Table 1. Examples of common drugs known to cause GI bleeding, dyspepsia, or ulceration. chloride, quinidine. * Increased risk of GI bleeds with these drugs. By minimizing the risk of drug-induced bleeding in patients, Certain drug classes are known to increase the risk of bleeding (TABLE 1) Of. Many drugs, herbs, vitamins and diet supplements may increase bleeding during surgery. Below is a list of the more common agents that may cause bleeding.
of Risk That Drugs Bleeding Increase
Among patients with bleeding, 20 Vitamin K was administered along with temporarily or permanent discontinuation of warfarin for the management of observed bleeding. Multivariate binary logistic regression analysis was used to assess factors associated with bleeding complications. Multivariate binary logistic regression analysis of factors associated with bleeding complications.
In this study a patient was prescribed a mean number of 6. The overall prevalence of DDIs was Higher prevalence of DDIs is expected from inpatients as compared to outpatients as more intensive management protocols are required to manage inpatients. Inpatients usually have multiple co-morbidities requiring many medications while outpatients are relatively stabilized. It might also be due to the limited options physicians had to treat a condition using non-interacting drugs which is a common problem in developing countries.
In the developed world Europe and USA anticouglation therapy is commonly used for elderly patients [ 3 , 9 , 19 , 21 ]. In contrast, in this study above half of the subjects on warfarin were in the age less than forty.
Such patients require prophylactic anticoagulation and in this study warfarin was commonly indicated for prevention and treatment of deep vein thrombosis. Rheumatic heart disease, hypertension and venous thrombosis were previously reported as the common types of cardiovascular diseases in Ethiopians, and affecting the young adults [ 23 , 24 ].
There are some reports of increasing physical inactivity, alcohol use, khat use, smoking and change in dietary habits among young adult Ethiopians [ 2 , 25 ]. Awareness, treatment and control of hypertension and other cardiovascular risk factors are very poor in the Ethiopian settings [ 2 ].
This may lead to development of cardiovascular diseases such as stroke and myocardial infarction at early age. But further studies are needed to investigate the increase in cardiovascular diseases among young adult Ethiopians. Commonly co-prescribed drugs found interacting with warfarin were antibiotics ciprofloxacin, norfloxacin, clarithromycin, cotrimoxazole, amoxicillin, cloxacillin, cephalosporins, erythromycin, metronidazole, ceftriaxone, rifampin, isoniazid, and nevirapine.
The finding of this study is consistent with previous studies [ 26 - 29 ]. Except rifampicin, most antibiotics are liver enzyme inhibitors and their interaction with warfarin may contribute to over anticoagulation. This finding is consistent with study by Kotirum, et al. Understanding the severity of the drug interaction is important for practitioners because major type of interaction is more likely to produce negative outcomes which include either ineffectiveness or over anticoagulation and bleeding risk.
According to this study about The nearest INR value at the time of screening for drug interaction and bleeding was considered as indicative of coagulation status. Most of the patients did not achieve their target INR values. This result showed that in The percentage of supratherapeutic in this study was much higher than a study by Verhovsek et al.
But this study took mean INR value of the patients while in this study the nearest INR value at the time of screening for drug interaction was considered. In addition, the higher number of patients with supratherapeutic values in the current study might be due to higher prevalence of DDIs and lack of frequent INR monitoring in such resource limited setting.
In this study prevalence of gastrointestinal bleeding was found to be But it was lower than that reported by Meegaard et al. This higher percentage might be due to inclusion of only those high risk patients with INR level greater than 6. Multivariate binary regression analysis of variables indicates that, INR value was statistically associated with bleeding.
Other factors such as age, concurrent drug use, dose, and duration of warfarin treatment were not significantly associated with bleeding complications in this study population. Even though none of the observed drug-interactions in this study had statistically significant association with risk of bleeding many other studies reported NSADs interacting with warfarin associated with increased risk of serious bleeding [ 8 , 21 , 34 - 38 ]. For instance, the combined use of warfarin and aspirin vs.
Some antibiotics were also reported to increase risk of warfarin bleeding. Compared with the use of warfarin alone, the use of either cephalosporins OR 1. In this study, the small sample size as compared to the above studies might have contributed for the lack of statistically significant association between the type of drug interaction and observed treatment outcomes.
In this study, drug-drug interactions were prevalent. Commonly co-prescribed drugs interacting with warfarin were antibiotics, anticoagulant, diuretics and NSAIDs. Bleeding complications were significantly associated with increased INR value. Clinicians should give attention to potential drug interaction while prescribing drugs in patients with warfarin. Frequent monitoring of INR value is vital to predict treatment outcome of patients on warfarin. Patients should also be counseled about drug interactions, sign and symptoms of warfarin related bleeding complications.
Non-steroidal anti-inflammatory drugs; OR: GT and NS contributed to study design, data collection, data analysis and developed of the draft manuscript. BL and MLB assisted with data analysis, interpretation of finding and revision of the manuscript. All authors have read and approved the final manuscript. The authors would like to thank the study patients for their willingness to participate in the study. We are also very much grateful to the data collectors and staff members of internal medicine ward, Ayder Referral Hospital for their kind cooperation during the data collection.
National Center for Biotechnology Information , U. Journal List Thromb J v. Published online Sep Author information Article notes Copyright and License information Disclaimer. Received Jan 28; Accepted Jul This article has been cited by other articles in PMC. Abstract Background Warfarin is known for its interaction with many drugs, resulting in undesired treatment outcomes such as bleeding. Methods A cohort of inpatients on warfarin treatment was prospectively followed from date of admission until discharge.
Results Of the total patients enrolled in the study, 78 Conclusion Drug-drug interactions with warfarin were prevalent in the study hospital. Drug-drug interaction, Warfarin, Bleeding, Ethiopia. Background Cardiovascular diseases are the most common causes of death worldwide [ 1 ]. Methods This study was conducted in the internal medicine ward of Ayder Referral Hospital situated in Mekelle town, northern Ethiopia.
Results Of the total patients enrolled in the study, 55 Table 1 Demographic characteristics of patients. Open in a separate window. Types of co-morbid conditions among patients on warfarin therapy. Table 2 Treatment characteristics of patients. Characteristic Frequency Percent Warfarin indication Prevention and treatment of deep vein thrombosis 82 Table 3 List of drugs interacting with warfarin.
Drug class Drugs No. Table 4 Multivariate binary logistic regression analysis of factors associated with bleeding complications. Discussion In this study a patient was prescribed a mean number of 6.
Conclusion In this study, drug-drug interactions were prevalent. Competing interests The authors declare that they have no competing interests. Authors' contributions GT and NS contributed to study design, data collection, data analysis and developed of the draft manuscript.
Acknowledgments The authors would like to thank the study patients for their willingness to participate in the study. McGraw Hill Medical; Epidemiology of cardiovascular diseases; pp. Epidemiology of cardiovascular disease risk factors in Ethiopia: Administrative claims analysis of the relationship between warfarin use and risk of hemorrhage including drug-drug and drug-disease interaction.
J Manag Care Pharm. Drug interactions involving warfarin: Epidemiology of sub therapeutic anticoagulation in the United States. Managing warfarin therapy in the community. Drug interactions and risk of acute bleeding leading to hospitalization or death in patients with chronic atrial fibrillation treated with warfarin.
Characteristics of ambulatory anticoagulant adverse drug events: Quality of anticoagulation and use of warfarin-interacting medications in long-term care: Drug-drug interactions in the hospital. Wadelius M, Pirmohamed M. Warfarin toxicity and individual variability: Toxins Basel ; 2 Chronic non-communicable diseases in Ethiopia-a hidden burden. Bleeding associated with their use is treated with the administration of RBCs and plasma, activated prothrombin complex concentrate, or recombinant factor VIIa, hemodialysis, or idarucizumab for dabigatran.
This symptom may be perplexing to patients who cannot differentiate between dyspepsia and abdominal pain associated with bleeding. Untreated constipation can lead to complications, including hemorrhoids, anal fissures with rectal bleeding, and rectal prolapse. Certain natural medicines and supplements have been reported to cause bleeding either on their own or when used in combination with other drugs. TABLE 3 lists common natural medicines that affect platelet aggregation and could elicit bleeding.
Medication reconciliation and patient education prevent moderate or significant drug-drug interactions. It is recommended to check the international normalized ratio INR 5 days after initiation of an antimicrobial or antibiotic in patients taking warfarin. Risk factors for increased bleeding include use of a drug or natural medicine that has the potential for bleeding TABLES ; concomitant use of drugs causing drug-drug interactions TABLE 4 ; advancing age; prior history of GI bleeding; decreased renal function; uncontrolled hypertension; regular or excessive use of alcohol; and the presence of Helicobacter pylori.
Prescribing information and FDA Medication Guides instruct patients to immediately contact their healthcare provider if symptoms of bleeding are present.
Signs and symptoms of minor bleeding include gum bleeding, occasional nosebleeds, easy bruising, or bleeding that takes longer than normal to stop. Education on reducing the risk of bleeding includes the recommendation to avoid all drugs that interact with anticoagulants and other drugs known to potentiate bleeding TABLES 1 and 2. If analgesia is needed, acetaminophen at a maximum dosage of 2 g per day may be used.
Patients should be counseled not to double up on doses in the event of missing a dose and not to skip doses in an effort to save money. Patients should be encouraged to document their compliance with an electronic device or on a calendar.
A current medication card should be maintained at all times so that all healthcare providers are aware of all medications. In some cases, a sudden or severe episode of headache, dizziness, faintness, or weakness will occur before the medical emergency.
Other emergency symptoms that are linked to bleeding or stroke include unusual pain or swelling and abnormalities in vision, speech, or gait.
Dietary guidelines to maintain a consistent diet are important for patients taking warfarin. Sudden changes in diet to include high or extra intake of green, leafy vegetables or other foods high in vitamin K will cause the blood to clot, resulting in a lower INR and an increased risk of bleeding. Finally, patients who are taking drugs that could potentiate bleeding because of constipation should be advised to increase fruit and vegetable intake, increase fluid intake, make sure that at least one-half of all grains they consume are whole grains, and consume 25 g to 38 g of fiber daily.
In addition to patient education on the signs of bleeding and how to minimize bleeding risk, pharmacists play an important role in helping reduce the risk of drug-induced bleeding by monitoring patient medication profiles for potential drug-drug interactions and by conducting patient interviews to identify other items that may increase risk, such as advanced age, alcohol consumption, use of natural medicines, past medical history, and family history.
Bleeding as a result of medication therapy is a severe complication that has a negative impact on patient safety. In many cases, bleeding is not easily identified as a drug-induced problem.
Pharmacists can play a pivotal role in minimizing the development of drug-induced bleeding by being aware of the contributing risk factors and medications. Coumadin warfarin product information. Bristol-Myers Squibb Co; October Risk of upper gastrointestinal bleeding with selective serotonin reuptake inhibitors with or without concurrent nonsteroidal anti-inflammatory use: Use of nonsteroidal anti-inflammatory drugs: Bleeding incidence with concomitant use of antidepressants and warfarin.
Inhibition of serotonin reuptake by antidepressants and upper gastrointestinal bleeding in elderly patients: Gastrointestinal bleeding with the new oral anticoagulants—defining the issues and the management strategies. Novel oral anticoagulants in gastroenterology practice. Bleeding risk with dabigatran in the frail elderly. N Engl J Med. Risk of gastrointestinal bleeding associated with oral anticoagulants: Pradaxa dabigatran product information. Boehringer Ingelheim Pharmaceuticals, Inc; September Handbook of Nonprescription Drugs: An Interactive Approach to Self-Care.
American Pharmacists Association;
Several factors may increase the risk of over-anticoagulation and bleeding; drug interactions usually account for the majority of the risk [4,13]. The drugs in this list are more usually associated with loss of INR control in patients already established on warfarin. This list is not exhaustive - refer to the. When patients are receiving none of the drugs considered to increase the risk for UGI bleeding, the risk is set at For the drugs in the Table.