Can I Take St John's Wort with Cialis (Tadalafil)?

Updated Jul 14, 2025

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Tadalafil (brand name Cialis, and also marketed as Adcirca for pulmonary arterial hypertension) is an oral PDE5 inhibitor approved by the FDA for erectile dysfunction, benign prostatic hyperplasia (BPH), and pulmonary arterial hypertension (PAH). St John's Wort (Hypericum perforatum) is an over-the-counter herbal supplement used mainly for mild mood support.

St John's Wort is a well-documented inducer of the liver enzyme CYP3A4, and tadalafil depends heavily on CYP3A4 for its clearance. FDA-approved prescribing information for tadalafil names St John's Wort as an agent that can lower tadalafil plasma concentrations. That said, no published pharmacokinetic trial has directly tested tadalafil combined with St John's Wort; the interaction is inferred from tadalafil's known metabolic pathway, from St John's Wort's well-characterized effect on that pathway, and from data on other CYP3A4-cleared drugs. This matters because the exact size of the effect on tadalafil specifically has not been measured in a published study we could verify, even though the direction of the effect (less active drug, not more) is well supported.

The practical answer: avoid combining the two unless a prescriber has specifically reviewed the situation. If you are already taking both, do not stop either one abruptly without a plan, and do not assume dose-timing tricks will help, because enzyme induction does not work that way.

The core fact, stated plainly

St John's Wort activates the pregnane X receptor and upregulates CYP3A4, the enzyme responsible for the majority of tadalafil's hepatic clearance; FDA-approved tadalafil labeling identifies St John's Wort by name as a CYP3A4 inducer capable of reducing tadalafil plasma concentrations. No dedicated tadalafil-plus-St John's Wort pharmacokinetic study has been published, so the magnitude of the interaction for tadalafil specifically is extrapolated rather than directly measured. Because the mechanism is enzyme induction rather than absorption competition, spacing the two substances apart by hours does not prevent the interaction, and the effect can persist for roughly two weeks after St John's Wort is stopped while enzyme levels return to baseline.

What is actually established versus extrapolated

The useful question here is not simply "does this interact," which is settled at the mechanism level, but "how confident can you be in the specific numbers you might see cited," which is not settled. Treat any precise percentage attached to tadalafil and St John's Wort together with caution unless your pharmacist can point you to the current label language or a verified primary study.

Claim	Evidence status	Basis	What to verify before relying on it
St John's Wort induces CYP3A4	Established	Long-standing pharmacology finding, reflected in FDA and EMA labeling for many CYP3A4-cleared drugs	Generally not in dispute
Tadalafil is cleared mainly via CYP3A4	Established	FDA-approved tadalafil prescribing information	Confirm you are looking at the current label revision
St John's Wort reduces tadalafil plasma levels	Plausible and labeled, but not directly trial-tested	FDA tadalafil labeling names St John's Wort as an interacting inducer; mechanism is consistent with effects seen on other CYP3A4 substrates	Ask your pharmacist whether a tadalafil-specific pharmacokinetic study exists; as of this writing we could not locate one
A specific number such as "50-70% reduction" for tadalafil and St John's Wort together	Not established for this exact pairing	Percentages of that size have been reported for other CYP3A4 inducer-substrate pairs, not confirmed for tadalafil plus St John's Wort in a study we could verify	Do not treat any single percentage as authoritative until your prescriber confirms it against current labeling or primary literature
A 14-day washout after stopping St John's Wort restores normal tadalafil exposure	Plausible, extrapolated from general CYP3A4 turnover kinetics	General enzyme induction/de-induction physiology, not a tadalafil-specific washout study	Confirm timing with your prescriber rather than self-scheduling redosing
Dose-timing separation prevents the interaction	Established as ineffective	Enzyme induction is systemic and continuous, not dependent on when each substance is taken	Not applicable, this is a mechanism-level conclusion
Risk is more serious in PAH patients on tadalafil than in ED/BPH patients	Plausible clinical reasoning	Subtherapeutic PDE5 inhibitor levels in PAH could plausibly worsen a serious cardiopulmonary condition, but this specific scenario has not been studied	Any PAH patient taking or considering St John's Wort should raise it with the prescribing cardiologist or pulmonologist directly, not manage it alone

Why the mechanism is taken seriously even without a tadalafil-specific trial

CYP3A4 handles the first-pass metabolism of a large share of prescription drugs, and St John's Wort's induction of this enzyme is one of the most consistently replicated herb-drug interactions in the literature. Regulatory bodies do not require a dedicated trial for every possible substrate before warning about the interaction category; instead, once a drug is established as CYP3A4-dependent, that drug is generally treated as at risk from known strong or moderate inducers. This is why the FDA-approved tadalafil label lists St John's Wort by name rather than leaving it as a generic "consult your doctor" caveat, even though the two have apparently not been tested together in a controlled pharmacokinetic study.

Enzyme induction with St John's Wort is not immediate. It typically develops over roughly one to two weeks of regular use as new enzyme protein is synthesized, and it fades over a similar timeframe after St John's Wort is stopped, as the enzyme protein degrades and synthesis returns to baseline. A single incidental dose of St John's Wort carries much less risk than sustained daily use, which is the pattern most people actually follow when using it for mood support.

Who this matters most for

People taking tadalafil for erectile dysfunction or BPH. If tadalafil that previously worked seems to stop working after starting St John's Wort, the supplement is a reasonable first thing to ask about, before assuming tolerance or disease progression. The practical consequence in this population is reduced effectiveness, not added danger.

People taking tadalafil for pulmonary arterial hypertension (Adcirca or generic tadalafil at PAH doses). Here the stakes are different. Subtherapeutic drug levels in PAH could plausibly correspond to reduced symptom control, though this exact scenario has not been directly studied. Anyone in this group should treat the combination as something to flag to their cardiologist or pulmonologist rather than something to manage independently.

People using St John's Wort for depression or low mood while also using tadalafil. Depression and erectile difficulty commonly occur together, which is part of why this combination shows up in practice. If depression or anxiety is the reason for taking St John's Wort, that is worth discussing with a clinician directly, since prescription antidepressants and structured psychotherapy are established first-line options and do not carry the same CYP3A4 induction risk. Note separately that St John's Wort has its own recognized interaction risk with serotonergic antidepressants (a pharmacodynamic, serotonin-related concern), which is a different issue from the CYP3A4 effect on tadalafil.

What to do if you are already taking both

Do not panic and do not simply double a tadalafil dose to compensate. Adjusting dosing on your own is not something this article can safely recommend; that decision belongs with a prescriber who knows your full medication list and medical history.
Talk to your prescriber or pharmacist before stopping anything. St John's Wort does not have a recognized withdrawal syndrome from stopping abruptly, but any decision about how to sequence stopping the supplement and reassessing tadalafil should involve the person managing your treatment, particularly if tadalafil is being used for PAH.
Expect a lag, not an instant change, in either direction. Because induction builds and fades over roughly one to two weeks, do not expect tadalafil's effect to change the same day you stop St John's Wort.
Ask your pharmacist to flag the combination in your record. This is a simple, low-cost step that prevents the interaction from being reintroduced by a future prescriber who does not know your supplement history.
If tadalafil is being used for PAH and you feel any worsening of breathlessness, exercise tolerance, or other PAH symptoms, treat this as something to bring to your treating specialist promptly rather than waiting for a routine visit.

Other CYP3A4 inducers worth mentioning to your prescriber

The same category of concern applies to other strong or moderate CYP3A4 inducers, including rifampin, certain anti-seizure medications (such as carbamazepine, phenytoin, and phenobarbital), and some HIV medications. The FDA-approved tadalafil label discusses rifampin specifically as a benchmark strong inducer. If you take any of these along with tadalafil, that combination deserves the same kind of direct conversation with your prescriber as the St John's Wort question, and the same general caution about not relying on an unverified specific percentage applies.

Grapefruit and Seville orange juice work in the opposite direction, inhibiting rather than inducing CYP3A4, which would tend to raise tadalafil levels rather than lower them; that is a separate interaction question and not addressed in depth here.

Does the interaction change tadalafil's side effects?

If St John's Wort lowers tadalafil exposure, the expected effect is reduced efficacy rather than increased side effects, since side effects generally track with drug concentration in the same direction as therapeutic effect. This is a reasonable pharmacological inference rather than a directly studied outcome for this specific pairing.

When to seek urgent care

Tadalafil interactions of this kind are not typically medical emergencies for ED or BPH use. Seek urgent medical attention for an erection lasting longer than four hours regardless of what else you are taking, and contact your treating specialist promptly if you have PAH and notice new or worsening shortness of breath, reduced exercise tolerance, chest discomfort, or swelling, since these could reflect undertreatment of a serious condition rather than routine symptom fluctuation.

Practical questions to ask your prescriber or pharmacist

Am I taking anything, including herbal supplements sold as Hypericum, SJW, or Perika, that could interact with my tadalafil dose?
Has a tadalafil-specific study on this interaction been published since this article was written, and does the current FDA or EMA label language differ from what I've read here?
If I stop St John's Wort, roughly how long should I expect before reassessing whether tadalafil is working as intended?
If I am on tadalafil for PAH, what symptoms should prompt me to call before my next scheduled visit?

Frequently asked questions

Can I take St John's Wort while on [Cialis](/cialis-tadalafil)?

It is not recommended without discussing it with your prescriber first. St John's Wort induces CYP3A4, the enzyme mainly responsible for clearing tadalafil, and FDA-approved tadalafil labeling names St John's Wort as an agent that can reduce tadalafil plasma concentrations. The exact size of that reduction for tadalafil specifically has not been measured in a published trial we could verify, but the direction of the effect (less effective Cialis) is well supported by the underlying pharmacology.

Does St John's Wort interact with Cialis?

Yes, at the mechanism level. St John's Wort upregulates CYP3A4 over roughly one to two weeks of regular use, and tadalafil depends on that enzyme for clearance. A direct pharmacokinetic study combining the two does not appear to be published, so the interaction is established by mechanism and by FDA labeling rather than by a dedicated trial.

How much does St John's Wort reduce tadalafil levels?

This has not been directly measured in a study we could locate. Reductions of roughly 50 to 70 percent have been reported for other CYP3A4-dependent drugs combined with St John's Wort, and the FDA label separately reports a much larger reduction with rifampin, a stronger inducer. Treat any specific number for the St John's Wort and tadalafil combination as an estimate rather than a confirmed figure, and ask your pharmacist to check current labeling.

How long after stopping St John's Wort can I take Cialis again with full confidence?

A commonly cited general guideline is to allow about two weeks for CYP3A4 activity to return toward baseline after stopping a strong inducer, based on general enzyme induction and turnover kinetics rather than a tadalafil-specific washout study. Confirm timing with your prescriber, especially if tadalafil is being used for a condition where consistent dosing matters, such as PAH.

Is this interaction dangerous or just a reduction in effectiveness?

For erectile dysfunction and BPH, the main concern is reduced effectiveness rather than added danger. For tadalafil used at PAH doses, reduced drug levels could plausibly correspond to worse symptom control, though this specific scenario has not been directly studied. Anyone on tadalafil for PAH should raise the combination with their treating specialist rather than assuming either outcome.

Does separating the timing of St John's Wort and tadalafil doses help?

No. Enzyme induction is a systemic, ongoing change in liver and gut enzyme activity, not a local absorption interaction. Taking the two substances hours apart does not prevent the effect.

Are other supplements or medications a concern in the same way?

Yes. Rifampin, and anti-seizure medications such as carbamazepine, phenytoin, and phenobarbital, are also recognized CYP3A4 inducers and raise the same category of concern discussed in tadalafil's FDA labeling. Grapefruit and Seville orange juice work in the opposite direction, inhibiting rather than inducing CYP3A4.

References

U.S. Food and Drug Administration, tadalafil (Cialis) prescribing information: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/021368s030lbl.pdf, verify you are viewing the current label revision, as labeling is updated periodically.
European Medicines Agency, Cialis (tadalafil) European Public Assessment Report: https://www.ema.europa.eu/en/medicines/human/EPAR/cialis

Several claims in earlier versions of this article cited specific journal studies (sildenafil crossover pharmacokinetics, systematic reviews of depression and erectile dysfunction, IIEF validation studies, and others) that could not be verified against the identifiers provided. Those citations have been removed or converted to general, hedged statements rather than presented as confirmed sources. A qualified reviewer with database access should confirm whether a direct tadalafil and St John's Wort pharmacokinetic study exists before this article states a specific interaction magnitude as fact.