Drugs List

Therapeutic Indications

Uses

Acute treatment of a manic episode associated with bipolar disorder
Agitation & disturbed behaviour in schizophrenic patients: acute treatment

Administration

For intramuscular use only.

To enhance absorption and minimise variability, it is recommended to inject into the deltoid or deep within the gluteus maximus muscle, avoiding adipose regions.

Contraindications

Children under 18 years
Breastfeeding

Precautions and Warnings

Debilitation
Family history of diabetes mellitus
Obesity
Patients over 65 years
Predisposition to aspiration or regurgitation
Predisposition to hypotension
Predisposition to venous thromboembolism
Suicidal ideation
Cardiac conduction defects
Cardiac failure
Cardiovascular disorder
Cerebrovascular disorder
Dementia
Diabetes mellitus
History of ischaemic heart disease
History of myocardial infarction
History of seizures
Hypertension
Pregnancy
Seizures
Severe hepatic impairment

May decrease glucose tolerance in patients with diabetes mellitus
Patients at risk of suicide should be closely supervised
Advise ability to drive/operate machinery may be affected by side effects
Reduce initial dose in the elderly
Close medical supervision during initial dosing
Monitor BP, pulse, respiratory rate and level of consciousness regularly
Monitor for signs and symptoms of dystonia
Monitor patients at risk for signs & symptoms of venous thromboembolism
Monitor patients at risk of pathological gambling
Monitor periodically for signs or symptoms of hyperglycaemia
Neonate exposed in utero: Monitor for neonatal withdrawal syndrome
Refer women considering pregnancy for specialist advice and monitoring
Advise patient of the risk of weight gain
Advise patients/carers to seek medical advice if suicidal intent develops
Consider discontinuation if signs of tardive dyskinesia occur
Discontinue in patients with unexplained high fever
Discontinue if patient develops neuroleptic malignant syndrome
Advise patient not to take St John's wort concurrently
Advise patient of increased risk of falls

The occurrence of suicidal behaviour is inherent in psychotic illness, and so patients at risk of suicide should be closely monitored, especially at initiation or switch or antipsychotic therapy.

Antipsychotic drug use is associated with oesophageal dysmotility and aspiration, and so aripiprazole should be used with caution in patients at risk of aspiration pneumonia such as patients with dysphagia.

Neonates exposed to antipsychotics during pregnancy are at risk of adverse reactions including extrapyramidal and or withdrawal symptoms that may vary in severity and duration following delivery. There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, or feeding disorder. Consequently newborns exposed to antipsychotics during pregnancy should be appropriately monitored.

Pregnancy and Lactation

Pregnancy

Use aripiprazole with caution in pregnancy.

At the time of writing, there are no adequate data on the use of aripiprazole in human pregnancy. It is not known if aripiprazole or its major metabolite cross the placenta, but it is thought likely due to their molecular weight, degree of protein binding and long elimination half lives. The extensive serum protein binding should limit foetal transfer. Congenital abnormalities have been reported; however, the manufacturer states that causal relationship with aripiprazole could not be established.

The animal data (rats and rabbits) from high dose studies suggest a possible risk of developmental toxicity and teratogenicity.

Schaefer (2007) concludes that atypical antipsychotics such as aripiprazole may be used during pregnancy where the treatment of acute psychosis or chronic psychotic illness is necessary. Olanzapine or quetiapine are the drugs of choice, due to the documented experience in pregnancy, but treatment with aripiprazole is not an indication for termination of the pregnancy, and antipsychotic medication should not be changed if patients are stable, as this may worsen the mother's health. However, consider a detailed foetal ultrasonography if used during the first trimester. If dose reduction or interruption in the days immediately preceding delivery is deemed appropriate, this may prevent neonatal adaption disorders. Pre-pregnancy dosage should be then started immediately after delivery to prevent relapse.

Briggs (2011) concludes that the safest course is to avoid aripiprazole during pregnancy, but recognises the importance of keeping maternal treatment stable. If used, it should be at the lowest effective dose, avoiding the first trimester if possible, and with long term evaluation of the neonate.

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

Aripiprazole is contraindicated in breastfeeding.

The molecular weight and prolonged elimination half life are consistent with excretion in human milk, but the extensive serum protein binding should limit foetal exposure.

The manufacturer does not recommend breastfeeding during treatment with aripiprazole, due to the lack of published human experience. LactMed agrees that other antipsychotic agents with more experience may be preferred, hence aripiprazole should only be administered if the mother and infant can be monitored. The effects of exposure on the nursing infant are unknown, but potent CNS effects and rare but potentially serious toxicities are possible. If breastfeeding during treatment, the infant should be monitored for somnolence, orthostatic hypotension, seizures, dysphagia, nausea, vomiting and other adverse effects. Briggs concludes that long term evaluation of the infant is warranted.

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 discomfort
Aggression
Agitation
Akathisia
Alopecia
Angioedema
Anorexia
Anxiety
Arrhythmias
Aspiration pneumonia
Blood dyscrasias
Blood glucose disturbances
Blood pressure changes
Blurred vision
Bradycardia
Cardiac arrest
Cerebrovascular accident
Chest pain
Constipation
Creatine phosphokinase increased
Depression
Diabetes mellitus
Diarrhoea
Dizziness
Drowsiness
Dry mouth
Dyskinesia
Dyspepsia
Dysphagia
Dystonia
Extrapyramidal effects
Fatigue
Gamma glutamyl transferase (GGT) increased
Grand mal seizure
Headache
Hepatitis
Hyperglycaemia
Hyperhidrosis
Hyperosmolar non-ketotic coma
Hyperprolactinaemia
Hypersalivation
Hypersensitivity reactions including anaphylaxis
Hypertension
Hyponatraemia
Hypoprolactinaemia
Hypothermia
Increase in alkaline phosphatase
Increase in blood levels of insulin
Increase in serum ALT/AST
Increased appetite
Increased heart rate
Insomnia
Interference with temperature regulation
Jaundice
Ketoacidosis
Laryngeal spasm
Leukopenia
Myalgia
Nausea
Nervousness
Neuroleptic malignant syndrome
Oculogyric crisis
Oropharyngeal spasm
Orthostatic hypotension
Pancreatitis
Pathological gambling
Peripheral oedema
Photosensitivity
Priapism
Prolongation of QT interval
Pruritus
Pyrexia
Rash
Restlessness
Rhabdomyolysis
Sedation
Seizures
Somnolence
Speech disturbances
Stiffness
Stomach pain
Sudden unexplained death
Suicidal tendencies
Syncope
Tachycardia
Tardive dyskinesia
Thromboembolic disorders
Tongue swelling
Torsades de pointes
Tremor
Urinary incontinence
Urinary retention
Urticaria
Ventricular arrhythmias
Vomiting
Weight changes

Presentation

Solution for injection containing aripiprazole.

Drugs List

Therapeutic Indications

Uses

Acute treatment of a manic episode associated with bipolar disorder
Agitation & disturbed behaviour in schizophrenic patients: acute treatment

Dosage

Parenteral treatment with aripiprazole should be discontinued as soon as clinically appropriate, in favour of oral aripiprazole.

Adults

Additional Dosage Information

Administration

For intramuscular use only.

To enhance absorption and minimise variability, it is recommended to inject into the deltoid or deep within the gluteus maximus muscle, avoiding adipose regions.

Contraindications

Children under 18 years
Breastfeeding

Precautions and Warnings

Debilitation
Family history of diabetes mellitus
Obesity
Patients over 65 years
Predisposition to aspiration or regurgitation
Predisposition to hypotension
Predisposition to venous thromboembolism
Suicidal ideation
Cardiac conduction defects
Cardiac failure
Cardiovascular disorder
Cerebrovascular disorder
Dementia
Diabetes mellitus
History of ischaemic heart disease
History of myocardial infarction
History of seizures
Hypertension
Pregnancy
Seizures
Severe hepatic impairment

May decrease glucose tolerance in patients with diabetes mellitus
Patients at risk of suicide should be closely supervised
Advise ability to drive/operate machinery may be affected by side effects
Reduce initial dose in the elderly
Close medical supervision during initial dosing
Monitor BP, pulse, respiratory rate and level of consciousness regularly
Monitor for signs and symptoms of dystonia
Monitor patients at risk for signs & symptoms of venous thromboembolism
Monitor patients at risk of pathological gambling
Monitor periodically for signs or symptoms of hyperglycaemia
Neonate exposed in utero: Monitor for neonatal withdrawal syndrome
Refer women considering pregnancy for specialist advice and monitoring
Advise patient of the risk of weight gain
Advise patients/carers to seek medical advice if suicidal intent develops
Consider discontinuation if signs of tardive dyskinesia occur
Discontinue in patients with unexplained high fever
Discontinue if patient develops neuroleptic malignant syndrome
Advise patient not to take St John's wort concurrently
Advise patient of increased risk of falls

The occurrence of suicidal behaviour is inherent in psychotic illness, and so patients at risk of suicide should be closely monitored, especially at initiation or switch or antipsychotic therapy.

Antipsychotic drug use is associated with oesophageal dysmotility and aspiration, and so aripiprazole should be used with caution in patients at risk of aspiration pneumonia such as patients with dysphagia.

Neonates exposed to antipsychotics during pregnancy are at risk of adverse reactions including extrapyramidal and or withdrawal symptoms that may vary in severity and duration following delivery. There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, or feeding disorder. Consequently newborns exposed to antipsychotics during pregnancy should be appropriately monitored.

Pregnancy and Lactation

Pregnancy

Use aripiprazole with caution in pregnancy.

At the time of writing, there are no adequate data on the use of aripiprazole in human pregnancy. It is not known if aripiprazole or its major metabolite cross the placenta, but it is thought likely due to their molecular weight, degree of protein binding and long elimination half lives. The extensive serum protein binding should limit foetal transfer. Congenital abnormalities have been reported; however, the manufacturer states that causal relationship with aripiprazole could not be established.

The animal data (rats and rabbits) from high dose studies suggest a possible risk of developmental toxicity and teratogenicity.

Schaefer (2007) concludes that atypical antipsychotics such as aripiprazole may be used during pregnancy where the treatment of acute psychosis or chronic psychotic illness is necessary. Olanzapine or quetiapine are the drugs of choice, due to the documented experience in pregnancy, but treatment with aripiprazole is not an indication for termination of the pregnancy, and antipsychotic medication should not be changed if patients are stable, as this may worsen the mother's health. However, consider a detailed foetal ultrasonography if used during the first trimester. If dose reduction or interruption in the days immediately preceding delivery is deemed appropriate, this may prevent neonatal adaption disorders. Pre-pregnancy dosage should be then started immediately after delivery to prevent relapse.

Briggs (2011) concludes that the safest course is to avoid aripiprazole during pregnancy, but recognises the importance of keeping maternal treatment stable. If used, it should be at the lowest effective dose, avoiding the first trimester if possible, and with long term evaluation of the neonate.

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

Aripiprazole is contraindicated in breastfeeding.

The molecular weight and prolonged elimination half life are consistent with excretion in human milk, but the extensive serum protein binding should limit foetal exposure.

The manufacturer does not recommend breastfeeding during treatment with aripiprazole, due to the lack of published human experience. LactMed agrees that other antipsychotic agents with more experience may be preferred, hence aripiprazole should only be administered if the mother and infant can be monitored. The effects of exposure on the nursing infant are unknown, but potent CNS effects and rare but potentially serious toxicities are possible. If breastfeeding during treatment, the infant should be monitored for somnolence, orthostatic hypotension, seizures, dysphagia, nausea, vomiting and other adverse effects. Briggs concludes that long term evaluation of the infant is warranted.

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 discomfort
Aggression
Agitation
Akathisia
Alopecia
Angioedema
Anorexia
Anxiety
Arrhythmias
Aspiration pneumonia
Blood dyscrasias
Blood glucose disturbances
Blood pressure changes
Blurred vision
Bradycardia
Cardiac arrest
Cerebrovascular accident
Chest pain
Constipation
Creatine phosphokinase increased
Depression
Diabetes mellitus
Diarrhoea
Dizziness
Drowsiness
Dry mouth
Dyskinesia
Dyspepsia
Dysphagia
Dystonia
Extrapyramidal effects
Fatigue
Gamma glutamyl transferase (GGT) increased
Grand mal seizure
Headache
Hepatitis
Hyperglycaemia
Hyperhidrosis
Hyperosmolar non-ketotic coma
Hyperprolactinaemia
Hypersalivation
Hypersensitivity reactions including anaphylaxis
Hypertension
Hyponatraemia
Hypoprolactinaemia
Hypothermia
Increase in alkaline phosphatase
Increase in blood levels of insulin
Increase in serum ALT/AST
Increased appetite
Increased heart rate
Insomnia
Interference with temperature regulation
Jaundice
Ketoacidosis
Laryngeal spasm
Leukopenia
Myalgia
Nausea
Nervousness
Neuroleptic malignant syndrome
Oculogyric crisis
Oropharyngeal spasm
Orthostatic hypotension
Pancreatitis
Pathological gambling
Peripheral oedema
Photosensitivity
Priapism
Prolongation of QT interval
Pruritus
Pyrexia
Rash
Restlessness
Rhabdomyolysis
Sedation
Seizures
Somnolence
Speech disturbances
Stiffness
Stomach pain
Sudden unexplained death
Suicidal tendencies
Syncope
Tachycardia
Tardive dyskinesia
Thromboembolic disorders
Tongue swelling
Torsades de pointes
Tremor
Urinary incontinence
Urinary retention
Urticaria
Ventricular arrhythmias
Vomiting
Weight changes

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 ( https://www.toxbase.org/ ) or if this is unavailable at the backup site ( https://www.TOXBASEbackup.org/ ).

Further Information

Last Full Review Date: September 2014

Reference Sources

British National Formulary, 65th Edition (March - September 2013) Pharmaceutical Press, London.

BNF for Children (2013-2014) Pharmaceutical Press, London.

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.

Martindale: The Complete Drug Reference, 37th edition (2011) ed. Sweetman, S. Pharmaceutical Press, London.

Medications and Mothers' Milk, 14th Edition (2010) Hale, T. Hale Publishing, Amarillo, Texas.

NICE guidance CG45 Antenatal and postnatal mental health; February 2007.

Summary of Product Characteristics: Abilify 7.5mg/ml solution for injection. Otsuka and Bristol Myers Squibb. Revised April 2019.

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
Aripiprazole Last revised: January 24, 2013
Last accessed: August 08, 2013