Can you take voltaren with warfarin

All statistical analyses were done with SPSS The study population consisted of 98 patients; the characteristics of whom are summarized in Table 1. Heart valve replacement was the most common indication for warfarin, followed by cerebral infarction, atrial fibrillation and venous thromboembolism.

Eighty patients used other medications than warfarin or NSAIDs; among these, 42 patients were taking comedications which might interact with warfarin The comedications included acetaminophen, amiodarone, aspirin, benzbromarone, bezafibrate, cefdinir, ceftizoxime, cilostazol, clopidogrel, deflazacort, fluconazole, hydrocortisone, indapamide, magnesium oxide, metronidazole, omeprazole, prednisolone, rosuvastatin, sertaconazole, simvastatin, SKX, sulfasalazine, sultamicillin, tramadol, trazodone, trimebutine, and valproic acid.

Five bleeding episodes were noted, including one intracranial hemorrhage ibuprofen , two epistaxis fenoprofen and aceclofenac , one hemoptysis ibuprofen and one muscle hematoma fenoprofen. We chose INR increase as the clinical endpoint of the study. Measurement of INR is the standard monitoring method in warfarin users for predicting bleeding complications 1 , 2.

Therefore, meticulous monitoring of INR is accepted as a reasonable approach to prevent bleeding complication when NSAIDs are administered to patients taking warfarin 10 , Since the fatal hemorrhagic complications can occur without any preceding minor bleeding, adjustment of medication should be strongly considered if INR increases. We defined an INR increase of more than Test variability of INR measurement is known to be Furthermore, test variability of PT in our hospital is less than 2.

Whether However, to the best of our knowledge, there has been no clear guideline on which percent increase of INR is clinically safe or risky. It has not been previously reported that the patients who need high maintenance doses of warfarin are more vulnerable to drug-interaction with NSAIDs. More saturation of plasma proteins or metabolic enzymes with warfarin might be the cause of more frequent drug interactions.

As described in the methods section, the study population used a wide range of comedications which were known to interact with warfarin.

Therefore, the presence of coadministered medication as a risk factor is reasonably expected result. Heterogeneity of comedications among the study population may result in pleiotropic effects. However, the result of our study reflects practical clinical settings where patients have different kinds of comorbid conditions requiring different kinds of medications.

This result comes from the fact that we defined INR increase as percent increase rather than absolute increase. Turck et al. Such divergent results can be explained as follows. First, clinical settings were different; the previous report was on 13 healthy persons, while our study represents real clinical settings where distinct kinds of medications were concomitantly used. Second, response to warfarin varies depending on ethnicity 18 - This difference is now beginning to be explained by genetic polymorphisms of the metabolic enzymes.

However, a cautious approach is needed for interpretation of the NSAID results for the following reasons. Second, there was no bleeding case with meloxicam in this study. Bleeding might be prevented with early detection of INR increase. If we consider bleeding cases of ibuprofen, fenoprofen and aceclofenac in our study, celecoxib or naproxen may be recommended as first line NSAIDs in warfarin users.

A prospective study with a large number of patients is warranted to prove this suggestion. A careful approach is still needed when adding a NSAID in warfarin users, regardless of its class, until our suggestion is proven.

Liver function test abnormalities were not a risk factor in our patient group. These results are consistent with a previous report that the disposition of warfarin is not affected by mild or moderate hepatic impairment However, since maximal levels of AST and ALT were within 5 times of the upper range, a cautious approach is needed when applying our results to the patients who have severe liver function abnormalities.

Interindividual variability in the response to warfarin is now beginning to be explained by pharmacogenetic polymorphisms. These results suggest that pharmacogenetic testing may be useful to refine the risk group for NSAID-warfarin interaction. Further studies are warranted on the role of genetic polymorphisms on the risk of NSAID-warfarin interaction.

There are several limitations in this study. First, the number of patients was limited so that all of the potential confounding variables which could affect the INR level could be evaluated simultaneously. The low number of patients might produce a type I and II errors in the interpretation. Second, the endpoint of the study was the INR value, a surrogate marker of hemorrhage rather than bleeding although bleeding may be more clinically important endpoint.

However, considering the potential seriousness of bleeding, clinicians may still have to use INR as a guideline for deciding their strategy when using warfarin. In this sense, our result will be helpful for clinicians. In conclusion, high maintenance dose of warfarin, the presence of coadministered medications, the use of meloxicam and low baseline INR value are the risk factors for INR increase in respect to NSAID-warfarin interaction.

Some can make warfarin less effective, for example St John's wort Hypericum perforatum , while others, such as ginseng , can do either. Some medicines, such as those below, can enhance the effect of warfarin. This may increase your INR and increase the risk of bleeding. Your INR should be checked more frequently if you take any of the following medicines with warfarin, particularly when starting or stopping treatment. Your warfarin dose may need reducing while you're taking one of these:.

Some medicines affect blood clotting and so may also increase the risk of bleeding if taken with warfarin, these include:. Some medicines, such as those below, may reduce the effect of warfarin. This could decrease your INR and make the warfarin less effective at preventing blood clots.

Your INR should be checked more frequently if you take any of these with warfarin, particularly when starting or stopping treatment. Your warfarin dose may need increasing while you are taking one of these:. The following medicines may also alter the effect of warfarin.

Your INR may be increased or reduced and your dose of warfarin may need to be adjusted up or down accordingly if you take one of these:. The weight loss medicine orlistat Xenical or Alli may reduce the absorption of vitamin K from food and may therefore affect the action of warfarin.

Your INR should be monitored if you start or stop taking orlistat while you are taking warfarin. Patients were excluded primarily for having other inflammatory conditions that might confound efficacy results or require systemic anti-inflammatory therapy. These included significant pain in the contralateral knee or a history or present evidence of secondary OA, rheumatoid arthritis, fibromyalgia, or other chronic inflammatory disease. Following a 7-day washout of analgesics, eligible patients were randomized in a ratio to receive DSG or its vehicle identical in composition except for the absence of diclofenac sodium.

Patients applied 4 g of DSG or vehicle to only the target knee 4 times daily for 12 weeks equivalent to 5 standard g tubes per month. Any other medications taken starting within 30 days before the screening visit and continuing through the end of the study were recorded.

All treatment-emergent AEs were reported and rated according to severity and relationship to treatment. All AEs occurring during the study were graded by investigators according to severity and likelihood of relatedness to study medication, and coded in the Medical Dictionary for Regulatory Activities v 7.

A total of patients were randomly assigned to receive DSG Figure 1. Demographic and clinical characteristics for the study population are presented in Table 1. The most frequently administered drugs were antihypertensive medications, antidepressants, and anti-inflammatories. Only 13 patients 5. Notes: a Discontinuation for unsatisfactory therapeutic effect occurred upon request of the patient; b discontinuation for protocol deviation was to occur only when the deviation created a safety issue in the judgment of the investigator.

The occurrence of treatment-emergent AEs was slightly higher However, of the eight patients with cardiovascular AEs in the DDI group, six had a medical history of hypertension. Of the 2 DDI-group patients without a history of cardiovascular disease, one experienced tachycardia and the other hypertension. A single fatal cardiovascular AE ventricular fibrillation was reported in a year-old man with multiple medical problems including hypercholesterolemia and hypothyroidism treated with levothyroxine but without a diclofenac DDI.

This event and all other cardiovascular AEs were considered unrelated to treatment. The frequencies of treatment-emergent gastrointestinal upper and lower , renal and hepatic AEs were similar regardless of the presence of diclofenac DDIs Table 4. Renal AEs consisted of blood creatinine increase and blood urea increase in one patient taking atenolol, and pollakiuria in one other patient taking furosemide. According to Drugs. One hepatic AE increased gamma glutamyl transferase was reported in a patient without a potential DDI.

This post hoc analysis was undertaken to consider the impact of potential DDIs of diclofenac with concomitant medications on the frequency of AEs. Possibly, the low systemic distribution of diclofenac associated with topical administration may have mitigated the risk of a clinically evident AE resulting from a potential DDI.

However, several medications with the potential to interact with diclofenac are prescribed for cardiovascular disease or for conditions associated with risk of cardiovascular disease Table 2 — anticoagulants, antihypertensives, digitalis alkaloids, glucose-lowering drugs ; therefore, patients taking these medications may have had a high risk of cardiovascular events based on the medical condition for which the medications were taken.

Indeed, six of eight patients in the DDI group who experienced a cardiovascular AE in this study had a medical history of cardiovascular disease. Osteoarthritis treatment guidelines recommend that NSAIDs be administered at the lowest effective dose to reduce the risk of dose-related AEs.

A limitation of this study is that the sample size was not large enough to allow for an analysis of AEs in patients with DDIs based on age and other demographic variables.

Topical application of DSG for knee osteoarthritis was associated with only a small increase in AEs when used concomitantly with medications known to have major or moderate interactions with diclofenac. Although the combination of drugs with known potential for adverse interactions should always be avoided, these results suggest that reducing NSAID dose by a strategy such as topical administration may mitigate the risk of a clinically evident AE following from a potential drug interaction.

Clinicians may cautiously consider topical DSG to treat osteoarthritis pain in the knees of patients receiving multiple medications. JP and LA received financial support as clinical trial investigators and presented research at scientific congresses with reimbursement of associated expenses by Endo Pharmaceuticals Inc.

The authors report no other conflicts of interest in this work. National Center for Biotechnology Information , U. Ther Clin Risk Manag.