Amisulpride

Amisulpride(中文:[[ ]]) is an atypical antipsychotic or 2nd Generation antipsychotic medication. It is used to treat acute and chronic schizophrenia, in which

• positive symptoms (such as delusions, hallucinations, thought disorders) and/or
• negative symptoms (such as blunted affect, emotional and social withdrawal) are prominent.

Pronunciation

Amisulpride 100mg

Amisulpride 400mg

Drug Names

Generic Name 藥名	HA Code 藥物代碼	Classification藥物分類
Amisulpride Tab 100 mg	AMIS01	P1S1S3
Amisulpride Tab 200 mg	AMIS02	P1S1S3
Amisulpride Tab 400 mg	AMIS04	P1S1S3

Mechanism of Action

Amisulpride selectively blocks dopamine D2 receptors in the brain. It has no affinity for serotonic, α-adrenergic, histamine H1 and cholinergic receptors. The effectiveness of amisulpride in treating the negative symptoms of schizophrenia is due to its blockade of the presynaptic dompamine D2 receptors. By blocking them amisulpride increases dopamine concentrations in the synapse. This increased dopamine is theorized to act on dopamine D1 receptors to relieve the negative symptoms of schizophrenia.

Dosage

Indication	Dose
Acute psychotic episode in Schizophrenia	By mouth ADULT: 400 - 800 mg daily in 2 divided doses, adjusted according to response; Maximum 1.2 g per day
Schizophrenia with predominantly negative symptoms	By mouth ADULT: 50 – 300 mg daily

How long does it take for Amisulpride to work?

The patient may start to feel better in a short time but it can take as long as 6 to 8 weeks before the benefits of this medicine is noticed.

Side Effects

It produces a moderate degree of extrapyramidal symptoms (EPS. These symptoms include:

• Drooling/trouble swallowing
• Restlessness/constant need to move
• Shaking (tremor)
• Shuffling walk
• Stiff muscles
• Severe muscle spasms/cramping (such as twisting neck, arching back, eyes rolling up)
• Mask-like expression of the face
• Tardive dyskinesia (any uncontrollable movements such as lip smacking, mouth puckering, tongue thrusting, chewing, or unusual arm/leg movements

Other adverse effects include the following:

Endocrine disorders	Common: 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) Rare: benign pituitary tumour such as prolactinoma
Muscle/Nervous system disorders:	Common: Extrapyramidal symptoms (EPS) -Tremor -Akathisia -Parkinsonism -hypersalivation Anticholinergic side-effects such as: -Dry mouth -Constipation -Blurred vision Insomnia Anxiety Agitation Nausea and vomiting Uncommon: tardive dyskinesia and seizures Rare: Neuroleptic malignant syndrome
Metabolism disorders	Uncommon: hyperglycemia Rare: Hyponatraemia Syndrome of inappropriate antidiuretic hormone secretion (SIADH)
Cardiac disorders	Common: hypotension Rare: Ventricular arrhythmia Ventricular fibrillation, or tachycardia QT interval prolongation
Hypersensitivity reactions	Increased sensitivity to the sun or notice symptoms of sunburn (such as redness, swelling, blistering) which may occur more quickly than normal
Investigations	Common: weight gain

Pharmacokinetics

Oral bioavailability	It is readily absorbed after oral doses.
Onset of action	It shows two absorption peaks: one is attained rapidly, one hour post-dose and a second between 3 and 4 hours after administration. Peak plasma concentrations are reached 1.5 – 6 hours after an oral dose.
Metabolism	It is metabolized in the liver
Elimination half-life	It is predominantly eliminated in the urine. The elimination half-life is approximately 12 hours.

Drug Management

Monitoring

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

• Elderly persons with susceptibility to drowsiness, confusion, and unsteadiness, which may increase the risk of fall
• Patients with severe liver and/or renal 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.
• May cause increased susceptibility to sunburn and individuals should avoid undue exposure to direct sunlight.
• 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. Ampisulpride 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 -An absence of monthly periods for 6 months or more

Drug interaction

The most common interactions encountered with amisulpride result from use with drugs that have similar pharmacological actions, for example:

Amisulpride may aggravate Parkinsonism and antagonize the action of levodopa.

Drugs given with amisulpride	Potential Effect
CNS-depressant drugs including alcohol, hypnotics, anxiolytics, sedative H1 antihistamines, central antihypertensives, baclofen, thalidomide and opioids.	Potentiates the sedative effect.
Antipsychotics such as clozapine	Imprudent to combine antipsychotics due to additive risk for tardive dyskinesia and neuroleptic malignant syndrome.
Lithium	Increased risk of extrapyramidal side-effects when antipsychotics given with lithium.
•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 impaired liver, kidney, and cardiovascular function
• In patients with a history of jaundice, parkinsonism
• 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 amisulpride should be avoided in individuals with:

• CNS depression
• Comatose states
• Phaeochromocytoma
• Prolactin-dependent tumours e.g. prolactinoma, breast cancer

Hepatic impairment

Since the drug is weakly metabolized a dosage reduction should not be necessary

Renal impairment

• Halve dose with creatinine clearance between 30 – 60 ml/minute
• Use one-third dose with creatinine clearance between 10 – 30 ml/minute

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.