Smoking and drug metabolism

Ingredients in tobacco smoke induce cytochrome P450 isoenzymes, which are involved in metabolising medicines via the liver. Enzymes affected include CYP1A1, CYP1A2, CYP1B1, CYP2B6, CYP2C19, CYP2E1, CYP3A4 and UDP-glucuronosyltransferases (UGTs).

Medicines metabolised by the induced enzymes may be cleared from the body more quickly. Changes in smoking status may impact blood levels of interacting medicines.

If a person starts (or restarts) smoking

Liver enzymes may be induced by smoking, thereby reducing blood levels of interacting medicines.

Enzyme induction is related to smoke exposure. If the person increases the amount they smoke, enzymes will be induced further.

It can take several weeks to achieve maximum induction while new enzymes are made.

Monitor individuals taking interacting medicines, particularly those with a narrow therapeutic index; titrate doses upwards if required.

If a person stops smoking

Enzyme induction down-regulates on stopping or reducing smoking. This may result in increased blood levels of interacting medicines. Reversal of induction can be rapid, particularly if the person stops smoking abruptly. Effects may be seen within three days; full reversal may take two to four weeks.

Monitor individuals taking interacting medicines and adjust doses if required. Take care with narrow therapeutic index medicines to avoid adverse or toxic effects.

Using vapes and stop-smoking aids

If an individual is using nicotine-containing vapes (e-cigarettes) or nicotine replacement therapy (NRT) to stop or reduce smoking, follow advice for if a person stops smoking.

There is no direct interaction with vapes or NRT; liver enzyme induction is due to components of tobacco smoke rather than nicotine.

Individuals most likely to be affected

A clinically relevant interaction is more likely in certain situations.

Heavy smokers

The extent of enzyme induction is related to smoke exposure. The more an individual smokes, the higher the rate of induction. The maximum inductive effect may be reached after smoking more than 10 cigarettes daily.

Abrupt cessation of smoking

Abrupt cessation leads to rapid loss of enzyme function, causing a rise in drug levels and increased risk of adverse effects.

Individuals such as hospital inpatients and immobile care home residents may be unable to access smoking areas. This makes them more likely to develop adverse effects from abrupt cessation of smoking.

Stop-smoking campaigns encourage quitting, with the use of NRT or nicotine vapes. This can have the same impact as abrupt cessation of smoking.

For people who switch to NRT in hospital, consider smoking-related interactions if they are likely to resume smoking on discharge.

Genetic predisposition

Distribution of CYP enzymes varies between individuals, resulting in metabolic rates ranging from poor to ultra-rapid. Changes in smoking status may have unexpected effects due to this difference in metaboliser status.

Additional dose adjustments and monitoring may be required in some individuals on a case-by-case basis.

Narrow therapeutic index medicines

A clinically relevant interaction is more likely if the medicine has a narrow therapeutic window. Changes in smoking status have an increased risk of subclinical or toxic effects.

Managing interactions with smoking

People differ in their response to smoking and medication.

It may take an individual several attempts to quit smoking successfully. It is good practice to check for changes in smoking status when prescribing new medicines, undertaking a medication review, or performing medicines reconciliation. If dose adjustments are required on stopping smoking, these will likely need to be reversed if the individual restarts.

For most medicines, dose adjustment will not be required when a person stops smoking. However, it is helpful to be aware of relevant medicines and to counsel individuals to watch for signs of toxicity when stopping smoking.

For some medicines, such as clozapine, a clinically relevant interaction can be predicted, and dose adjustment will be necessary with input from the specialist team.

Specific recommendations

The following resource contains specific recommendations for medicines that interact with tobacco smoking:

Further information

The following resource may be useful: Drug interactions: resources to support answering questions.

If further advice is required, or if the clinical scenario is complex, primary care healthcare professionals can seek further advice from our Medicines Advice Service.

Update history