Aripiprazole
ARIPIFY®
Category:
Antipsychotic
(USP DI)
Mechanism of action and Pharmacokinetics:
Aripiprazole activity is presumably due to the parent drug, aripiprazole and to a lesser extent, to its major metabolite dehydro-aripiprazole which has shown to have affinities for D2 receptors similar to parent drugs. The exact mechanism of action is not known. It is proposed that the drug exerts its pharmacological effects combination of partial agonist activity at D2 and 5-HT1A receptors and antagonist activity at 5-HT2A receptor.
(PDR)
Pharmacokinetics properties:
Bioavailability 87%
Oral absorption well absorbed from GIT, can be administered with or without food
Protein binding Very high (99%)
Elimination half life: 75 hrs for aripiprazole, 95 hrs for dehydro-aripiprazole and 146 hrs for poor metabolizers
T max 3-5 hrs
Excretion Renal: 25%
Fecal: 55%
Metabolism Dehydrogenation, hydroxylation and N-dealkylation by CYP3A4 and CYP2D6
(USP DI; Facts)
Indications:
• Bipolar disorder: for the acute and maintenance treatment of manic and mixed episodes associated with bipolar I disorder with or without psychotic features.
• MDD, adjunctive treatment: Adults- as an adjunctive treatment to antidepressants for MDD.
• Schizophrenia: Adults- for acute and maintenance treatment of schizophrenia.
Adolescents- for the treatment of schizophrenia in patients with 13-17 years of age.
(Facts)
Contraindication:
Hypersensitivity to aripiprazole, risk benefits have to be considered if there are: alcohol, drug abuse or dependence, history of Alzheimer dementia, aspiration pneumonia, cardiovascular disease, conduction abnormalities, dehydration, heart failure, hypovolemia, ischemic heart disease, MI, exposure to extreme heat, strenuous exercise, diabetes mellitus, obesity and family history of diabetes mellitus.
(PDR)
Warnings and precautions:
No tumorigenic potential was seen in male mice and rats. Increased in serum prolactin levels were observed in female mice. Aripiprazole and a metabolite were clastogenic in an in vitro chromosomal aberration assay in Chinese hamster lung cells with and without metabolic activity.
(USP DI)
Pregnancy:
FDA pregnancy category C, no adequate and well controlled studies in humans has been performed.
(PDR)
Breast feeding:
It is not known if aripiprazole is distributed in human breast milk. However it is distributed into the milk of lactating rats. It is recommended that women who take aripiprazole do not breast feed.
(PDR)
Drug interaction:
- Alcohol: aripiprazole may potentiate the cognitive and motor effects of alcohol
- Aripiprazole enhances the effect of antihypertensive medications with α1-adrenergic receptor antagonist.
- Carbamazepine and agents that induce CYP3A4 may increase aripiprazole clearance and lower its blood level by about 70%. The dose of aripiprazole should be doubled if carbamazepine is given along with it.
- Concomitant use of CNS stimulants or CNS depressants with aripiprazole.
- CYP3A4 inhibitors like itraconazole and ketoconazole may inhibit aripiprazole elimination and increase its blood level to 60%. The dose of aripiprazole should reduce to half if given with ketoconazole.
- CYP2D6 inhibitors including fluoxetine, paroxetine and quinidine may inhibit aripiprazole elimination and cause increased its blood level.
(PDR; Facts)
Adverse reactions:
Common adverse effects are GIT disorders such as constipation, dyspepsia, nausea and vomiting, headache, anxiety, insomnia, lightheadedness, drowsiness, gain weight, tardive dyskineasea, difficulty in speaking, drooling, loss of balance control, muscle trembling, jerking, restlessness, shuffling walk, stiffness of limbs, twisting movements of body, uncontrolled movement specially of face, neck and back, hypertension, blurred vision, dizziness, nervousness, pounding in ears and slow or fast heart beat.
(Fact)
Over dosage:
Common adverse reactions reported by aripiprazole over dosage include vomiting, somnolence and tremor. Other signs and symptoms of aripiprazole overdoses 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.
(PDR)
Storage:
Store blow 30°C and protect from humidity and direct light.
How supplied:
Aripiprazole is supplied as 10 mg oval, pink and scored tablets and 15 mg oval, yellow scored tablets. There are blisters of 10 in boxes of 30.
References:
1- Facts 2011
2- Martindale (37) 2011
3- PDR 2011
4- USP DI 2007