PainRelief.com Interview with: Benjamin W. Friedman, MD, MS, FAAEM, FACEP, FAHS Professor of Emergency Medicine Vice-chair for Clinical Investigation Department of Emergency Medicine Albert Einstein College of Medicine Montefiore Bronx, NY 10467
PainRelief.com: What is the background for this study? What are the main findings?
Response:A very large number of patients present to US EDs annually with back pain. No medications have proven more effective than NSAIDs for low back pain. Similarly, combining other medications such as skeletal muscle relaxants or opioids with NSAIDs does not improve outcomes more than NSAIDs alone.
Prior to our study, little was known about which NSAIDs were most efficacious for acute low back pain.
The main finding of our study is that ketorolac was more efficacious than ibuprofen for some two and five day outcomes that are important for patients.
Mary K. Mulcahey, MD, FAAOS, FAOA Director, Women’s Sports Medicine Program Associate Professor Assistant Program Director Department of Orthopaedic Surgery Tulane University School of Medicine New Orleans, LA
PainRelief.com: What is the background for this study? What are the main findings?
Response: Osteoarthritis Research Society (OARSI) guidelines include topical non-steroidal anti-inflammatory drugs (NSAIDs) as a level 1A recommendation for non-operative management of knee osteoarthritis, but previous reviews have demonstrated that clinical adoption of this treatment option lags. We conducted a systematic review and meta-analysis of 18 studies evaluating diclofenac, ketoprofen, and ibuprofen in topical preparations. We found that they are safe and effective for reducing pain and improving physical function in patients with knee osteoarthritis. Diclofenac had the strongest quality and number of studies and showed a moderate effect size for symptomatic improvement. With regards to safety, adverse events were low in the topical treatment groups, and topical preparations containing dimethyl sulfoxide (DMSO) showed a higher odds ratio for adverse events than preparations without DMSO.
PainRelief.com Interview with: Dr. Perez Cajaraville MD EDPM Clinical Director Pain Unit HM Hospitales Madrid. Spain
Dr. Cajaraville
PainRelief.com: What is the background for this study?
Response: The addition of L-arginine to the molecule of ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), in the salt form of ibuprofen arginate has the rationale to enhance the absorption rate of the active S-(+) enantiomer of ibuprofen to achieve a rapid onset analgesic action. Despite availability of ibuprofen arginate in the market for many years, a comprehensive review of the evidence of the analgesic efficacy, tolerability and safety in different pain models has not been previously reported.
PainRelief.com Interview with: Dr Thomas Perry PhD| Postdoctoral Research Fellow Versus Arthritis Centre for Sport, Exercise and Osteoarthritis Research Nuffield Department of Orthopaedics, Rheumatology & Musculoskeletal Sciences
Dr. Perry
PainRelief.com: What is the background for this study?
Response: Management of knee osteoarthritis (OA) is multi-factorial and routinely involves the use pharmacological interventions; with most medications aimed at alleviating painful symptoms and improving function.
Little is known of the long-term effects of such medications on the structural progression of radiographic knee OA. Through examining the relationship between pharmacological interventions and the disease pathway, this may, in turn, identify potential areas for disease-modifying treatment development.
MedicalResearch.com Interview with: Catherine Y. Chew, PharmD, BCGP Deputy Director, Division of Drug Information Center for Drug Evaluation and Research U.S. Food and Drug Administration
Dr. Chew
MedicalResearch.com: What actions is FDA taking regarding NSAID use during pregnancy?
Response: The U.S. Food and Drug Administration (FDA) is warning that use of prescription or over-the-counter (OTC) nonsteroidal anti-inflammatory drugs (NSAIDs) from around 20 weeks of pregnancy through the end of pregnancy may cause rare but serious kidney problems in an unborn baby. This can lead to low levels of amniotic fluid surrounding the unborn baby and possible complications.
For prescription NSAIDs, FDA is requiring changes to the prescribing information to describe the risk of kidney problems in unborn babies; these kidney problems can result in low amniotic fluid. FDA is recommending that pregnant women avoid NSAIDs from around 20 weeks of pregnancy. Prescribing information already recommends avoiding NSAIDs from around 30 weeks through the end of pregnancy because NSAIDs can cause a problem that may result in heart issues in the unborn baby. If NSAID use is necessary between 20 and 30 weeks of pregnancy, NSAID use should be limited to the lowest effective dose for the shortest possible duration. Health care professionals should consider ultrasound monitoring of amniotic fluid if a pregnant woman uses NSAIDs beyond 48 hours.
FDA will also work with sponsors to request updates of the Drug Facts labels of OTC NSAIDs intended for use in adults. These labels already warn to avoid using NSAIDs during the last three months of pregnancy because the medicines may cause problems in the unborn baby or complications during delivery. The Drug Facts labels also already advise pregnant and breastfeeding women to ask a health care professional before using these medicines.
MedicalResearch.com: What did FDA find?
Response: These labeling changes are based on cases reported to FDA about low amniotic fluid levels or kidney problems in unborn babies associated with NSAID use during pregnancy. FDA’s medical literature review also contributed to the basis for the labeling changes.
Among the 35 cases of low amniotic fluid levels or kidney problems reported to FDA through 2017, all were serious. Two newborns who died had kidney failure and confirmed low amniotic fluid when mothers took NSAIDs while pregnant; three other newborns who died had kidney failure without confirmed low amniotic fluid when mothers took NSAIDs while pregnant. The low amniotic fluid levels started as early as 20 weeks of pregnancy. In 11 cases where low amniotic fluid levels were detected during pregnancy, the fluid volume returned to normal after the woman stopped taking the NSAID.
FDA’s medical literature review yielded similar findings. In these publications, low amniotic fluid levels were detected with NSAID use for varying amounts of time, ranging from 48 hours to multiple weeks. In most cases, the condition was reversible within three to six days after stopping the NSAID. In many reports, the condition was reversed when the NSAID was stopped; the condition reappeared when the same NSAID was started again.
MedicalResearch.com: What are NSAIDs? Are all NSAIDs included in the new FDA recommendations to avoid NSAID use from around 20 weeks through the end of pregnancy?
Response: For decades, people have used NSAIDs to treat pain and fever from many different long- and short-term medical conditions, such as arthritis, menstrual cramps, headaches, colds, and the flu. NSAIDs work by blocking the production of certain chemicals in the body that cause inflammation. There are both prescription and OTC NSAIDs.
NSAIDs are available alone and combined with other medicines for the temporary relief of pain and fever, including pain or fever symptoms associated with colds, flu, and insomnia. Examples of NSAIDs include ibuprofen (Advil, Motrin), naproxen (Aleve), diclofenac (Voltaren), and celecoxib (Celebrex) and aspirin.
An exception to these new FDA recommendations is the use of the low-dose aspirin (81 mg) for certain pregnancy-related conditions at any point in pregnancy under the direction of a health care professional. Low-dose aspirin may be an important treatment for some women during pregnancy. The recommendations also do not apply to NSAIDs administered directly to the eye.
MedicalResearch.com: NSAIDs already carry a warning about use in late pregnancy. What is different about these labeling changes?
Response: Warnings to avoid taking NSAIDs after about 30 weeks of pregnancy are already included in the prescribing information because taking these medications during this time may lead to heart issues in the unborn baby. The new labeling changes recommend avoiding NSAIDs as early as about 20 weeks of pregnancy because of the risk of kidney problems that result in low amniotic fluid.
MedicalResearch.com:What should pregnant women and health care professionals do? What are other options for pain relief during pregnancy?
Response: Women should not use NSAIDs after around 20 weeks in pregnancy unless specifically advised to do so by a health care professional. Because many OTC medicines contain NSAIDs, pregnant women should read the Drug Facts labels to determine if the medicines contain an NSAID. If pregnant women are unsure if a medicine contains an NSAID, they should ask a pharmacist or health care professional for help.
Other medicines, such as acetaminophen (Tylenol), are available to treat pain and fever during pregnancy. Pregnant women should ask their pharmacist or health care professional for help deciding which medication might be best.
Health care professionals should limit prescribing NSAIDs between 20 to 30 weeks of pregnancy and avoid prescribing them after 30 weeks of pregnancy. If NSAID treatment is determined necessary, health care professionals should limit use to the lowest effective dose and shortest duration possible. They should also consider ultrasound monitoring of amniotic fluid if the pregnant woman regularly uses NSAIDs longer than 48 hours and discontinue the NSAID if low amniotic fluid levels are found.
The information on MedicalResearch.com is provided for educational purposes only, and is in no way intended to diagnose, cure, or treat any medical or other condition. Always seek the advice of your physician or other qualified health and ask your doctor any questions you may have regarding a medical condition. In addition to all other limitations and disclaimers in this agreement, service provider and its third party providers disclaim any liability or loss in connection with the content provided on this website.
Jeffrey Fudin, B.S., Pharm.D., FCCP, FASHP Diplomate, American Academy of Pain Management Section Editor, Pain Medicine
Dr. Fudin
PainRelief.com: What is the background for this study?
Response: Osteoarthritis (OA) affects over 14% of the United States population. As such it is important to establish effective, well-tolerated, and safe medication options. Topical nonsteroidal anti-inflammatory drugs (NSAIDs) act locally and are strongly recommended for patients with knee osteoarthritis as a first line option prior to chronic oral NSAID use in an effort to minimize systemic exposure, as oral products, result in tremendously higher blood levels compared to their topical counterpart.
PainRelief.com: What are the main findings?
Response: Diclofenac sodium gel 1% (DSG 1%), a topical NSAID, provided better pain relief than non-drug vehicle alone for patients with knee osteoarthritis in 3 clinical trials. A post-hoc meta-analysis of these trials was conducted to determine the percentage of patients achieving a minimal clinically important improvement (MCII) in pain and other symptoms of OA to gain insight into the real world clinical impact of topical diclofenac for patients. The MCII is defined as the smallest improvement in symptoms viewed as clinically meaningful for patients. In short, the MCII represents an improvement of relevance in a clinical trial and the minimal meaningful change at an individual level.
PainRelief.com Interview with: Anton Pottegård DMSc PhD Professor (MScPharm, PhD, DMSc) Clinical Pharmacology and Pharmacy, Department of Public Health University of Southern Denmark Head of Research, Hospital Pharmacy Funen Odense University Hospital
PainRelief.com: What is the background for this study?
Response: Early in the COVID-19 pandemic, concerns were raised that use of the common painkiller ibuprofen – a so-called NSAID – to treat symptoms of COVID-19 might lead to more severe disease. This started with tweets from the French health minister and culminated with a warning issued by the WHO. This warning was later retracted, but naturally patients and physicians were concerned regarding the safety of ibuprofen. We therefore established a nationwide Danish collaboration between researchers and regulators and established a prospective cohort of all Danish patients that contracted COVID-19, including data on what prescription medicines they used. We used these data to evaluate whether users of ibuprofen or other NSAIDs on average had a more severe course of COVID-19 than those not using these drugs.
PainRelief.com Interview with: Aldrin V. Gomes, Ph.D., FAHA Professor and Vice-Chair for Teaching, Department of Neurobiology, Physiology, and Behavior University of California, Davis Davis, CA 95616
Dr. Gomes
PainRelief.com: What is the background for this study?
Response: While many over the counter non-steroidal anti-inflammatory drugs (NSAIDs) now include a warning about potential cardiovascular disease, warnings about liver injury are hardly mentioned. This is because most NSAIDs including ibuprofen is considered to have very little potential to cause liver toxicity.
However, a 2018 publication (doi: https://doi.org/10.1016/j.cgh.2017.07.037) showed a relatively high prevalence of ibuprofen -induced liver injury in Spanish and Latin-American DILI (Drug induced liver injury) registries. As such, we were interested in determining what effects, if any, ibuprofen had on mice liver.
Charles H. Hennekens, M.D., Dr.P.H, FACPM, FACC Sir Richard Doll Professor and Senior Academic Advisor Charles E. Schmidt College of Medicine Florida Atlantic University
PainRelief.com: What is the
background for this study? What are the
main findings?
Response: About 29 million Americans use over-the-counter nonsteroidal anti-inflammatory drugs (NSAIDs) to treat pain. Every year in the United States (US), NSAID use is attributed to approximately 100,000 hospitalizations and 17,000 deaths. In addition, the U.S. Food and Drug Administration recently strengthened its warning about risks of non-aspirin NSAIDs on heart attacks and strokes.
While each over the counter and prescription pain reliever has benefits and risks, deciding which to use is complicated for healthcare providers and their patients.
Prof Chris Frampton PhD Department of Medicine
University of Otago
Christchurch, New Zealand
PainRelief.com: What is the background for this study?
Response: Acute pain is a significant burden to the individual and to society. In light of the ongoing opioid crisis, there is a need for effective nonopioid pain medications that provide improved analgesia over common analgesics, without compromising tolerability. Multimodal analgesia combines multiple drugs with different mechanisms of action to improve pain relief while limiting side effects. Fixed-dose combination tablets containing acetaminophen and ibuprofen are already available in many countries; however, the therapeutic advantages of such products are not available to patients in the United States. The US Food and Drug Administration (FDA) has restricted the dose of acetaminophen in prescription drugs to 325 mg per tablet, therefore an existing product containing acetaminophen 500 mg + ibuprofen 150 mg per tablet (two tablets per dose) has been downscaled to comply with FDA restrictions (acetaminophen 325 mg + ibuprofen 97.5 mg, three tablets per dose). The goal of this study was to determine the efficacy of the new fixed-dose combination of acetaminophen 975 mg and ibuprofen 292.5 mg (FDC 975/292.5) relative to acetaminophen or ibuprofen monotherapy, or placebo following the surgical removal of at least two impacted third molars.
The information on PainRelief.com is provided for educational purposes only, and is in no way intended to diagnose, endorese, cure, or treat any medical or other condition. Always seek the advice of your physician or other qualified health and ask your doctor any questions you may have regarding a medical condition. In addition to all other limitations and disclaimers in this agreement, service provider and its third party providers disclaim any liability or loss in connection with the content provided on this website. None of the content on PainRelief.com is warranted by the editors or owners of PainRelief.com or Eminent Domains Inc.
Thank you for visiting PainRelief.com
Senior Editor, Marie Benz MD.
For more information, or for advertising options please email: info@MedicalResearch.com or mariebenz@yahoo.com
