ABSTRACT
Warn patients of this additive effect. Consider increasing the dose of levodopa. Consider changing the formulation to a sublingual nitrate spray
ANTIPSYCHOTICS ALCOHOL Risk of excessive sedation Additive effect Warn patients of this effect, and advise them to drink alcohol only in moderation
ANTIPSYCHOTICS ANAESTHETICS – GENERAL Risk of hypotension Additive effect Monitor BP closely, especially during induction of anaesthesia
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NERVOUS SYSTEM DRUGS ANTIPSYCHOTICS
dol 2. Risk of agranulocytosis when azaproprazone given with clozapine
1. Unknown 2. Unknown 1. Avoid co-administration 2. Avoid co-administration
ANTIPSYCHOTICS OPIOIDS Risk of ≠ respiratory depression, sedation and ↓ BP. This effect seems to be particularly marked with clozapine
Additive effects Warn patients of these effects. Monitor BP closely. Titrate doses carefully
ANTIPSYCHOTICS TRAMADOL ≠ risk of fits Additive effects Consider using an alternative analgesic PHENOTHIAZINES, SULPIRIDE
ANTACIDS ↓ levels of these antipsychotics ↓ absorption Separate doses by 2 hours (in the case of sulpiride, give sulpiride 2 hours after but not before the antacid)
ANTIPSYCHOTICS ANTIARRHYTHMICS
ANTIPSYCHOTICS ADENOSINE Risk of ventricular arrhythmias, particularly torsades de pointes, with phenothiazines and pimozide. There is also a theoretical risk of Q-T prolongation with atypical antipsychotics
All of these drugs prolong the Q-T interval
Avoid co-administration of phenothiazines, amisulpride, pimozide or sertindole with adenosine. Monitor the ECG closely when adenosine is co-administered with atypical antipsychotics
AMISULPRIDE, PHENOTHIAZINES, PIMOZIDE, SERTINDOLE
FLECAINIDE Risk of arrhythmias Additive effect. Also, haloperidol and thioridazine inhibit CYP2D6mediated metabolism of flecainide
Avoid co-administration
ANTIPSYCHOTICS ANTIBIOTICS ➣ Q-T-prolonging drugs, above
ARIPIPRAZOLE, CLOZAPINE, HALOPERIDOL
RIFABUTIN, RIFAMPICIN ↓ levels of these antipsychotics ≠ metabolism Watch for poor response to these antipsychotics; consider increasing the dose
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Mechanism Precautions
Additive effect Avoid co-administration
CLOZAPINE, OLANZAPINE CIPROFLOXACIN ≠ clozapine levels and possibly ≠ olanzapine levels
Ciprofloxacin inhibits CYP1A2; clozapine is primarily metabolized by CYP1A2, while olanzapine is partly metabolized by it
Watch for the early features of toxicity to these antipsychotics. A ↓ in dose of clozapine and olanzapine may be required
CLOZAPINE MACROLIDES – ERYTHROMYCIN
≠ clozapine levels with risk of clozapine toxicity
Clozapine is metabolized by CYPIA2, which is moderately inhibited by erythromycin. Erythromycin is a potent inhibitor of CYP3A4, which has a minor role in the metabolism of clozapine. This may lead to ↓ clearance and therefore ≠ levels of clozapine
Cautious use advised
ANTIPSYCHOTICS ANTICANCER AND IMMUNOMODULATING DRUGS
CLOZAPINE CYTOTOXICS ≠ risk of bone marrow toxicity Additive effect Avoid co-administration CLOZAPINE, HALOPERIDOL, PERPHENAZINE, RISPERIDONE
IMATINIB Imatinib may cause ≠ plasma concentrations of these drugs with a risk of toxic effects
Inhibition of CYP2D6-mediated metabolism of these drugs
Watch for early features of toxicity of these drugs
CHLORPROMAZINE, FLUPHENAZINE
PORFIMER ≠ risk of photosensitivity reactions Attributed to additive effects Avoid exposure of skin and eyes to direct sunlight for 30 days after porfimer therapy
CLOZAPINE PROCARBAZINE, PENICILLAMINE
≠ risk of bone marrow toxicity Additive effect Avoid co-administration
FLUPENTIXOL, PIMOZIDE, ZUCLOPENTHIXOL
PROCARBAZINE Prolongation or greater intensity of sedative, hypotensive and anticholinergic effects
Additive effect Avoid co-administration
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NERVOUS SYSTEM DRUGS ANTIPSYCHOTICS
SULPIRIDE
Uncertain Watch for development of these symptoms
SERTINDOLE LITHIUM ≠ risk of ventricular arrhythmias Uncertain Avoid concomitant use ANTIPSYCHOTICS MAOIs Additive depression of CNS ranging
from drowsiness to coma and respiratory depression
Synergistic depressant effects on CNS function
Necessary to warn patients, particularly regards activities that require attention, e.g. driving or using machinery and equipment that could cause self-harm
ARIPIPRAZOLE, CLOZAPINE, HALOPERIDOL, PERPHENAZINE, RISPERIDONE, SERTINDOLE
SSRIs Possible ≠ plasma concentrations of these antipsychotics
Inhibition of CYP2D6-mediated metabolism of these drugs. The clinical significance of this depends upon whether alternative pathways of metabolism of these substrates are also inhibited by co-administered drugs. The risk is theoretically greater with clozapine, haloperidol and olanzapine because their CYP1A2-mediated metabolism is also inhibited by SSRIs
Warn patients to report ≠ side-effects of these drugs, and consider reducing the dose of the antipsychotic
PIMOZIDE SERTRALINE ≠ plasma concentrations of these drugs and potential risk of dangerous arrhythmias
Sertraline inhibits metabolism of pimozide. The precise site of inhibition is uncertain
Avoid co-administration
HALOPERIDOL TCAs Possible ≠ haloperidol levels Inhibition of CYP2D6-and CYP1A2-mediated metabolism of thioridazine
Warn patients to report ≠ side-effects of these drugs
HALOPERIDOL VENLAFAXINE ≠ haloperidol levels Inhibited metabolism Avoid co-administration
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Mechanism Precautions
of control of blood sugar
Clozapine can cause resistance to the action of insulin
Watch for diabetes mellitus in patients on long-term clozapine treatment
OLANZAPINE, PHENOTHIAZINES
REPAGLINIDE ↓ hypoglycaemic effect Antagonistic effect Higher doses of repaglinide needed
PHENOTHIAZINES METFORMIN May ≠ blood sugar-lowering effect and risk of hypoglycaemic episodes. Likely to occur with doses exceeding 100 mg/day
Phenothiazines such as chlorpromazine inhibit the release of epinephrine and ≠ risk of hypoglycaemia. May inhibit the release of insulin
Chlorpromazine is nearly always used in the long term. Watch for and warn patients about symptoms of hypoglycaemia ➣ For signs and symptoms of hypoglycaemia, see Clinical Features of Some Adverse Drug Interactions, Hypoglycaemia
PHENOTHIAZINES SULPHONYLUREAS May ≠ blood sugar-lowering effect and risk of hypoglycaemic episodes. Likely to occur with doses exceeding 100 mg/day
Phenothiazines such as chlorpromazine inhibit the release of epinephrine and ≠ risk of hypoglycaemia. May inhibit the release of insulin, which is the mechanism by which sulphonylureas act
Chlorpromazine is nearly always used in the long term. Watch for and warn patients about symptoms of hypoglycaemia ➣ For signs and symptoms of hypoglycaemia, see Clinical Features of Some Adverse Drug Interactions, Hypoglycaemia
RISPERIDONE NATEGLINIDE, REPAGLINIDE
≠ risk of hypoglycaemic episodes Attributed to a synergistic effect Watch for and warn patients about symptoms of hypoglycaemia ➣ For signs and symptoms of hypoglycaemia, see Clinical Features of Some Adverse Drug Interactions, Hypoglycaemia
PIMOZIDE ANTIEMETICS – APREPITANT
≠ aprepitant levels Inhibition of metabolism Avoid co-administration (manufacturers’ recommendation)
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NERVOUS SYSTEM DRUGS ANTIPSYCHOTICS
Antipsychotics lower seizure threshold
Watch for ≠ fit frequency; warn patients of this risk when starting antipsychotics, and take suitable precautions. Consider increasing the dose of antiepileptic
ANTIPSYCHOTICS CARBAMAZEPINE, PHENYTOIN, PHENOBARBITAL, PRIMIDONE
↓ levels of apiprazole (all), haloperidol (carbamazepine, phenobarbital), clozapine, quetiapine, sertindole (carbamazepine, phenytoin), risperidone and olanzapine (carbamazepine)
Induction of metabolism Watch for poor response to these antipsychotics, and consider increasing the dose
OLANZAPINE VALPROATE Risk of bone marrow toxicity Additive effect Monitor FBC closely; warn patients to report sore throat, fevers, etc.
