ADHD Medication Shared Care Agreement

Transcription

1 For the Treatment of Attention Deficit Hyperactivity Disorder in children aged 6 years of age and over AREAS OF RESPONSIBILITY FOR THE SHARING OF CARE This shared care agreement outlines suggested ways in which the responsibilities for managing the prescribing of methylphenidate, atomoxetine, lisdexamfetamine dimesylate and guanfacine can be shared between the specialist and general practitioner (GP). GPs are invited to participate. If the GP is not confident to undertake these roles, then he or she is under no obligation to do so. In such an event, the total clinical responsibility for the patient for the diagnosed condition remains with the specialist. Sharing of care assumes communication between the specialist, GP and patient. The intention to share care is usually explained to the patient by the specialist prescriber initiating treatment. It is important that patients/carers are consulted about treatment and are in agreement with it. Methylphenidate is indicated as part of a comprehensive treatment program for ADHD in children aged 6 years and over when remedial measures alone prove insufficient. Atomoxetine is indicated for the treatment of ADHD in children of 6 years and over. It is ideally a second line treatment if methylphenidate is considered to be clinically inadequate. Atomoxetine could be considered a first line treatment in children with certain co-morbid conditions e.g. tics, high anxiety, or if there are issues around drug misuse/diversion. Lisdexamfetamine dimesylate is indicated as part of a comprehensive treatment programme for ADHD in children aged 6 years and over when response to previous methylphenidate treatment is considered to be clinically inadequate. Guanfacine 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. The prescriber of the medication legally assumes clinical responsibility for the drug and the consequences of its use. ROLES and RESPONSIBILITIES Specialist Responsibilities 1. Initiate methylphenidate (1 st line), atomoxetine (1 st /2 nd line) or lisdexamfetamine dimesylate (2 nd line) and stabilise patient on a maintenance dose as part of a care package. 2. Discuss the benefits and side effects of treatment with the patient and parent/guardian. 3. Transfer all appropriate information of the treatment to the GP for effective shared care and continuity of care including follow up arrangement and when to refer back. 4. Ensure that the patient has enough medication, at least two weeks supply during transfer of care. Clearly indicate the brand name (for modified release formulations of methylphenidate), strength and dose of the drug, and any future dose changes in the letter to the patient s GP. 5. Communicate promptly any changes in treatment or doses. 6. Review and monitor treatment at least six monthly as stated in supporting information. 7. Have a mechanism in place for rapid referral in the event of an adverse event or if the patient s condition deteriorates. 8. Have a mechanism in place for annual supervision and assessment of a patient on a drug holiday. 9. Agree a medication review date(s) with the GP and give advice on stopping treatment. 10. Report adverse events to the MHRA and GP. Date Written: April 2016 Approved by: ACE, Dudley CCG May 2016 Review date: April of 11

2 11. Ensure that clear backup arrangements exist for GPs to obtain advice and support. 12. To obtain school and parental carer s reports to assist with the assessment of the patient s progress. General Practitioner (GP) Responsibilities 1. Reply to the request for shared care as soon as possible (within two weeks). 2. GP to ensure full understanding of their responsibilities for managing patients with ADHD on methylphenidate, atomoxetine or lisdexamfetamine dimesylate including side effects in line with the SPC. 3. Prescribe methylphenidate, atomoxetine or lisdexamfetamine dimesylate within the dose ranges and period of treatment specified or recommended. Adjust the dose as advised by the specialist. 4. Review patient at least annually between specialist reviews. 5. Monitor treatment as listed below and patient s response to the medication. 6. GP to check that the patient is attending six monthly specialist ADHD clinics and thus continued prescription is required. 7. Report to and seek advice from the specialist on any aspect of patient care that is of concern and may affect treatment 8. Refer patients to the specialist if his or her condition deteriorates or there are any concerns with patient compliance. 9. Stop treatment on the advice of the specialist or immediately if an urgent need to stop treatment arises. 10. Report adverse events to the specialist and MHRA Lisdexamfetamine dimesylate is a black triangle drug so patient/carer and clinicians should be especially vigilant in identifying and reporting suspected adverse events. 11. Inform specialist of all relevant medical information regarding the patient and any changes to the patient s medication irrespective of indication. Patient's / Carer s Role 1. Inform specialist or GP of any other medication being taken, including over-thecounter products. 2. Report to the specialist or GP if he or she does not have a clear understanding of the treatment. 3. Share any concerns in relation to treatment and report any adverse effects or problems to the specialist or GP whilst taking methylphenidate, atomoxetine or lisdexamfetamine dimesylate. 4. Attend specialist/gp appointments for review of treatment. 5. Patient/carer to inform GP/specialist if patient becomes pregnant, thinks she is pregnant, or is planning to have a baby. Date Written: April 2016 Approved by: ACE, Dudley CCG May 2016 Review date: April of 11

3 Effective Shared Care Agreement Form Effective Shared Care Agreement Form Name of patient: NHS No: Date of Birth: Address (include post code): Contact Telephone Numbers (Please supply minimum of two contacts points) & Patient Signature: Date: Advocate/Carer s Name: Contact Details: or Signature: Date: Consultant Name: Contact Address: or Signature: Date: General Practitioner s Name: Contact Address: or Signature: Date: GP s comment: Date Written: April 2016 Approved by: ACE, Dudley CCG May 2016 Review date: April of 11

4 BACK-UP ADVICE AND SUPPORT (Please contact the specialist who initiated the treatment) Contact details Telephone No. Specialist: Consultant Community Paediatricians (Walsall) Consultant Psychiatrist CAMHS (Walsall) Consultant Community Paediatrician (Dudley) Consultant Psychiatrist CAMHS (Dudley) Other: CCG Head of Medicines Management (Walsall CCG) Pharmaceutical Public Health Team, (Dudley CCG) Chief Pharmacist at Dudley and Walsall Mental Health Partnership Trust SUPPORTING INFORMATION METHYLPHENIDATE Also refer to information in the latest versions of the Summary of Product Characteristics (available on line at and British National Formulary ( Licensed indications Methylphenidate is indicated as part of the treatment of ADHD where non-pharmacological interventions alone have proven insufficient. It should be used as part of a total package of care including cognitive, educational, behavioural and social components. Dosage and administration Methylphenidate is available as standard and sustained-release preparations. The dose of standard-release methylphenidate is initially 5mg once or twice daily. The dose and frequency of administration may be increased if necessary by weekly increments of 5-10mg in the daily dose, increasing to a maximum of 60mg/day in divided doses. Methylphenidate usually starts to be clinically effective within minutes and wears off in 3-5 hours. If the effect of the drug wears off too early in the evening, rebound hyperactivity and/or inability to go to sleep may recur. A small evening dose may help to reduce the rebound hyperactivity. Children who develop insomnia should not receive medication later than 1pm. In contrast, children who do not develop insomnia may be helped significantly by a dose after school, which covers them for homework. Due to substantially greater costs modified release tablets should be restricted to second line therapy and only used where compliance is an issue e.g. where midday dosing at school is a problem. Modified release tablets are only suitable if they can be swallowed whole and should not be given to patients with severe GI narrowing or dysphagia or significant difficulties in swallowing tablets. The contents of modified release capsules can be sprinkled on a tablespoon of apple sauce then swallowed immediately without chewing, followed by a drink e.g. water. Please note although the modified release preparations are intended to have a duration of action lasting 24 hours it is the experience of local psychiatrists that the duration of action is sometimes shorter (sometimes as little as 8 hours). Although unlicensed, local Psychiatrists have occasionally prescribed Concerta XL twice daily with a second dose prescribed after school. If this is the case this must be specifically qualified in correspondence to GP to minimise confusion. o The initial dose of Concerta XL prolonged-release methylphenidate is 18mg once daily (every morning), increased gradually if necessary in steps of 18mg at weekly intervals up to a maximum of 54mg/day (15mg standard-release methylphenidate= 18mg sustained-release methylphenidate). o The initial dose of Equasym XL modified-release methylphenidate is 10mg once a day in the morning before breakfast increased gradually if necessary at weekly intervals to a maximum of 60mg daily. o The initial dose of Medikinet XL prolonged-release methylphenidate is 10mg once a day in the morning with breakfast, increased gradually if necessary in steps of 5 to 10mg at weekly intervals to a maximum of 60mg daily. NB The modified release products listed above have different release profiles; branded prescribing is essential. If improvement of symptoms is not observed over a one-month period, the drug should be discontinued. Robust arrangements for dosing during school hours should be agreed with the school. Treatment should be suspended periodically to assess the child s condition and the drug is usually discontinued during or after puberty. Abrupt withdrawal should be avoided. NB: methylphenidate is a schedule 2 controlled drug. Prescribers must ensure compliance with controlled drug writing requirements If uncertain please contact a pharmacist to clarify prescription requirements. Monitoring Consultant Baseline and 6-monthly: Height, weight, pulse, blood pressure, symptoms of suggestive heart disease, and appetite. Monitor for emergence/worsening of any psychiatric disorders. Blood parameters (complete and differential blood counts and platelet counts) should be performed periodically if patient on long term therapy (SPC recommendation). Date Written: April 2016 Approved by: ACE, Dudley CCG May 2016 Review date: April of 11

5 GP annual: Monitor and record blood pressure, any symptoms of suggestive heart disease, height, weight, and appetite. Monitor for emergence/worsening of any psychiatric disorders. Monitor for adverse drug reactions/interaction. (A guide to expected diastolic and systolic blood pressures for children and adolescents can be found in the Journal of Hypertension 2009, 27: , or Arch Dis Child 2007; 92: Contraindications and cautions for use The MHRA state that methylphenidate is contraindicated in those with a diagnosis or history of severe depression, anorexia nervosa or anorexic disorders, suicidal tendencies, psychotic symptoms, mania, schizophrenia, severe mood disorders, or psychopathic or borderline personality disorder, severe and episodic (type I) bipolar (affective) disorder that is not well-controlled, pre-existing cerebrovascular disorders e.g., cerebral aneurysm and vascular abnormalities, including vasculitis or stroke. The MHRA also states that, unless specialist cardiac advice has been obtained, methylphenidate is contraindicated in pre-existing cardiovascular disorders, including severe hypertension, heart failure, arterial occlusive disease, angina, haemodynamically significant congenital heart disease, cardiomyopathies, myocardial infarction, potentially life-threatening arrhythmias, and dysfunction of cardiac ion channels. The presence of marked anxiety, agitation or tension is a contra-indication to the use of methylphenidate. It is also contra-indicated in patients with drug or alcohol dependence, motor tics, tics in siblings, or a family history or diagnosis of Tourette s syndrome. Methylphenidate is contra-indicated in patients with hyperthyroidism, severe angina pectoris, glaucoma, and thyrotoxicosis or known sensitivity to methylphenidate/ excipients. It is cautioned in those whose medical conditions may be compromised by increases in blood pressure/heart rate. It is contraindicated in combination with monoamine oxidase inhibitors (MAOIs) or within 14 days of treatment. Methylphenidate is not recommended for use in children with known structural cardiac abnormalities, as sudden death has been reported. It is cautioned in epilepsy (discontinue if increased seizure frequency). Methylphenidate should not be used in children under 6 years of age, since safety and efficacy has not been established. It should not be used to treat severe exogenous or endogenous depression. Reports of suicidal ideation or suicidal intent have been received. Side Effects Sleeping difficulties (especially if medication is given late in day), decreased appetite, stomach aches, nausea, vomiting, dry mouth, headaches, transient depression of mood, nervousness, drowsiness, agitation, irritability, tachycardia and rash. Other adverse effects which require careful monitoring: changes in blood pressure (see above under monitoring) and heart rate (usually increased), growth retardation may occur during prolonged therapy, isolated cases of leucopoenia, thrombocytopenia and anaemia have been reported, occasionally increased seizure frequency and development of tics. Drug Interactions Methylphenidate may inhibit the metabolism of anticoagulants, some anticonvulsants (phenobarbital, phenytoin, primidone), phenylbutazone, tricyclic antidepressants and sympathomimetics. It should be used with caution in patients being treated with pressor agents. See above for MAOIs. Cost At current prices one year s treatment costs: 203 for methylphenidate 30mg/day (Ritalin) 211 for methylphenidate 30mg/day (Equasym) 516 for methylphenidate 36mg/day (Concerta XL) 426 for methylphenidate 30mg/day (Equasym XL) 406 for methylphenidate 30mg/day (Medikinet XL) References: NICE Technology Appraisal 98. Methylphenidate, atomoxetine and dexamfetamine for attention deficit hyperactivity disorder (ADHD) in children and adolescents BNF for Children (available at: Drug Tariff December 2013 Drug Safety Update Volume 2 Issue 6 March 2009 MHRA Methylphenidate ESCA Coventry and Warwickshire Area Prescribing Committee Date Written: April 2016 Approved by: ACE, Dudley CCG May 2016 Review date: April of 11

6 LISDEXAMFETAMINE DIMESYLATE Also refer to information in the latest versions of the Summary of Product Characteristics (available on line at and British National Formulary ( Licensed indications Lisdexamfetamine is indicated as part of a comprehensive treatment programme for attention deficit/hyperactivity disorder (ADHD) in children aged 6 years of age and over when response to previous methylphenidate treatment is considered clinically inadequate. Dosage and administration Lisdexamfetamine is a pharmacologically inactive prodrug. After oral administration, lisdexamfetamine is rapidly absorbed from the gastrointestinal tract and hydrolysed primarily by red blood cells to dexamfetamine. DOSE: The starting dose for all patients is 30mg once daily in the morning. This may be increased at approximately weekly intervals by 20mg increments, to a maximum of 70mg once daily. The lowest effective dose should be administered. Lisdexamfetamine may be taken with or without food. The capsules should be swallowed whole or opened, the contents dispersed in a glass of water (stir until completely dispersed) and the resulting solution swallowed immediately (a film of inactive ingredients may remain in the glass). Afternoon doses should be avoided (risk of insomnia). If there is a missed morning dose, wait until the following morning before administering the next dose. Treatment should be stopped if the symptoms do not improve after 1 month at an appropriate dose. Reduce the dosage if paradoxical aggravation of symptoms/other intolerable adverse events emerge. Monitoring NB: Lisdexamfetamine is classified as a Schedule 2 controlled drug. All prescriptions should be appropriately written to avoid dispensing delays. Abuse liability- the SPC gives details of abuse liability studies which showed that lisdexamfetamine has less potential for abuse than dexamfetamine. Consultant Baseline and 6-monthly: Height, weight, appetite, pulse and blood pressure; emergence of /worsening of preexisting psychiatric disorders; risk of diversion/misuse/abuse. GP annual Height, weight, appetite, pulse and blood pressure; emergence of /worsening of pre-existing psychiatric disorders; risk of diversion/misuse/abuse. Monitor for adverse drug reactions/interactions. (A guide to expected diastolic and systolic blood pressures for children and adolescents can be found in the Journal of Hypertension 2009, 27: , or Arch Dis Child 2007; 92: Contraindications and cautions for use CONTRAINDICATIONS: hypersensitivity to sympathomimetic amines or any of the excipients: concomitant use of monoamine oxidase inhibitors (MAOI) or within 14 days after MAOI treatment, hyperthyroidism or thyrotoxicosis, agitated states, symptomatic cardiovascular disease, advanced arteriosclerosis, moderate to severe hypertension, glaucoma. CAUTIONS: in patients with a history of substance abuse or dependence; should not be used if there are known serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, or other serious cardiac problems that may place them at increased vulnerability to the sympathomimetic effects. Caution is indicated in treating patients whose underlying medical conditions might be compromised by increases in blood pressure or heart rate. Cardiomyopathy has been reported. All patients should have a careful history (including assessment for a family history of sudden death or ventricular arrhythmia) and physical exam to assess for the presence of cardiac disease, and should receive further cardiac evaluation if findings suggest such disease. Patients who develop symptoms such as exertional chest pain, unexplained syncope, or other symptoms suggestive of cardiac disease during stimulant treatment should undergo a prompt cardiac evaluation. Administration may exacerbate symptoms of behaviour disturbance and thought disorder in patients with pre existing psychotic disorders. Take particular care in patients with comorbid bipolar disorder. Screen patients with comorbid depressive symptoms to determine if they are at risk for bipolar disorder before lisdexamfetamine treatment is started. If treatment emergent psychotic or manic symptoms occur; consideration should be given to a possible causal role of the stimulant, and possible discontinuation of treatment. Patients beginning treatment for ADHD should be monitored for the appearance/worsening of aggressive behaviour or hostility. Clinical evaluation for tics and Tourette's syndrome in children and their families should precede use. Growth should be monitored during treatment with stimulants, and patients who are not growing/ gaining weight as expected may need to have their treatment interrupted. In the presence of new onset or worsening seizures, lisdexamfetamine should be discontinued. Difficulties with accommodation and blurring of vision have been reported with stimulant treatment. Use with caution in patients taking other sympathomimetic drugs. Side Effects Very common: decreased appetite, insomnia, headache, dry mouth (adult), upper abdominal pain (6-12 yr), weight decreased (6-17 yr); common: anorexia, tic (6-12 yr), affect lability (6-17yr), psychomotor hyperactivity (6-12yr, adults), aggression (6-12yr), dizziness, restlessness (adult), tremor (13-17yr, adult), somnolence (6-12yr), mydriasis (6-12yr), tachycardia (13-17yr, adult), palpitation (13-17 yr, adult), dyspnoea ( 13-17yr, adult), dry mouth (6-17yr), diarrhoea, upper abdominal pain (13-17yr, adult), nausea, vomiting, (6-17yr), hyperhidrosis (adult), rash (6-12yr), erectile dysfunction (adult), irritability, fatigue, feeling jittery (adult), pyrexia (6-12yr), increased blood pressure (13-17, adults), and decreased weight (adult). See SPC for a full list of adverse effects that had a frequency occurrence of uncommon/rare or where the frequency was not known. Date Written: April 2016 Approved by: ACE, Dudley CCG May 2016 Review date: April of 11

7 Drug Interactions Amfetamines should not be administered during or within 14 days following the administration of monoamine oxidase inhibitors (MAOI) because they can increase the release of norepinephrine and other monoamines. This can cause severe headaches and other signs of hypertensive crisis. A variety of toxic neurological effects and malignant hyperpyrexia can occur, sometimes with fatal outcomes. Chlorpromazine blocks dopamine and norepinephrine receptors, thus inhibiting the central stimulant effects of amfetamines. Haloperidol blocks dopamine receptors, thus inhibiting the central stimulant effects of amfetamines. The anorectic and stimulatory effects of amfetamines may be inhibited by lithium carbonate. Amfetamines potentiate the analgesic effect of narcotic analgesics. Amfetamines may decrease the effectiveness of guanethidine or other antihypertensive medications. Ascorbic acid and other agents and conditions (diets high in fruits and vegetables, urinary tract infections and vomiting) that acidify urine increase urinary excretion and decrease the half-life of amfetamine. Sodium bicarbonate and other agents and conditions (thiazide diuretics, diets high in animal protein, diabetes, respiratory acidosis) that alkalinise urine decrease urinary excretion and extend the half-life of amfetamine. There are limited data on the possible interaction with alcohol. Amfetamines can cause a significant elevation in plasma corticosteroid levels. It may interfere with urinary steroid determinations. In vitro experiments with human microsomes indicate minor inhibition of CYP2D6 by amfetamine and minor inhibition of CYP1A2, 2D6, and 3A4 by one or more metabolites. Although the clinical significance of this interaction is likely to be minimal, consideration should be given when medications metabolised by these pathways are administered. Cost At current prices, one year s treatment at 50mg daily costs 835 (Drug Tariff, December 2013) References: SPC for Lisdexamfetamine dimesylate. Accessed 13/10/13. NICE Attention deficit hyperactivity disorder. Diagnosis and management of ADHD in children, young people and adults NICE CG72 (2008, modified March 2013) Drug Tariff, December 2013 Lisdexamfetamine Shared Care Agreement. Coventry and Warwickshire Area Prescribing Committee ATOMOXETINE Also refer to information in the latest versions of the Summary of Product Characteristics (available on line at and British National Formulary ( Licensed indications Atomoxetine is licensed for the treatment of attention deficit/hyperactivity disorder in children of at least 6 years of age, and adolescents, as part of a comprehensive treatment programme. Dosage and administration Atomoxetine is normally given as a single dose in the morning. Patients who suffer from side effects, or achieve minimal efficacy, may benefit from dividing the dose, which should then be taken in the morning and late afternoon or early evening. In some cases it might be appropriate to continue treatment into adulthood. NB Should not be initiated in adults. Consideration should be given to dose reduction or interrupting therapy in patients who are not growing or gaining weight satisfactorily. In cases of significant adverse effects, atomoxetine may be stopped abruptly; otherwise the drug may be tapered off over a suitable time period. Dosing of children/adolescents up to 70 kg body weight: atomoxetine should be initiated at a total daily dose of approximately 0.5mg/kg. The initial dose should be maintained for a minimum of 7 days prior to upward dose titration according to clinical response and tolerability. The recommended maintenance dose is approximately 1.2mg/kg/day (depending on the patient's weight and available dosage strengths of atomoxetine). Dosing of children/adolescents over 70 kg body weight: atomoxetine should be initiated at a total daily dose of 40mg. The initial dose should be maintained for a minimum of 7 days prior to upward dose titration according to clinical response and tolerability. The recommended maintenance dose is 80mg. No additional benefit has been demonstrated for doses higher than 80mg. The maximum recommended total daily dose is 100mg. Hepatic insufficiency: For patients with moderate hepatic insufficiency (Child-Pugh class B), initial and target doses should be reduced to 50% of the usual dose. For patients with severe hepatic insufficiency (Child-Pugh class C), initial dose and target doses should be reduced to 25% of usual dose. Renal insufficiency: Atomoxetine can be administered to ADHD patients with end stage renal disease or lesser degrees of renal insufficiency using the usual dosing regimen. Hypertension in patients with end stage renal disease may be exacerbated by atomoxetine. Monitoring Specialist: Baseline, 6-monthly - Blood pressure, pulse, weight and height; also any adverse effect on cognition or sexual maturation during long term therapy. GP annual - Blood pressure, heart rate, weight and height (A guide to expected diastolic and systolic blood pressures for children and adolescents can be found in the Journal of Hypertension 2009, 27: , or Arch DisChild 2007; 92: Date Written: April 2016 Approved by: ACE, Dudley CCG May 2016 Review date: April of 11

8 Contraindications and cautions for use Hypersensitivity to atomoxetine or to any of the excipients. Atomoxetine should not be used in patients with narrow angle glaucoma. Atomoxetine should not be used within a minimum of 2 weeks after discontinuing therapy with a MAOI. Treatment with a MAOI should not be initiated within 2 weeks after discontinuing atomoxetine. Sudden death has been reported in children and adolescents with structural cardiac abnormalities who were taking atomoxetine at usual doses. Although some serious structural cardiac abnormalities alone carry an increased risk of sudden death, atomoxetine should only be used with caution in children or adolescents with known serious structural cardiac abnormalities and in consultation with a cardiac specialist. Atomoxetine is cautioned in patients with hypertension, tachycardia, or cardiovascular or cerebrovascular disease. Orthostatic hypotension has been reported. Many patients taking atomoxetine experience a modest increase in pulse (mean <10 bpm) and/or increase in blood pressure (mean <5 mmhg). After an initial decrease in weight, patients treated with atomoxetine have shown a mean increase in weight during long-term treatment. Following rare reports of hepatic disorders, the MHRA has advised that patients and carers should be advised of the risk and be told how to recognise symptoms; prompt medical attention should be sought in case of abdominal pain, unexplained nausea, malaise, darkening of the urine or jaundice. Atomoxetine should be discontinued in patients with jaundice or laboratory evidence of liver injury, and should not be restarted. Patients should be carefully monitored for the appearance or worsening of suicide-related behaviour, hostility, and emotional lability. The MHRA has advised that patients and their carers should be informed about this risk and told to report clinical worsening, suicidal thoughts or behaviour, irritability, agitation, or depression. At normal doses, atomoxetine can be associated with treatment emergent psychotic or manic symptoms (e.g. hallucinations, delusional thinking, mania, or agitation) in children and adolescents without a history of psychotic illness or mania, or may exacerbate pre-existing symptoms. If such symptoms occur, consideration should be given to discontinuation of treatment. Use of atomoxetine is cautioned in patients with seizures; discontinuation should be considered in any patient developing a seizure or if there is an increase in seizure frequency where no other cause is identified. Atomoxetine should be used with caution in patients with congenital or acquired long QT or a family history of QT prolongation. Side effects These include anorexia, dry mouth, nausea, vomiting, abdominal pain, constipation, dyspepsia, flatulence, palpitation, tachycardia, increased blood pressure, postural hypotension, hot flushes, sleep disturbances, dizziness, headache, fatigue, lethargy, depression, anxiety, irritability, tremor, rigors, urinary retention, enuresis, prostatitis, sexual dysfunction, menstrual disturbances, priapism, mydriasis, conjunctivitis, dermatitis, pruritus, rash, sweating, weight changes. Drug interactions Atomoxetine should not be used in combination with monoamine oxidase inhibitors (MAOIs) or within 14 days. Atomoxetine should be administered with caution to patients being treated with high dose nebulised or systemically administered salbutamol (or other beta2 agonists). There is the potential for an increased risk of QT interval prolongation when atomoxetine is administered with other QT prolonging drugs (such as neuroleptics, class IA and III anti-arrhythmics, moxifloxacin, erythromycin, methadone, mefloquine, tricyclic antidepressants, lithium, cisapride), drugs that cause electrolyte imbalance (such as thiazide diuretics), and drugs that inhibit CYP2D6 (e.g. fluoxetine, paroxetine, quinidine, terbinafine). Dose adjustment and slower titration of atomoxetine may be necessary in patients who are taking CYP2D6 inhibitor drugs. If a CYP2D6 inhibitor is prescribed or discontinued after titration to the atomoxetine dose has occurred, the clinical response and tolerability should be re-evaluated to determine if dose adjustment is needed. Caution is advised with concomitant use of medicinal drugs that are known to lower the seizure threshold and pressor agents. Drugs that affect noradrenaline e.g. imipramine, venlafaxine, mirtazapine, pseudoephedrine, phenylephrine should be used cautiously when co-administered with atomoxetine because of the potential for additive or synergistic pharmacological effects. Cost At current prices, one year s treatment at 80mg daily dose will cost References MTRAC Guidance VS06/13 SPC Strattera 19/12/2013. Drug Tariff December 2013 BNF for Children NICE Technology Appraisal 98. Methylphenidate, atomoxetine and dexamfetamine for attention deficit hyperactivity disorder (ADHD) in children and adolescents Strattera2 (atomoxetine) conclusions of risk: benefit review 16/02/2006 Drug Safety Update Vol. 2 Issue 8 March 2009 MHRA Atomoxetine ESCA Coventry and Warwickshire Area Prescribing Committee Date Written: April 2016 Approved by: ACE, Dudley CCG May 2016 Review date: April of 11

9 GUANFACINE (Intuniv ) ADHD Medication Shared Care Agreement Also refer to information in the latest versions of the Summary of Product Characteristics (available on line at and British National Formulary ( Licensed indications Guanfacine 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. Guanfacine must be used as a part of a comprehensive ADHD treatment programme, typically including psychological, educational and social measures. Dosage and administration Careful dose titration and monitoring is necessary at the start of treatment with guanfacine 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 1mg per week. Dose should be individualised according to the patient's response and tolerability. Depending on the patient's response and tolerability for guanfacine the recommended maintenance dose range is 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 judgment of response and tolerability may occur at any weekly interval after the initial dose. Table 1 Dose Titration Schedule for Children Aged 6-12 years Weight Group Week 1 Week 2 Week 3 Week 4 25 kg and up 1 mg 2 mg 3 mg 4 mg Max Dose= 4 mg Table 2 Dose Titration Schedule for Adolescents (Aged Years) Weight Group a Week 1 Week 2 Week 3 Week 4 Week 5 Week 6 Week kg Max Dose= 4 mg kg Max Dose= 5 mg kg Max Dose= 6 mg 1 mg 2 mg 3 mg 4 mg 1 mg 2 mg 3 mg 4 mg 5 mg 1 mg 2 mg 3 mg 4 mg 5 mg 6 mg 58.5 kg and above 1 mg 2 mg 3 mg 4 mg 5 mg 6 mg 7 mg b Max Dose= 7 mg a Adolescent subjects must weigh at least 34kg. b Adolescents weighing 58.5 and above may be titrated to a 7mg/day dose after the subject has completed a minimum of 1 week of therapy on a 6mg/day dose and the physician has performed a thorough review of the subject's tolerability and efficacy. The physician who elects to use guanfacine for extended periods (over 12 months) should re-evaluate the usefulness of guanfacine every 3 months for the first year and then at least yearly based on clinical judgment, and consider trial periods off medication to assess the patient's functioning without pharmacotherapy, preferably during times of school holidays. Monitoring 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 judgment be exercised during this period. 6 monthly monitoring should follow thereafter, with more frequent monitoring following any dose adjustments Contraindications Hypersensitivity to guanfacine or to any of the excipients. Intuniv contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product. Special warnings and precautions for use Hypotension, bradycardia and syncope Intuniv can cause syncope, hypotension and bradycardia. Syncope may involve risks of falls or accidents, which could result in serious harm. Date Written: April 2016 Approved by: ACE, Dudley CCG May 2016 Review date: April of 11

10 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 Intuniv 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 with Intuniv 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. Patients should be advised to drink plenty of fluid. QTc interval In phase II-III randomised double-blind monotherapy studies respective increases in QT c 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 Intuniv patients. The clinical relevance of this finding is uncertain. Guanfacine should be prescribed with caution in patients with a known history of QT prolongation, risk factors for torsade de pointes (e.g. heart block, bradycardia, hypokalemia) or patients who are taking medicinal products known to prolong the QT interval. These patients should receive further cardiac evaluation based on clinical judgement. Sedation and somnolence Intuniv may cause somnolence and sedation predominantly at the start of treatment and could typically last for 2-3 weeks and longer in some cases. It is therefore recommended that patients will be closely monitored weekly during dose titration and stabilisation, and every 3 months during the first year, taking into consideration clinical judgement. Before Intuniv is used with any other centrally active depressants (such as alcohol, sedatives, phenothiazines, barbiturates, or benzodiazepines) the potential for additive sedative effects should be considered. Patients should not drink alcohol whilst taking Intuniv. Patients are advised against operating heavy equipment, driving or cycling until they know how they respond to treatment with Intuniv. Suicidal ideation Patients with emergent suicidal ideation or behaviour during treatment for ADHD should be evaluated immediately by their physician. Treatment of an underlying psychiatric condition may be necessary and consideration should be given to a possible change in the ADHD treatment programme. Effects on height, weight and Body Mass index (BMI) Children and adolescents treated with Intuniv may show an increase in their BMI. Therefore, monitoring of height, weight and BMI should be done prior to initiation of therapy and then 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. Side effects In the data set from controlled, doubled blinded and open-label clinical studies with Intuniv the most frequently reported adverse reactions (very common) include somnolence (40.6%), headache (27.4%), fatigue (18.1%), abdominal pain upper (12.0%), and sedation (10.2%). Serious adverse reactions commonly reported include hypotension (3.2%), weight increase (2.9%), bradycardia (1.5%) and syncope (uncommon) (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. Drug interactions When Intuniv is used concomitantly with CYP3A4/5 inhibitors and inducers, plasma concentrations of guanfacine may be elevated or lowered, potentially affecting the efficacy and safety of Intuniv. Intuniv can increase plasma concentrations of concomitantly administered medicinal products that are metabolised via CYP3A4/5. The pharmacodynamic effect of Intuniv can have an additive effect when taken with other products known to cause sedation, hypotension or QT prolongation. All drug-drug interaction studies have been performed in adults; however, the outcome is expected to be similar in the indicated paediatric age range. QT Prolonging medicinal products Intuniv causes a decrease in heart rate. Given the effect of Intuniv on heart rate, the concomitant use of Intuniv with QT prolonging medicinal products is generally not recommended. CYP3A4 and CYP3A5 inhibitors Caution should be used when Intuniv is administered to patients taking ketoconazole and other moderate and strong CYP3A4/5 inhibitors; a decrease in the dose of Intuniv within the recommended dose range is proposed. Co-administration of Intuniv 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 (C max) 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 Intuniv concomitantly with a CYP3A4 inducer, an increase in the dose of Intuniv within the recommended dose range is proposed. There was a significant decrease in the rate and extent of guanfacine exposure when co-administered with rifampin, a CYP3A4 inducer. The peak plasma concentrations (C max) and exposure (AUC) of guanfacine decreased by 54% and 70% respectively. Other CYP3A4 inducers may have a comparable effect, see table 3 for a list of examples of CYP3A4/5 inducers, this list is not definitive. Date Written: April 2016 Approved by: ACE, Dudley CCG May 2016 Review date: April of 11

11 Table 3 Moderate CYP3A4/5 inhibitors Strong CYP3A4/5 inhibitors CYP3A4 inducers Aprepitant Boceprevir Bosentan Atazanavir Chloramphenicol Carbamazepine Ciprofloxacin Clarithromycin Efavirenz Crizotinib Indinavir Etravirine Diltiazem Itraconazole Modafinil Erythromycin Ketoconazole Nevirapine Fluconazole Posaconazole Oxcarbazepine Fosamprenavir Ritonavir Phenobarbital Imatinib Saquinavir Phenytoin Verapamil Suboxone Primidone Grapefruit juice Telaprevir Rifabutin Telithromycin Rifampicin St. John's Wort Valproic acid Co-administration of Intuniv and valproic acid can result in increased concentrations of valproic acid. The mechanism of this interaction is unknown, although both guanfacine and valproic acid are metabolised by glucuronidation, possibly resulting in competitive inhibition. When Intuniv is co-administered with valproic acid, patients should be monitored for potential additive central nervous system (CNS) effects and consideration should be given to the monitoring of serum valproic acid concentrations. Adjustments in the dose of valproic acid and Intuniv may be indicated when co-administered. Antihypertensive medicinal products Caution should be used when Intuniv is administered concomitantly with antihypertensive medicinal products, due to the potential for additive pharmacodynamic effects such as hypotension and syncope. CNS depressant medicinal products Caution should be used when Intuniv is administered concomitantly with CNS depressant medicinal products (e.g. alcohol, sedatives, hypnotics, benzodiazepines, barbiturates, and antipsychotics) due to the potential for additive pharmacodynamic effects such as sedation and somnolence. Oral Methylphenidate In a drug interaction study, neither Intuniv nor Osmotic Release Oral System (OROS)-methylphenidate HCl extended-release were found to affect the pharmacokinetics of the other medicinal products when taken in combination. Lisdexamfetamine dimesylate In a drug interaction study, administration of Intuniv in combination with lisdexamfetamine dimesylate induced a 19% increase in guanfacine maximum plasma concentrations, whereas exposure (AUC) was increased by 7%. These small changes are not expected to be clinically meaningful. In this study, no effect on d-amphetamine exposure was observed following combination of Intuniv and lisdexamfetamine dimesylate. Food interactions Intuniv should not be administered with high fat meals due to increased exposure, as it has been shown that high fat meals have a significant effect on the absorption of guanfacine. Cost At current prices, one year s treatment at 80mg daily dose will cost References SPC Intuniv 04/2016 NICE ESNM70 Attention deficit hyperactivity disorder in children and young people: guanfacine prolonged-release Approved on: May, 2016 Review date: April, 2018 Date Written: April 2016 Approved by: ACE, Dudley CCG May 2016 Review date: April of 11