Drugs List

Therapeutic Indications

Uses

Schizophrenia - resistant to other treatment

Contraindications

Children under 18 years
Bradycardia with pulse rate at rest < 50 beats per minute
Breastfeeding
Cardiac arrhythmias
Cardiac hypertrophy
Congestive cardiac failure
Galactosaemia
History of severe cardiac disorder
Long QT syndrome
Pregnancy
QTc interval greater than 450 milliseconds in males
QTc interval greater than 470 milliseconds in female adults
Severe hepatic impairment
Torsade de pointes

Precautions and Warnings

Family history of long QT syndrome
Patients over 65 years
Cardiovascular disorder
Cerebrovascular disorder
CYP2D6 poor metaboliser genotype
Diabetes mellitus
Electrolyte imbalance
Glucose-galactose malabsorption syndrome
History of seizures
History of torsade de pointes
Hyperglycaemia
Lactose intolerance
Mild hepatic impairment
Parkinson's disease

Correct electrolyte disorders before treatment
Reduce dose in patients with hepatic impairment
Advise ability to drive/operate machinery may be affected by side effects
Concurrent benzodiazepine may be given for sedation
Contains lactose
Perform ECG before treatment
Consider monitoring ECG in patients at risk of QT prolongation
Diabetic control may need adjustment
Monitor blood pressure during titration and early maintenance treatment
Monitor ECG
Monitor ECG prior to and after increasing dose
Monitor serum electrolytes
Perform ECG if arrhythmic symptoms develop
Risk of cerebrovascular events
Consider discontinuation if signs of tardive dyskinesia occur
Increased risk for venous thromboembolism - take preventive measures
May cause postural hypotension
Potential for withdrawal symptoms
Use low starting dose to avoid postural effects
Avoid abrupt withdrawal
Discontinue if patient develops neuroleptic malignant syndrome
Discontinue treatment if QTc exceeds 500msec

Sertindole is only for use in patients who are enrolled in clinical studies and who are intolerant to at least one other anti-psychotic agent as sertindole prolongs the QT interval to a greater extent than some other anti-psychotics.

ECG monitoring should be conducted prior to and during treatment, as well as before and after any dose increases. Monitor ECG at baseline, upon reaching steady state after approximately 3 weeks or when reaching 16 mg, and again after 3 months of treatment. During maintenance therapy an ECG is required every 3 months.

ECG monitoring is ideally conducted in the morning, and the Bazett or Fridericia formulae for calculating the QTc interval are preferred.

A 3-fold increase in the risk of cerebrovascular events has been observed in patients treated with some atypical anti-psychotic drugs.

Postural hypotension may occur during initiation and dose titration. There is a higher risk of postural hypotension with high initial doses and a rapid increase in dose.

Anti-psychotic drugs may inhibit the effects of dopamine agonists, thus caution should be used in patients with Parkinson's disease

Hyperglycaemia or pre-existing diabetes has been reported in rare cases during treatment with sertindole. Appropriate clinical monitoring is suggested in diabetic patients and patients with risk factors for diabetes mellitus.

Pregnancy and Lactation

Pregnancy

Sertindole is contraindicated in pregnancy.

Safety in human pregnancy has not been established. Sertindole was not teratogenic in animal reproduction studies. A peri/postnatal study in rats showed a decrease in offspring fertility at a dose within the therapeutic range for humans.

Neonates exposed to sertindole during the third trimester are at risk of adverse reactions including extrapyramidal and/or withdrawal symptoms. These adverse reactions may include agitation, hypertonia, tremor, somnolence, respiratory distress or feeding disruptions. Therefore, newborns should be monitored carefully.

Schaefer (2007) suggests that the use of sertindole is not an indication for the termination of pregnancy. A pregnant patient who is stable with the use of sertindole should keep receiving the drug as changing to an alternative drug may worsen her health. Dose reduction during the days leading up to birth should be considered to prevent neonatal adaptation disorders. Dose should then be adjusted to pre-pregnancy levels immediately after delivery.

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

Sertindole is contraindicated in breastfeeding.

Studies in nursing mothers have not been performed, however it is expected that sertindole will be excreted in breast milk. If treatment is necessary, the manufacturer recommends that breastfeeding should be discontinued.

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

Convulsions
Decreased ejaculate volume
Deep vein thrombosis (DVT)
Dizziness
Dry mouth
Dyspnoea
Ejaculation disorders
Erectile dysfunction
Exacerbation of diabetes
Extrapyramidal effects
Failure of ejaculation
Galactorrhoea
Haematuria
Hyperglycaemia
Hyperprolactinaemia
Movement disturbances
Nasal congestion
Neuroleptic malignant syndrome
Paraesthesia
Peripheral oedema
Postural hypotension
Prolongation of QT interval
Pulmonary embolism
Reflex tachycardia
Rhinitis
Syncope
Tardive dyskinesia
Torsades de pointes
Weight gain
White blood cells in the urine

Presentation

Oral formulations of sertindole

Drugs List

Therapeutic Indications

Uses

Schizophrenia - resistant to other treatment

Dosage

Adults

Elderly

Patients with Hepatic Impairment

Additional Dosage Information

Contraindications

Children under 18 years
Bradycardia with pulse rate at rest < 50 beats per minute
Breastfeeding
Cardiac arrhythmias
Cardiac hypertrophy
Congestive cardiac failure
Galactosaemia
History of severe cardiac disorder
Long QT syndrome
Pregnancy
QTc interval greater than 450 milliseconds in males
QTc interval greater than 470 milliseconds in female adults
Severe hepatic impairment
Torsade de pointes

Precautions and Warnings

Family history of long QT syndrome
Patients over 65 years
Cardiovascular disorder
Cerebrovascular disorder
CYP2D6 poor metaboliser genotype
Diabetes mellitus
Electrolyte imbalance
Glucose-galactose malabsorption syndrome
History of seizures
History of torsade de pointes
Hyperglycaemia
Lactose intolerance
Mild hepatic impairment
Parkinson's disease

Correct electrolyte disorders before treatment
Reduce dose in patients with hepatic impairment
Advise ability to drive/operate machinery may be affected by side effects
Concurrent benzodiazepine may be given for sedation
Contains lactose
Perform ECG before treatment
Consider monitoring ECG in patients at risk of QT prolongation
Diabetic control may need adjustment
Monitor blood pressure during titration and early maintenance treatment
Monitor ECG
Monitor ECG prior to and after increasing dose
Monitor serum electrolytes
Perform ECG if arrhythmic symptoms develop
Risk of cerebrovascular events
Consider discontinuation if signs of tardive dyskinesia occur
Increased risk for venous thromboembolism - take preventive measures
May cause postural hypotension
Potential for withdrawal symptoms
Use low starting dose to avoid postural effects
Avoid abrupt withdrawal
Discontinue if patient develops neuroleptic malignant syndrome
Discontinue treatment if QTc exceeds 500msec

Sertindole is only for use in patients who are enrolled in clinical studies and who are intolerant to at least one other anti-psychotic agent as sertindole prolongs the QT interval to a greater extent than some other anti-psychotics.

ECG monitoring should be conducted prior to and during treatment, as well as before and after any dose increases. Monitor ECG at baseline, upon reaching steady state after approximately 3 weeks or when reaching 16 mg, and again after 3 months of treatment. During maintenance therapy an ECG is required every 3 months.

ECG monitoring is ideally conducted in the morning, and the Bazett or Fridericia formulae for calculating the QTc interval are preferred.

A 3-fold increase in the risk of cerebrovascular events has been observed in patients treated with some atypical anti-psychotic drugs.

Postural hypotension may occur during initiation and dose titration. There is a higher risk of postural hypotension with high initial doses and a rapid increase in dose.

Anti-psychotic drugs may inhibit the effects of dopamine agonists, thus caution should be used in patients with Parkinson's disease

Hyperglycaemia or pre-existing diabetes has been reported in rare cases during treatment with sertindole. Appropriate clinical monitoring is suggested in diabetic patients and patients with risk factors for diabetes mellitus.

Pregnancy and Lactation

Pregnancy

Sertindole is contraindicated in pregnancy.

Safety in human pregnancy has not been established. Sertindole was not teratogenic in animal reproduction studies. A peri/postnatal study in rats showed a decrease in offspring fertility at a dose within the therapeutic range for humans.

Neonates exposed to sertindole during the third trimester are at risk of adverse reactions including extrapyramidal and/or withdrawal symptoms. These adverse reactions may include agitation, hypertonia, tremor, somnolence, respiratory distress or feeding disruptions. Therefore, newborns should be monitored carefully.

Schaefer (2007) suggests that the use of sertindole is not an indication for the termination of pregnancy. A pregnant patient who is stable with the use of sertindole should keep receiving the drug as changing to an alternative drug may worsen her health. Dose reduction during the days leading up to birth should be considered to prevent neonatal adaptation disorders. Dose should then be adjusted to pre-pregnancy levels immediately after delivery.

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

Sertindole is contraindicated in breastfeeding.

Studies in nursing mothers have not been performed, however it is expected that sertindole will be excreted in breast milk. If treatment is necessary, the manufacturer recommends that breastfeeding should be discontinued.

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

Convulsions
Decreased ejaculate volume
Deep vein thrombosis (DVT)
Dizziness
Dry mouth
Dyspnoea
Ejaculation disorders
Erectile dysfunction
Exacerbation of diabetes
Extrapyramidal effects
Failure of ejaculation
Galactorrhoea
Haematuria
Hyperglycaemia
Hyperprolactinaemia
Movement disturbances
Nasal congestion
Neuroleptic malignant syndrome
Paraesthesia
Peripheral oedema
Postural hypotension
Prolongation of QT interval
Pulmonary embolism
Reflex tachycardia
Rhinitis
Syncope
Tardive dyskinesia
Torsades de pointes
Weight gain
White blood cells in the urine

Withdrawal Symptoms and Signs

Acute withdrawal symptoms including nausea, vomiting, sweating and insomnia have been described after abrupt cessation of antipsychotic drugs. Recurrence of psychotic symptoms may also occur, and the emergence of involuntary movement disorders (such as akathisia, dystonia and dyskinesia) has been reported. Therefore gradual withdrawal is advisable.

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: October 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.

Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press [Accessed on 05 September 2016].

Summary of Product Characteristics: Serdolect 4 mg tablets. Lundbeck. Revised April 2016.

Summary of Product Characteristics: Serdolect 12 mg tablets. Lundbeck. Revised April 2016.

Summary of Product Characteristics: Serdolect 16 mg tablets. Lundbeck. Revised April 2016.

Summary of Product Characteristics: Serdolect 20 mg tablets. Lundbeck. Revised April 2016.