chapter
Drug dependence therapies
Pages 4

Initiate therapy of these drugs, particularly those with a narrow therapeutic index, at the lowest effective dose. Interaction is likely to be important with substrates for which CYP2D6 is considered the only metabolic pathway (e.g. hydrocodone, oxycodone, desipramine, paroxetine, chlorpheniramine, mesoridazine, alprenolol, amphetamines, atomoxetine)

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NERVOUS SYSTEM DRUGS DRUG DEPENDENCE THERAPIES Bupropion

MODULATING DRUGS – corticosteroids, interferons 3. ANTIDEPRESSANTS – TCAs 4. ANTIMALARIALS – chloroquine, mefloquine 5. ANTIPSYCHOTICS 6. BRONCHODILATORS – theophylline 7. CNS STIMULANTS 8. PARASYMPATHOMIMETICS

patients with a history of seizures, with addiction to opiates/cocaine/ stimulants, and in diabetics treated with oral hypoglycaemics or insulin

Bupropion is associated with a dose-related risk of seizures. These drugs, which lower seizure threshold, are individually epileptogenic. Additive effects occur when combined

Extreme caution. The dose of bupropion should not exceed 450 mg/day (or 150 mg/day in patients with severe hepatic cirrhosis)

BUPROPION DRUGS WHOSE METABOLISM WOULD ALTER AFTER CESSATION OF SMOKING

BUPROPION 1. ANTIARRHYTHMICS – flecainide, mexiletine 2. ANTICOAGULANTS – warfarin 3. ANTIDEPRESSANTS – fluvoxamine 4. ANTIPSYCHOTICS – chlorpromazine, clozapine, haloperidol, olanzapine 5. BETABLOCKERS – propanolol 6. BRONCHODILATORS – theophylline

≠ plasma concentrations of these drugs, with risk of toxic/adverse effects

Smoking induces mainly CYP1A2 and CYP2E1. Thus de-induction takes place following cessation of smoking

Be aware, particularly with drugs with a narrow therapeutic index. Monitor clinically and biochemically (e.g. INR, plasma theophylline levels)

BUPROPION ANXIOLYTICS AND HYPNOTICS – ZOLPIDEM

Cases of agitation hallucinations Uncertain Avoid co-administration

BUPROPION DRUG DEPENDENCE THERAPIES – DISULFIRAM

Risk of psychosis Additive effects; these drugs interfere with dopamine metabolism

Caution with co-administration. Warn patients and carers to watch for early features

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Mechanism Precautions

DISULFIRAM ALCOHOL Disulfiram reaction See above Do not co-administer. Disulfiram must not be given within 12 hours of ingestion of alcohol

DISULFIRAM ANTIBIOTICS – METRONIDAZOLE

Report of psychosis Additive effect; both drugs may cause neurological/psychiatric side-effects (disulfiram by inhibiting the metabolism of dopamine, metronodazole by an unknown mechanism)

Caution with co-administration. Warn patients and carers to watch for early features

DISULFIRAM ANTICOAGULANTS – WARFARIN

≠ anticoagulant effect Uncertain at present Monitor INR at least weekly until stable

DISULFIRAM ANTIEPILEPTICS – PHENYTOIN

≠ phenytoin levels Inhibited metabolism Monitor phenytoin levels closely

DISULFIRAM ANTIVIRALS – PROTEASE INHIBITORS

≠ risk of disulfiram reaction with ritonavir (with or without lopinavir)

Ritonavir and lopinavir/ritonavir oral solutions contain 43% alcohol

Warn patients. Consider using capsule preparations as an alternative

DISULFIRAM ANXIOLYTICS AND HYPNOTICS

≠ BZD levels Inhibited metabolism Warn patients of risk of excessive sedation

DISULFIRAM BRONCHODILATORS – THEOPHYLLINE

≠ theophylline levels Disulfiram ↓ theophylline clearance by inhibiting hydroxylation and demethylation

Monitor theophylline levels before, during and after co-administration

DISULFIRAM DRUG DEPENDENCE THERAPIES – BUPROPION

Risk of psychosis Additive effects; these drugs interfere with dopamine metabolism

Caution with co-administration. Warn patients and carers to watch for early features

DISULFIRAM PROTON PUMP INHIBITORS – OMEPRAZOLE

Possible ≠ adverse effects of disulfiram

Accumulation of metabolites Monitor closely for ≠ side-effects, although patients have received combinations without reported problems