Drugs List

Therapeutic Indications

Uses

Schizophrenia and other psychoses

For the treatment of schizophrenia and other psychosis where patients have been stabilized on oral therapy before transferring to the injection.

Administration

For intramuscular administration only.

The appropriate presentation of flupentixol decanoate should be selected to achieve an injection volume not exceeding 2 ml. Volumes exceeding 2 ml should be distributed between 2 injection sites.

Contraindications

Children under 18 years
Hyperexcitability
Impaired consciousness
Agitation
Breastfeeding
Circulatory failure
Coma
Long QT syndrome
Torsade de pointes

Precautions and Warnings

Elderly
Family history of long QT syndrome
Predisposition to epileptic disorder
Predisposition to venous thromboembolism
Risk of cerebrovascular accident
Suicidal ideation
Brain damage
Cardiac arrhythmias
Cardiac disorder
Dementia
Diabetes mellitus
Electrolyte imbalance
Epileptic disorder
Hepatic impairment
History of alcohol abuse
History of jaundice
History of opioid abuse
History of torsade de pointes
Hyperthyroidism
Hypothyroidism
Myasthenia gravis
Narrow angle glaucoma
Parkinson's disease
Phaeochromocytoma
Porphyria
Pregnancy
Prostate disorder
Renal impairment
Severe respiratory disease

Correct electrolyte disorders before treatment
Patients at risk of suicide should be closely supervised
Advise ability to drive/operate machinery may be affected by side effects
Aspirate prior to injection to avoid intravascular administration
Consider monitoring ECG in patients at risk of QT prolongation
Diabetic control may need adjustment
Hypothermia may develop in the elderly
Monitor patients at risk for signs & symptoms of venous thromboembolism
Monitor serum electrolytes
Perform blood counts if signs of persistent infection exist
Risk of cerebrovascular events
Advise patients/carers to seek medical advice if suicidal intent develops
Increased risk for venous thromboembolism - take preventive measures
May cause postural hypotension especially in elderly
Potential for withdrawal symptoms
Reduce dose +/or add antiparkinsonian drug if extrapyramidal symptoms occur
Discontinue if patient develops neuroleptic malignant syndrome
Discontinue if tardive dyskinesia occurs
Reduce dose in elderly
Advise patient that the effects of alcohol may be potentiated
May cause impaired fertility
Advise patient that photosensitivity possible

Depression is associated with an increased risk of suicidal thoughts, self harm and suicide (suicide related events). This risk persists until significant remission occurs. As improvement may not occur during the first few weeks or more of treatment, patients should be closely monitored until such improvement occurs. It is general clinical experience that the risk of self harm is highest shortly after presentation and the risk of suicide may increase again in the early stages of recovery. Furthermore, there is evidence that in children and adolescents, antidepressants may increase the risk of suicidal thoughts and self harm.

Other psychiatric conditions for which flupentixol is prescribed can also be associated with an increased risk of suicide related events. In addition, these conditions may be co-morbid with major depressive disorder. The same precautions observed when treating patients with major depressive disorder should therefore be observed when treating patients with other psychiatric disorders.

Patients with a history of suicide related events, those exhibiting a significant degree of suicidal ideation prior to commencement of treatment, and young adults, are at a greater risk of suicidal thought or suicide attempt, and should receive careful monitoring during treatment.

Potential for withdrawal symptoms. Symptoms may persist for more than a week after discontinuation of oral neuroleptics, and longer for depot formulations.

Use with extreme caution in patients with organic brain syndrome, mental retardation and opiate or alcohol abuse, as cases of neuroleptic malignant syndrome are more likely to be fatal in these patients.

If clinical significant hyperprolactinaemia, galactorrhoea, amenorrhoea or sexual dysfunctions occur, a dose reduction (if possible) or discontinuation should be considered.

Flupentixol is considered to be unsafe in patients with porphyria because it has been shown to be porphyrinogenic in animals.

Pregnancy and Lactation

Pregnancy

Flupentixol should be used with caution in pregnancy.

Data describing the use of flupentixol in pregnancy is highly limited. Flupentixol crosses the placental barrier. The manufacturer suggests avoid the use of flupentixol during pregnancy, particularly during the first and last trimesters. Postulated risks to the newborn include lethargy, tremor, hyperexcitability and low apgar scores.

When neuroleptics have been used up to delivery, observation of the neonate for at least 2 days is recommended. In order to prevent neonatal adaptation disorders, prescribers are advised to reduce the dose or even interrupt treatment in the days immediately preceding delivery (Schaefer 2007).

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

Flupentixol is contraindicated in breastfeeding.

Flupentixol is excreted into breast milk. Although the effects of long-term exposure have not been studied it has been suggested that extended exposure to flupentixol may affect the nursing infant's neurobehavioral mechanisms. Currently no adverse effects have been reported in breast-feeding infants whose mothers were receiving flupentixol.

LactMed suggests that if flupentixol is used during breastfeeding careful monitoring of the infant should be conducted.

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

Abdominal pain
Abnormal vision
Agitation
Agranulocytosis
Akathisia
Altered liver function tests
Amenorrhoea
Anaphylactic reaction
Asthenia
Attention disturbances
Confusion
Constipation
Convulsions
Decreased glucose tolerance
Deep vein thrombosis (DVT)
Depression
Dermatitis
Diarrhoea
Disturbances in accommodation
Disturbances of appetite
Dizziness
Dry mouth
Dyskinesia
Dyspepsia
Dyspnoea
Dystonia
Erectile dysfunction
Extrapyramidal effects
Failure of ejaculation
Fatigue
Flatulence
Galactorrhoea
Gynaecomastia
Headache
Hot flushes
Hyperglycaemia
Hyperhidrosis
Hyperkinesia
Hyperprolactinaemia
Hypersalivation
Hypersensitivity reactions
Hypokinesia
Hypotension
Injection site reactions
Insomnia
Jaundice
Leukopenia
Micturition disorders
Muscle rigidity
Myalgia
Nausea
Nervousness
Neuroleptic malignant syndrome
Neutropenia
Oculogyration
Palpitations
Parkinsonism
Photosensitivity
Prolongation of QT interval
Pruritus
Pulmonary embolism
Rash
Reduced libido
Somnolence
Speech disturbances
Sudden unexplained death
Suicidal tendencies
Tachycardia
Tardive dyskinesia
Thrombocytopenia
Torsades de pointes
Tremor
Urinary retention
Venous thrombosis
Ventricular arrhythmias
Ventricular fibrillation
Ventricular tachycardia
Vomiting
Weight gain

Presentation

Oily solution for injection containing flupentixol decanoate.

Drugs List

Therapeutic Indications

Uses

Schizophrenia and other psychoses

For the treatment of schizophrenia and other psychosis where patients have been stabilized on oral therapy before transferring to the injection.

Dosage

Dosage and dosage interval should be adjusted to the patients symptoms and response to treatment.

Adequate control of severe psychotic symptoms may take up to 4 to 6 months at high enough dosage. Once stabilised lower maintenance doses may be considered, but must be high enough to prevent relapse.

Adults

Elderly

Patients with Renal Impairment

Additional Dosage Information

Administration

For intramuscular administration only.

The appropriate presentation of flupentixol decanoate should be selected to achieve an injection volume not exceeding 2 ml. Volumes exceeding 2 ml should be distributed between 2 injection sites.

Contraindications

Children under 18 years
Hyperexcitability
Impaired consciousness
Agitation
Breastfeeding
Circulatory failure
Coma
Long QT syndrome
Torsade de pointes

Precautions and Warnings

Elderly
Family history of long QT syndrome
Predisposition to epileptic disorder
Predisposition to venous thromboembolism
Risk of cerebrovascular accident
Suicidal ideation
Brain damage
Cardiac arrhythmias
Cardiac disorder
Dementia
Diabetes mellitus
Electrolyte imbalance
Epileptic disorder
Hepatic impairment
History of alcohol abuse
History of jaundice
History of opioid abuse
History of torsade de pointes
Hyperthyroidism
Hypothyroidism
Myasthenia gravis
Narrow angle glaucoma
Parkinson's disease
Phaeochromocytoma
Porphyria
Pregnancy
Prostate disorder
Renal impairment
Severe respiratory disease

Correct electrolyte disorders before treatment
Patients at risk of suicide should be closely supervised
Advise ability to drive/operate machinery may be affected by side effects
Aspirate prior to injection to avoid intravascular administration
Consider monitoring ECG in patients at risk of QT prolongation
Diabetic control may need adjustment
Hypothermia may develop in the elderly
Monitor patients at risk for signs & symptoms of venous thromboembolism
Monitor serum electrolytes
Perform blood counts if signs of persistent infection exist
Risk of cerebrovascular events
Advise patients/carers to seek medical advice if suicidal intent develops
Increased risk for venous thromboembolism - take preventive measures
May cause postural hypotension especially in elderly
Potential for withdrawal symptoms
Reduce dose +/or add antiparkinsonian drug if extrapyramidal symptoms occur
Discontinue if patient develops neuroleptic malignant syndrome
Discontinue if tardive dyskinesia occurs
Reduce dose in elderly
Advise patient that the effects of alcohol may be potentiated
May cause impaired fertility
Advise patient that photosensitivity possible

Depression is associated with an increased risk of suicidal thoughts, self harm and suicide (suicide related events). This risk persists until significant remission occurs. As improvement may not occur during the first few weeks or more of treatment, patients should be closely monitored until such improvement occurs. It is general clinical experience that the risk of self harm is highest shortly after presentation and the risk of suicide may increase again in the early stages of recovery. Furthermore, there is evidence that in children and adolescents, antidepressants may increase the risk of suicidal thoughts and self harm.

Other psychiatric conditions for which flupentixol is prescribed can also be associated with an increased risk of suicide related events. In addition, these conditions may be co-morbid with major depressive disorder. The same precautions observed when treating patients with major depressive disorder should therefore be observed when treating patients with other psychiatric disorders.

Patients with a history of suicide related events, those exhibiting a significant degree of suicidal ideation prior to commencement of treatment, and young adults, are at a greater risk of suicidal thought or suicide attempt, and should receive careful monitoring during treatment.

Potential for withdrawal symptoms. Symptoms may persist for more than a week after discontinuation of oral neuroleptics, and longer for depot formulations.

Use with extreme caution in patients with organic brain syndrome, mental retardation and opiate or alcohol abuse, as cases of neuroleptic malignant syndrome are more likely to be fatal in these patients.

If clinical significant hyperprolactinaemia, galactorrhoea, amenorrhoea or sexual dysfunctions occur, a dose reduction (if possible) or discontinuation should be considered.

Flupentixol is considered to be unsafe in patients with porphyria because it has been shown to be porphyrinogenic in animals.

Pregnancy and Lactation

Pregnancy

Flupentixol should be used with caution in pregnancy.

Data describing the use of flupentixol in pregnancy is highly limited. Flupentixol crosses the placental barrier. The manufacturer suggests avoid the use of flupentixol during pregnancy, particularly during the first and last trimesters. Postulated risks to the newborn include lethargy, tremor, hyperexcitability and low apgar scores.

When neuroleptics have been used up to delivery, observation of the neonate for at least 2 days is recommended. In order to prevent neonatal adaptation disorders, prescribers are advised to reduce the dose or even interrupt treatment in the days immediately preceding delivery (Schaefer 2007).

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

Flupentixol is contraindicated in breastfeeding.

Flupentixol is excreted into breast milk. Although the effects of long-term exposure have not been studied it has been suggested that extended exposure to flupentixol may affect the nursing infant's neurobehavioral mechanisms. Currently no adverse effects have been reported in breast-feeding infants whose mothers were receiving flupentixol.

LactMed suggests that if flupentixol is used during breastfeeding careful monitoring of the infant should be conducted.

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

Abdominal pain
Abnormal vision
Agitation
Agranulocytosis
Akathisia
Altered liver function tests
Amenorrhoea
Anaphylactic reaction
Asthenia
Attention disturbances
Confusion
Constipation
Convulsions
Decreased glucose tolerance
Deep vein thrombosis (DVT)
Depression
Dermatitis
Diarrhoea
Disturbances in accommodation
Disturbances of appetite
Dizziness
Dry mouth
Dyskinesia
Dyspepsia
Dyspnoea
Dystonia
Erectile dysfunction
Extrapyramidal effects
Failure of ejaculation
Fatigue
Flatulence
Galactorrhoea
Gynaecomastia
Headache
Hot flushes
Hyperglycaemia
Hyperhidrosis
Hyperkinesia
Hyperprolactinaemia
Hypersalivation
Hypersensitivity reactions
Hypokinesia
Hypotension
Injection site reactions
Insomnia
Jaundice
Leukopenia
Micturition disorders
Muscle rigidity
Myalgia
Nausea
Nervousness
Neuroleptic malignant syndrome
Neutropenia
Oculogyration
Palpitations
Parkinsonism
Photosensitivity
Prolongation of QT interval
Pruritus
Pulmonary embolism
Rash
Reduced libido
Somnolence
Speech disturbances
Sudden unexplained death
Suicidal tendencies
Tachycardia
Tardive dyskinesia
Thrombocytopenia
Torsades de pointes
Tremor
Urinary retention
Venous thrombosis
Ventricular arrhythmias
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: January 2016

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.

Joint Formulary Committee. British National Formulary(online) London: BMJ Group and Pharmaceutical Press Accessed on 19 August 2015.

Martindale: The Complete Drug Reference, 36th edition (2009) ed. Sweetman, S. Pharmaceutical Press, London.

Summary of Product Characteristics: Depixol Injection and Conc Injection. Lundbeck Limited. Revised October 2014.

Summary of Product Characteristics: Depixol Low Volume Injection. Lundbeck Limited. Revised October 2014.

The Renal Drug Handbook. 3rd edition. (2009) ed. Ashley, C and Currie, Radcliffe Publishing Ltd, Abingdon.

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
Flupentixol Last revised: 07 September 2013
Last accessed: 06 January 2016