ARIPITAS 20 TABLETS

Indications

• Schizophrenia
• Bipolar disorder (mania)
• Psychotic disorders

Dosage

Children: For children aged 13-17 years: Initially 2 mg once daily for 2 days, increased to 5 mg once daily for 2 days, then can be increased to 10 mg once daily, with further increments of 5 mg if needed. Maximum treatment duration is 12 weeks, and doses above 10 mg should only be used in exceptional cases.

Adults: Initially, 10-15 mg once daily, can be adjusted based on clinical response and tolerability, with a maximum dose of 30 mg daily.

Mechanism of action

Aripiprazole acts as a partial agonist at dopamine D2 receptors and serotonin 5-HT1A receptors, while also functioning as an antagonist at 5-HT2A receptors. This unique action helps to stabilize mood and reduce psychotic symptoms.

Pharmacodynamics

Aripiprazole has a complex pharmacodynamic profile, contributing to its antipsychotic effects by balancing dopaminergic and serotonergic activity in the central nervous system. This modulation helps alleviate both positive and negative symptoms of schizophrenia.

Pharmacokinetics

Aripiprazole is well absorbed orally and has a half-life of approximately 75 hours, allowing for once-daily dosing. It is extensively metabolized in the liver, primarily by CYP3A4 and CYP2D6, with less than 1% of the drug excreted unchanged in urine. Dose adjustments may be necessary in cases of renal impairment.

Contra-indications

• CNS depression
• Comatose state
• Phaeochromocytoma

Adverse effects

• Anxiety
• Breast pain
• Hypersalivation
• Muscle rigidity
• Nausea
• Oculogyric crisis
• Hyperglycaemia
• Angioedema
• Bone disorders
• Confusion
• Dyslipidaemia
• Hyponatraemia
• Nasal congestion
• Urticaria
• Vision disorders
• Depression
• Hiccups
• Sexual dysfunction
• Aggression
• Alopecia
• Cardiac arrest
• Chest pain
• Diabetic hyperosmolar coma
• Diabetic ketoacidosis
• Diarrhoea
• Dysphagia
• Generalised tonic-clonic seizures
• Rhabdomyolysis
• Serotonin syndrome
• Speech disorder
• Suicidal tendencies
• Syncope
• Temperature regulation disorder
• Thrombocytopenia
• Urinary incontinence
• Weight decreased

Interactions

• Bupropion: Unknown (increases exposure)
• Cinacalcet: Unknown (increases exposure)
• Cobicistat: Unknown (increases exposure)
• Idelalisib: Unknown (increases exposure)
• Mitotane: Unknown (decreases exposure)
• Clarithromycin: Unknown (increases exposure)

Precautions

• Cerebrovascular disease

Pregnancy

Avoid.

Breast-feeding

Avoid-no information available.

Storage

Store in a cool, dry place away from light.

Formulations

• Oral suspension
• Oral solution
• Tablets

Mechanism of action

The antipsychotic action of aripiprazole is likely due to its partial agonist activity on D2 and 5-HT_1A receptors as well as its antagonist activity at 5-HT_2A receptors; however, the exact mechanism has not been fully elucidated. One of the mechanisms that have been proposed is that aripiprazole both stimulates and inhibits dopamine as it engages the D2 receptor. It lowers dopamine neuronal firing at high dopamine concentrations and increases dopamine firing at low concentrations. Its partial agonist activity gives aripiprazole an intermediate level of dopaminergic neuronal tone between full agonist and antagonist of the D2 receptor. In addition, some adverse effects may be due to action on other receptors. For example, orthostatic hypotension may be explained by antagonism of the adrenergic alpha-1 receptors. The exact mechanism of antipsychotic action of aripiprazole has not been fully elucidated but, like that of other atypical antipsychotic agents (e.g.,olanzipine, risperidone, ziprasidon), may involve the drug's activity at dopamine D2 and serotonin type (5-HT1A) and type 2 (5-HT2A) receptors. However, aripiprazole appears to differ from other atypical antipsychotic agents because the drug demonstrates partial agonist activity at D2 and 5-HT1A receptors and antagonist activity at 5-HT2A receptors. Antagonism at other receptors (e.g., alpha1-adrenergic receptors, histamine H1 receptors) may contribute to other therapeutic and adverse effects (e.g., orthostatic hypotension, somnolence) observed with aripiprazole. ...Aripiprazole exhibits typical antagonism at dopamine (D2) receptors in the mesolimbic pathway, as well as having unique partial agonist activity at D2 receptors in the mesocortical pathway. As exemplified by other atypical antipsychotics, it displays strong 5-HT(2a) receptor antagonism and is similar to ziprasidone in also having agonistic activity at the 5-HT(1a) receptor. Among the atypical antipsychotics, aripiprazole displays the lowest affinity for alpha(1)adrenergic (alpha(1)), histamine (H1) and muscarinic (M1) receptors. This combination of effects may be responsible for its efficacy in positive and negative symptoms of schizophrenia and in bipolar disorder. ...Other early data suggest that aripiprazole may induce reductions in plasma prolactin, as well as in plasma glucose and lipid profiles ...

Pharmacodynamics

Aripiprazole exhibits high affinity for dopamine D₂ and D₃, serotonin 5-HT_1a and 5-HT_2a receptors (Ki values of 0.34 nM, 0.8 nM, 1.7 nM, and 3.4 nM, respectively), moderate affinity for dopamine D₄, serotonin 5-HT_2c and 5-HT₇, alpha₁-adrenergic and histamine H₁ receptors (Ki values of 44 nM, 15 nM, 39 nM, 57 nM, and 61 nM, respectively), and moderate affinity for the serotonin reuptake site (Ki=98 nM). Aripiprazole has no appreciable affinity for cholinergic muscarinic receptors (IC₅₀>1000 nM).