ABSTRACT
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
