Which agents are listed as inducers of CYP450 that can lead to subtherapeutic levels of coadministered drugs?

• A. Tobacco, Phenytoin, Carbamazepine, and Rifampin
• B. Grapefruit juice, Ketoconazole, Erythromycin, and Cimetidine
• C. Valproate, Lamotrigine, Topiramate, and Levetiracetam
• D. Acetaminophen, Ibuprofen, Aspirin, and Naproxen

Answer: (A)

Inducing CYP450 enzymes speeds up the metabolism of drugs that are substrates, which lowers their blood levels and can make them subtherapeutic. Among common inducers, tobacco smoke, phenytoin, carbamazepine, and rifampin are classic examples; they upregulate multiple CYP enzymes and accelerate drug clearance. Induction takes days to weeks to reach full effect and can persist after stopping, so the impact on coadministered medications may be gradual and long-lasting.

In contrast, substances like grapefruit juice, ketoconazole, erythromycin, and cimetidine inhibit CYP3A4 and other enzymes, leading to higher drug levels and potential toxicity rather than subtherapeutic effects. The other listed agents are not typical broad inducers of CYP450; their interactions are different and do not usually cause a need to compensate for subtherapeutic levels of coadministered drugs.

Clinically, when an inducer is started in a patient taking a CYP450 substrate, you’d expect reduced efficacy and may need to adjust the dose or choose an alternative drug, with careful monitoring for therapeutic response.