Applies to aripiprazole: intramuscular powder for injection extended release, intramuscular solution, oral solution, oral tablet, oral tablet disintegrating
Nervous system side effects have frequently included agitation (25%), anxiety (20% to 25%), insomnia (20% to 24%), akathisia (10% to 15%), lightheadedness (11%), somnolence (11% to 12%), dizziness (11%), sedation (7%), extrapyramidal syndrome (6%), tremor (3% to 9%), restlessness (5%), increased salivation (3%), nervousness, confusion, and abnormal gait. Twitch, cogwheel rigidity, impaired concentration, dystonia, vasodilation, paresthesia, impotence, extremity tremor, hypesthesia, vertigo, stupor, bradykinesia, apathy, decreased libido, hypersomnia, dyskinesia, ataxia, cerebrovascular accident, hypokinesia, depersonalization, impaired memory, delirium, dysarthria, tardive dyskinesia, tardive akathisia, amnesia, hyperactivity, increased libido, myoclonus, restless leg, neuropathy, dysphoria, hyperkinesia, cerebral ischemia, increased reflexes, akinesia, decreased consciousness, hyperesthesia, and slowed thinking have been reported infrequently. Blunted affect, euphoria, incoordination, hypotonia, buccoglossal syndrome, decreased reflexes, and intracranial hemorrhage have been reported rarely. Seizures have been reported in less than 0.1% to 0.3% of patients. Grand mal seizures have been reported in postmarketing experience.
Tardive dyskinesia involves involuntary, dyskinetic, repetitive movements and may be more common in the elderly, especially elderly women, receiving antipsychotics, such as aripiprazole. The exact etiology for the development of tardive dyskinesia secondary to treatment with antipsychotics is unknown. However, research has suggested that the chance of developing tardive dyskinesia and the likelihood that it will be irreversible are increased as the total duration of treatment and the total cumulative dose of antipsychotic medication administered to the patient increase. If a patient receiving aripiprazole therapy shows signs and/or symptoms of tardive dyskinesia discontinuation of therapy should be considered; however, this may not be a clinically feasible option for all patients.
The manufacturer reports elderly patients (mean = 84 years old) enrolled in placebo-controlled studies examining the use of aripiprazole for the treatment of dementia-related psychosis showed an increased incidence of cerebrovascular side effects, e.g. stroke and transient ischemia attacks, including fatalities. The incidence of these effects may be dose related.
A dose-response relationship may exist between aripiprazole and somnolence (placebo, 7.7%; 15 mg, 8.7%; 20 mg, 7.5%; 30 mg, 15.3%).
A possible worsening of preexisting agitation with the initiation of aripiprazole therapy has been reported.
Two cases of aripiprazole-induced acute dystonia have been reported. In one case, symptoms resolved following treatment with trihexyphenidyl and in the other case after discontinuation of aripiprazole. 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 drugs. An elevated risk of acute dystonia is observed in males and younger age groups.
At least two cases of aripiprazole-induced seizures have been reported. Conditions that lower the seizure threshold, e.g., Alzheimer's dementia, may be more prevalent in a population over 64 years of age.
Gastrointestinal side effects have included nausea (14% to 16%), dyspepsia (15%), constipation (10% to 13%), vomiting (11% to 12%), dry mouth (5%), abdominal discomfort (3%), and salivary hypersecretion (2%). Increased appetite, dysphagia, gastroenteritis, flatulence, tooth caries, gastritis, gingivitis, gastrointestinal hemorrhage, hemorrhoids, gastroesophageal reflux, periodontal abscess, fecal incontinence, rectal hemorrhage, stomatitis, colitis, tongue edema, cholecystitis, mouth ulcer, oral moniliasis, eructation, fecal impaction, loose stools, abdominal distention, hematochezia, gingival pain, lower abdominal pain, oral pain, retching, fecaloma, tooth fracture, dry lip, and cholelithiasis have been reported infrequently. Esophagitis, hematemesis, intestinal obstruction, gum hemorrhage, peptic ulcer, glossitis, melena, duodenal ulcer, cheilitis, abdominal tenderness, chapped lips, periodontitis, aptyalism, gastrointestinal pain, oral hypoesthesia, inguinal hernia, hyperchlorhydria, irritable bowel syndrome, esophagitis, gingival bleeding, glossodynia, melena, and pancreatitis have been reported rarely.
Dermatologic side effects have frequently included skin ulcer, sweating, and dry skin. Pruritus, vesiculobullous rash, acne, eczema, skin discoloration, alopecia, seborrhea, cellulitis, onychomycosis, and psoriasis have been reported infrequently. Maculopapular rash, exfoliative dermatitis, folliculitis, pustular rash, and urticaria have been reported rarely.
Several cases of aripiprazole-associated neuroleptic malignant syndrome (NMS) have been reported. It should be noted that NMS which is usually characterized by muscle rigidity, dysphagia, tremor, fever, diaphoresis, anxiety, tachycardia, labile blood pressure, and altered consciousness may present in an atypical manner with aripiprazole (the active ingredient contained in Abilify) (i.e., delayed or late onset of typical symptoms such as hyperthermia). One identified potential risk factor for developing NMS is the period during a switch from one antipsychotic treatment to another.
Other side effects have frequently included headache (31% to 32%), asthenia (7% to 8%), accidental injury (5% to 6%), fatigue (6%), pain (3%), fever (2%), peripheral edema (2%), flu syndrome, chest pain, neck pain, pelvic pain, and rigidity in the neck and/or extremities. Face edema, suicide attempt, malaise, chills, photosensitivity, arm rigidity, jaw pain, bloating, tightness (abdomen, back, extremity, head, jaw, neck, and tongue), enlarged abdomen, chest tightness, throat pain, ear pain, tinnitus, otitis media, altered taste, pyrexia, gait disturbance, edema, general physical health deterioration, feeling jittery, decreased mobility, thirst, feeling cold, difficulty in walking, facial pain, sluggishness, candidiasis, and deafness have been reported infrequently. Moniliasis, head heaviness, throat tightness, Mendelson's syndrome, heat stroke, otitis externa, vertigo, localized inflammation, swelling, increased energy, abasia, xerosis, hyperthermia, hypothermia, septic shock, appendicitis, and neuroleptic malignant syndrome have been reported rarely.
Collective data gathered from 17 placebo-controlled clinical studies (n=5106) involving the use of atypical antipsychotic agents, including aripiprazole (the active ingredient contained in Abilify) for the treatment of behavioral disorders in the elderly patient with dementia showed a risk of death 1.6 to 1.7 times greater in the drug- treated patient than in the placebo- treated patient. The average length of duration for the trials was 10 weeks with the cause of death in the majority of cases, though not all, reported as either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. Aripiprazole is not approved by the FDA for use in the treatment of behavioral disorders in elderly patients with dementia.
An increased risk of mortality, possibly due to an infection such as pneumonia, has been reported with the use of aripiprazole in the treatment of behavioral disorders in the elderly patient with dementia.
Respiratory side effects have frequently included bronchitis (6%), pharyngitis (4%), rhinitis (4%), coughing (3%), sinusitis, dyspnea, pneumonia, and asthma. Epistaxis, hiccup, laryngitis, and aspiration pneumonia have been reported infrequently. Pulmonary edema, increased sputum, pulmonary embolism, hypoxia, respiratory failure, apnea, dry nasal passages, and hemoptysis have been reported rarely.
Musculoskeletal side effects have frequently included arthralgia (5%), myalgia (4%), pain in extremities (4%), and muscle cramp. Myasthenia, arthrosis, bone pain, arthritis, muscle weakness, spasm, bursitis, and myopathy have been reported infrequently. Rheumatoid arthritis, rhabdomyolysis, tendonitis, and tenosynovitis have been reported rarely.
Ocular side effects have frequently included blurred vision (3%) and conjunctivitis. Dry eye, eye pain, cataract, blepharitis, eye redness, eye irritation, blepharospasm, visual disturbance, eye discharge, increased lacrimation, and eye hemorrhage have been reported infrequently. Diplopia, frequent blinking, ptosis, amblyopia, photophobia, eyelid function disorder, eyelid edema, and oculogyric crisis have been reported rarely.
Hypersensitivity side effects have rarely included anaphylactic reaction, angioedema, laryngospasm, oropharyngeal spasm, pruritus, and urticaria.
Aripiprazole may be associated with orthostatic hypotension.
Collective data gathered from 17 placebo-controlled clinical studies (n=5106) involving the use of atypical antipsychotic agents, including aripiprazole (the active ingredient contained in Abilify) for the treatment of behavioral disorders in the elderly patient with dementia showed a risk of death 1.6 to 1.7 times greater in the drug-treated patient than in the placebo-treated patient. The average length of duration for the trials was 10 weeks with the cause of death in the majority of cases, though not all, reported as either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. Similar results (i.e., increased risk of mortality with atypical antipsychotics) were reported in another meta-analysis involving elderly dementia patients that consisted of 15 randomized, placebo-controlled trials (n=3353) of 10 to 12 weeks in duration. Aripiprazole is not approved by the FDA for use in the treatment of behavioral disorders in elderly patients with dementia.
An increased risk of mortality, possibly due to heart failure or sudden death, has been reported with the use of aripiprazole in the treatment of behavioral disorders in the elderly patient with dementia.
One case of dose-dependent incomplete right bundle-branch block has been reported following use of aripiprazole. Electrocardiographic findings returned to normal after discontinuation of aripiprazole.
A case of hypertensive crisis with tachycardia, confirmed upon rechallenge, has been reported following treatment with aripiprazole.
Cardiovascular side effects have frequently included hypertension (2%), hypotension, bradycardia, and both ventricular and supraventricular tachycardia. Palpitation, hemorrhage, heart failure, myocardial infarction, cardiac arrest, atrial fibrillation, AV block, prolonged QT interval, extrasystoles, myocardial ischemia, deep vein thrombosis, angina pectoris, pallor, cardiopulmonary arrest, cyanosis, and phlebitis have been reported infrequently. Bundle branch block, atrial flutter, vasovagal reaction, cardiomegaly, cardiomyopathy, thrombophlebitis, and cardiopulmonary failure have been reported rarely.
Possible risk factors for leukopenia/neutropenia include preexisting low white blood cell count (WBC) and history of drug-induced leukopenia/neutropenia. Patients with a history of a clinically significant low WBC or drug-induced leukopenia/neutropenia should have their complete blood count (CBC) monitored frequently during the first few months of therapy and discontinuation of aripiprazole (the active ingredient contained in Abilify) should be considered at the first sign of a clinically significant decline in WBC in the absence of other causative factors.
Patients with clinically significant neutropenia should be carefully monitored for fever or other symptoms or signs of infection and treated promptly if such symptoms or signs occur. Patients with severe neutropenia (absolute neutrophil count less than 1000/mm3) should discontinue aripiprazole and have their WBC followed until recovery.
Hematologic side effects have frequently included ecchymosis and anemia. Hypochromic anemia, leukocytosis, leukopenia, lymphadenopathy, eosinophilia, and macrocytic anemia have been reported infrequently. Thrombocythemia, thrombocytopenia, idiopathic thrombocytopenic purpura, and petechiae have been reported rarely. A reversible case of elevated triglyceride levels has also been reported.
In clinical trial and/or postmarketing experience, events of leukopenia/neutropenia have been reported temporally related to antipsychotic agents, including aripiprazole. Agranulocytosis has also been reported.
Metabolic side effects have frequently included weight loss, increased creatine phosphokinase, and dehydration. Edema, hyperglycemia, hypercholesterolemia, hypokalemia, diabetes mellitus, hypoglycemia, hyperlipemia, increased SGPT, thirst, increased BUN, hyponatremia, increased SGOT, increased creatinine, cyanosis, increased alkaline phosphatase, bilirubinemia, iron deficiency anemia, hyperkalemia, hyperuricemia, and obesity have been reported infrequently. Increased lactic dehydrogenase, hypernatremia, gout, and hypoglycemic reaction have been reported rarely.
Extreme cases of hyperglycemia associated with ketoacidosis, hyperosmolar coma, or death have been reported in patients treated with atypical antipsychotics. There have been few reports of hyperglycemia in patients treated with aripiprazole.
Although rare, aripiprazole-induced hyponatremia has been reported. In one case, hyponatremia developed two days after initiating therapy with aripiprazole 10 mg daily and resolved one week after discontinuation of treatment.
Psychiatric side effects have frequently included depression, schizophrenic reaction, hallucination, hostility, paranoid reaction, suicidal thought, manic reaction, delusions, and abnormal dream. Emotional lability, panic attack, manic depressive reaction, and visual hallucination have been reported infrequently. Obsessive thought and derealization have been reported rarely. In addition, at least one case of worsening psychosis has been associated with aripiprazole (the active ingredient contained in Abilify)
A possible worsening of preexisting schizoaffective disorder with the initiation of aripiprazole therapy has been reported.
Two cases of treatment-emergent psychosis and induction of mania have been reported in patients with schizoaffective disorder- bipolar type being switched to aripiprazole from high-potency dopamine receptor antagonists (i.e., perphenazine, fluphenazine). Symptoms resolved in both patients following discontinuation of aripiprazole.
Genitourinary side effects have frequently included vaginitis (6%), urinary tract infection (5%), and urinary incontinence. Urinary frequency, leukorrhea, urinary retention, cystitis, hematuria, dysuria, amenorrhea, vaginal hemorrhage, abnormal ejaculation, kidney failure, vaginal moniliasis, urinary urgency, gynecomastia, kidney calculus, albuminuria, breast pain, vaginal infection, vaginal mycosis, vaginal candidiasis, pyelonephritis, and urinary burning have been reported infrequently. Nocturia, polyuria, menorrhagia, anorgasmy, glycosuria, cervicitis, uterus hemorrhage, female lactation, urolithiasis, and priapism have been reported rarely.
One case of recurrent priapism associated with the use of aripiprazole has been reported. In this case, the first episode of priapism occurred within hours of the first dose of aripiprazole and following treatment for priapism the patient proceeded to have additional episodes of priapism over a period of 7 days even though no additional doses of aripiprazole were taken. The authors suggest that the recurrence of priapism over a week can be explained by aripiprazole's long half-life.
Hepatic side effects have rarely included hepatitis, hepatomegaly, cholecystitis, and cholelithiasis. Jaundice has been reported in postmarketing experience.
Endocrine side effects have infrequently included hypothyroidism. Goiter, hyperthyroidism, and hyperparathyroidism have been reported rarely.
In general, the incidence of side effects does not appear to be influenced by the age, gender, or race of the patient. Side effects associated with aripiprazole (the active ingredient contained in Abilify) are generally reported within the first week of therapy and resolve within 7 days.