INTUNIV

Treatment must be initiated under the supervision of an appropriate specialist in childhood and/or adolescent behavioural disorders. Pre-treatment screening Prior to prescribing, it is necessary to conduct a baseline evaluation to identify patients at increased risk of somnolence and sedation, hypotension and bradycardia, QT-prolongation arrhythmia and weight increase/risk of obesity.

4). Posology Careful dose titration and monitoring is necessary at the start of treatment since clinical improvement and risks for several clinically significant adverse reactions (syncope, hypotension, bradycardia, somnolence and sedation) are dose- and exposure-related.

Patients should be advised that somnolence and sedation can occur, particularly early in treatment or with dose increases. If somnolence and sedation are judged to be clinically concerning or persistent, a dose decrease or discontinuation should be considered.

For all patients, the recommended starting dose is 1 mg of guanfacine, taken orally once a day. The dose may be adjusted in increments of not more than 1 mg per week. Dose should be individualised according to the patient’s response and tolerability.

12 mg/kg/day. The recommended dose titration for children and adolescents is provided below (see tables 1 and 2). Dose adjustments (increase or decrease) to a maximum tolerated dose within the recommended optimal weight-adjusted dose range based upon clinical judgement of response and tolerability may occur at any weekly interval after the initial dose.

Monitoring during titration During dose titration, weekly monitoring for signs and symptoms of somnolence and sedation, hypotension and bradycardia should be performed. Ongoing monitoring During the first year of treatment, the patient should be assessed at least every 3 months for: • Signs and symptoms of: o somnolence and sedation o hypotension o bradycardia • weight increase/risk of obesity It is recommended clinical judgement be exercised during this period.

4). 5 kg and above Max Dose = 7 mg 1 mg 2 mg 3 mg 4 mg 5 mg 6 mg 7 mgb a Adolescent subjects must weigh at least 34 kg. 5 kg and above may be titrated to a 7 mg/day dose after the subject has completed a minimum of 1 week of therapy on a 6 mg/day dose and the physician has performed a thorough review of the subject’s tolerability and efficacy.

2%). 7%). The adverse reactions somnolence and sedation occurred predominantly at the start of treatment and may typically last for 2-3 weeks and longer in some cases. Tabulated list of adverse reactions The following table presents all adverse reactions based on clinical trials and spontaneous reporting.

All adverse reactions from post-marketing experience are italicised. The following definitions apply to the frequency terminology used hereafter: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1 000 to < 1/100), rare (≥ 1/10 000 to < 1/1 000), very rare (< 1/10 000) and not known (cannot be estimated from the available data).

Table 4. Adverse reactions System/Organ Class Adverse reaction Incidence Category Immune system disorders Hypersensitivity Uncommon Metabolism and nutrition disorders Decreased appetite Common Psychiatric disorders Depression Common Anxiety Common Affect lability Common Insomnia Common Middle insomnia Common Nightmare Common Agitation Uncommon Table 4.

Adverse reactions System/Organ Class Adverse reaction Incidence Category Aggression Uncommon Hallucination Uncommon Nervous system disorders Somnolence Very common Headache Very common Sedation Common Dizziness Common Lethargy Common Convulsion Uncommon Syncope/loss of consciousness Uncommon Postural dizziness Uncommon Hypersomnia Rare Cardiac disorders Bradycardia Common Atrioventricular block first degree Uncommon Tachycardia Uncommon Sinus arrhythmia Uncommon Vascular disorders Hypotension Common Orthostatic hypotension Common Pallor Uncommon Hypertension Rare Hypertensive encephalopathy Very rare Respiratory, thoracic, and mediastinal disorders Asthma Uncommon Gastrointestinal disorders Abdominal pain Very common Vomiting Common Diarrhoea Common Nausea Common Constipation Common Abdominal/stomach discomfort Common Dry mouth Common Dyspepsia Uncommon Skin and subcutaneous tissue disorders Rash Common Pruritus Uncommon Renal and urinary disorders Enuresis Common Pollakiuria Uncommon Reproductive system and breast disorders Table 4.

Hypotension, bradycardia and syncope Guanfacine can cause syncope, hypotension and bradycardia. 7). Prior to initiation of treatment, patient’s cardiovascular status including heart rate and blood pressure parameters, family history of sudden cardiac death /unexplained death, should be assessed to identify patients at increased risk of hypotension, bradycardia, and QT-prolongation/risk of arrhythmia.

Monitoring of heart rate and blood pressure parameters should continue on a weekly basis during dose titration and stabilisation and at least every 3 months for the first year, taking into consideration clinical judgement. 6 monthly monitoring should follow thereafter, with more frequent monitoring following any dose adjustment.

Caution is advised when treating patients with guanfacine who have a history of hypotension, heart block, bradycardia, or cardiovascular disease, or who have a history of syncope or a condition that may predispose them to syncope, such as hypotension, orthostatic hypotension, bradycardia, or dehydration.

5). Patients should be advised to drink plenty of fluid. Blood pressure and heart rate increase upon discontinuation Blood pressure and pulse may increase following discontinuation of guanfacine. 8). 2). Blood pressure and pulse should be monitored when reducing the dose or discontinuing treatment.

1%) among guanfacine patients. 8). 2). 5). 8). Sedation and somnolence Guanfacine may cause somnolence and sedation predominantly at the start of treatment and could typically last for 2-3 weeks and longer in some cases. 2), and every 3 months during the first year, taking into consideration clinical judgement.

5). Patients should not drink alcohol whilst taking guanfacine. 7). Suicidal ideation There have been post-marketing reports of suicide-related events (including suicidal ideation, attempts and completed suicide) in patients treated with guanfacine.

1.