Arilan Adverse Reactions

Summary of the safety profile: The most commonly reported adverse reactions in placebo-controlled trials are akathisia and nausea each occurring in more than 3% of patients treated with oral aripiprazole.
List of adverse reactions: The incidences of the adverse drug reactions (ADRs) associated with aripiprazole therapy are listed as follows. The list is based on adverse events reported during clinical trials and/or post-marketing use.
All ADRs are listed by system organ class and frequency: 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).
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
The frequency of adverse reactions reported during post-marketing use cannot be determined as they are derived from spontaneous reports. Consequently, the frequency of these adverse events is qualified as "not known".
Blood and lymphatic system disorders: Not known: Leukopenia, neutropenia, thrombocytopenia.
Immune system disorders: Not known: Allergic reaction (e.g. anaphylactic reaction, angioedema including swollen tongue, tongue oedema, face oedema, pruritus, or urticaria).
Endocrine disorders: Uncommon: Hyperprolactinaemia.
Not known: Diabetic hyperosmolar coma, diabetic ketoacidosis.
Metabolism and nutrition disorder: Common: Diabetes mellitus.
Uncommon: Hyperglycaemia.
Not known: Hyponatraemia, anorexia, weight decreased, weight gain.
Psychiatric disorders: Common: Insomnia, anxiety, restlessness.
Uncommon: Depression, hypersexuality.
Not known: Suicide attempt, suicidal ideation and completed suicide (see Precautions), pathological gambling, impulse-control disorders, binge eating, compulsive shopping, poriomania, aggression, agitation, nervousness.
Nervous system disorders: Common: Akathisia, extrapyramidal disorder, tremor, headache, sedation, somnolence, dizziness.
Uncommon: Tardive dyskinesia, dystonia.
Not known: Neuroleptic malignant syndrome (NMS), grand mal convulsion, serotonin syndrome, speech disorder.
Eye disorders: Common: Vision blurred.
Uncommon: Diplopia.
Cardiac disorders: Uncommon: Tachycardia.
Not known: Sudden unexplained death, Torsades de pointes, QT prolongation, ventricular arrhythmias, cardiac arrest, bradycardia.
Vascular disorders: Uncommon: Orthostatic hypotension.
Not known: Venous thromboembolism (including pulmonary embolism and deep vein thrombosis), hypertension, syncope.
Respiratory, thoracic and mediastinal disorders: Uncommon: Hiccups.
Not known: Aspiration pneumonia, laryngospasm, oropharyngeal spasm.
Gastrointestinal disorders: Common: Constipation, dyspepsia, nausea, salivary hypersecretion, vomiting.
Not known: Pancreatitis, dysphagia, diarrhoea, abdominal discomfort, stomach discomfort.
Hepatobiliary disorders: Not known: Hepatic failure, hepatitis, jaundice, increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), increased gamma glutamyl transferase (GGT), increased alkaline phosphatase.
Skin and subcutaneous tissue disorders: Not known: Rash, photosensitivity reaction, alopecia, hyperhidrosis.
Musculoskeletal and connective tissue disorders: Not known: Rhabdomyolysis, myalgia, stiffness.
Renal and urinary disorders: Not known: Urinary incontinence, urinary retention.
Pregnancy puerperium and perinatal conditions: Not known: Drug withdrawal syndrome neonatal (see Use in Pregnancy & Lactation).
Reproductive system and breast disorders: Not known: Priapism.
General disorders and administration site conditions: Common: Fatigue.
Not known: Temperature regulation disorder (e.g. hypothermia, pyrexia), chest pain, peripheral oedema.
Investigations: Not known: Blood glucose increased, glycosylated haemoglobin increased, blood glucose fluctuation, increased creatinine phosphokinase.
Description of selected adverse reactions: Adults: Extrapyramidal symptoms (EPS): Schizophrenia: In a long term 52-week controlled trial, aripiprazole-treated patients had an overall-lower incidence (25.8%) of EPS including parkinsonism, akathisia, dystonia and dyskinesia compared with those treated with haloperidol (57.3%). In a long term 26-week placebo-controlled trial, the incidence of EPS was 19% for aripiprazole-treated patients and 13.1 % for placebo-related patients. In another long-term 26-week controlled trial, the incidence of EPS was 14.8% for aripiprazole-treated patients and 15.1% for olanzapine-treated patients.
Manic episodes in Bipolar I Disorder: In a 12-week controlled trial, the incidence of EPS was 23.5% for aripiprazole-treated patients and 53.3% for haloperidol-treated patients. In another 12-week trial, the incidence of EPS was 26.6% for patients treated with aripiprazole and 17.6% for those treated with lithium. In the long term 26-week maintenance phase of a placebo-controlled trial, the incidence of EPS was 18.2% for aripiprazole-treated patients and 15.7% for placebo-treated patients.
Akathisia: In placebo-controlled trials, the incidence of akathisia, in bipolar patients was 12.1% with aripiprazole 3.2% with placebo. In schizophrenia patients the incidence of akathisia was 6.2% with aripiprazole and 3.0% with placebo.
Dystonia: Class Effect: Symptoms of dystonia, prolonged abnormal contractions of muscle groups, may occur in susceptible individuals during the first few days of treatment. Dystonic symptoms include: spasm of the neck muscles, sometimes progressing to tightness of the throat, swallowing difficulty, difficulty breathing, and/or protrusion of the tongue. While these symptoms can occur at low doses, they occur more frequently and with greater severity with high potency and at higher doses of first generation antipsychotic medicinal products. An elevated risk of acute dystonia is observed in males and younger age groups.
Prolactin: In clinical trials for the approved indications and post-marketing, both increase and decrease in serum prolactin as compared to baseline was observed with aripiprazole (see Pharmacology: Pharmacodynamics under Actions).
Laboratory parameters: Comparisons between aripiprazole and placebo in the proportions of patients experiencing potentially clinically significant changes in routine laboratory and lipid parameters (see Pharmacology: Pharmacodynamics under Actions) revealed no medically important differences.
Elevations of CPK (creatine phosphokinase), generally transient and asymptomatic, were observed in 3.5% of aripiprazole treated patients as compared to 2.0% of patients who received placebo.
Paediatric population: Schizophrenia in adolescents aged 15 years and older: In a short-term placebo-controlled clinical trial involving 302 adolescents (13-17 years) with schizophrenia, the frequency and cancel type of adverse reactions were similar to those in adults except for the following reactions that were reported more frequently in adolescents receiving aripiprazole than in adults receiving aripiprazole (and more frequently than placebo): somnolence/sedation and extrapyramidal disorder were reported very commonly (≥1/10), and dry mouth, increased appetite, and orthostatic hypotension were reported commonly (≥1/100, to <1/10). The safety profile in a 26-week open-label extension trial was similar to that observed in the short-term placebo-controlled trial.
The safety profile of a long-term, double-blind placebo-controlled trial was also similar except for the following reactions that were reported more frequently than paediatric patients taking placebo: weight decreased, blood insulin increased, arrhythmia and leukopenia reported commonly (≥1/100, to <1/10).
In the pooled adolescent schizophrenia population (13-17 years) with exposure up to 2 years, incidence of low serum prolactin levels in females (<3 ng/mL) and males (<2 ng/mL) was 29.5% and 48.3%, respectively. In the adolescent (13-17 years) schizophrenia population with aripiprazole exposure of 5 to 30 mg up to 72 months, incidence of low serum prolactin levels in females (<3 ng/mL) and males (<2 ng/mL) was 25.6% and 45.0%, respectively.
In two long term trials with adolescent (13-17 years) schizophrenia and bipolar patients treated with aripiprazole incidence of low serum prolactin levels in females (<3 ng/mL) and males (<2 ng/mL) was 37.0% and 59.4%, respectively.
Manic episodes in Bipolar I Disorder in adolescents aged 13 years and older: The frequency and type of adverse reactions in adolescents with Bipolar I Disorder were similar to those in adults except for the following reactions: very commonly (≥1/10) somnolence (23.0%), extrapyramidal disorder (18.4%), akathisia (16.0%), and fatigue (11.8%); and commonly (≥1/100, <1/10) abdominal pain upper, heart rate increased, weight increased, increased appetite muscle twitching and dyskinesia.
The following adverse reactions had a possible dose response relationship; extrapyramidal disorder (incidences were 10 mg, 9.1%, 30 mg, 28.8%, placebo, 1.7%), and akathisia (incidences were 10 mg, 12.1%, 30 mg, 20.3%, placebo, 1.7%).
Mean changes in body weight in adolescents with Bipolar I Disorder at 12 and 30 weeks for aripiprazole were 2.4 kg and 5.8 kg, and for placebo 0.2 kg and 2.3 kg, respectively.
In the paediatric population somnolence and fatigue were observed more frequently in patients with bipolar disorder compared to patients with schizophrenia.
In the paediatric bipolar population (10-17 years) with exposure up to 30 weeks, incidence of low serum prolactin levels in females (<3 ng/mL) and males (<2 ng/mL) was 28.0% and 53.3% respectively.
Pathological gambling and other impulse control disorders: Pathological gambling, hypersexuality, compulsive shopping and binge or compulsive eating can occur in patients treated with aripiprazole (see Precautions).