Intuniv (Guanfacine Hydrochloride) - Drug Interactions, Contraindications, Overdosage, etc

DRUG INTERACTIONS

CYP3A4/5 Inhibitors

Use caution when INTUNIV™ is administered to patients taking ketoconazole and other strong CYP3A4/5 inhibitors, since elevation of plasma guanfacine concentration increases the risk of adverse events such as hypotension, bradycardia, and sedation. There was a substantial increase in the rate and extent of guanfacine exposure when administered with ketoconazole; the guanfacine exposure increased 3-fold (AUC).

CYP3A4 Inducers

When patients are taking INTUNIV™ concomitantly with a CYP3A4 inducer, an increase in the dose of INTUNIV™ within the recommended dose range may be considered. There was a significant decrease in the rate and extent of guanfacine exposure when co-administered with rifampin, a CYP3A4 inducer. The exposure to guanfacine decreased by 70% (AUC).

Valproic Acid

Co-administration of guanfacine and valproic acid can result in increased concentrations of valproic acid. The mechanism of this interaction is unknown, although both guanfacine (via a Phase I metabolite, 3-hydroxy guanfacine) and valproic acid are metabolized by glucuronidation, possibly resulting in competitive inhibition. When INTUNIV™ is co-administered with valproic acid, monitor patients for potential additive CNS effects, and consider monitoring serum valproic acid concentrations. Adjustments in the dose of valproic acid may be indicated when co-administered with INTUNIV™.

Antihypertensive Drugs

Use caution when INTUNIV™ is administered concomitantly with antihypertensive drugs, due to the potential for additive pharmacodynamic effects. (e.g., hypotension, syncope) [see Warnings and Precautions ].

CNS Depressant Drugs

Caution should be exercised when INTUNIV™ is administered concomitantly with CNS depressant drugs (e.g. alcohol, sedative/hypnotics, benzodiazepines, barbiturates, and antipsychotics) due to the potential for additive pharmacodynamic effects. (e.g., sedation, somnolence) [see Warnings and Precautions ].

OVERDOSAGE

Symptoms

Two cases of accidental overdose of INTUNIV™ were reported in clinical trials in pediatric ADHD patients. These reports included adverse reactions of sedation and bradycardia in one patient and somnolence and dizziness in the other patient.

During post-marketing surveillance of guanfacine as an antihypertensive treatment for adults, drowsiness, lethargy, bradycardia and hypotension have been observed following overdose. Similar symptoms have been described in voluntary reports to the American Association of Poison Control Center's National Poison Data System. Miosis of the pupils may be noted on examination . No fatal overdoses of guanfacine have been reported in published literature.

Treatment

Consult a Certified Poison Control Center for up to date guidance and advice. Gastric lavage may be indicated if performed soon after ingestion. Activated charcoal may be useful in limiting absorption. Guanfacine is not dialyzable in clinically significant amounts (2.4%).

Management of INTUNIV^™ overdose should include monitoring for and the treatment of hypotension, bradycardia, lethargy and respiratory depression. Children and adolescents who develop lethargy should be observed for the development of more serious toxicity including coma, bradycardia and hypotension for up to 24 hours, due to the possibility of delayed onset hypotension.

CONTRAINDICATIONS

Patients with a history of hypersensitivity to INTUNIV^™, its inactive ingredients [see Description ], or other products containing guanfacine (e.g. TENEX®) should not take INTUNIV™.

DRUG ABUSE AND DEPENDENCE

Controlled Substance

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