Pentosan Polysulfate Sodium with St John's Wort Interaction Details
Brand Names Associated with Pentosan Polysulfate Sodium
- Elmiron®
- Pentosan Polysulfate
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Jan 02, 2024
Interaction Effect
Decreased warfarin plasma concentrations leading to reduced anticoagulant effectiveness
Interaction Summary
In an open-label, randomized, crossover study, the coadministration of St John's Wort with warfarin significantly reduced warfarin bioavailability, causing clinically meaningful reductions in the International Normalized Ratio. Several case reports have shown decreases in INR when patients stabilized on warfarin added St. John's Wort . In healthy volunteers, St. John's Wort significantly decreased the AUC of phenprocoumon, an anticoagulant similar to warfarin . The mechanism of the interaction is not fully understood. St. John's Wort induced cytochrome P450 3A4 in humans ; and had no effect on CYP1A2 or 2C9 in humans , though induction of CYP1A2 was hypothesized to be the reason for the significant decrease in theophylline levels observed in one case report and supported by an in vitro study . CYP3A4 and CYP1A2 metabolizes R-warfarin, and CYP2C9 metabolizes S-warfarin. Alteration of S-warfarin primarily affects warfarin efficacy, with R-warfarin metabolism of less importance . If patients elect to remain on St. John's Wort, symptoms of decreased anticoagulant efficacy and prothrombin times should be closely monitored. A stable dose of St. John's Wort is recommended and patients should be advised not to discontinue St. John's Wort without consulting their physician.
Severity
Major
Onset
Delayed
Evidence
Probable
How To Manage Interaction
Concomitant use of anticoagulants with St. John's Wort is not recommended. If patients elect to remain on St. John's Wort, symptoms of decreased anticoagulant efficacy and prothrombin times should be closely monitored. Upward dose titration of the anticoagulant should be undertaken only if the patient takes a consistent daily dose of St. John's Wort with a reputable product containing a consistent amount of active ingredients of St. John's Wort. Patients should be advised that if they discontinue use of St. John's Wort, they may have an increased risk of bleeding complications. Patients should not discontinue St. John's Wort without notifying their health care provider.
Mechanism Of Interaction
St. John's Wort-mediated induction of cytochrome isoforms P450 3A4 and 1A2 (mediates R-warfarin metabolism) and cytochrome P450-2C9 (mediates S-warfarin metabolism),
Literature Reports
A) The coadministration of St John's Wort with warfarin significantly reduced warfarin bioavailability, causing clinically meaningful reductions in the International Normalized Ratio (INR). In an open-label, randomized, 3-way cross-over study, healthy subjects (n=12) received a single oral dose of racemic warfarin 25 milligrams (mg) with or without pretreatment using either Panax ginseng (2 capsules given 3 times daily for 1 week) or St John's Wort (1 tablet 3 times daily for 2 weeks, per customary recommended dosing). Each treatment period was separated by a washout period, minimum of 2 weeks duration. Dosing of St John's Wort continued for 1 week after administration of the warfarin dose. Serial blood pharmacokinetic and INR analysis occurred from 48 hours pre-warfarin dose to 168 hours after administration of warfarin. Significant changes were not observed in warfarin pharmacokinetics with coadministration of Panax ginseng with warfarin. However, when compared with warfarin alone, the concomitant administration of St John's Wort and warfarin significantly reduced mean ratios of the area under the concentration-time curve for both R- and S-warfarin enantiomers (AUC, 0-infinity; by approximately 23% and 27% , respectively; p less than 0.05), and similarly reduced plasma half lives for the R-warfarin and S-warfarin enantiomer (by 21%, both enantiomers, p less than 0.05). The mean ratio for apparent total clearance was increased for both R- and S-warfarin (by 23% and 29%, respectively; p less than 0.05). The mean ratio of the AUC (0-168) for warfarin-mediated INR with versus without St John's Wort was 0.79 .
B) Seven case reports have shown an approximate 50% decrease in the International Normalized Ratio (INR) when patients stabilized on warfarin began taking St. John's Wort. None of the patients experienced thromboembolic complications. After St. John's Wort was discontinued or the warfarin dose increased, the INR returned to the target range. Induction of cytochrome P450 2C9 was suggested as a mechanism for the decreased effect of warfarin .
C) In a randomized, single blind, placebo-controlled cross-over study of 10 healthy volunteers, St. John's Wort 900 mg/day for 11 days significantly decreased the AUC of free phenprocoumon after a single 12 mg dose (p=0.007). Hypothesized causes of the interaction were forced elimination, induction of CYP450 enzymes, or inhibition of absorption .
Pentosan Polysulfate Sodium Overview
-
Pentosan polysulfate is used to relieve bladder pain and discomfort related to interstitial cystitis, a disease that causes swelling and scarring of the bladder wall. Pentosan polysulfate is similar to a class of medications called low molecular weight heparins. It works by preventing irritation of the bladder walls.
Return To Our Drug Interaction Homepage
Feedback, Question Or Comment About This Information?
Ask Dr. Brian Staiger, PharmD, our medical editor, directly! He's always more than happy to assist.
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:
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.