chapter
Antipsychotics
Pages 12

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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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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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.