Anaesthetics, local + Rifampicin (Rifampin) and/or Tobacco - Drug Interactions

Rifampicin increases metabolism of ropivacaine, but thisprobably has little clinical relevance to its use as a local anaesthetic. Smoking appears to have only a minor effect on ropivacainepharmacokinetics. Tobacco smoking may enhance cocaine-associated myocardial ischaemia.

Clinical evidence,mechanism, importance and management

In a study involving 42 smokers (36 with proven coronary artery disease) mean product of heart rate and systolic arterial pressure increased by 11 % after intranasal cocaine 2 mg/kg, by 12 % after one cigarette and by 45 % after both cocaine use and one cigarette. Compared with baseline measurements, diameters of non-diseased coronary arterial segments decreased on average by 7 % after cocaine use, 7 % after smoking and 6 % after cocaine and smoking. However, diameters of diseased segments decreased by 9%, 5 % and 19%, respectively (See reference number 1). Cigarette smoking increases myocardial oxygen demand and induces coronary-artery vasoconstriction through an alpha-adrenergic mechanism similar to cocaine and therefore tobacco smoking may enhance cocaine-associated myocardial ischaemia (See reference number 1,2).

A study in 10 healthy non-smokers and 8 healthy smokers given ropivacaine 600 micrograms/kg by intravenous infusion over 30 minutes found that smoking increased urinary excretion of metabolite 3-hydroxyropivacaine and decreased urinary excretion of 2,6-pipecoloxylidide by 62%, but did not significantly affect ropivacaine AUC. However, pretreatment with rifampicin 600mg daily for 5 days increased clearance (by 93 % and 46%) and decreased AUC by 52 % and 38 % and half-life of ropivacaine in both non-smokers and smokers, respectively.(See reference number 3) Ropivacaine undergoes oxidative hepatic metabolism mainly by cytochrome P450 isoenzymes CYP1A2 and CYP3A4. Cigarette smoking may increase CYP1A2-mediated metabolism of ropivacaine, and elimination of ropivacaine may be considerably accelerated by rifampicin, which is a potent cytochrome P450 enzyme inducer. However, in clinical use local anaesthetic is given near nerves to be desensitised and induction of isoenzymes is not likely to affect local anaesthetic before it enters systemic blood circulation.(See reference number 3) This interaction is therefore of little clinical relevance.

Rifampicin may also increase metabolism of lidocaine to a minor extent, see Lidocaine + Rifampicin (Rifampin) interaction, and smoking may reduce oral bioavailability of lidocaine, .

Moliterno DJ,Willard JE, Lange RA, Negus BH, Boehrer JD, Glamann DB, Landau C, RossenJD, Winniford MD, Hillis LD. Coronary-artery vasoconstriction induced by cocaine, cigarettesmoking, or both. N Engl J Med (1994) 330, 454–9.

Hollander JE. The management of cocaine-associated myocardial ischemia. N Engl J Med (1995) 333,1267–72.

Jokinen MJ,Olkkola KT, Ahonen J, Neuvonen PJ. Effect of rifampin and tobacco smoking onthe pharmacokinetics of ropivacaine. Clin Pharmacol Ther (2001) 70, 344–50.