ABILIFY (Page 14 of 24)

Dystonia

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.

Additional Findings Observed in Clinical Trials

Adverse Reactions in Long-Term, Double-Blind, Placebo-Controlled Trials

The adverse reactions reported in a 26-week, double-blind trial comparing oral ABILIFY and placebo in patients with schizophrenia were generally consistent with those reported in the short-term, placebo-controlled trials, except for a higher incidence of tremor [8% (12/153) for ABILIFY vs. 2% (3/153) for placebo]. In this study, the majority of the cases of tremor were of mild intensity (8/12 mild and 4/12 moderate), occurred early in therapy (9/12 ≤49 days), and were of limited duration (7/12 ≤10 days). Tremor infrequently led to discontinuation (<1%) of ABILIFY. In addition, in a long-term (52 week), active-controlled study, the incidence of tremor was 5% (40/859) for ABILIFY. A similar profile was observed in a long-term monotherapy study and a long-term adjunctive study with lithium and valproate in bipolar disorder.

Other Adverse Reactions Observed During the Premarketing Evaluation of ABILIFY

The following listing does not include reactions: 1) already listed in previous tables or elsewhere in labeling, 2) for which a drug cause was remote, 3) which were so general as to be uninformative, 4) which were not considered to have significant clinical implications, or 5) which occurred at a rate equal to or less than placebo.

Reactions are categorized by body system according to the following definitions: frequent adverse reactions are those occurring in at least 1/100 patients; infrequent adverse reactions are those occurring in 1/100 to 1/1000 patients; rare reactions are those occurring in fewer than 1/1000 patients:

Adults — Oral Administration

Blood and Lymphatic System Disorders:

rare

— thrombocytopenia

Cardiac Disorders:

infrequent

– bradycardia, palpitations, rare – atrial flutter, cardio-respiratory arrest, atrioventricular block, atrial fibrillation, angina pectoris, myocardial ischemia, myocardial infarction, cardiopulmonary failure

Eye Disorders:

infrequent

– photophobia; rare — diplopia

Gastrointestinal Disorders:

infrequent

— gastroesophageal reflux disease

General Disorders and Administration Site Conditions:

frequent

— asthenia; infrequent – peripheral edema, chest pain; rare – face edema

Hepatobiliary Disorders:

rare

— hepatitis, jaundice

Immune System Disorders:

rare

– hypersensitivity

Injury, Poisoning, and Procedural Complications:

infrequent

– fall; rare – heat stroke

Investigations:

frequent

— weight decreased, infrequent — hepatic enzyme increased, blood glucose increased, blood lactate dehydrogenase increased, gamma glutamyl transferase increased; rare – blood prolactin increased, blood urea increased, blood creatinine increased, blood bilirubin increased, electrocardiogram QT prolonged, glycosylated hemoglobin increased

Metabolism and Nutrition Disorders:

frequent

– anorexia; infrequent — rare — hypokalemia, hyponatremia, hypoglycemia

Musculoskeletal and Connective Tissue Disorders:

infrequent

— muscular weakness, muscle tightness; rare – rhabdomyolysis, mobility decreased

Nervous System Disorders:

infrequent

— parkinsonism, memory impairment, cogwheel rigidity, hypokinesia, myoclonus, bradykinesia; rare – akinesia, myoclonus, coordination abnormal, speech disorder, Grand Mal convulsion; <1/10,000 patients — choreoathetosis

Psychiatric Disorders:

infrequent

– aggression, loss of libido, delirium; rare – libido increased, anorgasmia, tic, homicidal ideation, catatonia, sleep walking

Renal and Urinary Disorders:

rare

— urinary retention, nocturia

Reproductive System and Breast Disorders:

infrequent

— erectile dysfunction; rare – gynaecomastia, menstruation irregular, amenorrhea, breast pain, priapism

Respiratory, Thoracic, and Mediastinal Disorders:

infrequent

— nasal congestion, dyspnea

Skin and Subcutaneous Tissue Disorders:

infrequent

— rash, hyperhidrosis, pruritus, photosensitivity reaction, alopecia; rare — urticaria

Vascular Disorders:

infrequent

– hypotension, hypertension

Pediatric Patients — Oral Administration

Most adverse events observed in the pooled database of 1,686 pediatric patients, aged 6 to 18 years, were also observed in the adult population. Additional adverse reactions observed in the pediatric population are listed below.

Eye Disorders

infrequent

— oculogyric crisis

Gastrointestinal Disorders:

infrequent

-tongue dry, tongue spasm

Investigations:

frequent

— blood insulin increased

Nervous System Disorders:

infrequent

— sleep talking

Renal and Urinary Disorders

frequent

– enuresis

Skin and Subcutaneous Tissue Disorders:

infrequent

— hirsutism

Adults — Intramuscular Injection

Most adverse reactions observed in the pooled database of 749 adult patients treated with ABILIFY injection, were also observed in the adult population treated with oral ABILIFY. Additional adverse reactions observed in the ABILIFY injection population are listed below.

General Disorders and Administration Site Conditions:

≥1/100 patients

— injection site reaction; ≥1/1000 patients and <1/100 patients — venipuncture site bruise

6.2 Postmarketing Experience

The following adverse reactions have been identified during post-approval use of ABILIFY. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to establish a causal relationship to drug exposure: occurrences of allergic reaction (anaphylactic reaction, angioedema, laryngospasm, pruritus/urticaria, or oropharyngeal spasm), pathological gambling, hiccups and blood glucose fluctuation.

7 DRUG INTERACTIONS

7.1 Drugs Having Clinically Important Interactions with ABILIFY

Table 25: Clinically Important Drug Interactions with ABILIFY:

Concomitant Drug Name or Drug Class	Clinical Rationale	Clinical Recommendation
Strong CYP3A4 Inhibitors (e.g., itraconazole, clarithromycin) or strong CYP2D6 inhibitors (e.g., quinidine, fluoxetine, paroxetine)	The concomitant use of ABILIFY with strong CYP 3A4 or CYP2D6 inhibitors increased the exposure of aripiprazole compared to the use of ABILIFY alone [see CLINICAL PHARMACOLOGY (12.3)].	With concomitant use of ABILIFY with a strong CYP3A4 inhibitor or CYP2D6 inhibitor, reduce the ABILIFY dosage [see DOSAGE AND ADMINISTRATION (2.7)].
Strong CYP3A4 Inducers (e.g., carbamazepine, rifampin)	The concomitant use of ABILIFY and carbamazepine decreased the exposure of aripiprazole compared to the use of ABILIFY alone [see CLINICAL PHARMACOLOGY (12.3)].	With concomitant use of ABILIFY with a strong CYP3A4 inducer, consider increasing the ABILIFY dosage [see DOSAGE AND ADMINISTRATION (2.7)].
Antihypertensive Drugs	Due to its alpha adrenergic antagonism, aripiprazole has the potential to enhance the effect of certain antihypertensive agents.	Monitor blood pressure and adjust dose accordingly [see WARNINGS AND PRECAUTIONS (5.7)].
Benzodiazepines (e.g., lorazepam)	The intensity of sedation was greater with the combination of oral aripiprazole and lorazepam as compared to that observed with aripiprazole alone. The orthostatic hypotension observed was greater with the combination as compared to that observed with lorazepam alone [see WARNINGS AND PRECAUTIONS (5.7)]	Monitor sedation and blood pressure. Adjust dose accordingly.