Drugs List

Therapeutic Indications

Uses

Monosymptomatic hypochondrial psychosis
Paranoid psychosis
Schizophrenia

Treatment of symptoms and prevention of relapse in chronic schizophrenia.
Other psychoses, including paranoid and monosymptomatic hypochondriacal psychoses (e.g. delusional parasitosis).

Unlicensed Uses

Gilles de la Tourette syndrome

Gilles de la Tourette syndrome

Contraindications

Children under 2 years
Family history of long QT syndrome
Breastfeeding
Cardiac failure
Coma
Depression
History of cardiac arrhythmias
History of torsade de pointes
Hypocalcaemia
Hypokalaemia
Hypomagnesaemia
Long QT syndrome
Parkinson's disease
Recent myocardial infarction
Severe bradycardia
Severe cardiac disorder
Severe central nervous system depression

Precautions and Warnings

Children aged 2 to 12 years
Elderly
Predisposition to epileptic disorder
Predisposition to prolongation of QT interval
Alcohol withdrawal syndrome
Benign prostatic hyperplasia
Brain damage
Cardiovascular disorder
Dehydration
Dementia
Electrolyte imbalance
Epileptic disorder
Haematological disorder
Hepatic impairment
History of jaundice
History of seizures
History of venous thromboembolism
Myasthenia gravis
Narrow angle glaucoma
Non-cirrhotic alcoholic liver disease
Phaeochromocytoma
Pregnancy
Respiratory disease
Severe renal impairment
Thyrotoxicosis

Correct electrolyte disorders before treatment
Reduce dose in patients with severe renal impairment
Advise impaired alertness may affect ability to drive or operate machinery
Treatment to be initiated and supervised by a specialist
Perform ECG before treatment
Elderly more susceptible to sedation, hypotensive & temp regulatory effects
Monitor cardiac function during prolonged treatment
Monitor ECG
Monitor patients at risk for signs & symptoms of venous thromboembolism
Monitor serum electrolytes
Perform blood counts if unexplained infection or fever develops
Fine vermicular movements of the tongue may be sign of tardive dyskinesia
May cause or exacerbate extrapyramidal symptoms
May impair ability to reduce core body temperature
Potential for withdrawal symptoms
Avoid abrupt withdrawal
Discontinue if patient develops neuroleptic malignant syndrome
Discontinue if tardive dyskinesia occurs
Discontinue treatment if QTc exceeds 500msec
If ECG changes or arrhythmias develop review and withdraw or reduce dose
Maintain treatment at the lowest effective dose
Reduce dose in elderly
Advise that effects are potentiated by CNS depressants (including alcohol)
Advise patient grapefruit products may increase plasma level
Avoid direct exposure to sunlight

Baseline ECG should be taken prior to commencing treatment, and then annually or more frequently thereafter. Treatment should be reviewed and either gradually withdrawn or the dose reduced under close supervision if the repolarization changes (prolongation of QT interval, T-wave changes or U-wave development) or arrhythmias develop. If QT or QTc exceeds 500 msec, discontinue pimozide.

Consider possible risk factors for VTE before and during the treatment, preventive measures should be taken. Cases of venous thromboembolism have been reported (pulmonary embolism, deep vein thrombosis).

Discontinue if unexplained fever occurs as this may be a sign of neuroleptic malignant syndrome associated with antipsychotic drugs (pallor, hyperthermia, autonomic dysfunction, altered consciousness, muscle rigidity). Signs of autonomic dysfunction such as sweating, tachycardia, and arterial instability may precede the onset of hyperthermia and serve as early warning signs. Perform blood counts if unexplained infection or fever develops.

During treatment with pimozide, the bodies ability to reduce core temperature may be reduced as with other antipsychotics - caution should be observed in those exposed to extreme heat, dehydration or exercising strenuously. The elderly are particularly susceptible to postural hypotension and to hyperthermia and hypothermia in hot or cold weather.

Data from studies showed a small risk of death in elderly people with dementia who are treated with antipsychotics. Not licensed for the treatment of dementia-related behavioural disturbances.

Pregnancy and Lactation

Pregnancy

Pimozide should be used with caution in pregnancy.

Safety in humans has not been established. Studies in animals have not demonstrated teratogenic effects. Some animal reproduction studies show decreased pregnancies, retarded foetal development, embryo toxicity and increased resorption. So it is recommended that pimozide should be avoided if possible, especially in the 1st trimester. However it should not be with held if it is the best drug for the patient.

There are insufficient data from human exposures to exclude a risk of malformations or other risks to the foetus. Extrapyramidal effects have been reported in neonates with use of antipsychotics in the third trimester. If an infant has been exposed in utero to pimozide in the last trimester, observation of the neonate for adaptation problems, extrapyramidal and withdrawal symptoms for at least 2 days is recommended.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Pimozide is contraindicated in breastfeeding.

Highly limited data is available on the secretion of pimozide into breast milk. The molecular weight (462) and prolonged elimination half-life suggest that the drug will be excreted into breast milk. If use is considered essential, breastfeeding should be discontinued as other drugs are prefered.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Agitation
Agranulocytosis
Akathisia
Amenorrhoea
Anorexia
Antimuscarinic effects
Apathy
Arrhythmias
Blood dyscrasias
Blurred vision
Bradykinesia
Cardiac arrest
Cholestatic jaundice
Confusion
Constipation
Contact sensitisation
Convulsions
Corneal opacities
Depression
Difficulty in micturition
Dizziness
Drowsiness
Dry mouth
Dysarthria
Dyskinesia
Dystonia
ECG changes
Erectile dysfunction
Excitement
Exhaustion
Extrapyramidal effects
Facial oedema
Galactorrhoea
Gastro-intestinal disturbances
Glycosuria
Grand mal seizure
Gynaecomastia
Headache
Hyperglycaemia
Hyperhidrosis
Hypersalivation
Hyperthermia
Hypokinesia
Hyponatraemia
Hypotension
Hypothermia
Impaired consciousness
Impotence
Increased prolactin
Insomnia
Interference with temperature regulation
Jaundice
Lens opacities
Lethargy
Leucopenia
Loss of libido
Menstrual disturbances
Muscle rigidity
Muscle spasm
Nasal congestion
Neck stiffness
Neuroleptic malignant syndrome
Nocturia
Oculogyric crisis
Oily skin
Pallor
Parkinsonism
Photosensitivity
Prolongation of QT interval
Pruritus
Purplish pigmentation of cornea, conjunctiva, retina
Purplish pigmentation of skin
Rash
Restlessness
Somnolence
Sudden unexplained death
Tachycardia
Tardive dyskinesia
Torsades de pointes
Tremor
Urinary frequency
Urinary incontinence
Urticaria
Venous thrombosis
Ventricular fibrillation
Ventricular tachycardia
Vomiting
Weight gain

Presentation

Tablets containing pimozide

Drugs List

Therapeutic Indications

Uses

Monosymptomatic hypochondrial psychosis
Paranoid psychosis
Schizophrenia

Treatment of symptoms and prevention of relapse in chronic schizophrenia.
Other psychoses, including paranoid and monosymptomatic hypochondriacal psychoses (e.g. delusional parasitosis).

Unlicensed Uses

Gilles de la Tourette syndrome

Gilles de la Tourette syndrome

Dosage

Dose should be individually determined, and is best initiated and titrated under close clinical supervision.

In determining the initial dosage, consideration should be given to the patient's age, severity of symptoms and previous response to other neuroleptic drugs.

Dose increases should be made at weekly intervals or longer, by increments of 2mg to 4mg in the daily dose.

Maintenance dose should be the most effective dose at the lowest level possible.

Adults

Elderly

Children

Patients with Renal Impairment

Contraindications

Children under 2 years
Family history of long QT syndrome
Breastfeeding
Cardiac failure
Coma
Depression
History of cardiac arrhythmias
History of torsade de pointes
Hypocalcaemia
Hypokalaemia
Hypomagnesaemia
Long QT syndrome
Parkinson's disease
Recent myocardial infarction
Severe bradycardia
Severe cardiac disorder
Severe central nervous system depression

Precautions and Warnings

Children aged 2 to 12 years
Elderly
Predisposition to epileptic disorder
Predisposition to prolongation of QT interval
Alcohol withdrawal syndrome
Benign prostatic hyperplasia
Brain damage
Cardiovascular disorder
Dehydration
Dementia
Electrolyte imbalance
Epileptic disorder
Haematological disorder
Hepatic impairment
History of jaundice
History of seizures
History of venous thromboembolism
Myasthenia gravis
Narrow angle glaucoma
Non-cirrhotic alcoholic liver disease
Phaeochromocytoma
Pregnancy
Respiratory disease
Severe renal impairment
Thyrotoxicosis

Correct electrolyte disorders before treatment
Reduce dose in patients with severe renal impairment
Advise impaired alertness may affect ability to drive or operate machinery
Treatment to be initiated and supervised by a specialist
Perform ECG before treatment
Elderly more susceptible to sedation, hypotensive & temp regulatory effects
Monitor cardiac function during prolonged treatment
Monitor ECG
Monitor patients at risk for signs & symptoms of venous thromboembolism
Monitor serum electrolytes
Perform blood counts if unexplained infection or fever develops
Fine vermicular movements of the tongue may be sign of tardive dyskinesia
May cause or exacerbate extrapyramidal symptoms
May impair ability to reduce core body temperature
Potential for withdrawal symptoms
Avoid abrupt withdrawal
Discontinue if patient develops neuroleptic malignant syndrome
Discontinue if tardive dyskinesia occurs
Discontinue treatment if QTc exceeds 500msec
If ECG changes or arrhythmias develop review and withdraw or reduce dose
Maintain treatment at the lowest effective dose
Reduce dose in elderly
Advise that effects are potentiated by CNS depressants (including alcohol)
Advise patient grapefruit products may increase plasma level
Avoid direct exposure to sunlight

Baseline ECG should be taken prior to commencing treatment, and then annually or more frequently thereafter. Treatment should be reviewed and either gradually withdrawn or the dose reduced under close supervision if the repolarization changes (prolongation of QT interval, T-wave changes or U-wave development) or arrhythmias develop. If QT or QTc exceeds 500 msec, discontinue pimozide.

Consider possible risk factors for VTE before and during the treatment, preventive measures should be taken. Cases of venous thromboembolism have been reported (pulmonary embolism, deep vein thrombosis).

Discontinue if unexplained fever occurs as this may be a sign of neuroleptic malignant syndrome associated with antipsychotic drugs (pallor, hyperthermia, autonomic dysfunction, altered consciousness, muscle rigidity). Signs of autonomic dysfunction such as sweating, tachycardia, and arterial instability may precede the onset of hyperthermia and serve as early warning signs. Perform blood counts if unexplained infection or fever develops.

During treatment with pimozide, the bodies ability to reduce core temperature may be reduced as with other antipsychotics - caution should be observed in those exposed to extreme heat, dehydration or exercising strenuously. The elderly are particularly susceptible to postural hypotension and to hyperthermia and hypothermia in hot or cold weather.

Data from studies showed a small risk of death in elderly people with dementia who are treated with antipsychotics. Not licensed for the treatment of dementia-related behavioural disturbances.

Pregnancy and Lactation

Pregnancy

Pimozide should be used with caution in pregnancy.

Safety in humans has not been established. Studies in animals have not demonstrated teratogenic effects. Some animal reproduction studies show decreased pregnancies, retarded foetal development, embryo toxicity and increased resorption. So it is recommended that pimozide should be avoided if possible, especially in the 1st trimester. However it should not be with held if it is the best drug for the patient.

There are insufficient data from human exposures to exclude a risk of malformations or other risks to the foetus. Extrapyramidal effects have been reported in neonates with use of antipsychotics in the third trimester. If an infant has been exposed in utero to pimozide in the last trimester, observation of the neonate for adaptation problems, extrapyramidal and withdrawal symptoms for at least 2 days is recommended.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Pimozide is contraindicated in breastfeeding.

Highly limited data is available on the secretion of pimozide into breast milk. The molecular weight (462) and prolonged elimination half-life suggest that the drug will be excreted into breast milk. If use is considered essential, breastfeeding should be discontinued as other drugs are prefered.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Counselling

Advise patients not to drink or eat grapefruit products.

Advise patients alertness may be impaired and not to drive or operate machinery if so affected.

Avoid alcohol.

Photosensitisation may occur on high doses, avoid sunlight.

Some medicines may interact with this medicine, including those available to purchase, patients should consult their doctor or pharmacist before self-medicating.

Advise patients that an unexplained rise in body temperature may be an indicator of a rare reaction to the medicine, and that if affected, they should consult their physician immediately.

During treatment with pimozide, the body's ability to reduce core temperature may be reduced - caution should be observed in those exposed to extreme heat, dehydration or exercising strenuously.

Side Effects

Agitation
Agranulocytosis
Akathisia
Amenorrhoea
Anorexia
Antimuscarinic effects
Apathy
Arrhythmias
Blood dyscrasias
Blurred vision
Bradykinesia
Cardiac arrest
Cholestatic jaundice
Confusion
Constipation
Contact sensitisation
Convulsions
Corneal opacities
Depression
Difficulty in micturition
Dizziness
Drowsiness
Dry mouth
Dysarthria
Dyskinesia
Dystonia
ECG changes
Erectile dysfunction
Excitement
Exhaustion
Extrapyramidal effects
Facial oedema
Galactorrhoea
Gastro-intestinal disturbances
Glycosuria
Grand mal seizure
Gynaecomastia
Headache
Hyperglycaemia
Hyperhidrosis
Hypersalivation
Hyperthermia
Hypokinesia
Hyponatraemia
Hypotension
Hypothermia
Impaired consciousness
Impotence
Increased prolactin
Insomnia
Interference with temperature regulation
Jaundice
Lens opacities
Lethargy
Leucopenia
Loss of libido
Menstrual disturbances
Muscle rigidity
Muscle spasm
Nasal congestion
Neck stiffness
Neuroleptic malignant syndrome
Nocturia
Oculogyric crisis
Oily skin
Pallor
Parkinsonism
Photosensitivity
Prolongation of QT interval
Pruritus
Purplish pigmentation of cornea, conjunctiva, retina
Purplish pigmentation of skin
Rash
Restlessness
Somnolence
Sudden unexplained death
Tachycardia
Tardive dyskinesia
Torsades de pointes
Tremor
Urinary frequency
Urinary incontinence
Urticaria
Venous thrombosis
Ventricular fibrillation
Ventricular tachycardia
Vomiting
Weight gain

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: July 2015

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Medications and Mothers' Milk, Sixteenth Edition (2014) Hale, T and Rowe, H, Hale Publishing, Plano, Texas.

Summary of Product Characteristics: Orap 4mg tablets. Eumedica S.A. Revised July 2016.

The Renal Drug Handbook. Fourth Edition (2014) ed. Ashley, C and Dunleavy, A, Radcliffe Publishing Ltd, London.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 06 September 2017

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Pimozide Last revised: 10 March 2015
Last accessed: 17 July 2015