Aristada Initio Drug Information
Generic name: ARIPIPRAZOLE LAUROXIL
Uses of Aristada Initio
ARISTADA INITIO, in combination with oral aripiprazole, is indicated for the initiation of ARISTADA when used for the treatment of schizophrenia in adults.
Dosage & Administration of Aristada Initio
Recommended Dosage ARISTADA INITIO is only to be used as a single dose to initiate ARISTADA treatment or as a single dose to re-initiate ARISTADA treatment following a missed dose of ARISTADA. ARISTADA INITIO is not for repeated dosing. ARISTADA INITIO is not interchangeable with ARISTADA due to differing pharmacokinetic profiles.
ARISTADA INITIO is to be administered as an intramuscular injection by a healthcare professional. For patients who have never taken aripiprazole, establish tolerability with oral aripiprazole prior to initiating treatment with ARISTADA INITIO. Due to the half-life of oral aripiprazole, it may take up to 2 weeks to fully assess tolerability.
Refer to the prescribing information of oral aripiprazole for the recommended dosage and administration of the oral formulation. The first ARISTADA injection may be administered on the same day as ARISTADA INITIO or up to 10 days thereafter. See the ARISTADA prescribing information for additional information regarding dosage and administration of ARISTADA.
Avoid injecting both ARISTADA INITIO and ARISTADA concomitantly into the same deltoid or gluteal muscle.
Missed Doses of ARISTADA ARISTADA INITIO may be used to re-initiate treatment with ARISTADA following a missed dose of ARISTADA. When a dose of ARISTADA is missed, administer the next injection of ARISTADA as soon as possible. Depending on the time elapsed since the last ARISTADA injection, supplement the next ARISTADA injection as recommended in Table 1 below.
Table 1: Recommendation for Concomitant Supplementation Following Missed Doses of ARISTADA
Dose Adjustments for CYP450 Considerations ARISTADA INITIO is only available at a single strength as a single-dose pre-filled syringe, so dosage adjustments are not possible. Therefore, avoid use in patients who are known CYP2D6 poor metabolizers or taking strong CYP3A4 inhibitors, strong CYP2D6 inhibitors, or strong CYP3A4 inducers.
Important Administration Instructions
The kit contains a syringe containing ARISTADA INITIO sterile aqueous extended-release injectable suspension and 3 safety needles (a 2-inch 20 gauge needle with yellow needle hub, a 1 ½-inch 20 gauge needle with yellow needle hub, and a 1-inch 21 gauge needle with green needle hub) for intramuscular injection. Store all materials at room temperature. TAP and vigorously SHAKE the syringe. 1a.
Tap the syringe at least 10 times to dislodge any material which may have settled. 1b. Shake the syringe vigorously for a minimum of 30 seconds to ensure a uniform suspension. If the syringe is not used within 15 minutes, shake again for 30 seconds. 2.
SELECT the injection needle. 2a. Select injection site. 2b. Select needle length based on injection site.
For patients with a larger amount of subcutaneous tissue overlaying the injection site muscle, use the longer of the needles provided. Table 2: ARISTADA INITIO 3. ATTACH the injection needle.
Attach the appropriate needle securely with a clockwise twisting motion. Do NOT overtighten. Overtightening could lead to needle hub cracking. 4.
PRIME the syringe to remove air. 4a. Bring the syringe into upright position and tap the syringe to bring air to the top. 4b. Depress the plunger rod to remove air until a few drops are released.
It is normal to see small air bubbles remaining in the syringe. 5. Inject in a RAPID and CONTINUOUS manner. Product requires a RAPID injection.
Do not hesitate. Administer the entire content intramuscularly. Do not inject by any other route. 6.
DISPOSE of the needle. Cover the needle by pressing the safety device. Dispose of used and unused items in a proper waste container.
Figure Figure Figure Figure Figure Figure Figure Figure
| Dose of Patient's Last ARISTADA Injection | Length of Time Since Last Injection | ||
|---|---|---|---|
| 441 mg | ≤ 6 weeks | > 6 and ≤ 7 weeks | > 7 weeks |
| 662 mg | ≤ 8 weeks | > 8 and ≤ 12 weeks | > 12 weeks |
| 882 mg | ≤ 8 weeks | > 8 and ≤ 12 weeks | > 12 weeks |
| 1064 mg | ≤ 10 weeks | > 10 and ≤ 12 weeks | > 12 weeks |
| Dosage and Administration for Re-initiation of ARISTADA | No Supplementation Required | Supplement with a Single Dose of ARISTADA INITIO | Re-initiate with a Single Dose of ARISTADA INITIO and a Single Dose of Oral Aripiprazole 30 mg |
| Injection Site | Needle Length |
|---|---|
| 675 mg dose | |
| Deltoid | 21 gauge, 1-inch or 20 gauge, 1½-inch |
| Gluteal | 20 gauge, 1½-inch or 20 gauge, 2-inch |
Side Effects of Aristada Initio
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 Commonly Observed Adverse Reactions with Aripiprazole Lauroxil 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 Occurring at an Incidence of 2% or More in Aripiprazole Lauroxil-Treated Patients 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.
Injection Site Reactions 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. Other injection site reactions (induration, swelling and redness) occurred at less than 1%. 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.
Other Adverse Reactions Observed in Clinical Studies with Aripiprazole Lauroxil 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 Adverse Reactions Reported in Clinical Trials with Oral Aripiprazole 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: blood prolactin decreased, 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, blood glucose fluctuation, oculogyric crisis, drug reaction with eosinophilia and systemic symptoms (DRESS), and fecal incontinence.
Warnings & Cautions for Aristada Initio
Increased Mortality in Elderly Patients with Dementia-related Psychosis Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Analyses of 17 placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6 to 1.7 times the risk of death in placebo-treated patients. Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group.
Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality. The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear.
ARISTADA INITIO is not approved for the treatment of patients with dementia-related psychosis.
Cerebrovascular Adverse Reactions, Including Stroke
In placebo-controlled trials with risperidone, aripiprazole, and olanzapine in elderly patients with dementia, there was a higher incidence of cerebrovascular adverse reactions (cerebrovascular accidents and transient ischemic attacks) including fatalities compared to placebo-treated patients.
Potential for Dosing and Medication Errors
Medication errors, including substitution and dispensing errors, between ARISTADA INITIO and ARISTADA could occur. ARISTADA INITIO is intended for single administration only. Do not substitute ARISTADA INITIO for ARISTADA because of differing pharmacokinetic profiles.
Neuroleptic Malignant Syndrome
A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) may occur in association with antipsychotic drugs, including ARISTADA INITIO. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia). Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure.
The diagnostic evaluation of patients with this syndrome is complicated. In arriving at a diagnosis, it is important to identify cases in which the clinical presentation includes both serious medical illness (e.g., pneumonia, systemic infection, etc.) and untreated or inadequately treated extrapyramidal signs and symptoms (EPS). Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, drug fever, and primary central nervous system pathology.
The management of NMS should include: immediate discontinuation of antipsychotic drugs and other drugs not essential to concurrent therapy; intensive symptomatic treatment and medical monitoring; and treatment of any concomitant serious medical problems for which specific treatments are available. There is no general agreement about specific pharmacological treatment regimens for uncomplicated NMS. If a patient appears to require antipsychotic drug treatment after recovery from NMS, reintroduction of drug therapy should be closely monitored, since recurrences of NMS have been reported.
Tardive Dyskinesia
A syndrome of potentially irreversible, involuntary, dyskinetic movements may develop in patients treated with antipsychotic drugs. Although the prevalence of the syndrome appears to be highest among the elderly, especially elderly women, it is impossible to predict which patients will develop the syndrome. Whether antipsychotic drug products differ in their potential to cause tardive dyskinesia is unknown.
The risk of developing tardive dyskinesia and the likelihood that it will become irreversible appear to increase as the duration of treatment and the total cumulative dose of antipsychotic drugs administered to the patient increase, but the syndrome can develop after relatively brief treatment periods at low doses, although this is uncommon. Tardive dyskinesia may remit, partially or completely, if antipsychotic treatment is withdrawn. Antipsychotic treatment itself may suppress (or partially suppress) the signs and symptoms of the syndrome and may thus mask the underlying process.
The effect of symptomatic suppression on the long-term course of the syndrome is unknown. Given these considerations, antipsychotics should be prescribed in a manner that is most likely to minimize the occurrence of tardive dyskinesia. Chronic antipsychotic treatment should generally be reserved for patients who suffer from a chronic illness that is known to respond to antipsychotic drugs.
In patients who do require chronic treatment, the smallest dose and the shortest duration of treatment producing a satisfactory clinical response should be sought. The need for continued treatment should be reassessed periodically. If signs and symptoms of tardive dyskinesia appear in a patient treated with antipsychotics, consider discontinuation of the antipsychotic drug.
However, some patients may require antipsychotic treatment despite the presence of the syndrome.
Metabolic Changes
Atypical antipsychotic drugs have been associated with metabolic changes that include hyperglycemia/diabetes mellitus, dyslipidemia, and weight gain. While all drugs in the class have been shown to produce some metabolic changes, each drug has its own specific risk profile. Hyperglycemia/ Diabetes Mellitus Hyperglycemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, has been reported in patients treated with atypical antipsychotics.
There have been reports of hyperglycemia in patients treated with oral aripiprazole. Assessment of the relationship between atypical antipsychotic use and glucose abnormalities is complicated by the possibility of an increased background risk of diabetes mellitus in patients with schizophrenia and the increasing incidence of diabetes mellitus in the general population. Given these confounders, the relationship between atypical antipsychotic use and hyperglycemia-related adverse events is not completely understood.
However, epidemiological studies suggest an increased risk of hyperglycemia-related adverse reactions in patients treated with the atypical antipsychotics. Patients with an established diagnosis of diabetes mellitus who are started on atypical antipsychotics should be monitored regularly for worsening of glucose control. Patients with risk factors for diabetes mellitus (e.g., obesity, family history of diabetes) who are starting treatment with atypical antipsychotics should undergo fasting blood glucose testing at the beginning of treatment and periodically during treatment.
Any patient treated with atypical antipsychotics should be monitored for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness. Patients who develop symptoms of hyperglycemia during treatment with atypical antipsychotics should undergo fasting blood glucose testing. In some cases, hyperglycemia has resolved when the atypical antipsychotic was discontinued; however, some patients require continuation of anti-diabetic treatment despite discontinuation of the suspect drug.
Dyslipidemia Undesirable alterations in lipids have been observed in patients treated with atypical antipsychotics. Weight Gain Weight gain has been observed with atypical antipsychotic use. Clinical monitoring of weight is recommended.
Pathological Gambling and Other Compulsive Behaviors
Post-marketing case reports suggest that patients can experience intense urges, particularly for gambling, and the inability to control these urges while taking aripiprazole. Other compulsive urges, reported less frequently include: sexual urges, shopping, eating or binge eating, and other impulsive or compulsive behaviors. Because patients may not recognize these behaviors as abnormal, it is important for prescribers to ask patients or their caregivers specifically about the development of new or intense gambling urges, compulsive sexual urges, compulsive shopping, binge or compulsive eating, or other urges while being treated with aripiprazole.
It should be noted that impulse-control symptoms can be associated with the underlying disorder. In some cases, although not all, urges were reported to have stopped when the dose was reduced or the medication was discontinued. Compulsive behaviors may result in harm for the patient and others if not recognized.
If compulsive urges develop, consider discontinuing aripiprazole.
Orthostatic Hypotension Aripiprazole may cause orthostatic hypotension, perhaps due to its α 1 -adrenergic receptor antagonism. Associated adverse reactions related to orthostatic hypotension can include dizziness, lightheadedness and tachycardia. Generally, these risks are greatest at the beginning of treatment and during dose escalation.
Patients at increased risk of these adverse reactions or at increased risk of developing complications from hypotension include those with dehydration, hypovolemia, treatment with antihypertensive medication, history of cardiovascular disease (e.g., heart failure, myocardial infarction, ischemia, or conduction abnormalities), history of cerebrovascular disease, as well as patients who are antipsychotic-naïve. In such patients, monitor orthostatic vital signs.
Falls
Antipsychotics including ARISTADA INITIO may cause somnolence, postural hypotension, or motor and sensory instability, which may lead to falls and, consequently, fractures or other injuries. For patients with diseases, conditions, or medications that could exacerbate these effects, complete fall risk assessments when initiating antipsychotic treatment and recurrently for those patients on long-term antipsychotic therapy.
Leukopenia, Neutropenia, and Agranulocytosis
In clinical trials and/or postmarketing experience, events of leukopenia and neutropenia have been reported temporally related to antipsychotic agents. Agranulocytosis has also been reported. Possible risk factors for leukopenia/neutropenia include pre-existing low white blood cell count (WBC)/absolute neutrophil count (ANC) and history of drug-induced leukopenia/neutropenia.
In patients with a history of a clinically significant low WBC/ANC or drug-induced leukopenia/neutropenia, perform a complete blood count (CBC) frequently during the first few months of therapy. In such patients, consider discontinuation of antipsychotics at the first sign of a clinical significant decline in WBC in the absence of other causative factors. Monitor patients with clinically significant neutropenia for fever or other symptoms or signs of infection and treat promptly if such symptoms or signs occur.
Discontinue antipsychotics in patients with severe neutropenia (absolute neutrophil count <1000/mm 3 ) and follow their WBC until recovery.
Seizures As with other antipsychotic drugs, use ARISTADA
INITIO cautiously in patients with a history of seizures or with conditions that lower the seizure threshold. Conditions that lower the seizure threshold may be more prevalent in a population of 65 years or older.
Potential for Cognitive and Motor Impairment ARISTADA
INITIO, like other antipsychotics, has the potential to impair judgment, thinking or motor skills. Patients should be cautioned about operating hazardous machinery, including automobiles, until they are reasonably certain that therapy with ARISTADA INITIO does not affect them adversely.
Body Temperature Regulation Disruption of the body's ability to reduce core body temperature has been attributed to antipsychotic agents. Appropriate care is advised when prescribing ARISTADA INITIO for patients who will be experiencing conditions which may contribute to an elevation in core body temperature, (e.g., exercising strenuously, exposure to extreme heat, receiving concomitant medication with anticholinergic activity, or being subject to dehydration).
Dysphagia
Esophageal dysmotility and aspiration have been associated with antipsychotic drug use. ARISTADA INITIO and other antipsychotic drugs should be used cautiously in patients at risk for aspiration pneumonia.
Drug Interactions with Aristada Initio
- Drugs Having Clinically Important Interactions with ARISTADA INITIO Table 4: Clinically Important Drug Interactions with ARISTADA INITIO Strong CYP3A4 Inhibitors and CYP2D6 Inhibitors Clinical Impact: Concomitant use of oral aripiprazole with strong CYP3A4 or CYP2D6 inhibitors increased the exposure of aripiprazole compared to the use of oral aripiprazole alone.
- Intervention: Avoid concomitant use of ARISTADA INITIO with strong CYP3A4 or strong CYP2D6 inhibitors because the dosage of ARISTADA INITIO cannot be modified.
- Examples: itraconazole, clarithromycin, quinidine, fluoxetine, paroxetine Strong CYP3A4 Inducers Clinical Impact: Concomitant use of oral aripiprazole and carbamazepine decreased the exposure of aripiprazole compared to the use of oral aripiprazole alone. Avoid concomitant use of ARISTADA INITIO with antihypertensive drugs because the dosage of ARISTADA INITIO cannot be modified.
- Examples: carvedilol, lisinopril, prazosin Benzodiazepines Clinical Impact: 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.
- Example: lorazepam
Drugs Having No Clinically Important Interactions with ARISTADA INITIO Based on pharmacokinetic studies with oral aripiprazole, no dosage adjustment of ARISTADA INITIO is required when administered concomitantly with famotidine, valproate, or lithium. In addition, no dosage adjustment is necessary for substrates of CYP2D6 (e.g., dextromethorphan, fluoxetine, paroxetine, or venlafaxine), CYP2C9 (e.g., warfarin), CYP2C19 (e.g., omeprazole, warfarin, escitalopram), or CYP3A4 (e.g., dextromethorphan) when co-administered with ARISTADA INITIO. Additionally, no dosage adjustment is necessary for valproate, lithium, lamotrigine, or sertraline when co-administered with ARISTADA INITIO.
| Strong CYP3A4 Inhibitors and CYP2D6 Inhibitors | |
| Clinical Impact: | Concomitant use of oral aripiprazole with strong CYP3A4 or CYP2D6 inhibitors increased the exposure of aripiprazole compared to the use of oral aripiprazole alone [see Clinical Pharmacology ( 12.3 )]. |
| Intervention: | Avoid concomitant use of ARISTADA INITIO with strong CYP3A4 or strong CYP2D6 inhibitors because the dosage of ARISTADA INITIO cannot be modified [see Dosage and Administration ( 2.3 )]. |
| Examples: | itraconazole, clarithromycin, quinidine, fluoxetine, paroxetine |
| Strong CYP3A4 Inducers | |
| Clinical Impact: | Concomitant use of oral aripiprazole and carbamazepine decreased the exposure of aripiprazole compared to the use of oral aripiprazole alone [see Clinical Pharmacology ( 12.3 )]. |
| Intervention: | Avoid concomitant use of ARISTADA INITIO with strong CYP3A4 inducers because the dosage of ARISTADA INITIO cannot be modified [see Dosage and Administration ( 2.3 )]. |
| Examples: | carbamazepine, rifampin |
| Antihypertensive Drugs | |
| Clinical Impact: | Due to its alpha adrenergic antagonism, aripiprazole has the potential to enhance the effect of certain antihypertensive agents. |
| Intervention: | Avoid concomitant use of ARISTADA INITIO with antihypertensive drugs because the dosage of ARISTADA INITIO cannot be modified [see Warnings and Precautions ( 5.8 )]. |
| Examples: | carvedilol, lisinopril, prazosin |
| Benzodiazepines | |
| Clinical Impact: | 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 ( 5.8 )]. |
| Intervention: | Avoid concomitant use of ARISTADA INITIO with benzodiazepines because the dosage of ARISTADA INITIO cannot be modified [see Warnings and Precautions ( 5.8 )]. |
| Example: | lorazepam |
Pregnancy Safety for Aristada Initio
Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ARISTADA INITIO during pregnancy. For more information, contact the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or visit http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/. Risk Summary Neonates exposed to antipsychotic drugs, including ARISTADA INITIO, during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery (see Clinical Considerations ).
Overall available data from published epidemiologic studies of pregnant women exposed to aripiprazole have not established a drug-associated risk of major birth defects, miscarriage, or adverse maternal outcomes. There are risks to the mother associated with untreated schizophrenia and with exposure to antipsychotics, including ARISTADA INITIO, during pregnancy (see Clinical Considerations ). Aripiprazole exposure during pregnancy may decrease milk supply in the post-partum period.
No teratogenicity was observed in animal reproductive studies with intramuscular administration of aripiprazole lauroxil to rats and rabbits during organogenesis at doses up to 8 and 23 times, respectively, the maximum recommended human dose (MRHD) of 675 mg based on body surface area (mg/m 2 ). However, aripiprazole caused developmental toxicity and possible teratogenic effects in rats and rabbits. The background risk of major birth defects and miscarriage for the indicated population are unknown.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is respectively. Advise pregnant women of the potential risk to a fetus. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk There is a risk to the mother from untreated schizophrenia, including increased risk of relapse, hospitalization, and suicide.
Schizophrenia is associated with increased adverse perinatal outcomes, including preterm birth. It is not known if this is a direct result of the illness or other comorbid factors. Fetal/Neonatal Adverse Reactions Extrapyramidal and/or withdrawal symptoms, including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress and feeding disorder have been reported in neonates who were exposed to antipsychotic drugs during the third trimester of pregnancy.
These symptoms have varied in severity. Monitor neonates for extrapyramidal and/or withdrawal symptoms and manage symptoms appropriately. Some neonates recover within hours or days without specific treatment; others required prolonged hospitalization.
Treatment at the highest dose caused a slight prolongation of gestation and delay in fetal development, as evidenced by decreased fetal weight, and undescended testes. Delayed skeletal ossification was observed at 3 and 10 times the oral MRHD based on mg/m 2. At 3 and 10 times the oral MRHD based on mg/m 2, delivered offspring had decreased body weights.
Increased incidences of hepatodiaphragmatic nodules and diaphragmatic hernia were observed in offspring from the highest dose group (the other dose groups were not examined for these findings). A low incidence of diaphragmatic hernia was also seen in the fetuses exposed to the highest dose. Postnatally, delayed vaginal opening was seen at 3 and 10 times the oral MRHD based on mg/m 2 and impaired reproductive performance (decreased fertility rate, corpora lutea, implants, live fetuses, and increased post-implantation loss, likely mediated through effects on female offspring) along with some maternal toxicity were seen at the highest dose; however, there was no evidence to suggest that these developmental effects were secondary to maternal toxicity.
Decreased fetal weight and increased incidence of fused sternebrae were observed at 3 and 11 times the oral MRHD based on AUC. An increase in stillbirths and decreases in pup weight (persisting into adulthood) and survival were also seen at this dose.
Pediatric Use of Aristada Initio
Pediatric Use Safety and effectiveness of ARISTADA INITIO in pediatric patients have not been established.
Contraindications for Aristada Initio
ARISTADA INITIO is contraindicated in patients with a known hypersensitivity reaction to aripiprazole. Hypersensitivity reactions have ranged from pruritus/urticaria to anaphylaxis. Known hypersensitivity to aripiprazole.
Overdosage Information for Aristada Initio
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.
Clinical Studies of Aristada Initio
The effectiveness of ARISTADA INITIO, in combination with oral aripiprazole, for initiation of ARISTADA when used for the treatment of schizophrenia in adults was established by adequate and well-controlled studies of oral aripiprazole and ARISTADA in adult patients with schizophrenia and a single PK bridging study.
Drug information sourced from the FDA. This content is for informational purposes only and does not constitute medical advice. Consult a healthcare professional before making any medication decisions.
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