Zuclopenthixol (brand names Cisordinol, Clopixol and others), also known as zuclopentixol, is a medication used to treat

schizophrenia Schizophrenia is a mental disorder characterized by continuous or relapsing episodes of psychosis. Major symptoms include hallucinations (typically hearing voices), delusions, and disorganized thinking. Other symptoms include social w ...

and other

psychoses Psychosis is a condition of the mind that results in difficulties determining what is Reality, real and what is not real. Symptoms may include delusions and hallucinations, among other features. Additional symptoms are thought disorder, incohe ...

. It is classed, pharmacologically, as a

typical antipsychotic Typical antipsychotics (also known as major tranquilizers, and first generation antipsychotics) are a class of antipsychotic drugs first developed in the 1950s and used to treat psychosis (in particular, schizophrenia). Typical antipsychotics ma ...

. Chemically it is a

thioxanthene Thioxanthene is a chemical compound in which the oxygen atom in xanthene is replaced with a sulfur atom. It is also related to phenothiazine. Several of its derivatives are used as typical antipsychotics in the treatment of schizophrenia and othe ...

. It is the '' cis''-

isomer In chemistry, isomers are molecules or polyatomic ions with identical molecular formulae – that is, same number of atoms of each element – but distinct arrangements of atoms in space. Isomerism is existence or possibility of isomers. Is ...

of clopenthixol (Sordinol, Ciatyl). Clopenthixol was introduced in 1961, while zuclopenthixol was introduced in 1978. Zuclopenthixol is a D₁ and D₂ antagonist, α₁-adrenergic and 5-HT₂ antagonist. While it is approved for use in Australia, Canada, Ireland, India, New Zealand, Singapore, South Africa and the UK it is not approved for use in the United States.

Medical uses

Available forms

Zuclopenthixol is available in three major preparations: * As zuclopenthixol decanoate (Clopixol Depot, Cisordinol Depot), it is a long-acting intramuscular injection. Its main use is as a long-acting injection given every two or three weeks to people with

who have a poor compliance with medication and suffer frequent relapses of illness. There is some evidence it may be more helpful in managing aggressive behaviour. * As zuclopenthixol acetate (Clopixol-Acuphase, Cisordinol-Acutard), it is a shorter-acting intramuscular injection used in the acute sedation of psychotic inpatients. The effect peaks at 48–72 hours providing 2–3 days of sedation. * As zuclopenthixol dihydrochloride (Clopixol, Cisordinol), it is a tablet used in the treatment of schizophrenia in those who are compliant with oral medication. It is also used in the treatment of acute bipolar mania.

Dosing

As a long-acting injection, zuclopenthixol decanoate comes in a 200 mg and 500 mg ampoule. Doses can vary from 50 mg weekly to the maximum licensed dose of 600 mg weekly. In general, the lowest effective dose to prevent relapse is preferred. The interval may be shorter as a patient starts on the medication before extending to 3 weekly intervals subsequently. The dose should be reviewed and reduced if side effects occur, though in the short-term an anticholinergic medication

benztropine Benzatropine ( INN), known as benztropine in the United States and Japan, is a medication used to treat movement disorders like parkinsonism and dystonia, as well as extrapyramidal side effects of antipsychotics, including akathisia. It is not u ...

may be helpful for tremor and stiffness, while

diazepam Diazepam, first marketed as Valium, is a medicine of the benzodiazepine family that acts as an anxiolytic. It is commonly used to treat a range of conditions, including anxiety, seizures, alcohol withdrawal syndrome, muscle spasms, insomnia, ...

may be helpful for akathisia. 100 mg of zuclopenthixol decanoate is roughly equivalent to 20 mg of flupentixol decanoate or 12.5 mg of

fluphenazine Fluphenazine, sold under the brand name Prolixin among others, is a high-potency typical antipsychotic medication. It is used in the treatment of chronic psychoses such as schizophrenia, and appears to be about equal in effectiveness to low-pote ...

decanoate. In acutely psychotic and agitated inpatients, 50 – 200 mg of zuclopenthixol acetate may be given for a calming effect over the subsequent three days, with a maximum dose of 400 mg in total to be given. As it is a long-acting medication, care must be taken not to give an excessive dose. In oral form zuclopenthixol is available in 10, 25 and 40 mg tablets, with a dose range of 20–60 mg daily.

Side effects

Chronic administration of zuclopenthixol (30 mg/kg/day for two years) in rats resulted in small, but significant, increases in the incidence of thyroid parafollicular carcinomas and, in females, of mammary adenocarcinomas and of pancreatic islet cell adenomas and carcinomas. An increase in the incidence of mammary adenocarcinomas is a common finding for D₂ antagonists which increase prolactin secretion when administered to rats. An increase in the incidence of pancreatic islet cell tumours has been observed for some other D₂ antagonists. The physiological differences between rats and humans with regard to prolactin make the clinical significance of these findings unclear.

Withdrawal syndrome Drug withdrawal, drug withdrawal syndrome, or substance withdrawal syndrome, is the group of symptoms that occur upon the abrupt discontinuation or decrease in the intake of pharmaceutical or recreational drugs. In order for the symptoms of with ...

: Abrupt cessation of therapy may cause acute withdrawal symptoms (eg, nausea, vomiting, or insomnia). Symptoms usually begin in 1 to 4 days of withdrawal and subside within 1 to 2 week

https://www.uptodate.com/contents/zuclopenthixol-united-states-not-available-drug-information?search=Zuclopenthixol&topicRef=15250&source=see_link#F236382] Other permanent side effects are similar to many other typical antipsychotics, namely

extrapyramidal symptoms Extrapyramidal symptoms (EPS) are symptoms that are archetypically associated with the extrapyramidal system of the brain's cerebral cortex. When such symptoms are caused by medications or other drugs, they are also known as extrapyramidal side ...

as a result of dopamine blockade in subcortical areas of the brain. This may result in symptoms similar to those seen in

Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms beco ...

and include a restlessness and inability to sit still known as

akathisia Akathisia is a movement disorder characterized by a subjective feeling of inner restlessness accompanied by mental distress and an inability to sit still. Usually, the legs are most prominently affected. Those affected may fidget, rock back a ...

, a slow tremor and stiffness of the limbs. Zuclopenthixol is thought to be more sedating than the related

flupentixol Flupentixol (INN), also known as flupenthixol (former BAN), marketed under brand names such as Depixol and Fluanxol is a typical antipsychotic drug of the thioxanthene class. It was introduced in 1965 by Lundbeck. In addition to single drug pre ...

, though possibly less likely to induce extrapyramidal symptoms than other typical depots. As with other dopamine antagonists, zuclopenthixol may sometimes elevate

prolactin Prolactin (PRL), also known as lactotropin, is a protein best known for its role in enabling mammals to produce milk. It is influential in over 300 separate processes in various vertebrates, including humans. Prolactin is secreted from the pi ...

levels; this may occasionally result in

amenorrhoea Amenorrhea is the absence of a menstrual period in a woman of reproductive age. Physiological states of amenorrhoea are seen, most commonly, during pregnancy and lactation (breastfeeding). Outside the reproductive years, there is absence of mense ...

galactorrhoea Galactorrhea ( also spelled galactorrhoea) ( galacto- + -rrhea) or lactorrhea ( lacto- + -rrhea) is the spontaneous flow of milk from the breast, unassociated with childbirth or nursing. Galactorrhea is reported to occur in 5–32% of women. M ...

in severe cases.

Neuroleptic malignant syndrome Neuroleptic malignant syndrome (NMS) is a rare but life-threatening reaction that can occur in response to neuroleptic or antipsychotic medication. Symptoms include high fever, confusion, rigid muscles, variable blood pressure, sweating, and fa ...

is a rare but potentially fatal side effect. Any unexpected deterioration in mental state with confusion and muscle stiffness should be seen by a physician. Zuclopenthixol decanoate induces a transient dose-dependent sedation. However, if the patient is switched to maintenance treatment with zuclopenthixol decanoate from oral zuclopenthixol or from i.m. zuclopenthixol acetate the sedation will be no problem. Tolerance to the unspecific sedative effect develops rapidly. ;Very common Adverse Effects (≥10% incidence) * Dry Mouth *

Somnolence Somnolence (alternatively sleepiness or drowsiness) is a state of strong desire for sleep, or sleeping for unusually long periods (compare hypersomnia). It has distinct meanings and causes. It can refer to the usual state preceding falling asleep ...

Akathisia Akathisia is a movement disorder characterized by a subjective feeling of inner restlessness accompanied by mental distress and an inability to sit still. Usually, the legs are most prominently affected. Those affected may fidget, rock back a ...

Hyperkinesia Hyperkinesia refers to an increase in muscular activity that can result in excessive abnormal movements, excessive normal movements, or a combination of both. Hyperkinesia is a state of excessive restlessness which is featured in a large variet ...

Hypokinesia Hypokinesia is one of the classifications of movement disorders, and refers to decreased bodily movement. Hypokinesia is characterized by a partial or complete loss of muscle movement due to a disruption in the basal ganglia. Hypokinesia is a sy ...

;Common (1%≤incidence≤10%) *

Tachycardia Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal ( ...

Heart palpitations Palpitations are perceived abnormalities of the heartbeat characterized by awareness of cardiac muscle contractions in the chest, which is further characterized by the hard, fast and/or irregular beatings of the heart. Symptoms include a rapi ...

Vertigo Vertigo is a condition where a person has the sensation of movement or of surrounding objects moving when they are not. Often it feels like a spinning or swaying movement. This may be associated with nausea, vomiting, sweating, or difficulties w ...

* Accommodation disorder * Abnormal vision * Salivary hypersecretion * Constipation * Vomiting *

Dyspepsia Indigestion, also known as dyspepsia or upset stomach, is a condition of impaired digestion. Symptoms may include upper abdominal fullness, heartburn, nausea, belching, or upper abdominal pain. People may also experience feeling full earlier ...

Diarrhoea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin w ...

Asthenia Weakness is a symptom of a number of different conditions. The causes are many and can be divided into conditions that have true or perceived muscle weakness. True muscle weakness is a primary symptom of a variety of skeletal muscle diseases, i ...

* Fatigue *

Malaise As a medical term, malaise is a feeling of general discomfort, uneasiness or lack of wellbeing and often the first sign of an infection or other disease. The word has existed in French since at least the 12th century. The term is often used ...

* Pain (at the injection site) * Increased appetite * Weight gain *

Myalgia Myalgia (also called muscle pain and muscle ache in layman's terms) is the medical term for muscle pain. Myalgia is a symptom of many diseases. The most common cause of acute myalgia is the overuse of a muscle or group of muscles; another li ...

* Tremor *

Dystonia Dystonia is a neurological hyperkinetic movement disorder in which sustained or repetitive muscle contractions result in twisting and repetitive movements or abnormal fixed postures. The movements may resemble a tremor. Dystonia is often int ...

Hypertonia Hypertonia is a term sometimes used synonymously with spasticity and rigidity in the literature surrounding damage to the central nervous system, namely upper motor neuron lesions. Impaired ability of damaged motor neurons to regulate descending ...

* Dizziness * Headache *

Paraesthesia Paresthesia is an abnormal sensation of the skin (tingling, pricking, chilling, burning, numbness) with no apparent physical cause. Paresthesia may be transient or chronic, and may have any of dozens of possible underlying causes. Paresthesias ar ...

* Disturbance in attention *

Amnesia Amnesia is a deficit in memory caused by brain damage or disease,Gazzaniga, M., Ivry, R., & Mangun, G. (2009) Cognitive Neuroscience: The biology of the mind. New York: W.W. Norton & Company. but it can also be caused temporarily by the use ...

* Abnormal gait *

Insomnia Insomnia, also known as sleeplessness, is a sleep disorder in which people have trouble sleeping. They may have difficulty falling asleep, or staying asleep as long as desired. Insomnia is typically followed by daytime sleepiness, low energy, ...

* Depression *

Anxiety Anxiety is an emotion which is characterized by an unpleasant state of inner turmoil and includes feelings of dread over anticipated events. Anxiety is different than fear in that the former is defined as the anticipation of a future threat wh ...

* Abnormal dreams * Agitation * Decreased libido * Nasal congestion *

Dyspnoea Shortness of breath (SOB), also medically known as dyspnea (in AmE) or dyspnoea (in BrE), is an uncomfortable feeling of not being able to breathe well enough. The American Thoracic Society defines it as "a subjective experience of breathing dis ...

Hyperhidrosis Hyperhidrosis is a condition characterized by abnormally increased sweating, in excess of that required for regulation of body temperature. Although primarily a benign physical burden, hyperhidrosis can deteriorate quality of life from a psychologi ...

Pruritus Itch (also known as pruritus) is a sensation that causes the desire or reflex to scratch. Itch has resisted many attempts to be classified as any one type of sensory experience. Itch has many similarities to pain, and while both are unpleasant ...

;Uncommon (0.1%≤incidence≤1%) *

Hyperacusis Hyperacusis is the increased sensitivity to sound and a low tolerance for environmental noise. Definitions of hyperacusis can vary significantly; it can refer to normal noises being perceived as: loud, annoying, painful, fear-inducing, or a combina ...

Tinnitus Tinnitus is the perception of sound when no corresponding external sound is present. Nearly everyone experiences a faint "normal tinnitus" in a completely quiet room; but it is of concern only if it is bothersome, interferes with normal hearin ...

Mydriasis Mydriasis is the dilation of the pupil, usually having a non-physiological cause, or sometimes a physiological pupillary response. Non-physiological causes of mydriasis include disease, trauma, or the use of certain types of drugs. Normally, a ...

* Abdominal pain * Nausea * Flatulence * Thirst * Injection site reaction *

Hypothermia Hypothermia is defined as a body core temperature below in humans. Symptoms depend on the temperature. In mild hypothermia, there is shivering and mental confusion. In moderate hypothermia, shivering stops and confusion increases. In severe ...

Pyrexia Fever, also referred to as pyrexia, is defined as having a temperature above the normal range due to an increase in the body's temperature set point. There is not a single agreed-upon upper limit for normal temperature with sources using va ...

* Liver function test abnormal * Decreased appetite * Weight loss * Muscle rigidity *

Trismus Trismus, commonly called ''lockjaw'' as associated with tetanus, is a condition of limited jaw mobility. It may be caused by spasm of the muscles of mastication or a variety of other causes. Temporary trismus occurs much more frequently than perma ...

Torticollis Torticollis, also known as wry neck, is a dystonic condition defined by an abnormal, asymmetrical head or neck position, which may be due to a variety of causes. The term ''torticollis'' is derived from the Latin words ''tortus, meaning "twisted ...

Tardive dyskinesia Tardive dyskinesia (TD) is a disorder that results in involuntary repetitive body movements, which may include grimacing, sticking out the tongue or smacking the lips. Additionally, there may be rapid jerking movements or slow writhing movemen ...

Hyperreflexia Hyperreflexia is overactive or overresponsive bodily reflexes. Examples of this include twitching and spastic tendencies, which indicate upper disease of the upper motor neurons and the lessening or loss of control ordinarily exerted by higher ...

Dyskinesia Dyskinesia refers to a category of movement disorders that are characterized by involuntary muscle movements, including movements similar to tics or chorea and diminished voluntary movements. Dyskinesia can be anything from a slight tremor of ...

Parkinsonism Parkinsonism is a clinical syndrome characterized by tremor, bradykinesia (slowed movements), rigidity, and postural instability. These are the four motor symptoms found in Parkinson's disease (PD), after which it is named, dementia with Lew ...

* Syncope *

Ataxia Ataxia is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in eye movements. Ataxia is a clinical manifestation indicating dysfunction of ...

* Speech disorder *

Hypotonia Hypotonia is a state of low muscle tone (the amount of tension or resistance to stretch in a muscle), often involving reduced muscle strength. Hypotonia is not a specific medical disorder, but a potential manifestation of many different diseases ...

* Convulsion *

Migraine Migraine (, ) is a common neurological disorder characterized by recurrent headaches. Typically, the associated headache affects one side of the head, is pulsating in nature, may be moderate to severe in intensity, and could last from a few hou ...

* Apathy * Nightmares * Libido increased * Confused state * Ejaculation failure * Erectile dysfunction * Female orgasmic disorder * Vulvovaginal * Dryness * Rash *

Photosensitivity Photosensitivity is the amount to which an object reacts upon receiving photons, especially visible light. In medicine, the term is principally used for abnormal reactions of the skin, and two types are distinguished, photoallergy and phototoxicit ...

* Pigmentation disorder *

Seborrhoea A sebaceous gland is a microscopic exocrine gland in the skin that opens into a hair follicle to secrete an oily or waxy matter, called sebum, which lubricates the hair and skin of mammals. In humans, sebaceous glands occur in the greatest number ...

* Dermatitis *

Purpura Purpura () is a condition of red or purple discolored spots on the skin that do not blanch on applying pressure. The spots are caused by bleeding underneath the skin secondary to platelet disorders, vascular disorders, coagulation disorders, ...

Hypotension Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the di ...

* Hot flush ;Rare (0.01%≤incidence≤0.1%) *

Thrombocytopenia Thrombocytopenia is a condition characterized by abnormally low levels of platelets, also known as thrombocytes, in the blood. It is the most common coagulation disorder among intensive care patients and is seen in a fifth of medical patients a ...

Neutropenia Neutropenia is an abnormally low concentration of neutrophils (a type of white blood cell) in the blood. Neutrophils make up the majority of circulating white blood cells and serve as the primary defense against infections by destroying bacteri ...

Leukopenia Leukopenia () is a decrease in the number of leukocytes (WBC). Found in the blood, they are the white blood cells, and are the body's primary defense against an infection. Thus the condition of leukopenia places individuals at increased risk of ...

Agranulocytosis Agranulocytosis, also known as agranulosis or granulopenia, is an acute condition involving a severe and dangerous lowered white blood cell count (leukopenia, most commonly of neutrophils) and thus causing a neutropenia in the circulating blood. ...

QT prolongation Long QT syndrome (LQTS) is a condition affecting repolarization (relaxing) of the heart after a heartbeat, giving rise to an abnormally lengthy QT interval. It results in an increased risk of an irregular heartbeat which can result in fainting, ...

Hyperprolactinaemia Hyperprolactinaemia is the presence of abnormally high levels of prolactin in the blood. Reference ranges for common blood tests, Normal levels average to about 13 ng/mL in women, and 5 ng/mL in men, with an upper normal limit of serum ...

* Hypersensitivity *

Anaphylactic reaction Anaphylaxis is a serious, potentially fatal allergic reaction and medical emergency that is rapid in onset and requires immediate medical attention regardless of use of emergency medication on site. It typically causes more than one of the follo ...

* Hyperglycaemia * Glucose tolerance impaired *

Hyperlipidaemia Hyperlipidemia is abnormally elevated levels of any or all lipids (fats, cholesterol, or triglycerides) or lipoproteins in the blood. citing: and The term ''hyperlipidemia'' refers to the laboratory finding itself and is also used as an umbre ...

Gynaecomastia Gynecomastia (also spelled gynaecomastia) is the abnormal non-cancerous enlargement of one or both breasts in males due to the growth of breast tissue as a result of a hormone imbalance between estrogens and androgens. Updated by Brent Wisse ( ...

Galactorrhoea Galactorrhea ( also spelled galactorrhoea) ( galacto- + -rrhea) or lactorrhea ( lacto- + -rrhea) is the spontaneous flow of milk from the breast, unassociated with childbirth or nursing. Galactorrhea is reported to occur in 5–32% of women. M ...

Amenorrhoea Amenorrhea is the absence of a menstrual period in a woman of reproductive age. Physiological states of amenorrhoea are seen, most commonly, during pregnancy and lactation (breastfeeding). Outside the reproductive years, there is absence of mense ...

* Priapism * Withdrawal symptoms ;Very rare (incidence<0.01%) * Cholestatic hepatitis *

Jaundice Jaundice, also known as icterus, is a yellowish or greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving abnormal heme meta ...

Venous thromboembolism Venous thrombosis is blockage of a vein caused by a thrombus (blood clot). A common form of venous thrombosis is deep vein thrombosis (DVT), when a blood clot forms in the deep veins. If a thrombus breaks off (embolizes) and flows to the lungs to ...

Pharmacology

Pharmacodynamics

Zuclopenthixol antagonises both dopamine D₁ and D₂ receptors, α₁-adrenoceptors and 5-HT₂ receptors with a high affinity, but has no affinity for muscarinic acetylcholine receptors. It weakly antagonises the histamine (H₁) receptor but has no α₂-adrenoceptor blocking activity . Evidence from ''in vitro'' work and clinical sources (i.e. therapeutic drug monitoring databases) suggests that both

CYP2D6 Cytochrome P450 2D6 (CYP2D6) is an enzyme that in humans is encoded by the ''CYP2D6'' gene. ''CYP2D6'' is primarily expressed in the liver. It is also highly expressed in areas of the central nervous system, including the substantia nigra. CYP2D ...

and

CYP3A4 Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine. It oxidizes small foreign organic molecules ( xenobiotics), such as toxins or drugs, so that they can be removed from ...

play important roles in zuclopenthixol metabolism.

Pharmacokinetics

History

Zuclopenthixol was introduced by Lundbeck in 1978.

References

External links

# Product information for Zuclopenthixol (CLOPIXOL), provided by the

Therapeutic Goods Administration The Therapeutic Goods Administration (TGA) is the medicine and therapeutic regulatory agency of the Australian Government. As part of the Department of Health and Aged Care, the TGA regulates the quality, supply and advertising of medicines, p ...

— https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-PI-05705-3 {{Tricyclics Typical antipsychotics Alcohols Chloroarenes CYP2D6 inhibitors Piperazines Thioxanthene antipsychotics Enantiopure drugs