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Smoking cessation induces toxic dose levels of certain drugs

Toxic dose levels (alias overdose) of certain drugs have been observed a few weeks after the patient stopped smoking. Some had serious consequences, especially those involving a drug with a narrow therapeutic index.

Smoking accelerates the metabolism of certain drugs, some of which have a narrow therapeutic index, which means that there is little margin between a therapeutic dose and a toxic dose. When a patient stops smoking, this accelerated metabolism gradually recedes (within 2 to 3 weeks), putting the patient at risk of developing potentially serious adverse effects through an overdose of the drug. It is difficult to stop smoking completely and for good. Many patients therefore make several cessation attempts, with this phenomenon recurring each time.

Tobacco smoke is the cause of this accelerated metabolism. Nicotine is not responsible in this type of drug interaction. This means that the use of nicotine replacement therapy does not prevent these effects on the patient’s treatment.

This phenomenon has mainly been observed in patients taking clozapine or warfarin. Increased plasma concentrations of various other drugs have been reported, such as fluvoxamine, flecainide, propranolol and theophylline.

When a patient taking a drug with a narrow therapeutic index stops being exposed to tobacco smoke, careful monitoring is warranted for about a month. Dose adjustment is sometimes required to prevent adverse effects resulting from overdose.

©Prescrire 1 February 2021

Source: "Smoking cessation: toxic dose levels of certain drugs" Prescrire International 2021; 30 (223): 43-44. Subscribers only.

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