INTUNIV

What it is

INTUNIV is guanfacine hydrochloride. INTUNIV modified release tablet contains guanfacine hydrochloride equivalent to 1 mg, 2 mg, 3 mg, or 4 mg of guanfacine base. INTUNIV was developed as a tablet for once-a-day oral administration. Guanfacine is a selective alpha 2A-adrenergic receptor agonist.

Approved indications

— Treatment of attention deficit hyperactivity disorder (ADHD) in children and adolescents 6–17 years old, as monotherapy when stimulants or atomoxetine are not suitable, not tolerated or have been shown to be ineffective. — Treatment of attention deficit hyperactivity disorder (ADHD) in children and adolescents 6–17 years old, as adjunctive therapy to psychostimulants where there has been a sub-optimal response to psychostimulants. INTUNIV must be used as part of a comprehensive ADHD management programme, typically including psychological, educational and social measures.

Dosing overview

The recommended starting dose for INTUNIV is 1 mg, taken orally once a day, for both monotherapy and when co-administered with psychostimulants. The dose is adjusted in increments of no more than 1 mg/week for both monotherapy and when co-administered with psychostimulants. The recommended maintenance dose range depending on clinical response and tolerability for INTUNIV is 0.05–0.12 mg/kg/day (total daily dose between 1–7 mg). For children weighing 25.0–33.9 kg the target dose range is 2–3 mg/day; 34.0–41.4 kg is 2–4 mg/day; 41.5–49.4 kg is 3–5 mg/day; 49.5–58.4 kg is 3–6 mg/day; 58.5–91.0 kg is 4–7 mg/day; and 91.0 kg or greater is 5–7 mg/day. Doses above 4 mg/day have not been studied in co-administration trials and therefore are not recommended. The total daily dose should be tapered in decrements of no more than 1 mg every 3 to 7 days to minimize the risk of an increase in blood pressure upon discontinuation.

Key safety warnings

INTUNIV can cause syncope, hypotension, and bradycardia. In short-term paediatric monotherapy and co-administration trials, dose-dependent decreases in mean heart rate (6–9 bpm) and decreases in mean blood pressure (systolic [4–5 mm/Hg] and diastolic [3 mm/Hg]) were observed. Measure patients' heart rates and blood pressures prior to initiation of treatment, following dose increases, and periodically while on therapy. Measurements of heart rate and blood pressure should be performed prior to initiating therapy, following dose adjustments, periodically during treatment and following drug discontinuation. INTUNIV may cause somnolence and sedation. Before INTUNIV is used with other centrally active depressants (such as alcohol, sedatives, hypnotics, antipsychotics, phenothiazines, barbiturates, or benzodiazepines), the potential for additive sedative effects should be considered. There have been post-marketing reports of suicide-related events in patients treated with ADHD drugs. ADHD and its related co-morbidities may be associated with increased risk of suicidal ideation and/or behaviour. Therefore, it is recommended for patients treated with ADHD drugs that caregivers and physicians monitor for signs of suicide-related behaviour, including at dose initiation/optimisation and drug discontinuation. Blood pressure and pulse may increase following discontinuation of INTUNIV. Abrupt discontinuation of INTUNIV can lead to clinically significant and persistent rebound hypertension. In the post-marketing setting, cases of rebound hypertension including hypertensive encephalopathy have been reported rarely following discontinuation or treatment interruption.

Contraindications

INTUNIV is contraindicated in patients with a history of hypersensitivity to INTUNIV, its excipients, or other products containing guanfacine.

PBS listing

INTUNIV is listed on the PBS in 1 mg, 2 mg, 3 mg and 4 mg tablet strengths, each as one PBS item with streamlined restriction. The ex-manufacturer price for all strengths is A$48.21.

Regulatory history

INTUNIV was first registered on the ARTG on 22 August 2017 in all four strengths (1 mg, 2 mg, 3 mg and 4 mg modified release tablets). The PBAC recommended INTUNIV in July 2017 on a cost-minimisation basis with atomoxetine for patients contraindicated or intolerant to stimulant therapy. In July 2018, the PBAC recommended INTUNIV for attention deficit hyperactivity disorder as add-on therapy in conjunction with optimised stimulant therapy with an Authority Required (Streamlined) listing.