Methotrexate and Nonsteroidal Antiinflammatory Drug Interactions

1992 ◽  
Vol 26 (2) ◽  
pp. 234-237 ◽  
Author(s):  
Maureen L. Frenia ◽  
Kimberly S. Long ◽  
Edward A. Hartshorn
Keyword(s):  
Case Reports ◽  
Clinical Manifestations ◽  
Hepatic Metabolism ◽  
Antiinflammatory Drug ◽  
Nonsteroidal Antiinflammatory Drugs ◽  
Nonsteroidal Antiinflammatory Drug ◽  
Pharmacokinetic Studies ◽  
Hematologic Toxicity ◽  
Antiinflammatory Drugs ◽  
Clinically Significant

OBJECTIVE: To determine if the coadministration of methotrexate (MTX) and nonsteroidal antiinflammatory drugs (NSAIDs) results in a clinically significant drug interaction. DATA SOURCES: A case report of hematologic toxicity following the administration of MTX and flurbiprofen at our institution is presented. Six previously published case reports and five pharmacokinetic studies regarding MTX and NSAID interactions are available to assist in the evaluation of this potential interaction. DATA SYNTHESIS: Cases of various clinical manifestations during concomitant MTX and NSAID administration, including acute renal failure and pancytopenia, have been reported. The exact mechanism of the interaction has not been fully elucidated. Suggested theories to explain the mechanism of MTX toxicity include reduction in MTX clearance secondary to renal capillary constriction induced by NSAIDs, displacement of MTX or its metabolite from plasma proteins, competition between MTX and NSAIDs for renal tubular excretion, or impairment of hepatic metabolism of MTX by NSAIDs. Studies comparing MTX pharmacokinetics with or without concurrent NSAID therapy have not shown statistical differences in the parameters evaluated. However, one study did demonstrate differences in the pharmacokinetics of 7-hydroxymethotrexate, the active metabolite of MTX, when MTX was administered with aspirin. CONCLUSIONS: Although a clinically significant interaction does not occur in all patients, numerous case reports are available that demonstrate possible problems following the coadministration of MTX and NSAIDs. To date, the specific circumstances during which the reaction may occur have not been well defined.

Nonsteroidal Antiinflammatory Drug-Induced Pseudoporphyria: A Case Series

2002 ◽  
Vol 6 (4) ◽  
pp. 320-326 ◽  
Author(s):  
Jeffrey R. LaDuca ◽  
Peter H. Bouman ◽  
Anthony A. Gaspari
Keyword(s):  
Clinical Symptoms ◽  
Porphyria Cutanea Tarda ◽  
Case Series ◽  
Antiinflammatory Drug ◽  
Nonsteroidal Antiinflammatory Drugs ◽  
Nonsteroidal Antiinflammatory Drug ◽  
Sustained Remission ◽  
Antiinflammatory Drugs ◽  
Drug Induced ◽  
Antibiotic Drugs

Background: Pseudoporphyria is a diagnosis that is used when porphyria-like clinical lesions arise in the setting of normal porphyrin levels. This condition was first described in the 1960s and was initially related to the use of certain antibiotic drugs. In 1985, pseudoporphyria was first attributed to the use of nonsteroidal antiinflammatory drugs (NSAIDs). Subsequently, a host of NSAIDs and other drugs have been found to elicit the same clinical entity. The exact mechanism by which certain drugs create clinical lesions resembling porphyria cutanea tarda or erythropoietic protoporphyria is still unknown. A phototoxic mechanism is hypothesized. Objective: We describe six patients diagnosed with pseudoporphyria and detail the diagnostic tests leading to the eventual diagnosis. Results: The patients ranged in age from 27 to 59 years and had a female:male predominance of 2:1. The offending NSAID was DayPro (oxaprozin) for three of the patients, Relafen (nabumetone) for two of the patients, and Aleve (naproxen) for one patient. For each patient, histology and immunofluorescence was either consistent with the diagnosis of porphyria cutanea tarda or nonspecific, while serum, stool, and urine porphyrins did not support that diagnosis. Withdrawal of the offending agent provided relief from the clinical symptoms for each patient. None of our patients were rechallenged with the putative offending drug. However, prolonged avoidance has provided a sustained remission from symptoms in all six patients. Conclusions: Pseudoporphyria is a relatively rarely reported condition. Clinical suspicion with appropriate laboratory and histopathologic findings help to make this diagnosis, and exclude true porphyrias. Rechallenge with the offending drug to produce symptom relapse has been proposed to be helpful in confirming this diagnosis of exclusion. Since all 6 patients with drug-induced pseudoporphyria experienced resolution of their symptoms after discontinuing the offending agent, we propose that this clinical correlation alone is sufficient to confirm this diagnosis. Our observation of six new cases of NSAID-induced pseudoporphyria over a two-year interval suggests that this is not a rare entity.

Nonsteroidal Antiinflammatory Drug-Induced Renal Dysfunction Related to Inhibition of Renal Prostaglandins

1987 ◽  
Vol 21 (12) ◽  
pp. 954-960 ◽  
Author(s):  
Richard G. D'Angio
Keyword(s):  
Renal Dysfunction ◽  
Antiinflammatory Drug ◽  
Nonsteroidal Antiinflammatory Drugs ◽  
Nonsteroidal Antiinflammatory Drug ◽  
Antiinflammatory Drugs ◽  
Drug Induced ◽  
Frequent Use ◽  
The Face ◽  
Patients At Risk

This article reviews the role of prostaglandins (PG) in maintaining renal function in the face of vasoconstrictive substances and decreased renal blood flow. Inhibition of the synthesis of renal PG by nonsteroidal antiinflammatory drugs (NSAID) may lead to the development of hemodynamically induced renal dysfunction in patients with a decreased effective plasma volume or chronic renal insufficiency. The importance of stimulation of renal PG activity to the action of diuretics and a pharmacodynamic mechanism for NSAID-induced diuretic resistance are presented. Evidence for the relative selectivity of sulindac in inhibiting systemic PG without inhibiting renal PG is also reviewed. Inhibition of renal PG synthesis has been postulated to be a contributing factor for other forms of NSAID-induced renal dysfunction (interstitial nephritis, analgesic-associated nephropathy). The relationship between renal PG inhibition by NSAID and these syndromes is briefly discussed. Considering the frequent use of NSAID, it is important that practitioners are aware of the mechanisms whereby patients may develop NSAID-induced renal dysfunction and that they are able to identify patients at risk.

scholarly journals Association Between Nonsteroidal Antiinflammatory Drug Use and Adverse Clinical Outcomes Among Adults Hospitalized With Coronavirus 2019 in South Korea: A Nationwide Study

2020 ◽  
Author(s):  
Han Eol Jeong ◽  
Hyesung Lee ◽  
Hyun Joon Shin ◽  
Young June Choe ◽  
Kristian B Filion ◽  
...  
Keyword(s):  
Renal Failure ◽  
Acute Renal Failure ◽  
Antiinflammatory Drug ◽  
Cardiovascular Complications ◽  
Nonsteroidal Antiinflammatory Drugs ◽  
Nonsteroidal Antiinflammatory Drug ◽  
Hospital Death ◽  
Cohort Entry ◽  
Antiinflammatory Drugs ◽  
Healthcare Database

Abstract Background Nonsteroidal antiinflammatory drugs (NSAIDs) may exacerbate coronavirus disease 2019 (COVID-19) and worsen associated outcomes by upregulating the enzyme that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to in order to enter cells. Methods We conducted a cohort study using South Korea’s nationwide healthcare database, which contains data for all individuals who received a COVID-19 test (n = 69 793) as of 8 April 2020. We identified adults hospitalized with COVID-19, where cohort entry was the date of hospitalization. NSAID users were those prescribed NSAIDs in the 7 days before and including cohort entry, and nonusers were those not prescribed NSAIDs during this period. Our primary outcome was a composite of in-hospital death, intensive care unit admission, mechanical ventilation use, and sepsis; our secondary outcomes were cardiovascular complications and acute renal failure. We conducted logistic regression analysis to estimate odds ratio (OR) with 95% confidence intervals (CIs) using inverse probability of treatment weighting to minimize confounding. Results Of 1824 adults hospitalized with COVID-19 (mean age, 49.0 years; female, 59%), 354 were NSAID users and 1470 were nonusers. Compared with nonuse, NSAID use was associated with increased risks of the primary composite outcome (OR, 1.54; 95% CI, 1.13–2.11) but insignificantly associated with cardiovascular complications (OR, 1.54; 95% CI, 0.96–2.48) or acute renal failure (OR, 1.45; 95% CI, 0.49–4.14). Conclusions While awaiting the results of confirmatory studies, we suggest NSAIDs be used with caution for COVID-19 patients as the harms associated with their use may outweigh their benefits.

Electrochemical Determination of Non-Steroidal Anti-Inflammatory Drugs

2019 ◽  
Vol 15 (4) ◽  
pp. 485-501 ◽  
Author(s):  
Leyla Karadurmus ◽  
I. Firat Sahin ◽  
Sevinc Kurbanoglu ◽  
Sibel A. Ozkan
Keyword(s):  
Gouty Arthritis ◽  
Differential Pulse ◽  
Antiinflammatory Drug ◽  
Electrochemical Determination ◽  
Nonsteroidal Antiinflammatory Drugs ◽  
Nonsteroidal Antiinflammatory Drug ◽  
Antiinflammatory Drugs ◽  
Voltammetric Method ◽  
Anti Inflammatory

Electrochemical methods have been used for the determination of nonsteroidal antiinflammatory drugs (NSAID) just as used in the determination of various drugs. Among voltammetric methods; differential pulse voltammetric method, square wave voltammetric method and linear sweep voltammetric method are the most commonly used ones. NSAIDs are widely used in the treatment of inflammatory conditions such as musculoskeletal disorders (rheumatoid arthritis, osteoarthritis, acute gouty arthritis) and dental pain, menstrual pain, postoperative pain and migraine. In this review, some selected recent electrochemical studies were selected related to the nonsteroidal antiinflammatory drug analyzes. The aim of this review is to evaluate and discuss the advantages, details and usages of electroanalytical methods in the determination of nonsteroidal anti-inflammatory drug.

Nonsteroidal antiinflammatory drugs for cancer pain: comparison between misoprostol and ranitidine in prevention of upper gastrointestinal damage.

1995 ◽  
Vol 13 (10) ◽  
pp. 2637-2642 ◽  
Author(s):  
M Valentini ◽  
R Cannizzaro ◽  
M Poletti ◽  
R Bortolussi ◽  
A Fracasso ◽  
...  
Keyword(s):  
Cancer Pain ◽  
Cancer Patients ◽  
Treated Patient ◽  
Antiinflammatory Drug ◽  
Nonsteroidal Antiinflammatory Drugs ◽  
Nonsteroidal Antiinflammatory Drug ◽  
Gastric Ulcers ◽  
High Dose ◽  
Antiinflammatory Drugs ◽  
Upper Gastrointestinal

PURPOSE The prophylactic strategy of nonsteroidal antiinflammatory drug (NSAID)-induced upper gastrointestinal (UGI) damage has largely been studied in arthritic patients, but not in cancer patients. The efficacy of misoprostol and ranitidine in the prevention of gastroduodenal damage in patients taking diclofenac for their cancer pain has been compared in this study. PATIENTS AND METHODS Patients who needed high-dose (200 to 300 mg/d) diclofenac for cancer pain and without mucosal lesions at baseline gastroduodenal endoscopy were randomized to receive misoprostol (200 micrograms twice daily; M group) or ranitidine (150 mg twice daily; R group). UGI endoscopy was repeated after 4 weeks. RESULTS Twenty-three patients treated with misoprostol and 26 treated with ranitidine concluded the study. The M group showed a significantly (P < .02) lower incidence of gastroduodenal lesions (two patients; 8.7%) than the R group (10 patients; 38.5%). Gastric ulcers occurred in one (4%) misoprostol-treated patient and in six (23%) ranitidine-treated patients. Six of seven patients with ulcers were asymptomatic. Seventy-one percent and 86% of ulcers occurred in patients older than 60 years and in those who received greater than 3.1 mg/kg of diclofenac, respectively. CONCLUSION Misoprostol was significantly more effective than ranitidine in the prevention of gastroduodenal lesions in cancer patients receiving diclofenac.

Necrotizing Fasciitis Associated with Nonsteroidal Antiinflammatory Drug Use

1998 ◽  
Vol 14 (2) ◽  
pp. 58-62 ◽  
Author(s):  
Michael P Rivey ◽  
Douglas R Allington ◽  
Amanda L Henry Dunham
Keyword(s):  
Necrotizing Fasciitis ◽  
Clinical Course ◽  
Causative Factor ◽  
Antiinflammatory Drug ◽  
Nonsteroidal Antiinflammatory Drugs ◽  
Nonsteroidal Antiinflammatory Drug ◽  
Antiinflammatory Drugs ◽  
Over The Counter ◽  
Medical Disorder ◽  
Case Summary

Objective: To describe a case of necrotizing fasciitis (NF) that occurred following minor clean surgery in a seemingly otherwise healthy man who was taking over-the-counter (OTC) ibuprofen 200 mg and aspirin 325 mg before surgery. Case Summary: A 71-year-old white man underwent an uncomplicated laparoscopic cholecystectomy. His only medical disorder prior to surgery was osteoarthritis, for which he took OTC-strength ibuprofen; his only other regular medication was one aspirin 325-mg tablet daily for prevention of cardiac disease. Within 48 hours of the surgery, the onset of NF was apparent, and extensive tissue excision and debridement was required 1 week after the operation. All nonsteroidal antiinflammatory drugs (NSAIDs) were withheld. The patient survived a complicated clinical course over the next month. Discussion: A review of proposed risk factors for the development of NF in the patient indicated surgery and NSAID use. Analysis of the probability of NSAID use as a causative factor for the adverse reaction of NF suggests a possible role. This case suggests that NSAID use in lower OTC dosages may contribute to the onset or course of NF. The case report adds to existing literature suggesting an association between NSAID use and the development or course of NF. Conclusions: NSAIDs are widely used drugs, and any association as a causative or provocative factor for NF is a rare finding. However, practitioners should be aware of the proposed association.

Prescription Drug Use Patterns of Human Immunodeficiency Virus-Infected Patients Taking Zidovudine

DICP ◽  
1989 ◽  
Vol 23 (9) ◽  
pp. 698-702
Author(s):  
Abraham G. Hartzema ◽  
Miquel S. Porta ◽  
Hugh H. Tilson ◽  
Darrel C. Bjornson ◽  
David E. Meyer ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Prescription Drug ◽  
Pneumocystis Carinii ◽  
Nonsteroidal Antiinflammatory Drugs ◽  
Inhalation Therapy ◽  
Hematologic Toxicity ◽  
Antiinflammatory Drugs ◽  
Medical Specialties ◽  
Prescription Drug Use ◽  
Immunodeficiency Virus

Prescription drug profiles of 116 human immunodeficiency virus (HIV)-infected patients taking zidovudine in 1988 were surveyed. Patients received the drug an average of 236 days. About one-third (32 percent) required reduced dosage presumably because of hematologic toxicity and this was associated with length of time on the drug. Zidovudine dosage reduction was not associated with concurrent therapy with either acetaminophen or acyclovir. Concomitant drug therapy was common, especially with systemic antifungals (47 percent), antivirals (33 percent), nonsteroidal antiinflammatory drugs (23 percent), and antidepressants (20 percent), as well as topical fungicides (35 percent) and antiinflammatory agents (28 percent). Over three-fourths of patients on zidovudine were on chemoprophylaxis for Pneumocystis carinii pneumonia, most often with pentamidine inhalation therapy. This study showed that the HIV-infected patient population is being treated concomitantly with many pharmacologic agents prescribed by various medical specialties.

scholarly journals Adverse Effects of Topical Nonsteroidal Antiinflammatory Drugs in Older Adults with Osteoarthritis: A Systematic Literature Review

2010 ◽  
Vol 37 (6) ◽  
pp. 1236-1243 ◽  
Author(s):  
UNA E. MAKRIS ◽  
MINNA J. KOHLER ◽  
LIANA FRAENKEL
Keyword(s):  
Older Adults ◽  
Adverse Effects ◽  
Case Reports ◽  
Nonsteroidal Antiinflammatory Drugs ◽  
Withdrawal Rate ◽  
Treatment Modalities ◽  
Application Site ◽  
Topical Nsaid ◽  
Antiinflammatory Drugs ◽  
Oral Nsaid

Objective.To systematically review the literature on reported adverse effects (AE) associated with use of topical nonsteroidal antiinflammatory drugs (NSAID) in older adults with osteoarthritis (OA).Methods.A systematic search of Medline (1950 to November 2009), Scopus, Embase, Web of Science, Cochrane databases, Dissertation and American College of Rheumatology meeting abstracts was performed to identify original randomized controlled trials, case reports, observational studies, editorials, or dissertations reporting AE from topical NSAID in older adults with OA. Information was sought on study and participant characteristics, detailed recording of application site, and systemic AE as well as withdrawals due to AE.Results.The initial search yielded 953 articles of which 19 met eligibility criteria. Subjects receiving topical NSAID reported up to 39.3% application site AE, and up to 17.5% systemic AE. Five cases of warfarin potentiation with topical agents were reported, 1 resulting in gastrointestinal bleeding. In formal trials, the withdrawal rate from AE ranged from 0 to 21% in the topical agents, 0 to 25% in the oral NSAID, and 0 to 16% in the placebo group.Conclusion.Although topical NSAID are safer than oral NSAID (fewer severe gastrointestinal AE), a substantial proportion of older adults report systemic AE with topical agents. The withdrawal rate due to AE with topical agents is comparable to that of oral NSAID. Given the safety profile and withdrawal rates described in this study, further data are needed to determine the incremental benefits of topical NSAID compared to other treatment modalities in older adults with OA.

Aspirin Synergistically Potentiates Isoflurane Minimum Alveolar Concentration Reduction Produced by Morphine in the Rat 

1998 ◽  
Vol 89 (6) ◽  
pp. 1489-1494 ◽  
Author(s):  
Ignacio A. Gomez de Segura ◽  
Ana B. Criado ◽  
Martin Santos ◽  
Francisco J. Tendillo
Keyword(s):  
Side Effects ◽  
Minimum Alveolar Concentration ◽  
Synergistic Effects ◽  
Objective Measure ◽  
Nonsteroidal Antiinflammatory Drugs ◽  
Antiinflammatory Drugs ◽  
Before And After ◽  
Male Wistar Rats ◽  
Clinically Significant ◽  
Analgesic Potency

Background The combination of opioids and nonsteroidal antiinflammatory drugs is more analgesic than the summed effect of each drug administered separately. This synergism has been used to obtain analgesia in the postoperative period at doses at which side effects are minimal. The aim of this study is to evaluate the analgesic interaction between aspirin and morphine in the rat during isoflurane anesthesia. The reduction in minimum alveolar concentration of isoflurane (MAC(ISO)) was used as an objective measure of the analgesic potency of individual drugs and their use in combination. Methods Thirty-seven male Wistar rats were anesthetized with isoflurane in oxygen, and the MAC(ISO) was determined before and after the intravenous administration of aspirin and morphine. Rats were administered morphine alone (1, 3, and 10 mg/kg) or morphine (1 and 3 mg/kg) and aspirin (30 mg/kg). The MAC(ISO) was determined from alveolar gas samples at the time of tail clamp. The duration of MAC(ISO) reduction was recorded. Results Aspirin did not have an effect on MAC(ISO), (average, 1.35+/-0.1%), whereas the combination of morphine (1 and 3 mg/kg) and aspirin (30 mg/kg) produced a reduction in the dose of morphine needed to produce the same degree of MAC(ISO) reduction. Actual MAC(ISO+drug) data were as follows: 1 mg/kg morphine, 1.17+/-0.14%; 3 mg/kg morphine, 0.98+/-0.15%; 1 mg/kg morphine plus aspirin, 0.90+/-0.04%; 10 mg/kg morphine, 0.63+/-0.13%; and 3 mg/kg morphine plus aspirin, 0.64+/-0.06%. Conclusions The synergistic effects of aspirin and morphine allow a clinically significant reduction in the requirements of isoflurane and isoflurane plus morphine, and these drug combinations may decrease the side effects associated with the use of single higher, equianalgesic doses of these drugs.

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