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| Clinical data | |
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| Trade names | Aristada, Aristada Initio |
| Other names | N-Lauroyloxymethylaripiprazole; ALKS-9070; ALKS-9072; RDC-3317;Dodecanoic acid-[7-[4-[4-(2,3-dichlorophenyl)-1-piperazinyl]butoxy]-3,4-dihydro-2-oxo-1(2H)-quinolinyl]methyl ester |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a615048 |
| License data | |
| Pregnancy category | |
| Routes of administration | Intramuscular |
| ATC code |
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| Legal status | |
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| Identifiers | |
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| CAS Number | |
| PubChemCID | |
| DrugBank | |
| ChemSpider | |
| UNII | |
| KEGG | |
| ChEBI | |
| ChEMBL | |
| CompTox Dashboard(EPA) | |
| ECHA InfoCard | 100.261.570 |
| Chemical and physical data | |
| Formula | C36H51Cl2N3O4 |
| Molar mass | 660.72 g·mol−1 |
| 3D model (JSmol) | |
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Aripiprazole lauroxil, sold under the brand nameAristada among others, is along-actinginjectableatypical antipsychotic that was developed byAlkermes.[4][5][6] It is an N-acyloxymethylprodrug ofaripiprazole that is administered viaintramuscular injection once every four to eight weeks for the treatment ofschizophrenia.[4][5][6] Aripiprazole lauroxil was approved by the USFood and Drug Administration (FDA) in October 2015.[7][8][9]
Aripiprazole lauroxil isindicated for the treatment of schizophrenia in adults.[2]
Aripiprazole lauroxil is a longer-lasting and injectable version of the schizophrenia pillaripiprazole.[2] Aripiprazole lauroxil, along with other drugs in its family, are not approved for treatment of the elderly withdementia-related psychosis.[2][10]
The most common side effects areakathisia. According to the drug's warning label and safety information, the side effects are large in variety.[11]
The complete list of side effects include: akathisia, contraindication cerebrovascular adverse reactions (including stroke),neuroleptic malignant syndrome, tardive dyskinesia, metabolic changes,hyperglycemia/diabetes mellitus,dyslipidemia, weight gain,orthostatic hypotension,leukopenia,neutropenia,agranulocytosis, seizures, potential for cognitive and motor impairment, difficulties with body temperature regulation,dysphagia, injection site reactions (rash, swelling, redness, irritation at the point of injection),dystonia and pregnancy and nursing complications.[2]
TheBritish National Formulary recommends a gradual withdrawal when discontinuing antipsychotics to avoid acute withdrawal syndrome or rapid relapse.[12] Symptoms of withdrawal commonly include nausea, vomiting, and loss of appetite.[13] Other symptoms may include restlessness, increased sweating, and trouble sleeping.[13] Less commonly there may be a feeling of the world spinning, numbness, or muscle pains.[13] Symptoms generally resolve after a short period of time.[13]
There is tentative evidence that discontinuation of antipsychotics can result in psychosis.[14] It may also result in reoccurrence of the condition that is being treated.[15] Rarely tardive dyskinesia can occur when the medication is stopped.[13]
The largest known case of ingestion with a known outcome involved a 1260 mg of oral aripiprazole, 42 times the recommended dose. The patient survived and fully recovered.[citation needed]
Common adverse reactions, reported in at least 5% of overdose cases, includedvomiting,somnolence, and tremor. Other clinically important signs and symptoms of overdoses includeacidosis,aggression,atrial fibrillation,bradycardia,coma, confusion,convulsion, depressed level of consciousness,hypertension,hypokalemia,hypotension,lethargy, loss of consciousness, pneumonia aspiration,respiratory arrest,status epilepticus, andtachycardia.[16]
Arristada is injected intramuscularly as an atypicalantipsychotic. In one 12-week clinical trial involving 622 participants, the efficacy of extended aripiprazole was demonstrated.[10][2] Its mechanism of action is not completely known, but is thought to be converted by enzyme-mediatedhydrolysis to N-hydroxymethyl aripiprazole. The hydroxymethyl aripiprazole is thenhydrolysed to aripiprazole. Efficacy could be mediated through a combination of partial agonist activity D2 and5-HT1A receptors and antagonist activity at5-HT2A receptors. Since it is a newly[when?] approved drug by the FDA, many validation of mechanisms of action are still being studied.[2][needs update]
Aripiprazole exhibits high affinity forserotonin5-HT1A,5-HT2A receptors,dopamine D2, anddopamine D3. Moderate affinity is exhibited for serotonin5-HT7, α1-adrenergic,dopamine D4,histamine H1, and serotonin re-uptake site. No affinity for cholinergic muscarinic receptors have been found.[2]
Aristada's activity in the body is due to aripiprazole and also dehydro-aripiprazole. Dehydro-aripiprazole has been shown to have affinities for D2 receptors. These D2 receptors have similarities to aripiprazole whereas they represent 30-40% of exposure of aripiprazole in plasma.[citation needed]
After five to six days of the single intramuscular injection appearance of aripiprazole in circulation, it additionally will be released for 36 days. In the fourth monthly injection, consecutive doses of Aristada will reach steady-state. With additional supplements of the oral aripiprazole at a dosage of 21 days during the first dose of Aristada, aripiprazole concentrations within 4 days can reach therapeutic levels.[2]
| Medication | Brand name | Class | Vehicle | Dosage | Tmax | t1/2 single | t1/2 multiple | logPc | Ref |
|---|---|---|---|---|---|---|---|---|---|
| Aripiprazole lauroxil | Aristada | Atypical | Watera | 441–1064 mg/4–8 weeks | 24–35 days | ? | 54–57 days | 7.9–10.0 | |
| Aripiprazole monohydrate | Abilify Maintena | Atypical | Watera | 300–400 mg/4 weeks | 7 days | ? | 30–47 days | 4.9–5.2 | |
| Bromperidol decanoate | Impromen Decanoas | Typical | Sesame oil | 40–300 mg/4 weeks | 3–9 days | ? | 21–25 days | 7.9 | [17] |
| Clopentixol decanoate | Sordinol Depot | Typical | Viscoleob | 50–600 mg/1–4 weeks | 4–7 days | ? | 19 days | 9.0 | [18] |
| Flupentixol decanoate | Depixol | Typical | Viscoleob | 10–200 mg/2–4 weeks | 4–10 days | 8 days | 17 days | 7.2–9.2 | [18][19] |
| Fluphenazine decanoate | Prolixin Decanoate | Typical | Sesame oil | 12.5–100 mg/2–5 weeks | 1–2 days | 1–10 days | 14–100 days | 7.2–9.0 | [20][21][22] |
| Fluphenazine enanthate | Prolixin Enanthate | Typical | Sesame oil | 12.5–100 mg/1–4 weeks | 2–3 days | 4 days | ? | 6.4–7.4 | [21] |
| Fluspirilene | Imap, Redeptin | Typical | Watera | 2–12 mg/1 week | 1–8 days | 7 days | ? | 5.2–5.8 | [23] |
| Haloperidol decanoate | Haldol Decanoate | Typical | Sesame oil | 20–400 mg/2–4 weeks | 3–9 days | 18–21 days | 7.2–7.9 | [24][25] | |
| Olanzapine pamoate | Zyprexa Relprevv | Atypical | Watera | 150–405 mg/2–4 weeks | 7 days | ? | 30 days | – | |
| Oxyprothepin decanoate | Meclopin | Typical | ? | ? | ? | ? | ? | 8.5–8.7 | |
| Paliperidone palmitate | Invega Sustenna | Atypical | Watera | 39–819 mg/4–12 weeks | 13–33 days | 25–139 days | ? | 8.1–10.1 | |
| Perphenazine decanoate | Trilafon Dekanoat | Typical | Sesame oil | 50–200 mg/2–4 weeks | ? | ? | 27 days | 8.9 | |
| Perphenazine enanthate | Trilafon Enanthate | Typical | Sesame oil | 25–200 mg/2 weeks | 2–3 days | ? | 4–7 days | 6.4–7.2 | [26] |
| Pipotiazine palmitate | Piportil Longum | Typical | Viscoleob | 25–400 mg/4 weeks | 9–10 days | ? | 14–21 days | 8.5–11.6 | [19] |
| Pipotiazine undecylenate | Piportil Medium | Typical | Sesame oil | 100–200 mg/2 weeks | ? | ? | ? | 8.4 | |
| Risperidone | Risperdal Consta | Atypical | Microspheres | 12.5–75 mg/2 weeks | 21 days | ? | 3–6 days | – | |
| Zuclopentixol acetate | Clopixol Acuphase | Typical | Viscoleob | 50–200 mg/1–3 days | 1–2 days | 1–2 days | 4.7–4.9 | ||
| Zuclopentixol decanoate | Clopixol Depot | Typical | Viscoleob | 50–800 mg/2–4 weeks | 4–9 days | ? | 11–21 days | 7.5–9.0 | |
| Note: All byintramuscular injection.Footnotes:a =Microcrystalline ornanocrystallineaqueous suspension.b = Low-viscosityvegetable oil (specificallyfractionated coconut oil withmedium-chain triglycerides).c = Predicted, fromPubChem andDrugBank.Sources:Main: See template. | |||||||||
In contrast to many otherdepot antipsychotics, aripiprazole lauroxil is described as a non-esterchemical modification.[27] It is specificallyN-lauroyloxymethylaripiprazole.[27] However, theN-lauroyloxymethylmoiety contains alaurate ester, technically making aripiprazole lauroxil anantipsychotic ester.[28] More specifically, aripiprazole lauroxil is thelaurate ester ofN-hydroxymethylaripiprazole.[4] Followingcleavage of the laurate ester,N-hydroxymethylaripiprazole is further metabolized to aripiprazole, making aripiprazole lauroxil aprodrug of aripiprazole withN-hydroxymethylaripiprazole as an intermediate.[28][27]
Withdrawal of antipsychotic drugs after long-term therapy should always be gradual and closely monitored to avoid the risk of acute withdrawal syndromes or rapid relapse.
