A patient on montelukast for asthma takes St John's Wort for low mood and experiences worsening asthma symptoms and increased use of inhalers. What is the most likely drug interaction?

• A. Montelukast reduces St John's Wort efficacy
• B. St John's Wort increases montelukast absorption
• C. There is no interaction
• D. St John's Wort increases metabolism of montelukast, reducing its effectiveness

Answer: (D)

St John’s Wort can act as a strong inducer of hepatic enzymes, especially CYP3A4. Montelukast is broken down by these enzymes, so taking St John’s Wort speeds up its metabolism and lowers its plasma concentration. With less montelukast available, its anti-inflammatory effect in the airways diminishes, so asthma control worsens and the patient may rely more on rescue inhalers. That’s why the most likely interaction is increased metabolism of montelukast, reducing its effectiveness. The idea that St John’s Wort would increase montelukast absorption or that there’s no interaction doesn’t fit the observed worsening control.