3.12 Important drug interactions

Concomitant administration of an antipsychotic with a drug which is sedative (eg alcohol) or which reduces blood pressure (eg ACE inhibitor) can increase the potential for these effects.

Many antipsychotic drugs have the potential to affect heart rhythm; the risk of arrhythmia is increased when such an antipsychotic drug is combined with other drugs that affect rhythm or drugs that increase the concentration of the antipsychotic (eg azole antifungal drugs). Drugs which reduce serum potassium can increase the risk of adverse effects arising from QT-interval prolongation. The table below lists common drugs that can interact to prolong the QT interval; a comprehensive list of drugs that prolong the QT interval should be consulted where necessary.

Rarely, antipsychotics can reduce white cell and red cell count; concomitant use with other drugs that interfere with bone-marrow function (myelosuppressants) might increase the risk of reducing blood cells and, possibly, platelets.

Consult summaries of product characteristics and other sources of information on the interactions of individual antipsychotics

Interacting drug or drug class	Effect of interaction	Risk-reduction measures
ACE inhibitors and angiotensin-II receptor antagonists¹	Increased hypotensive effect	Monitor blood pressure and ask about postural hypotension
Alcohol	Increased sedation	Warn patient of excessive sedation and of psychomotor impairment
Amantadine	Increased risk of extrapyramidal effects²
Amphotericin	Hypokalaemia increases risk of adverse effects of QT-interval³ prolongation	Ensure any hypokalaemia is corrected
Anaesthetics, general	Increased hypotensive effect	Monitor blood pressure and ask about postural hypotension
Anti-arrhythmics with QT-interval prolonging properties (eg amiodarone, disopyramide, flacainide, and sotalol)	Increased risk of QT-interval⁴ prolongation	Preferably avoid concomitant use of drugs that prolong QT interval
Antidepressants, tricyclic	Increased risk of arrhythmias Antimuscarinic⁵ effects, especially of phenothiazine antipsychotics, increased
Antidepressants, tricyclic and SSRIs	Increased risk of seizures
Citalopram and escitalopram	Increased risk of QT-interval⁶ prolongation	Preferably avoid concomitant use of drugs that prolong QT interval
Antiepileptics	Epilepsy control may be impaired
Antihistamines⁷, sedative	Increased sedation	Select non-sedative antihistamine; warn patient of excessive sedation and of psychomotor impairment
Anxiolytic and hypnotic drugs (eg benzodiazepines)	Increased sedation	Warn patient of excessive sedation and of psychomotor impairment
Atomoxetine	Increased risk of QT-interval⁸ prolongation	Preferably avoid concomitant use of drugs that prolong QT interval
Beta-blockers	Increased hypotensive effect	Monitor blood pressure and ask about postural hypotension
Calcium-channel blockers	Increased hypotensive effect	Monitor blood pressure and ask about postural hypotension
Clonidine	Increased hypotensive effect	Monitor blood pressure and ask about postural hypotension
Corticosteroids⁹	Hypokalaemia increases risk of adverse effects of QT-interval¹⁰ prolongation Increased risk of metabolic effects such as weight gain and diabetes	Ensure any hypokalaemia is corrected
Diuretics (loop and thiazide)	Hypokalaemia increases risk of adverse effects of QT-interval prolongation Increased hypotensive effect	Ensure any hypokalaemia is corrected Monitor blood pressure and ask about postural hypotension
Dopamine agonists¹¹ (eg drugs used for Parkinson’s disease)	Antipsychotics inhibit antiparkinsonian effects of dopamine agonists
Lithium	Increased risk of neuroleptic malignant syndrome, extrapyramidal side effects and CNS toxicity	If concomitant administration necessary, adjust dose so plasma-lithium concentration is at minimum effective level; monitor closely for side effects
Methadone	Increased risk of QT-interval¹² prolongation	Preferably avoid concomitant use of drugs that prolong QT interval
Macrolide antibiotics (eg erythromycin, clarithromycin)	Increased risk of QT-interval¹³ prolongation	Preferably avoid concomitant use of drugs that prolong QT interval
Metoclopramide	Increased risk of extrapyramidal effects¹⁴
Moxifloxacin	Increased risk of QT-interval¹⁵ prolongation	Preferably avoid concomitant use of drugs that prolong QT interval
Opioid analgesics	Increased hypotensive and sedative effect	Monitor blood pressure and ask about postural hypotension; warn patient of excessive sedation and of psychomotor impairment
Tramadol	Increased risk of seizures

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²
³
⁴
⁵
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⁷
⁸
⁹
¹⁰
¹¹
¹²
¹³
¹⁴
¹⁵

A substance that binds to a receptor but produces no effect and inhibits an agonist from binding to the receptor↩
Extrapyramidal symptoms or side effects describe movement disorders such as acute dystonia, parkinsonian effects, akathisia and tardive dyskinesia; these effects result from disturbance—by dopamine antagonists—of the extrapyramidal system, which is responsible for involuntary reflexes and coordination of movement. (The voluntary movement system runs through the ‘pyramidal pathways’ of the medulla of the brain)↩
The period between the start of the QRS complex (on an electrocardiogram [ECG]) to the end of the T wave. Prolongation of the QT interval is associated with potentially very serious rhythm disorders such as torsades de pointes↩
The period between the start of the QRS complex (on an electrocardiogram [ECG]) to the end of the T wave. Prolongation of the QT interval is associated with potentially very serious rhythm disorders such as torsades de pointes↩
Reduction or blocking of the effects of parasympathetic nerves; antimuscarinic effects include dry mouth, difficulty swallowing, blurred vision, confusion, palpitations, constipation, and urine retention↩
The period between the start of the QRS complex (on an electrocardiogram [ECG]) to the end of the T wave. Prolongation of the QT interval is associated with potentially very serious rhythm disorders such as torsades de pointes↩
A substance that blocks the effects of histamine. Histamine is released when the body mounts an immune response; also, histamine is a neurotransmitter and it regulates the functioning of the gastrointestinal system. Of the histamine receptors; histamine H₁ receptor is involved in immune reactions, motion sickness and sleep regulation, while histamine H₃ receptor is activated by histamine acting as a neurotransmitter↩
The period between the start of the QRS complex (on an electrocardiogram [ECG]) to the end of the T wave. Prolongation of the QT interval is associated with potentially very serious rhythm disorders such as torsades de pointes↩
Substances that mimic effects of hormones produced by the adrenal cortex. The term corticosteroids covers glucocorticoids (steroids which reduce inflammation) and mineralocorticoids (steroids which act on the kidneys to retain sodium and water and promote excretion of potassium)↩
The period between the start of the QRS complex (on an electrocardiogram [ECG]) to the end of the T wave. Prolongation of the QT interval is associated with potentially very serious rhythm disorders such as torsades de pointes↩
A chemical substance that binds to a receptor and mimics the effect of the physiological (endogenous) substance binding to the receptor↩
The period between the start of the QRS complex (on an electrocardiogram [ECG]) to the end of the T wave. Prolongation of the QT interval is associated with potentially very serious rhythm disorders such as torsades de pointes↩
The period between the start of the QRS complex (on an electrocardiogram [ECG]) to the end of the T wave. Prolongation of the QT interval is associated with potentially very serious rhythm disorders such as torsades de pointes↩
Extrapyramidal symptoms or side effects describe movement disorders such as acute dystonia, parkinsonian effects, akathisia and tardive dyskinesia; these effects result from disturbance—by dopamine antagonists—of the extrapyramidal system, which is responsible for involuntary reflexes and coordination of movement. (The voluntary movement system runs through the ‘pyramidal pathways’ of the medulla of the brain)↩
The period between the start of the QRS complex (on an electrocardiogram [ECG]) to the end of the T wave. Prolongation of the QT interval is associated with potentially very serious rhythm disorders such as torsades de pointes↩