Aripiprazole Lauroxil Injectable Suspension

ARISTADA INITIO contains aripiprazole lauroxil, an atypical antipsychotic.

The chemical name of aripiprazole lauroxil is 7-{4-[4-(2,3-dichlorophenyl)-piperazin-1- yl]butoxy}-2-oxo-3,4-dihydro-2H-quinolin-1-yl)methyl dodecanoate. The empirical formula is C36H51Cl2N3O4 and its molecular weight is 660.7 g/mol. The chemical structure is:

ARISTADA INITIO is available as a white to off-white sterile aqueous extended-release injectable suspension for intramuscular injection in the following strength of aripiprazole lauroxil (and deliverable volume from a single-dose pre-filled syringe): 675 mg (2.4 mL). This product’s specific extended-release and dosing characteristics are derived from aripiprazole lauroxil’s submicron particle size distribution. The inactive ingredients include polysorbate 20 (16.2 mg/mL), sodium chloride (3.3 mg/mL), sodium citrate dihydrate (8.1 mg/mL), sodium phosphate dibasic anhydrous, sodium phosphate monobasic and water for injection.

Dosage Forms And Strengths

ARISTADA INITIO is a white to off-white aqueous extended-release injectable suspension provided in a single-dose pre-filled syringe (see Table 3).

Table 3: Presentation of ARISTADA INITIO

Storage And Handling

ARISTADA INITIO extended-release injectable suspension is available in a strength of 675 mg in 2.4 mL. The kit contains a 5-mL pre-filled syringe containing ARISTADA INITIO as a sterile white to off-white aqueous extended-release injectable suspension with safety needles.

A 675 mg strength kit (NDC 65757-500-03; gray label) contains three safety needles; a 1-inch (25 mm) 21 gauge, a 1½-inch (38 mm) 20 gauge, and a 2-inch (50 mm) 20 gauge needle.

Store at room temperature 20°C to 25°C (68°F to 77°F) with excursions permitted between 15°C and 30°C (between 59°F and 86°F). Do not freeze.

Manufactured and marketed by: Alkermes, Inc., 852 Winter Street, Waltham, MA 02451-1420. Revised: Jun 2018

Human Experience

Common adverse reactions (reported in at least 5% of all overdose cases) reported with oral aripiprazole overdosage (alone or in combination with other substances) include vomiting, somnolence, and tremor. Other clinically important signs and symptoms observed in one or more patients with aripiprazole overdoses (alone or with other substances) include acidosis, aggression, aspartate aminotransferase increased, atrial fibrillation, bradycardia, coma, confusional state, convulsion, blood creatine phosphokinase increased, depressed level of consciousness, hypertension, hypokalemia, hypotension, lethargy, loss of consciousness, QRS complex prolonged, QT prolonged, pneumonia aspiration, respiratory arrest, status epilepticus, and tachycardia.

Management Of Overdosage

In case of overdosage, call the Poison control center immediately at 1-800-222-1222.

The following are discussed in more details in other sections of the labeling:

• Increased Mortality in Elderly Patients with Dementia-related Psychosis [see BOXED WARNING, WARNINGS AND PRECAUTIONS]
• Cerebrovascular Adverse Reactions, Including Stroke [see BOXED WARNING, WARNINGS AND PRECAUTIONS]
• Neuroleptic Malignant Syndrome [see WARNINGS AND PRECAUTIONS]
• Tardive Dyskinesia [see WARNINGS AND PRECAUTIONS]
• Metabolic Changes [see WARNINGS AND PRECAUTIONS]
• Pathological Gambling and Other Compulsive Behaviors [see WARNINGS AND PRECAUTIONS]
• Orthostatic Hypotension [see WARNINGS AND PRECAUTIONS]
• Falls [see WARNINGS AND PRECAUTIONS]
• Leukopenia, Neutropenia, and Agranulocytosis [see WARNINGS AND PRECAUTIONS]
• Seizures [see WARNINGS AND PRECAUTIONS]
• Potential for Cognitive and Motor Impairment [see WARNINGS AND PRECAUTIONS]
• Body Temperature Regulation [see WARNINGS AND PRECAUTIONS]
• Dysphagia [see WARNINGS AND PRECAUTIONS]

Clinical Studies Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety of ARISTADA INITIO, in combination with oral aripiprazole, for the initiation of ARISTADA when used for the treatment of schizophrenia in adults has been established and is based on clinical trials of ARISTADA (aripiprazole lauroxil) including 1019 adult patients with schizophrenia.

Patient Exposure

ARISTADA INITIO has been evaluated for safety in 170 adult patients in clinical trials in schizophrenia.

In pharmacokinetic studies, the safety profile of ARISTADA INITIO was generally consistent with that observed for ARISTADA.

ARISTADA (Aripiprazole Lauroxil) Trials In Adults With Schizophrenia

The most common adverse reaction (incidence ≥5% and at least twice the rate of placebo in patients treated with aripiprazole lauroxil was akathisia.

Adverse reactions associated with the use of aripiprazole lauroxil (incidence of 2% or greater, rounded to the nearest percent and aripiprazole lauroxil incidence greater than placebo) that occurred were: injection site pain, increased weight, increased blood creatinine phosphokinase, akathisia, headache, insomnia, and restlessness.

ARISTADA INITIO

In pharmacokinetic studies evaluating ARISTADA INITIO, the incidences of injection site reactions with ARISTADA INITIO were similar to the incidence observed with aripiprazole lauroxil.

ARISTADA (Aripiprazole Lauroxil)

Injection site reactions were reported by 4% of patients treated with 441 mg aripiprazole lauroxil and 5% of patients treated with 882 mg aripiprazole lauroxil compared to 2% of patients treated with placebo. Most of these were injection site pain (3%, 4% and 2% in the 441 mg aripiprazole lauroxil, 882 mg aripiprazole lauroxil and placebo groups, respectively). Other injection site reactions (induration, swelling and redness) occurred at less than 1%.

In a schizophrenia efficacy study in aripiprazole lauroxil-treated patients, the incidence of other EPS-related events, excluding akathisia and restlessness, was 5% and 7% for patients on 441 mg and 882 mg, respectively, versus 4% for placebo-treated patients.

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.

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.

Cardiac - angina pectoris, tachycardia, palpitations

Gastrointestinal disorders - constipation, dry mouth

General disorders - asthenia

Musculoskeletal - muscular weakness

Nervous system disorders - dizziness

Psychiatric disorders - anxiety, suicide

The following is a list of additional adverse reactions that have been reported in clinical trials with oral aripiprazole and not reported above for ARISTADA INITIO or aripiprazole lauroxil.

Blood and Lymphatic System Disorders: thrombocytopenia

Cardiac Disorders: bradycardia, atrial flutter, cardiorespiratory arrest, atrioventricular block, atrial fibrillation, myocardial ischemia, myocardial infarction, cardiopulmonary failure

Eye Disorders: photophobia, diplopia

Gastrointestinal Disorders: gastroesophageal reflux disease

General Disorders and Administration Site Conditions: peripheral edema, chest pain, face edema

Hepatobiliary Disorders: hepatitis, jaundice

Immune System Disorders: hypersensitivity

Injury, Poisoning, and Procedural Complications: fall, heat stroke

Investigations: weight decreased, hepatic enzyme increased, blood glucose increased, blood lactate dehydrogenase increased, gamma glutamyl transferase increased, blood prolactin increased, blood urea increased, blood creatinine increased, blood bilirubin increased, electrocardiogram QT prolonged, glycosylated hemoglobin increased

Metabolism and Nutrition Disorders: anorexia, hypokalemia, hyponatremia, hypoglycemia

Musculoskeletal and Connective Tissue Disorders: muscle tightness, rhabdomyolysis, mobility decreased

Nervous System Disorders: memory impairment, cogwheel rigidity, hypokinesia, bradykinesia, akinesia, myoclonus, coordination abnormal, speech disorder, choreoathetosis

Psychiatric Disorders: aggression, loss of libido, delirium, libido increased, anorgasmia, tic, homicidal ideation, catatonia, sleep walking

Renal and Urinary Disorders: urinary retention, nocturia

Reproductive System and Breast Disorders: erectile dysfunction, gynaecomastia, menstruation irregular, amenorrhea, breast pain, priapism

Respiratory, Thoracic, and Mediastinal Disorders: nasal congestion, dyspnea

Skin and Subcutaneous Tissue Disorders: rash, hyperhidrosis, pruritus, photosensitivity reaction, alopecia, urticaria

Vascular Disorders: hypotension, hypertension

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of oral aripiprazole. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or 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.

Read the entire FDA prescribing information for Aristada Initio (Aripiprazole Lauroxil Injectable Suspension)

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