Intuniv · 4.6 Fertility, pregnancy and lactation · 1

HOS-097012 · has-adverse-reaction-information · PDF-Seite 10

Summary of the safety profile The most frequently reported adverse reactions include somnolence (40.6%), headache (27.4%), fatigue (18.1%), abdominal pain upper (12.0%), and sedation (10.2%). The most serious adverse reactions commonly reported include hypotension (3.2%), weight increase (2.9%), bradycardia (1.5%) and syncope (0.7%). 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). 10 Table 4. Adverse reactions System/Organ Class Incidence Category Adverse reaction 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 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

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HOS-097008 · has-contraindication-information · PDF-Seite 6

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

HOS-097007 · has-indication-information · PDF-Seite 3

Intuniv is indicated for the treatment of attention deficit hyperactivity disorder (ADHD) in children and adolescents 6-17 years old for whom stimulants are not suitable, not tolerated or have been shown to be ineffective. Intuniv must be used as a part of a comprehensive ADHD treatment programme, typically including psychological, educational and social measures.

HOS-097010 · has-interaction-information · PDF-Seite 8

When guanfacine is used concomitantly with CYP3A4/5 inhibitors or inducers, plasma concentrations of guanfacine may be elevated or lowered, potentially affecting the efficacy and safety of guanfacine. Guanfacine can increase plasma concentrations of concomitantly administered medicinal products that are metabolised via CYP3A4/5 (see sections 4.2, 4.4 and 5.2). Guanfacine is an in vitro inhibitor of MATE1 and the clinical relevance of MATE1 inhibition cannot be excluded. Concomitant administration of guanfacine with MATE1 substrates may result in increases in the plasma concentrations of these medicinal products. Furthermore, based on in vitro studies, guanfacine may be an inhibitor of OCT1 at maximal portal vein concentrations. Concomitant administration of guanfacine with OCT1 substrates with a similar Tmax (e.g., metformin) may result in increases in Cmax of these medicinal products. The pharmacodynamic effect of guanfacine can have an additive effect when taken with other products known to cause sedation, hypotension or QT prolongation (see section 4.4). Interaction studies have only been performed in adults. However, the outcome is expected to be similar in the indicated paediatric age range. QT prolonging medicinal products Guanfacine causes a decrease in heart rate. Given the effect of guanfacine on heart rate, the concomitant use of guanfacine with QT prolonging medicinal products is generally not recommended (see section 4.4). CYP3A4 and CYP3A5 inhibitors Caution should be used when guanfacine is administered to patients taking ketoconazole and other moderate and strong CYP3A4/5 inhibitors, a decrease in the dose of guanfacine within the recommended dose range is proposed (see section 4.2). Co-administration of guanfacine with moderate and strong CYP3A4/5 inhibitors elevates plasma guanfacine concentrations and increases the risk of adverse reactions 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 peak plasma concentrations (Cmax) and exposure (AUC) increased 2- and 3-fold, respectively. Other CYP3A4/5 inhibitors may have a comparable effect, see table 3 for a list of examples of moderate and strong CYP3A4/5 inhibitors, this list is not definitive. CYP3A4 inducers When patients are taking guanfacine concomitantly with a CYP3A4 inducer, an increase in the dose of guanfacine within the recommended dose range is p

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HOS-097011 · has-pregnancy-information · PDF-Seite 10

Pregnancy There are no or limited amount of data from the use of guanfacine in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). Guanfacine is not recommended during pregnancy and in women of childbearing potential not using contraception. Breast-feeding It is unknown whether guanfacine and its metabolites are excreted in human milk. Available pharmacodynamic and toxicological data in animals have shown excretion of guanfacine and its metabolites in milk (see section 5.3). Therefore, a risk on the breast-fed infant cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue and/or abstain from guanfacine therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman. Fertility There are no or limited amount of data regarding effect on fertility from the use of guanfacine in humans. Animal studies indicate an effect on male fertility (see section 5.3).

HOS-097009 · has-warning-information · PDF-Seite 6

Hypotension, bradycardia and syncope Guanfacine can cause syncope, hypotension and bradycardia. Syncope may involve risks of falls or accidents, which could result in serious harm (see sections 4.8 and 4.7). 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. Caution is also advised when treating patients who are being treated concomitantly with antihypertensives or other medicinal products that can reduce blood pressure or heart rate or increase the risk of syncope (see section 4.5). 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. In post-marketing experience, hypertensive encephalopathy has been very rarely reported upon abrupt discontinuation of treatment (see section 4.8). To minimise the risk of an increase in blood pressure upon discontinuation, the total daily dose should be tapered in decrements of no more than 1 mg every 3 to 7 days (see section 4.2). Blood pressure and pulse should be monitored when reducing the dose or discontinuing treatment. 6 QTc interval In phase II-III randomised double-blind monotherapy studies respective increases in QTc interval prolongation that exceeded change from baseline greater than > 60 ms Fridericia-correction and Bazett-correction were 0 (0.0%) and 2 (0.3%) among placebo and 1 (0.1%) and 1 (0.1%) among guanfacine patients. During post-marketing, there have been reports of prolonged QT/QTc interval (see section 4.8). In case of Electrocar

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