Strattera® (atomoxetine): Undesirable effects

Paediatric population:

Summary of the safety profile

In paediatric placebo-controlled trials, headache, abdominal pain¹ and decreased appetite are the adverse events most commonly associated with atomoxetine, and are reported by about 19%, 18% and 16% of patients, respectively, but seldom lead to drug discontinuation (discontinuation rates are 0.1% for headache, 0.2 % for abdominal pain and 0.0% for decreased appetite). Abdominal pain and decreased appetite are usually transient.

Associated with decreased appetite, some patients experienced growth retardation early in therapy in terms of both weight and height gain. On average, after an initial decrease in weight and height gain, patients treated with atomoxetine recovered to mean weight and height as predicted by group baseline data over the long-term treatment.

Nausea, vomiting and somnolence² can occur in about 10% to 11% of patients, particularly during the first month of therapy. However, these episodes were usually mild to moderate in severity and transient, and did not result in a significant number of discontinuations from therapy (discontinuation rates ≤ 0.5%).

In both paediatric and adult placebo-controlled trials, patients taking atomoxetine experienced increases in heart rate, systolic and diastolic blood pressure.

Because of its effect on noradrenergic tone, orthostatic hypotension (0.2%) and syncope (0.8%) have been reported in patients taking atomoxetine. Atomoxetine should be used with caution in any condition that may predispose patients to hypotension.

The following table of undesirable effects is based on adverse event reporting and laboratory investigations from clinical trials and post-marketing spontaneous reports in children and adolescents:

Tabulated list of adverse reactions

Frequency estimate: 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).

System Organ Class	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
Metabolism and nutrition disorders	Appetite decreased	Anorexia (loss of appetite)
Psychiatric disorders		Irritability, mood swings, insomnia3, agitation , anxiety, depression and depressed mood, tics	Suicide-related events, aggression, hostility, emotional lability Psychosis (including hallucinations)
Nervous system disorders	Headache, somnolence2	Dizziness	Syncope, tremor, migraine, paraesthesia, hypoaesthesia, Seizure
Eye disorders		Mydriasis	Vision blurred
Cardiac disorders			Palpitations, sinus tachycardia. QT interval prolongation
Vascular disorders				Raynaud’s phenomenon
Respiratory, thoracic and mediastinal disorders			Dyspnoea
Gastro-intestinal disorders	Abdominal pain1, vomiting, nausea	Constipation, dyspepsia
Hepatobiliary disorders			Blood bilirubin increased	Abnormal/ increased liver function tests, jaundice, hepatitis, liver injury, acute hepatic failure
Skin and subcutaneous tissue disorders		Dermatitis, pruritis, rash	Hyperhydrosis, allergic reactions
Renal and urinary disorders				Urinary hesitation, urinary retention
Reproductive system and breast disorders				Priapism, male genital pain
General disorders and administration site conditions		Fatigue, lethargy, chest pain	Asthenia
Investigations	Blood pressure increased4, heart rate increased4	Weight decreased

¹Also includes abdominal pain upper, stomach discomfort, abdominal discomfort and epigastric discomfort.

² Also includes sedation

³ Includes initial, middle and terminal (early morning wakening) insomnia

⁴ Heart rate and blood pressure findings are based on measured vital signs.

CYP2D6 poor metabolisers (PM):

The following adverse events occurred in at least 2% of CYP2D6 poor metaboliser (PM) patients and were statistically significantly more frequent in PM patients compared with CYP2D6 extensive metaboliser (EM) patients: appetite decreased (24.1% of PMs, 17.0% of EMs); insomnia combined (including insomnia, middle insomnia and initial insomnia, 14.9% of PMs, 9.7% of EMs); depression combined (including depression, major depression, depressive symptom, depressed mood and dysphoria, 6.5% of PMs and 4.1% of EMs), weight decreased (7.3% of PMs, 4.4% of EMs), constipation 6.8% of PMs, 4.3% of EMs); tremor (4.5% of PMs, 0.9% of EMs); sedation (3.9% of PMs, 2.1% of EMs); excoriation (3.9% of PMs, 1.7% of EMs); enuresis (3.0% of PMs, 1.2% of EMs); conjunctivitis (2.5% of PMs, 1.2% of EMs); syncope (2.5% of PMs, 0.7% of EMs); early morning awakening (2.3% of PMs, 0.8% of EMs); mydriasis (2.0% of PMs, 0.6% of EMs). The following event did not meet the above criteria but is noteworthy: generalised anxiety disorder (0.8% of PMs and 0.1% of EMs). In addition, in trials lasting up to 10 weeks, weight loss was more pronounced in PM patients (mean of 0.6 kg in EM and 1.1kg in PM).

Adults:

Summary of the safety profile:

In adult ADHD clinical trials, the following system organ classes had the highest frequency of adverse events during treatment with atomoxetine: gastrointestinal, nervous system and psychiatric disorders. The most common adverse events (≥5%) reported were appetite decreased (14.9%), insomnia (11.3%), headache (16.3%), dry mouth (18.4%) and nausea (26.7%). The majority of these events were mild or moderate in severity and the events most frequently reported as severe were nausea, insomnia, fatigue and headache. A complaint of urinary retention or urinary hesitancy in adults should be considered potentially related to atomoxetine.

The following table of undesirable effects is based on adverse event reporting and laboratory investigations from clinical trials and post-marketing spontaneous reports in adults.

Tabulated list of adverse reactions

Frequency estimate: 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).

System Organ Class	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
Metabolism and nutrition disorders	Appetite decreased
Psychiatric disorders	Insomnia2	Agitation, libido decreased, sleep disorder, depression and depressed mood, anxiety	Suicide-related events, aggression, hostility and emotional lability, restlessness, tics	Psychosis (including hallucinations)
Nervous system disorders	Headache	Dizziness, dysgeusia, paraesthesia, somnolence (including sedation), tremor	Syncope, migraine, Hypoaesthesia	Seizure
Eye disorders			Vision blurred
Cardiac disorders		Palpitations, tachycardia	QT interval prolongation
Vascular disorders		Flushing, hot flush	Peripheral coldness	Raynaud’s phenomenon
Respiratory, thoracic and mediastinal disorders			Dyspnoea
Gastrointestinal disorders	Dry mouth, nausea	Abdominal pain1, constipation, dyspepsia, flatulence, vomiting
Hepato-biliary disorders				Abnormal/increas ed liver function tests, jaundice, hepatitis, liver injury, acute hepatic failure, blood bilirubin increased
Skin and subcutaneous tissue disorders		Dermatitis, hyperhydrosis, rash	Allergic reactions4, pruritis, urticaria
Musculoskeletal and connective tissue disorders			Muscle spasms
Renal and urinary disorders		Dysuria, pollakuria, urinary hesitation, urinary retention	Micturation urgency
Reproductive system and breast disorders		Dysmenorrhoea, ejaculation disorder, erectile dysfunction, prostatitis, male genital pain	Ejaculation failure, menstruation irregular, orgasm abnormal	Priapism
General disorders and administration site conditions		Asthenia, fatigue, lethargy, chills, feeling jittery, irritability, thirst	Feeling cold, chest pain
Investigations	Blood pressure increased3, heart rate increased3	Weight decreased

¹Also includes abdominal pain upper, stomach discomfort, abdominal discomfort and epigastric discomfort.

² Also includes initial insomnia, middle insomnia and terminal (early morning wakening) insomnia.

³ Heart rate and blood pressure findings are based on measured vital signs.

⁴ Includes anaphylactic reactions and angioneurotic oedema.

CYP2D6 poor metabolisers (PM)

The following adverse events occurred in at least 2% of CYP2D6 poor metaboliser (PM) patients and were statistically significantly more frequent in PM patients compared with CYP2D6 extensive metaboliser (EM) patients: vision blurred (3.9% of PMs, 1.3% of EMs), dry mouth (34.5% of PMs, 17.4% of EMs), constipation (11.3% of PMs, 6.7% of EMs), feeling jittery (4.9% of PMs, 1.9% of EMs), decreased appetite (23.2% of PMs, 14.7% of EMs), tremor (5.4% of PMs, 1.2% of EMs), insomnia (19.2% of PMs, 11.3% of EMs), sleep disorder (6.9% of PMs, 3.4% of EMs), middle insomnia (5.4% of PMs, 2.7% of EMs), terminal insomnia (3 % of PMs, 0.9% of EMs), urinary retention (5.9% of PMs, 1.2% of EMs), erectile dysfunction (20.9% of PMs, 8.9% of EMs), ejaculation disorder (6.1% of PMs, 2.2% of EMs), hyperhidrosis (14.8% of PMs, 6.8% of EMs), peripheral coldness (3% of PMs, 0.5% of EMs).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via Yellow Card Scheme, Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

REFERENCE

Strattera Summary of Product Characteristics