Which Medication Interacts With St John's Wort Quizlet

St. John’s Wort (Hypericum perforatum) is a widely used herbal supplement known for its mood‑enhancing properties, but its powerful effect on the cytochrome P450 enzyme system means it can dramatically alter the metabolism of many prescription drugs. When you search “which medication interacts with st john’s wort quizlet,” you are likely looking for a concise list of pharmaceuticals that become less effective or more toxic when combined with this herb. Understanding these interactions is essential for clinicians, pharmacists, and patients who want to avoid adverse outcomes ranging from reduced therapeutic benefit to life‑threatening toxicity.

What Makes St. John’s Wort So Interaction‑Prone?

St. John’s Wort contains a constellation of bioactive compounds—hypericin, hyperforin, flavonoids, and naphthodianthrones—that potently induce several members of the CYP450 family, especially CYP3A4, CYP2C19, and CYP2C9. In addition, the herb activates the nuclear receptor PXR (pregnane X receptor), which amplifies the expression of drug‑metabolizing enzymes and transporters such as P‑glycoprotein (ABCB1). The net result is accelerated clearance of co‑administered medications, often leading to sub‑therapeutic plasma concentrations. Conversely, some drugs that inhibit these pathways can increase St. John’s Wort levels, raising the risk of side effects such as photosensitivity, serotonin syndrome, or gastrointestinal upset.

Which Medication Interacts with St. John’s Wort? – A Comprehensive Overview

Below is a structured breakdown of the most clinically significant drug classes that interact with St. John’s Wort. The list is organized by therapeutic category, with the most dangerous or frequent interactions highlighted in bold.

1. Antidepressants and Psychiatric Medications

• Selective Serotonin Reuptake Inhibitors (SSRIs) – Fluoxetine, Sertraline, Paroxetine
• Serotonin‑Norepinephrine Reuptake Inhibitors (SNRIs) – Venlafaxine, Duloxetine
• Tricyclic Antidepressants (TCAs) – Amitriptyline, Nortriptyline
• Monoamine Oxidase Inhibitors (MAOIs) – Phenelzine, Tranylcypromine

These agents increase synaptic serotonin levels. Because St. John’s Wort also has serotonergic activity, combining it with SSRIs or SNRIs can precipitate serotonin syndrome, a potentially fatal condition characterized by agitation, hyperthermia, tachycardia, and neuromuscular rigidity. Moreover, St. John’s Wort induces CYP2D6 and CYP3A4, which can lower plasma levels of many antidepressants, diminishing their efficacy.

2. Oral Contraceptives and Hormonal Therapies

• Combined Oral Contraceptives – Ethinyl estradiol + levonorgestrel
• Progestin‑only pills – Norethindrone

St. John’s Wort accelerates the metabolism of ethinyl estradiol and progestins via CYP3A4 induction, reducing contraceptive efficacy and raising the risk of unintended pregnancy. Women using hormonal contraception should consider non‑hormonal backup methods while taking St. John’s Wort.

3. Anticoagulants and Antiplatelet Agents

• Warfarin – Coumadin
• Direct Factor Xa Inhibitors – Rivaroxaban, Apixaban
• Clopidogrel – Plavix

The herb’s induction of CYP2C9 and CYP3A4 can lower warfarin concentrations, decreasing its anticoagulant effect and increasing the chance of thromboembolic events. Similarly, reduced levels of direct oral anticoagulants may compromise protection against stroke or systemic embolism. Patients on these drugs should monitor INR or have anti‑Xa activity checked more frequently when St. John’s Wort is introduced.

4. Immunosuppressants

• Cyclosporine – Neoral
• Tacrolimus – Prograf

Both are narrow‑therapeutic‑index drugs metabolized by CYP3A4. St. John’s Wort can cut their blood levels by up to 50%, heightening the risk of graft rejection or organ transplant failure. Therapeutic drug monitoring is strongly advised whenever these agents are co‑administered with the herb.

5. Antiretrovirals (HIV Therapy)

• Protease Inhibitors – Ritonavir, Indinavir
• Non‑nucleoside Reverse Transcriptase Inhibitors (NNRTIs) – Efavirenz, Nevirapine

St. John’s Wort induces CYP3A4 and the transporter P‑glycoprotein, leading to sub‑therapeutic antiretroviral concentrations. This can foster viral resistance and compromise treatment success. Current guidelines discourage the use of St. John’s Wort in patients on HIV regimens.

6. Cardiovascular Medications

• Statins – Atorvastatin, Simvastatin (especially those metabolized by CYP3A4)
• Calcium Channel Blockers – Diltiazem, Verapamil

Induction of CYP3A4 reduces statin exposure, raising the possibility of myopathy or rhabdomyolysis, particularly with simvastatin. Calcium channel blockers may also lose potency, potentially worsening hypertension or angina.

7. Antiepileptics

• Carbamazepine, Phenytoin, Phenobarbital

These drugs are both substrates and inducers of CYP3A4. Adding St. John’s Wort can create a feedback loop of enzyme induction, dramatically lowering plasma levels of antiepileptics and precipitating breakthrough seizures. Dose adjustments and careful clinical monitoring are mandatory.

8. Theophylline and Other Methylxanthines

• Theophylline – Aerolate, Elixophyll

St. John’s Wort increases the clearance of theophylline, often necessitating dose escalation to maintain therapeutic serum concentrations. Failure to adjust can result in respiratory insufficiency or, paradoxically, toxicity if the dose is inadvertently increased without monitoring.