Background
Methods
Results
Medications
Drug | Date of Authorisation (Renewal Date) | Date of Last Substantive† Revision to SPC Text | Reason for Revision |
---|---|---|---|
Strattera® | May 2004 (May 2009) | 27 September 2011 | Addition of contraindication and changes to wording on cardiovascular effects, allergic events, depression, tics, anxiety and overdose (Sections 4.3, 4.4, 4.8, 4.9 and 5.1) |
3 November 2011 | Change to wording on hepatic function (Sections 4.4 and 4.8) Addition of comparator data trial outcomes (Section 5.1) Addition of cytochrome P450 wording to Pharmacokinetic properties (Section 5.2) | ||
25 November 2011 | Addition of cardiovascular contraindication and change to wording on cardiovascular status (Sections 4.2, 4.3 and 4.4) | ||
Ritalin® | October 1997 (April 2004) | 12 May 2011 | Expanded wording in the aggression and hostility warnings/overdose section relating to effects of titration from long acting preparations (Sections 4.4, 4.9 and 10) |
Concerta® 18-36 mg | February 2002 (June 2007) | 17 June 2011 | Change to prescribing information relating to continuation use in adulthood (Sections 4.2, 4.4, 4.8, 5.1 and 10) |
Concerta® 27 mg | March 2007 | 17 June 2011 | |
Equasym XL® | February 2005 | 10 October 2011 | Bruxism added as a common adverse drug reaction under Undesirable Effects (Section 4.8) |
Medikinet® | February 2007 (November 2008) | 3 February 2010 | Numerous sections updated as per article 31 Referral |
Medikinet XL® 10-40 mg | February 2007 (November 2008) | 3 February 2010 | Update as per article 31 Referral |
Medikinet XL® 5 mg | January 2011 | 24 August 2011 | Addition to eMC of new SPC for new product |
Dexamfetamine** | October 1992 | Not available | Not applicable |
Category | Non-stimulant | Stimulants | |||||
---|---|---|---|---|---|---|---|
Brand Name | Strattera® | Ritalin® | Concerta® (18-36/27 mg) | Equasym XL® | Medikinet® | Medikinet XL® (5/10-40 mg) | Not applicable |
Generic Name | Atomoxetine | MPH | MPH | MPH | MPH | MPH | Dexamfetamine |
General
| |||||||
Hypersensitivity | X | X | X | X | X | X | X |
(Narrow angle) Glaucoma | (X) | X | X | X | X | X | X |
With MAIOs/Within 14 days | X | X | X | X | X | X | X |
Pregnancy/lactation | X | ||||||
Pronounced anacidity of the stomach | X | ||||||
With H2-receptor blockers/antacid therapy | X | ||||||
Sucrose/lactose intolerances and related disorders | X | ||||||
Porphyria | X | ||||||
Pheochromocytoma | X | X | X | X | X | X | |
Psychiatric
| |||||||
Hyperexcitability | X | ||||||
Severe depression | X | X | X | X | X | ||
Anorexia nervosa | X | X | X | X | X | ||
Psychopatho-logical personality structure | X | X | X | X | X | ||
Suicidal tendency | X | X | X | X | X | ||
Psychotic symptoms | X | X | X | X | X | ||
Schizophrenia | X | X | X | X | X | ||
Mania/bipolar disorder | X | X | X | X | X | ||
Severe mood disorders | X | X | X | X | X | ||
Drug or alcohol abuse | X | ||||||
Endocrinological
| |||||||
Hyperthyroidism/thyrotoxicosis | X | X | X | X | X | X | |
Cardiac
| |||||||
Patients with severe cardiovascular § or cerebrovascular † disorders whose condition would be expected to deteriorate if they experienced increases in blood pressure or heart rate that could be clinically important | X | ||||||
Pre existing cardiovascular disorders:§* | |||||||
Angina | X | X | X | X | X | ||
Life threatening arrhythmias and channelopathies | X | X | X | X | X | ||
(Moderate or) Severe hypertension | X | X | X | X | X | (X) | |
Heart failure | X | X | X | X | X | ||
Myocardial infarction | X | X | X | X | X | ||
Arterial occlusive disease | X | X | X | X | X | ||
Haemodynamically significant congenital heart disease | X | X | X | X | X | ||
Cardiomyopathies | X | X | X | X | X | ||
Known risk factors for cerebrovascular disorder | X | ||||||
Structural cardiac abnormality | X | ||||||
Symptomatic cardiovascular disease | X | ||||||
Advanced arteriosclerosis | X | ||||||
Pre-existing (severe) cerebrovascular disorders | (X)† | X | X | X | X | X | |
Neurological
| |||||||
Tourette's syndrome/similar dystonias | X |
UK national guidelines
NICE Guideline Recommendation | Conflict (emphasis in bold reflects SPC) |
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Warn of suicidal problems and self harming behaviour with atomoxetine | Suicidal problems are a contraindication to the use of methylphenidate (omitted) Self-harm is not listed anywhere on the atomoxetine SPC Similar warnings are listed on SPCs for both atomoxetine and methylphenidate |
Use MPH in adults | Most forms of methylphenidate are unlicensed. Atomoxetine and all strengths of Concerta are licensed in adults who were prescribed atomoxetine/Concerta in childhood and who continue to demonstrate a favourable response |
Use methylphenidate or atomoxetine when stimulant misuse or risk of stimulant diversion are present | There are specific warnings on methylphenidate SPCs about risk of misuse, diversion and related issues. In high risk cases, the advice on methylphenidate SPCs is to use atomoxetine Atomoxetine has no warnings or precautions relating to drug misuse |
In people with ADHD, heart rate and blood pressure should be monitored and recorded on a centile chart before and after each dose change and routinely every 3 months | Atomoxetine and methylphenidate-Blood pressure and pulse should be recorded on a centile chart at each adjustment of dose and then at least every 6 months Dexamfetamine-Blood pressure should be monitored at appropriate intervals in all patients taking dexamfetamine, especially those with hypertension |
In people taking methylphenidate, atomoxetine, or dexamfetamine: | Growth and development should be monitored during treatment with atomoxetine |
• height should be measured every 6 months in children and young people | Methylphenidate-Height, weight and appetite should be recorded at least 6 monthly with maintenance of a growth chart |
• weight should be measured 3 and 6 months after drug treatment has started and every 6 months thereafter in children, young people and adults | Dexamfetamine-Height and weight should be carefully monitored in children as growth retardation may occur |
In young people and adults, sexual dysfunction (i.e., erectile and ejaculatory dysfunction) and dysmenorrhoea should be monitored as potential side-effects of atomoxetine | This warning is not contained within the SPC for atomoxetine. Clinical trial data in adults shows sexual dysfunction as an undesirable effect. Post-marketing surveillance data in children, adolescents and adults list priapism and male genital pain as an undesirable effect |
Use methylphenidate or atomoxetine with tics/Tourette's | In a controlled study of paediatric patients with ADHD and co morbid chronic motor tics or Tourette's Disorder, atomoxetine-treated patients did not experience worsening of tics compared to placebo-treated patients. There have been very rare post-marketing reports of tics in patients taking atomoxetine). Patients who are being treated for ADHD with atomoxetine should be monitored for the appearance or worsening of tics |
Methylphenidate is associated with the onset or exacerbation of motor and verbal tics. Worsening of Tourette's syndrome has also been reported. Family history should be assessed and clinical evaluation for tics or Tourette's syndrome in children should precede use of methylphenidate. Patients should be regularly monitored for the emergence or worsening of tics during treatment with methylphenidate. Monitoring should be at every adjustment of dose and then at least every 6 months or every visit | |
Use methylphenidate or atomoxetine with anxiety disorder | In two controlled studies (one in paediatric patients and one in adult patients) of patients with ADHD and co-morbid anxiety disorders, atomoxetine-treated patients did not experience worsening of anxiety compared to placebo-treated patients. |
There have been rare post-marketing reports of anxiety in patients taking atomoxetine. Patients who are being treated for ADHD with atomoxetine should be monitored for the appearance or worsening of anxiety symptoms. | |
Methylphenidate is associated with the worsening of pre-existing anxiety, agitation or tension. Clinical evaluation for anxiety, agitation or tension should precede use of methylphenidate and patients should be regularly monitored for the emergence or worsening of these symptoms during treatment, at every adjustment of dose and then at least every 6 month or every visit | |
In particular, those treated with atomoxetine should be closely observed for agitation, irritability, suicidal thinking and self-harming behaviour, and unusual changes in behaviour, particularly during the initial months of treatment, or after a change in dose | Atomoxetine SPC-Treatment emergent agitation in children and adolescents without a prior history of psychotic illness or mania can be caused by atomoxetine at usual doses. Irritability is a common adverse event but has no monitoring requirement specifically |
Methylphenidate SPCs-Psychiatric disorders to monitor for... include (but are not limited to)... agitation, irritability. Methylphenidate is associated with the worsening of... agitation or tension. Clinical evaluation for... agitation or tension should precede use of methylphenidate and patients should be regularly monitored for the emergence or worsening of these symptoms during treatment, at every adjustment of dose and then at least every 6 month or every visit. Irritability is a common adverse effect of methylphenidate and patients receiving long-term therapy should be monitored for this amongst other psychiatric adverse effects. | |
Suicidal ideation is an uncommon side effect on both methylphenidate and atomoxetine SPCs. Self harm is not mentioned on either SPC |
SIGN Guideline Recommendation | Conflict (emphasis in bold reflects SPC) |
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Use of modified release formulations or atomoxetine should be considered where there is likelihood of diversion | Particular warnings on methylphenidate SPC about risk of misuse, diversion and related issues. In high risk cases, advised on methylphenidate SPC to use atomoxetine. Atomoxetine has no such warnings or precautions |
Where atomoxetine is prescribed, clinicians should review at least 6 monthly, including assessment of ongoing efficacy and adverse effects and measurement of growth, pulse and blood pressure (with correct cuff size) using appropriate centile charts | Atomoxetine-Where patients are continuing treatment with atomoxetine beyond 1 year, re-evaluation of the need for therapy by a specialist in the treatment of ADHD is recommended. Growth and development should be monitored during treatment with atomoxetine. Blood pressure and pulse should be recorded on a centile chart at each adjustment of dose and then at least every 6 months Methylphenidate- The physician who elects to use methylphenidate for extended periods (over 12 months) in children and adolescents with ADHD should periodically re-evaluate the long-term usefulness of the drug for the individual patient with trial periods off medication to assess the patient's functioning without pharmacotherapy. It is recommended that methylphenidate is de-challenged at least once yearly to assess the child's condition (preferable during times of school holidays). Improvement may be sustained when the drug is either temporarily or permanently discontinued. Blood pressure and pulse should be recorded on a centile chart at each adjustment of dose and then at least every 6 months. Height, weight and appetite should be recorded at least 6 monthly with maintenance of a growth chart |
Dexamfetamine- Blood pressure should be monitored at appropriate intervals in all patients taking dexamfetamine, especially those with hypertension. Height and weight should be carefully monitored in children as growth retardation may occur | |
(Atomoxetine)Additional monitoring is advised for those at risk of increased cardiovascular, hepatobiliary risk, seizure risk and potential suicidal ideation | Atomoxetine- Blood pressure and pulse should be recorded on a centile chart at each adjustment of dose and then at least every 6 months. No specified requirement for hepatic or seizure monitoring. |
Methylphenidate SPC-Patients on long-term therapy (i.e. over 12 months) must have careful ongoing monitoring according to the guidance in Sections 4.2 and 4.4 for cardiovascular status. Cardiovascular status should be carefully monitored |