and periodically while on therapy. Use INTUNIV® with caution in patients with a history of hypotension, heart block, bradycardia, or cardiovascular disease, because it hear rate. Use caution in treating patients who have a can d crease blood pressure and he history of syncope or may have a condition that predisposes them to syncope, such as hypotension, orthostatic hypotension, bradycardia, or dehydration. Use INTUNIV® with caution in patients treated concomitantly with antihypertensives or other drugs that can reduce blood pressure or heart rate or increase the risk of syncope. Advise patients to avoid becoming dehydrated or overheated.

Sedation and Somnolence

Somnolence and sedation were commonly reported adverse reactio ns in clinical studies ® (38% for INTUNIV vs. 12% for placebo in monotherapy studies and 18% for INTUNIV® vs. 7% for placebo in the adjunctive study) in children and adolescents with ADHD, especially during initial use [see ADVERSE REACTIONS]. Before using INTUNIV® with other centrally active depressants (such as phenothiazines, barbiturates, or benzodiazepines), 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.

Other Guanfacine-Containing Products

Guanfacine, the active ingredient in INTUNIV®, is also approved as an antihypertensive. Do not use INTUNIV® in patients concomitantly taking other guanfacine-containing products (e.g., Tenex).

Patient Counseling Information

[See FDA-Approved Patient Labeling.]

Dosing and Administration

Instruct patients to swallow INTUNIV® whole with water, milk or other liquid. Tablets should not be crushed, chewed or broken prior to administration because this may increase the rate of release of the active drug. Patients should not take INTUNIV® together with a high-fat meal, since this can raise blood levels of INTUNIV®. Instruct the parent or caregiver to supervise the child or adolescent taking INTUNIV® and to keep the bottle of tablets out of reach of children.

Instruct patients on how to properly taper the medication, if the physician decides to discontinue treatment.

Adverse Reactions

Advise patients that sedation can occur, particularly early in treatment or with dose increases. Caution against operating heavy equipment or driving until they know how they respond to treatment with INTUNIV®. Headache and abdominal pain can also occur. If any of these symptoms persist, or other symptoms occur, the patient should be advised to discuss the symptoms with the physician.

Advise patients to avoid becoming dehydrated or overheated, and to avoid use with alcohol.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

No carcinogenic effect of guanfacine was observed in studies of 78 weeks in mice or 102 weeks in rats at doses up to 6-7 times the maximum recommended human dose of 4 mg/day on a mg/ m² basis.

Guanfacine was not genotoxic in a variety of test models, including the Ames test and an in vitro chromosomal aberration test; however, a marginal increase in numerical aberrations (polyploidy) was observed in the latter study.

No adverse effects were observed in fertility studies in male and female rats at doses up to 30 times the maximum recommended human dose on a mg/ m² basis.

Use In Specific Populations

Pregnancy

Pregnancy Category B

Rat experiments have shown that guanfacine crosses the placenta. However, administration of guanfacine to rats and rabbits at 6 and 4 times, respectively, the maximum recommended human dose of 4 mg/day on a mg/m² basis resulted in no evidence of harm to the fetus. Higher doses (20 times the maximum recommended human dose in both rabbits and rats) were associated with reduced fetal survival and maternal toxicity. There are no adequate and well-controlled studies of guanfacine in pregnant women. INTUNIV® should be used during pregnancy only if the potential benefit to the mother outweighs the potential risk to the fetus.

Nursing Mothers

It is not known whether guanfacine is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when INTUNIV® is administered to a nursing woman. Experiments with rats have shown that guanfacine is excreted in the milk.

Pediatric Use

The safety and efficacy of INTUNIV® in pediatric patients less than 6 years of age have not been established. For children and adolescents 6 years and older, efficacy beyond 9 weeks and safety beyond 2 years of treatment have not been established [see ADVERSE REACTIONS and Clinical Studies].

Geriatric Use

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

Use in Patients with Renal or Hepatic Impairment

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. It may be necessary to adjust the dose in patients with significant impairment of renal function.

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. It may be necessary to adjust the dose in patients with significant impairment of hepatic function.

Last reviewed on RxList: 6/17/2011
This monograph has been modified to include the generic and brand name in many instances.