Champix Drug Interactions

Based on varenicline characteristics and clinical experience to date, no clinically meaningful drug interactions have been identified. No dosage adjustment of varenicline or co-administered drugs listed as follows is recommended.
In vitro studies indicate that varenicline is unlikely to alter the pharmacokinetics of compounds that are primarily metabolized by cytochrome P450 enzymes.
In vitro studies demonstrate that varenicline does not inhibit cytochrome P450 enzymes (IC₅₀ >6,400 ng/ml). The P450 enzymes tested for inhibition were: 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4/5. Also, in human hepatocytes in vitro, varenicline was shown to not induce the activity of cytochrome P450 enzymes 1A2 and 3A4. Therefore, varenicline is unlikely to alter the pharmacokinetics of compounds that are primarily metabolised by cytochrome P450 enzymes.
In vitro studies demonstrate that active renal secretion of varenicline is mediated by the human organic cation transporter, OCT2. Co-administration with inhibitors of OCT2 does not require a dose adjustment of varenicline as the increase in systemic exposure to varenicline tartrate is not expected to be clinically meaningful (see Cimetidine interaction as follows). Furthermore since metabolism of varenicline represents less than 10% of its clearance, active substances known to affect the cytochrome P450 system are unlikely to alter the pharmacokinetics of varenicline (see Pharmacology: Pharmacokinetics: Metabolism under Actions) and therefore a dose adjustment of varenicline would not be required.
In vitro studies demonstrate that varenicline does not inhibit human renal transport proteins at therapeutic concentrations. Therefore, medicinal products that are cleared by renal secretion (e.g., metformin - see as follows) are unlikely to be affected by varenicline.
Metformin: Varenicline (1 mg twice daily) did not affect the pharmacokinetics of metformin (500 mg twice daily), which is a substrate of OCT2. Metformin had no effect on varenicline pharmacokinetics.
Cimetidine: Co-administration of an OCT2 inhibitor, cimetidine (300 mg four times daily), with varenicline (2 mg single dose) increased the systemic exposure of varenicline by 29% due to a reduction in varenicline renal clearance.
Digoxin: Varenicline (1 mg twice daily) did not alter the steady-state pharmacokinetics of digoxin administered as a 0.25 mg daily dose.
Warfarin: Varenicline (1 mg twice daily) did not alter the pharmacokinetics of a single 25 mg dose of (R,S) warfarin. Prothrombin time (INR) was not affected by varenicline. Smoking cessation itself may result in changes to warfarin pharmacokinetics (see Effect of smoking cessation under Precautions).
Alcohol: There are limited clinical data on any potential interaction between alcohol and varenicline. There have been post-marketing reports of increased intoxicating effects of alcohol in patients treated with varenicline. A causal relationship between these events and varenicline use has not been established.
Use with other therapies for smoking cessation: Bupropion: Varenicline (1 mg twice daily) did not alter the steady-state pharmacokinetics of bupropion (150 mg twice daily).
Safety and efficacy of varenicline in combination with other smoking cessation therapies have not been studied.
Nicotine replacement therapy (NRT): When varenicline (1 mg twice daily) and NRT (transdermal 21 mg/day) were co-administered to smokers (N=24) for 12 days, there was a statistically significant decrease in average systolic blood pressure (mean 2.6 mmHg) measured on the final day of the study. In this study, the incidence of nausea, headache, vomiting, dizziness, dyspepsia, and fatigue was greater for the combination than for NRT alone.
Safety and efficacy of varenicline in combination with other smoking cessation therapies have not been studied.