Term
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Definition
Trade Name: Abilify
Dosage Forms: Tablet,Oral Soln,IM
Indications:
Treatment of schizophrenia; stabilization and maintenance therapy of bipolar disorder (with acute manic or mixed episodes); agitation associated with schizophrenia or bipolar mania
MOA:
Aripiprazole is a quinolinone atypical antipsychotic which exhibits high affinity for D2, D3, 5-HT1A, and 5-HT2A receptors; moderate affinity for D4, 5-HT2C, 5-HT7, alpha1 adrenergic, and H1 receptors. It also possesses moderate affinity for the serotonin reuptake transporter; has no affinity for muscarinic (cholinergic) receptors. Aripiprazole functions as a partial agonist at the D2 and 5-HT1A receptors, and as an antagonist at the 5-HT2A receptor
PK:
1-3 week onset.CYP2D6, CYP3A4 metabolism.Half life 74 hours.Renal elimination 25%. Protein bound 99%. IM 100% BioA, Oral 87%
MPs:
VS,FLP,FBG/HgbA1c (prior to treatment, at 3 months, then annually); BMI, personal/family history of diabetes, waist circumference,BP,mental status,abnormal involuntary movement scale (AIMS),extrapyramidal symptoms (EPS).Weight should be assessed prior to treatment, at 4 weeks, 8 weeks, 12 weeks, and then at quarterly intervals. Consider titrating to a different antipsychotic agent for a weight gain ≥5% of the initial weight.
DIs:
Aripiprazole is a major substrate of CYP2D6/3A4
Acetylcholinesterase inhibitors (central): May increase the risk of antipsychotic-related extrapyramidal symptoms; monitor.
Carbamazepine: Carbamazepine may decrease aripiprazole levels. Manufacturer recommends a doubling of the aripiprazole dose when carbamazepine is added.
CNS depressants: May increase the adverse effects/toxicity of other CNS depressants; monitor.
CYP2D6 inhibitors: May increase the levels/effects of aripiprazole. Example inhibitors include chlorpromazine, delavirdine, fluoxetine, miconazole, paroxetine, pergolide, quinidine, quinine, ritonavir, and ropinirole.
CYP3A4 inducers: CYP3A4 inducers may decrease the levels/effects of aripiprazole. Example inducers include aminoglutethimide, carbamazepine, nafcillin, nevirapine, phenobarbital, phenytoin, and rifamycins.
CYP3A4 inhibitors: May increase the levels/effects of aripiprazole. Example inhibitors include azole antifungals, clarithromycin, diclofenac, doxycycline, erythromycin, imatinib, isoniazid, nefazodone, nicardipine, propofol, protease inhibitors, quinidine, telithromycin, and verapamil.
Ketoconazole: Ketoconazole may increase aripiprazole levels. Manufacturer recommends a 50% reduction in aripiprazole dose during concurrent ketoconazole therapy.
Lithium: May increase neurotoxic effects of antipsychotics; monitor.
Quinidine: May increase the levels/effects of aripiprazole. Manufacturer recommends a 50% reduction in aripiprazole dose during concomitant therapy.
ADR:
>10%:
Central nervous system: Headache (31%; injection 12%), agitation (25%), anxiety (20%), insomnia (20%), extrapyramidal symptoms (6% to 17%), somnolence (12% to 15%, dose related; injection 7%), akathisia (12% to 15%; injection 2%), lightheadedness (11%)
Gastrointestinal: Nausea (16%; injection 9%), dyspepsia (15%; injection 1%), constipation (11% to 13%), vomiting (11%; injection 3%), weight gain (8% to 30%, highest frequency in patients with BMI <23)
CI:
Dementia
Patients with dementia-related psychosis treated with atypical antipsychotics are at an increased risk of death compared to placebo. An increased incidence of cerebrovascular adverse events (including fatalities) has been reported in elderly patients with dementia-related psychosis. Risk may be increased by dehydration; use caution with concurrent diuretics. Aripiprazole is not approved for this indication.
Counsel:
Avoid EtOH
Meals high in fat delay peak plasma
Monitor BG.
2-3L fluid/day
HA,dizziness,anxiety,N/V,ortho HoTN
Potential weight gain
Pregnancy Category C |
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