Aripiprazole

Aripiprazole (中文:阿立哌唑) is an atypical antipsychotic or 2nd Generation antipsychotic medication. It is mainly used in the treatment of

• Schizophrenia: there is little difference in effectiveness between antipsychotics in prevention of relapse, the specific choice of antipsychotic be chosen based on person’s preference and side-effect profile.
• bipolar disorder: aripiprazole is effective for the treatment of acute manic episodes of bipolar disorder.It is useful for the prevention of manic episodes, but is not useful for bipolar depression.
• adjuinct treatment of major depressive disoreder

Aripiprazole rebalances dopamine and serotonin to improve thinking, mood and behaviour.

Drug Names

Generic Name 藥名	HA Code 藥物代碼	Classification藥物分類
Aripiprazole Tab 5 mg	ARIP03	P1S1S3
Aripiprazole Tab 10 mg	ARIP01	P1S1S3
Aripiprazole Tab 15 mg	ARIP02	P1S1S3

Mechanism of Action

Aripiprazole is a dopamine D2 partial agonist. It is also a partial activator of serotonin 5-HT1A receptors. Aripiprazole acts by modulating neurotransmission overactivity of dopamine, which is thought to mitigate schizophrenia symptoms.

Dosage

Indication	Dose
Schizophrenia	By mouth ADULT: 10 – 15 mg once daily, Maximum 30 mg once daily
Treatment and recurrence prevention of mania	By mouth ADULT: 15 mg once daily Maximum 30 mg once daily
Adjunct treatment of major depressive disorder	By mouth ADULT: Initially 2- 5 mg once daily, Increased to 5 – 10 mg once daily Maximum 15 mg once daily

How long does it take for Amisulpride to work? The patient may start to feel better in a few days but it can take as long as 4 to 6 weeks before the full effects of this medication is noticed.

Side Effects

All side-effects are listed by system organ and frequency.

• Common ( ≥ 1/100 to < 1/10)
• Uncommon (≥ 1/1000 to < 1/100)

Endocrine disorders	Uncommon: hyperprolactinaemia (elevated levels of the hormone prolactin, which for females may result in Galactorrhea (unwanted breast milk) amornorrhea (missed/stopped periods), For males it may result in decreased sexual ability, or gynecomastia (enlarged breast)
Muscle/Nervous system disorders:	Common: Extrapyramidal symptoms (EPS) -Tremor -Akathisia -Parkinsonism Anticholinergic side-effects such as: -Dry mouth -Constipation -Blurred vision headache sedation somnolence dizziness salivary hypersecretion Uncommon: tardive dyskinesia and seizures Not known: Neuroleptic malignant syndrome
Psychiatric disorders	Common: Insomnia Anxiety Restlessness Uncommon: Depression hypersexuality
Metabolism disorders	Common: diabetes mellitus weight gain Uncommon: Hyponatraemia Anorexia
Cardiac disorders	Uncommon: tachycardia orthostatic hypotension

Pathological gambling, compulsive shopping and binge eating can occur in patients treated with aripiprazole.

It is not recommended for older people with dementia-related psychosis due to an increased risk of death. Discontinuation

It is recommended that gradual withdrawal when discontinuing antipsychotics. Symptoms of withdrawal commonly include nausea, vomiting and loss of appetite. Symptoms generally resolve after a short period of time.

Pharmacokinetics

Oral bioavailability	It is readily absorbed after oral doses.
Onset of action	Peak plasma concentrations are achieved 3 – 5 hours after an oral dose.
Metabolism	It is metabolized in the liver, principally by the enzymes CYP2D6 and CYP3A4
Elimination half-life	It is eliminated via urine and faeces. The elimination half-life is approximately 75 hours. Steady-state plasma concentrations are achieved in about 14 days.

Drug Management

Monitoring

The following populations must be closely monitored after administration of aripiprazole:

• Elderly persons with susceptibility to drowsiness, confusion, and unsteadiness, which may increase the risk of fall
• Patients with severe liver failure because of the risk of accumulation.
• Patients on long-term treatment should receive regular eye examinations.
• Diabetic patients should get monitoring blood sugar levels during treatment.
• Changes in mood, the development or worsening depression, and/or any thoughts or behaviour of suicide.
• Be careful while taking antihistamines (chlorpheniramine), sleeping tablets while taking this medicine. Aripiprazole can increase drowsiness caused by medicines affecting the nervous system.
• Tell the doctor if notice any of the following:

-Abnormal movements of the face or tongue -Yellowing of the skin and eyes, that is jaundice -Muscle twitching

• Report to the doctor if absence of monthly periods for 6 months or more

Drug interaction

Aripiprazole is metabolized by multiple pathways involving the CYP2D6 and CYP3A4 enzymes but not CYP1A enzymes. Thus, no dosage adjustment is required for smokers.

Drugs given with aripiprazole	Potential Effect
CNS-depressant drugs including alcohol, hypnotics, anxiolytics, sedative H1 antihistamines, central antihypertensives, baclofen, thalidomide and opioids.	Potentiates the sedative effect.
Strong CYP2D6 inhibitors such as qunindine, fluoxetine and paroxetine.	May result in higher plasma concentrations of aripiprazole, aripiprazole dose should be reduced to approximately one-half of its prescribed dose.
Strong CYP3A4 inhibitors, such as itraconazole and HIV protease inhibitors	May result in higher plasma concentrations of aripiprazole, so aripiprazole dose should be reduced.
Strong CYP3A4 inducers, such as carbamazepine, rifampicin, phenytoin, phenobarbitone and St John’s Wort.	May lower plasma concentrations of aripiprazole, so should increase aripiprazole dose.
Antiparkinsonian drugs (amantadine, bromocriptine, levodopa, ropinirole)	Antipsychotics with dopamine-blocking activity and dopaminergic drugs such as those used to treat parkinsonism may be mutually antagonistic.
Drugs that prolong the QT interval e.g. amiodarone, sotalol, quinidine Drugs which induce bradycardia e.g. diltiazem, verapamil Drugs which can cause hypokalaemia such as diuretics e.g. frusemide	An increased risk of ventricular arrhythmias – avoid concomitant use.

Caution

• In patients with cerebrovascular disease
• In patients with a history of jaundice or who have blood dyscrasias (perform blood counts if unexplained infection or fever develops)
• In patients with Parkinson’s disease
• In patients with epilepsy
• In patients with myasthenia gravis
• A susceptibility to angle-closure glaucoma
• In those with diabetes mellitus
• In patients with paralytic ileus
• In patients with prostatic hyperplasia or urinary retention
• The elderly, especially those with dementia.

Contra-indications

Use of aripiprazole should be avoided in individuals with:

• CNS depression
• Comatose states
• Phaeochromocytoma

Hepatic impairment

Use with caution in severe impairment

Pregnancy

Should be avoided in pregnancy.

Breast-feeding

Use during breast feeding should be avoided.

Driving and skilled tasks

Drivers and machine operators should be told about the risk of drowsiness with this medication especially at the start of treatment. Affected patients should not drive or operate machinery.

FAQ

How should I take the tablet?

You will be prescribed the lowest dose needed to control your symptoms. The tablet should be swallowed whole with a glass of water. It may take 4 to 6 weeks before you get the full benefit of this medication. Do not stop taking this medication without consulting your doctor. You may experience symptoms such as upset stomach, nausea, vomiting, dizziness and shakiness.

What should I avoid while taking?

Avoid drinking alcohol while taking aripiprazole because it may enhance the side effects of sedation.

Avoid getting up too fast from a sitting or lying position, or you may feel dizzy.

What happen if I overdose?

A : Contact your primary care doctor. If emergency situation, call 999

What happen if I miss a dose?

Take it as soon as you remember. If it is near the time of the next dose, skip the missed dose. Take your next dose at the regular time. Do not double the dose to catch up.