Rivastigmine is metabolised mainly through hydrolysis by esterases. Minimal metabolism occurs via the major cytochrome P450 isoenzymes. Thus, no pharmacokinetic interactions are anticipated with other drugs metabolised by these enzymes.
Anticipated interactions resulting in a concomitant use not recommended: Metoclopramide: Considering the possibility of an additive extra-pyramidal effect the concomitant use of metoclopramide and rivastigmine is not recommended.
Drugs acting on cholinergic system: In view of its pharmacodynamic effects, rivastigmine should not be given concomitantly with other cholinomimetic drugs due to possible additive effect. Rivastigmine might also interfere with the activity of anticholinergic medications (e.g. oxybutynin, tolterodine).
Succinylcholine-type muscle relaxants: As a cholinesterase inhibitor, rivastigmine may exaggerate the effects of succinylcholine-type muscle relaxants during anaesthesia.
Observed interactions to be considered: Beta-blockers: Additive effects leading to bradycardia (which may result in syncope) have been reported with the combined use of various beta-blockers (including atenolol) and rivastigmine. Cardioselective beta-blockers are expected to be associated with the greatest risk, but reports have also been received in patients using other beta-blockers.
Interaction with nicotine: A population pharmacokinetic analysis showed that nicotine use increases the oral clearance of rivastigmine by 23% in patients with Alzheimer's dementia (n=75 smokers and 549 non-smokers) following rivastigmine oral capsule doses of up to 12 mg/day.
Interactions with commonly used concomitant drugs: No pharmacokinetic interaction was observed between oral rivastigmine and digoxin, warfarin, diazepam or fluoxetine in studies in healthy volunteers. The increase in prothrombin time induced by warfarin is not affected by administration of rivastigmine. No untoward effects on cardiac conduction were observed following concomitant administration of digoxin and rivastigmine.
Concomitant administration of rivastigmine with commonly prescribed medications, such as antacids, antiemetics, antidiabetics, centrally acting antihypertensives, calcium channel blockers, inotropic drugs, antianginals, non-steroidal anti-inflammatory drugs, oestrogens, analgesics, benzodiazepines and antihistamines, was not associated with an alteration in the kinetics of rivastigmine, or an increased risk of clinically relevant untoward effects.