Rosuvastatin with St John's Wort Interaction Details

Brand Names Associated with Rosuvastatin

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 10, 2023

Interaction Effect

Reduced effectiveness of rosuvastatin

Interaction Summary

Concomitant use of rosuvastatin and St. John's Wort may result in reduced efficacy of rosuvastatin. Simvastatin bioavailability was significantly reduced by St. John's Wort in healthy volunteers, while pravastatin pharmacokinetics were not significantly affected. The interaction with simvastatin was attributed to induction of CYP3A4 and P-glycoprotein by St. John's Wort. In another study, St. John's Wort significantly increased P-glycoprotein expression and associated drug efflux . St. John's Wort may not interact with rosuvastatin since it is metabolized primarily by CYP2C9 and 2C19. However, patients taking St. John's Wort with rosuvastatin should be monitored for continued lipid-lowering effectiveness.

Severity

Moderate

Onset

Delayed

Evidence

Theoretical

How To Manage Interaction

St. John's Wort may not affect the metabolism of rosuvastatin. However, patients taking St. John's Wort with rosuvastatin should be monitored for continued lipid-lowering effectiveness. If a patient has been taking rosuvastatin and St. John's Wort, advise the patient to consult with his/her healthcare provider before discontinuing St. John's Wort, as stopping St. John's Wort my lead to increased rosuvastatin levels and subsequently to adverse effects.

Mechanism Of Interaction

Unknown

Literature Reports

A) St. John's Wort significantly decreased the AUC (0-24) of the active metabolite of simvastatin, simvastatin hydroxy acid, but not of pravastatin, in a randomized, double-blind, placebo-controlled, crossover study of 16 healthy male subjects (age range 26 to 44 years). All subjects took St. John's Wort (standardized to 0.3% hypericin) 300 mg three times daily for 14 days. On day 14 after an overnight fast, subjects received simvastatin 10 mg (two 5 mg tablets) or placebo in study 1 and pravastatin 20 mg (two 10 mg tablets) or placebo in study 2. AUC (0 to 24) of the active metabolite simvastatin hydroxy acid was significantly reduced from 14.64 nanograms (ng)/mL/hour with placebo to 5.54 ng/mL/hour with St. John's Wort (ratio, 0.48 of placebo; p less than 0.05), while maximum concentration (Cmax) tended to be reduced (2.3 ng/mL with placebo versus 1.1 ng/mL with St. John's Wort, ratio, 0.72 of placebo). Cmax and AUC (0-24) of simvastatin lactone were nonsignificantly reduced by St. John's Wort (Cmax ratio, 0.88 of placebo; AUC (0-24) ratio, 0.66 of placebo). AUC (0-24) of total simvastatin (lactone plus hydroxy acid) was significantly decreased (p less than 0.05). Pravastatin pharmacokinetics were not significantly affected. Time to maximum concentration (Tmax) and elimination half-life of simvastatin lactone and pravastatin were not significantly affected. Four weeks elapsed between treatment periods when patients were crossed over to the other therapy. Subjects did not take any continuous medications, and were asked not to consume grapefruit, grapefruit juice, herbal dietary supplements, and herbal tea. Caffeine was withheld starting the night before the study day until after the final blood sampling .

B) The interaction with simvastatin was attributed to induction of cytochrome P450 (CYP) 3A4 and P-glycoprotein by St. John's Wort. The authors suggested that a similar interaction may occur with lovastatin and atorvastatin, since CYP3A4 plays a major role in their metabolism. Lovastatin and atorvastatin have similar lipophilicity to simvastatin and may also be substrates for P-glycoprotein, though lipophilicity is not the sole determinant of P-glycoprotein affinity. It was suggested that St. John's Wort may not interact with fluvastatin since it is metabolized primarily by CYP2C9 and did not show affinity for P-glycoprotein, even though it is lipophilic. Pravastatin is hydrophilic and did not show affinity for P-glycoprotein, and CYP3A4 has a minor role in pravastatin metabolism. Clinical effect on cholesterol levels was not studied .

C) St. John's Wort significantly increased P-glycoprotein expression and associated drug efflux in a randomized, single-blind, placebo-controlled trial of 22 healthy subjects (13 female, 9 male). Subjects received St. John's Wort (standardized to 0.15% hypericin) 600 mg (n=15) or placebo (n=7) three times daily for 16 days. P-glycoprotein expression in peripheral blood mononuclear cells increased 4.2-fold with St. John's Wort after 16 days (29.5 +/- 14.3 median fluorescence intensity (MFI, a measure of P-glycoprotein expression) versus 7 +/- 1.9 MFI, p less than 0.05, 95% confidence interval (CI): 13.5, 31.6). Individual variability occurred with a range of 1.09 to 9.06 MFI after St. John's Wort. No change in P-glycoprotein expression occurred in subjects receiving placebo. P-glycoprotein expression returned to baseline 16 days after discontinuing St. John's Wort. Efflux of the known P-glycoprotein substrate rhodamine was increased with St. John's Wort (p less than 0.05); no change in efflux occurred with placebo. Ritonavir (5 micromoles), known to reverse P-glycoprotein drug efflux, was significantly less effective in reducing rhodamine efflux in subjects treated with St. John's Wort (75.4 +/- 16.4% versus 23.9 +/- 15.3%, p less than 0.01, 95% CI: 43.7, 70.1). Three subjects receiving St. John's Wort withdrew from the study, one experienced adverse effects (nausea, dry mouth), and two needed potentially interacting medications. Analyses of 2 capsules from 3 batches of St. John's Wort with high performance liquid chromatography verified the hypericin content to be 0.15%, 0.14%, and 0.15% .

Rosuvastatin Overview

• Rosuvastatin is used together with diet, weight-loss, and exercise to reduce the risk of heart attack and stroke and to decrease the chance that heart surgery will be needed in people who have heart disease or who are at risk of developing heart disease. Rosuvastatin is also used to decrease the amount of cholesterol such as low-density lipoprotein (LDL) cholesterol ('bad cholesterol') and triglycerides in the blood and to increase the amount of high-density lipoprotein (HDL) cholesterol ('good cholesterol') in the blood. Rosuvastatin may also be used together with diet to decrease the amount of cholesterol and other fatty substances in the blood in children and teenagers 8 to 17 years of age who have familial heterozygous hypercholesterolemia (an inherited condition in which cholesterol cannot be removed from the body normally). Rosuvastatin is used together with diet, and alone or in combination with other medications, to decrease the amount of cholesterol and other fatty substances in the blood in adults and children and teenagers 7 to 17 years of age who have familial homozygous hypercholesterolemia (an inherited condition in which cholesterol cannot be removed from the body normally). Rosuvastatin is in a class of medications called HMG-CoA reductase inhibitors (statins). It works by slowing the production of cholesterol in the body to decrease the amount of cholesterol that may build up on the walls of the arteries and block blood flow to the heart, brain, and other parts of the body.

• Accumulation of cholesterol and fats along the walls of your arteries (a process known as atherosclerosis) decreases blood flow and, therefore, the oxygen supply to your heart, brain, and other parts of your body. Lowering your blood level of cholesterol and fats with rosuvastatin has been shown to prevent heart disease, angina (chest pain), strokes, and heart attacks.

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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.