Propranolol with St John's Wort Interaction Details

Brand Names Associated with Propranolol

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 15, 2023

Interaction Effect

Decreased effectiveness of beta-adrenergic blockers

Interaction Summary

This interaction has not been reported clinically; it is based on the interaction of St. John's Wort with other drugs metabolized through the same pathway. St. John's Wort has been shown to induce cytochrome P450 3A4 in human subjects . In human hepatocytes, hyperforin, a component of St. John's Wort, was found to activate the pregnane X receptor, which regulates CYP3A4 expression . In contrast, two in vitro studies found extracts of St. John's Wort to inhibit cytochrome P450 isoenzymes including CYP3A4 . Until this interaction is more fully characterized, concomitant use of St. John's Wort and drugs metabolized by cytochrome P450 3A4 such as beta-adrenergic blockers should be avoided.

Severity

Moderate

Onset

Delayed

Evidence

Probable

How To Manage Interaction

Concomitant use of St. John's Wort and beta-adrenergic blockers is not recommended. If patients elect to take St. John's Wort and a beta-adrenergic blocker, increased dosage of the beta-adrenergic blocker may be necessary to achieve therapeutic goals. Patients should not discontinue St. John's Wort without consulting their physician as downward dose adjustment of the beta-adrenergic blocker may be required.

Mechanism Of Interaction

Induction of cytochrome P450 3A4, increased metabolism of beta-adrenergic blockers

Literature Reports

A) In 8 healthy male volunteers, St. John's Wort significantly induced intestinal P-glycoprotein/MDR1 and hepatic cytochrome P450 3A4. Subjects were nonsmokers, aged 23-35 years, and abstained from caffeine, alcohol, citrus fruits, and medications for 5 days prior to and during the study. Biopsy specimens of the duodenal intestinal mucosa were obtained to determine P-gycoprotein/MDR1, CYP3A4 expression, and villin content at baseline and on days 15 and 16. Erythromycin breath test was performed on days 2, 15 and 16 to determine effect on CYP3A4 function. Digoxin 0.5 milligrams (mg) was given orally on day 2 for pharmacokinetic analysis. St. John's Wort extract (LI 160, Lichtwer Pharma AG, Berlin) was given as 300 mg three times daily for 14 days, digoxin 0.5 mg was given again on day 16. Digoxin bioavailability was increased by 18% after St. John's Wort administration. Mean intestinal P-glycoprotein/villin ratios increased 1.37 +/- 0.31 times following St. John's Wort (p equal to 0.025). One subject demonstrated a decreased P-glycoprotein/villin ratio, indicating that interindividual variability is possible. Mean CYP3A4/villin ratios increased 1.48 +/- 0.17 times following St. John's Wort (p equal to 0.012). Induction of CYP3A4 was further evidenced by increased demethylation of erythromycin, 1.44 +/- 0.28 times over baseline, by the erythromycin breath test .

B) St. John's Wort has been reported to induce cytochrome P450 isoenzyme 3A4 as measured by urinary 6-beta-hydroxycortisol to cortisol ratios in a study of 13 healthy volunteers treated with St. John's Wort for 2 weeks. Compared to baseline, mean urinary 6-beta hydroxycortisol to cortisol ratios increased from 7.1 to 13.0 (p equal to 0.003). One subject experienced an unexplained 25% decrease in urinary 6-beta hydroxycortisol to cortisol ratio. The results suggest that recommended doses of St. John's Wort induce CYP3A4 activity .

C) Hyperforin was shown to activate the pregnane X receptor (PXR), which regulates expression of CYP3A4 in primary human hepatocytes. Levels of hyperforin in humans taking standard doses of St. John's Wort (300 mg three times daily) are well above those required for hyperforin to activate PXR. All three St. John's Wort extracts tested activated PXR to an extent comparable to that of rifampicin, which is a known activator of PXR and CYP3A4 expression .

Propranolol Overview

• Propranolol is used to treat high blood pressure, irregular heart rhythms, pheochromocytoma (tumor on a small gland near the kidneys), certain types of tremor, and hypertrophic subaortic stenosis (a heart muscle disease). It is also used to prevent angina (chest pain), migraine headaches, and to improve survival after a heart attack. Propranolol is in a class of medications called beta blockers. It works by relaxing blood vessels and slowing heart rate to improve blood flow and decrease blood pressure.

• High blood pressure is a common condition and when not treated, can cause damage to the brain, heart, blood vessels, kidneys and other parts of the body. Damage to these organs may cause heart disease, a heart attack, heart failure, stroke, kidney failure, loss of vision, and other problems. In addition to taking medication, making lifestyle changes will also help to control your blood pressure. These changes include eating a diet that is low in fat and salt, maintaining a healthy weight, exercising at least 30 minutes most days, not smoking, and using alcohol in moderation.

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Definitions

Severity Categories

Contraindicated

These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.

Major

This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.

Moderate

This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.

Minor

While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.

Onset

Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.

Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.

Evidence

Level of documentation of the interaction.

Established: The interaction is documented and substantiated in peer-reviewed medical literature.

Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.

How To Manage The Interaction

Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.

It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.

Mechanism Of Interaction

The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.

Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.

Where Does Our Information Come From?

Information for our drug interactions is compiled from several drug compendia, including:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

The prescribing information for each drug, as published on DailyMED, is also used. 

Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.

The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.