Drugs List

Therapeutic Indications

Uses

Depressive illness

For the symptomatic treatment of depression with or without anxiety

Contraindications

Children under 18 years
Hyperexcitability
Impaired consciousness
Agitation
Breastfeeding
Circulatory failure
Coma
Galactosaemia
Long QT syndrome
Mania
Severe depression requiring ECT or hospitalisation
Torsade de pointes

Precautions and Warnings

Debilitation
Elderly
Family history of long QT syndrome
Predisposition to epileptic disorder
Risk of cerebrovascular accident
Suicidal ideation
Benign prostatic hyperplasia
Brain damage
Cardiac arrhythmias
Cardiac disorder
Dementia
Diabetes mellitus
Electrolyte imbalance
Epileptic disorder
Glucose-galactose malabsorption syndrome
Hepatic impairment
History of alcohol abuse
History of herpes gestationis
History of jaundice
History of opioid abuse
History of torsade de pointes
Hyperthyroidism
Hypothyroidism
Lactose intolerance
Myasthenia gravis
Narrow angle glaucoma
Parkinson's disease
Phaeochromocytoma
Porphyria
Pregnancy
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
Hepatic Impairment: Discontinue if no response after 1 week at max dosage
Contains lactose
Consider monitoring ECG in patients at risk of QT prolongation
Diabetic control may need adjustment
Hypothermia may develop in the elderly
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
Avoid abrupt withdrawal
Discontinue if patient develops neuroleptic malignant syndrome
Discontinue if tardive dyskinesia occurs
Reduce dose in elderly
Advise patient to avoid alcohol during treatment
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.

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.

Patients (and caregivers of patients) should be alerted about the need to monitor for the emergence of suicidal thoughts and behaviour, and to seek medical advice immediately if these symptoms present.

Concomitant treatment with antipsychotics should be avoided.

An increased risk of cerebrovascular events was identified in clinical trials when elderly patients with dementia were treated with certain antipsychotics. The pharmacological mechanisms involved have not been identified. Therefore similar risks with flupentixol cannot be excluded, even when treating other patient populations. Use with caution in patients with risk factors for stroke.

Potential for withdrawal symptoms, gradual withdrawal is therefore recommended. Symptoms may persist for more than a week after discontinuation of oral neuroleptics.

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

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
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

Tablets containing flupentixol dihydrochloride

Drugs List

Therapeutic Indications

Uses

Depressive illness

For the symptomatic treatment of depression with or without anxiety

Dosage

Adults

Elderly

Patients with Renal Impairment

Patients with Hepatic Impairment

Additional Dosage Information

Contraindications

Children under 18 years
Hyperexcitability
Impaired consciousness
Agitation
Breastfeeding
Circulatory failure
Coma
Galactosaemia
Long QT syndrome
Mania
Severe depression requiring ECT or hospitalisation
Torsade de pointes

Precautions and Warnings

Debilitation
Elderly
Family history of long QT syndrome
Predisposition to epileptic disorder
Risk of cerebrovascular accident
Suicidal ideation
Benign prostatic hyperplasia
Brain damage
Cardiac arrhythmias
Cardiac disorder
Dementia
Diabetes mellitus
Electrolyte imbalance
Epileptic disorder
Glucose-galactose malabsorption syndrome
Hepatic impairment
History of alcohol abuse
History of herpes gestationis
History of jaundice
History of opioid abuse
History of torsade de pointes
Hyperthyroidism
Hypothyroidism
Lactose intolerance
Myasthenia gravis
Narrow angle glaucoma
Parkinson's disease
Phaeochromocytoma
Porphyria
Pregnancy
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
Hepatic Impairment: Discontinue if no response after 1 week at max dosage
Contains lactose
Consider monitoring ECG in patients at risk of QT prolongation
Diabetic control may need adjustment
Hypothermia may develop in the elderly
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
Avoid abrupt withdrawal
Discontinue if patient develops neuroleptic malignant syndrome
Discontinue if tardive dyskinesia occurs
Reduce dose in elderly
Advise patient to avoid alcohol during treatment
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.

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.

Patients (and caregivers of patients) should be alerted about the need to monitor for the emergence of suicidal thoughts and behaviour, and to seek medical advice immediately if these symptoms present.

Concomitant treatment with antipsychotics should be avoided.

An increased risk of cerebrovascular events was identified in clinical trials when elderly patients with dementia were treated with certain antipsychotics. The pharmacological mechanisms involved have not been identified. Therefore similar risks with flupentixol cannot be excluded, even when treating other patient populations. Use with caution in patients with risk factors for stroke.

Potential for withdrawal symptoms, gradual withdrawal is therefore recommended. Symptoms may persist for more than a week after discontinuation of oral neuroleptics.

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

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

Counselling

Patients and caregivers should be alerted about the need to monitor for the emergence of suicidal thoughts and behaviour and the need to seek medical advice immediately if they present.

Advise patients that flupentixol may impair alertness, particularly at the start of treatment or following the consumption of alcohol. Patients should be advised not to drive or operate machinery until their individual susceptibility is known. Patients should not drive if they have blurred vision.

Advise patients that flupentixol may cause an increased susceptibility to sunburn.

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
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

Withdrawal Symptoms and Signs

Acute withdrawal symptoms include nausea, vomiting, anorexia, diarrhoea, rhinorrhoea, sweating, myalgias, paraesthesia, insomnia, restlessness, anxiety and agitation. Recurrence of psychotic symptoms may also occur, and the emergence of involuntary movement disorders has been reported. Therefore gradual withdrawal is recommended.

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: September 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.

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

Summary of Product Characteristics: Fluanxol tablets. Lundbeck Limited. Revised May 2014.

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

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: 04 September 2015