Significant antineoplastic drugs, such as irinotecan, should not be used with Hypericum perforatum as the combination reduces the plasma levels of irinotecan and may have an impact on the treatment outcome, as seen in one randomized crossover study.[1]
St. John’s wort may also cause a higher risk of hypoglycemia when used in combination with tolbutamide.[2]
HP may also play a role in reducing the plasma concentration of many opioids such as oxycodone, dextromethorphan, and pethidine.[3]
Hypertensive medications can also be affected. Calcium channel blockers such as nifedipine interact with HP, which induces the metabolism of nifedipine and increases the plasma concentration of dehydronifedipine.[4] Hypericum perforatum also interacts with verapamil by decreasing its bioavailability through the induction of CYP3A4.[5]
Furthermore, taking theophylline (a bronchodilator) with 300mg of HP resulted in acutely decreased blood concentrations of theophylline through CYP3A4 inhibition.[6] However, when the combination was taken for 15 days, it was found that HP did not play a role in theophylline plasma or urine levels; proper monitoring is recommended when they are given together.[7]
The interaction between HP and medications metabolized through the CYP pathway is generally considered unsafe due to the potential for significant effects on drug metabolism and efficacy. However, one study has explored the combination of HP with clopidogrel (an anticoagulant medication converted to its active metabolite by CYP enzymes) for people with reduced responsiveness to the drug, aiming to enhance its effect.[8]