Evolving Therapeutic Strategies to Improve Nonsteroidal Anti-inflammatory Drug Safety

The question of how to treat chronic pain is one that seems to be drawing more and more attention. As people are living longer, more will eventually come to face chronic pain caused by osteoarthritis, diabetes neuropathy, or other chronic conditions. Additionally, increasing misuse of opioid pain medications and the dangerous side effects associated with medications like NSAIDs has pressed for development of alternative forms of pain management. This retrospective analysis of 2177 patient charts looked at the comparative effectiveness of three topical options for chronic pain management: two compounded creams and one NSAID based gel.

Cream I creams contained 20% Flurbiprofen, 5% Tramadol, 0.2% Clonidine, 4% Cyclobenzaprine, and 3% Bupivacaine. Cream II contained 20% Flurbiprofen, 2% Baclofen, 0.2% Clonidine, 10% Gabapentin, and 5% Lidocaine. The NSAID based gel, Voltaren, contains 1% diclofenac sodium. 1141 patients were given Cream I, 527 received Cream II, and 509 patients received Voltaren gel.  Voltaren gel caused a decrease in pain intensity score of 19%, which is statistically significant to be less than the pain intensity decrease caused by both Cream I (37% ) and Cream II (35%). It is hypothesized in the journal article that this increase in efficacy of the two compounded creams stems from the inclusion of multiple active ingredients with different mechanisms of action.

Use of a cream for chronic pain treatment is beneficial in many areas. It can be topically administered at the site of the pain and will have lower systemic bioavailability.  This will lead to less of the dose-limiting adverse effects commonly seen with oral medications such as NSAIDs and opioids. Do you think topical pain medication should always be an option for patients with chronic pain? Can you think of an example of when it may not be as effective as an oral medication?


Somberg JC, Molnar J. Retrospective Evaluation on the Analgesic Activities of 2 Compounded Topical Creams and Voltaren Gel in Chronic Noncancer Pain. Am J Ther. 2015;22:342-349.


The Burden of Opioid-Induced Constipation: Discordance Between Patient and Health Care Provider Reports

Opioid medications are the most commonly prescribed medications for the treatment of chronic non-cancer pain.  However, the side effects and risks of addiction often prevent problems with patients with long term use of opioids.  In particular, opioid-induced constipation (OIC) is one of the most common side effects that impact patient quality of life, with patient surveys suggesting that as many as 17-67% of opioid patients experiencing GI immobility while on the medication.  Although this is a commonly recognized issue related to opioid therapy, there appears to be a lack of communication between patients and physicians about treatment and the role it plays in patient quality of life.

A recent study published on behalf of AstraZeneca Pharmaceuticals attempted to look at the prevalence of OIC, and the differences in patient and provider perception of the issue.  The researchers performed a perspective, longitudinal cohort study on 489 patients being treated with opioids for chronic pain in the U.S, Canada, U.K., and Germany.  Patients were selected based on chronic pain conditions that would be treated for >6 months, diagnosed with OIC based on patient reported symptoms.  Both patients and health care providers were asked to complete online surveys to assess their experience with OIC, quality of life, treatment options, concerns, and patient-provider interaction.

The results of the study showed that most providers reported discussing the potential for OIC and its impact on the patients medication experience.  However, just over half of patients reported disclosing instances of OIC with their doctor.  Most patients took OTC laxatives to cope with the OIC, and many reported lower quality of life.  Some patients reported lowering their opioid dose to alleviate OIC symptoms, but reported a corresponding increase in their level of chronic pain.  There was a reported lack of communication between patients and providers about the problem, with both sides reporting confusion over who was the anticipated initiator of the conversation.  There was also a lack of understanding from patients in available options for OIC treatment, as well as provider reported differences in priority of OIC between patients and their physicians.  The study concluded that there is a noticeable rift between patients and their providers over the perceived impact that OIC has on pain management.  They believe that an increase in communication related to opioid side effects, and resolution discussions will help lower patient anxiety over symptoms and increase quality of life without sacrificing pain management.

This problem clearly highlights some of the issues that still plague the pain management care field.  Clearly there is a communication issue between patients and their doctors that needs to be resolved in order to reduce OIC incidence and impact on pain therapy.  As pharmacists, we have an opportunity to address concerns with OIC, offer medication treatment options, and open dialogue between the patients and their primary care physicians.  Is this an area that pharmacists should prioritize in patient care? If so what options are there for getting more involved in opioid therapy and the risk of OIC?

Article Link

Locasale, Robert. Datto, Catherine. Wilson, Hilary. Yeomans, Karen. Coyne, Karin. The Burden of Opioid-Induced Constipation: Discordance Between Patient and Health Care Provider Reports. J Manag Care Spec Pharm. 2016; 22 (3): 236-245.

A Mind-Body Program for Older Adults With Chronic Low Back Pain

Approximately 100 million individuals in the United States suffer from chronic pain. Pain is prevalent in 52.9% of the older adult population ages 65 and older. Of the 52.9% experiencing pain, 30.3% were experiencing chronic back pain. Analgesics commonly cause severe adverse effects in older adults. Because of this prevalent drug therapy problem, nonpharmacologic treatments must often be utilized for effective management of chronic low back pain.

An experimental study was conducted among 282 patients with low chronic back pain 65 years or older. The goal of this study was to assess the effectiveness of a mind-body program at increasing function and reducing pain. The patients received an 8-week group program followed by 6 monthly sessions. The program was modeled on the Mindfulness-Based Stress Reduction program. This program took regular activities such as sitting, walking, and lying down and transformed then into meditation through breathing exercises and mindful awareness of thoughts and sensations. Compared with the control group, those receiving this mind-body treatment improved short-term function and long-term current and most severe pain.

The trial did not yield sustained results in treatment of lower chronic back pain, suggesting that future development of this intervention should focus on durability. This article was particularly of interest to me because it combined two of my interest in medicine with my interest in meditation. I often use meditation as a form of stress relief, and it is intriguing to see that meditation could also be used in pain management. Prescription pain medication is not the answer  for every patient and it is very often over-prescribed. I believe that is important for pharmacists to be aware of other pain management methods and share these methods with their patients. Although I do not believe that meditation alone is the answer, I think that a combination of medication therapy and meditation could be a very effective treatment for a lot of patients suffering from chronic pain.

JAMA Intern Med. Published online February 22, 2016.

Link to article

Ibuprofen: Risk, Comorbidities, and Pain Management

Non-Steroidal Anti-inflammatories (NSAIDS) are a commonly used class of drug for pain management, as well as their anti-inflammatory component, and many patients seem to falsely believe that they are harmless. This leads to patients taking them when they may not necessarily need to, without concern for drug interactions or long-term effects. After a recent safety review, the FDA is requesting updated warning labels for over-the-counter NSAIDS. The FDA warns that NSAIDS can increase the risk of heart attack, heart failure, and stroke, not only for patients with heart disease, but also for those without heart disease or risk factors.

NSAIDS are especially useful in treating patients with arthritis, but the American College of Rheumatology advises patients with heart disease to take acetaminophen instead, due to an extensive list of side effects and potential risks. Before recommending OTC pain medications, a healthcare provider should be aware of disease states or conditions, such as kidney or liver disease, hypertension, asthma, patient age, and other medications such as steroids, diuretics, and anticoagulants. Although Tylenol can cause serious liver damage, and lacks anti-inflammatory properties, it is just as effective as ibuprofen for pain and fever reduction, without the extensive side effect profile.

Topical NSAIDS are another potentially safer method of treatment for osteoarthritis inflammation. Because they remain more localized, systemic effects are not as prevalent, and adverse effects were found to be minimal. This information came from a review of randomized, double-blind trials, published in Cochrane Database Systemic Reviews by researchers at Oxford. Ultimately, patients need to be made more aware of the risks associated with NSAIDS, especially such it is such a commonly used prescription and OTC pain medication.

As pharmacists, I think this raises important points about what information to gather from a patient, such as their disease states and medications, before recommending OTC pain medications. With topical pain medications gaining more momentum, and more information available on their side effect profile, do you think this will change the nature of OTC pain medication counseling?

Anderson, Jennifer. Ibuprofen: Risk, Comorbidities, and Pain Management. Today’s Geriatric Medicine.


Post-surgical Pain Management Guideline

There is a new guideline released by The American Pain Society that addresses practices to improve pain management postoperative. They complied this guideline from reviews of more than 6500 scientific abstracts and clinical studies and is based on that there is often inadequate pain relief leading to larger, prolonged negative outcomes. The panel that wrote the guideline includes 23 members and incorporate anesthesia, pain management, nursing, and surgery specialties. There are 32 recommendations that are rated based on the quality of evidence as strong, moderate, or weak. There are four recommendations graded as strong. The first recommendation is that there should be wider use of a variety of analgesic medications and techniques. Multimodal anesthesia that specifically target different mechanisms of actions in the nervous systems have shown better pain relief than single medications using one technique. The second recommendation is to use acetaminophen and/or NSAIDs as part of the multimodal management post-surgery. The third recommendation is for clinicians to consider peripheral, regional anesthetic techniques at the surgical site. The fourth recommendation is for patients at risk for cardiac and pulmonary complications or prolonged intestinal distress that spinal analgesia is appropriate in major thoracic and abdominal procedures. They authors of the guideline state that the intended audience of their guideline is all clinicians who manage pain after surgery. How does the pharmacist fit into the target audience, and how could they use these guidelines within their field of practice?

J Pain. 2016;17(2):131-157

The Need for More Education on Prescribing Opioids

When hearing the term “opioids” several ideas come to mind: addiction, abuse, under-treatment, overtreatment, severe pain, and suspicion are just a few. Opioids are undoubtedly an extremely successful route of treatment for severe pain and play a huge role in daily pain management cases. However, there is always a discussion of the risks associated with prescribing this medication.

There is often an air of distrust between physician and patient when a patient insists on opioid therapy. Unfortunately, pain cannot be measured, and there needs to be trust when prescribing this drug class. The prescriber will not know if the patient really needs the opioid for pain management or if they have developed a dependence on it. The physician is put in a position where they could under-treat the patient by refusing therapy because of the risk of abuse, or they could over-treat the patient by believing their plea for a medication they were addicted to.

There are several guidelines already in place regarding opioid prescribing, but still, much of it is up to the physician’s discretion. Right now, there is a big push for more prescriber education on the topic. For example, in 2012, the FDA encouraged a single shared Risk Evaluation and Mitigation Strategy (REMS) which required manufacturers of extended release or long acting opioids to fund accredited education on safe opioid prescribing. Currently, this program has not reached its goal number of prescribers. However, I believe with the advancement of this program, physicians will be able to make more educated and thorough decisions when it comes to prescribing opioids.

Managing pain is extremely complex, yet education on the topic is lacking. The ultimate goal would be to maintain a patient-centered approach and treat the patient in a manner in which they are comfortable and compliant with. Perhaps with more education on the topic, the physician and pharmacist can work together to make a confident decision in how to proceed with drug therapy, and hopefully avoid the mistakes that have been occurring concerning opioid therapy.

I personally see this as an opportunity for pharmacists to get more involved in the prescribing process, as they have a stronger background education on the topic. Do you think this could play a role in pharmacists eventually gaining prescribing rights?


Read the full article here.

Alford, Daniel P.  Opioid Prescribing for Chronic Pain — Achieving the Right Balance through Education. N Engl J Med. 2016;374:301-3


Effect of Opioids vs NSAIDs and Larger vs Smaller Chest Tube Size on Pain Control and Pleurodesis Efficacy Among Patients With Malignant Pleural Effusion

Pleural effusion is a condition in which fluid collects between tissues lining the lung and chest.  This condition can be painful and may lead to infection.  It can often be treated with antibiotics or diuretics, but sometimes it is necessary to physically deplete the space between the tissue via a surgical procedure known as pleurodesis.  This randomized clinical trial compared the efficacy of pain treatment for the procedure between opioids, which are the current go-to treatment, and NSAIDs.

NSAIDs had previously been avoided for this type of procedure due to fear that they might decreases the efficacy of pleurodesis; however, this study found that not only did the NSAIDs result in similar pain scores, but they also resulted in noninferior pleurodesis efficacy.  These results demonstrate that NSAIDs are essentially equivalent to opioids in effective pain management following pleurodesis, while also not negatively affecting the efficacy of pleurodesis itself.

These results offer an interesting and favorable pain management option. The growing incidence rates of opioid abuse and opioid-related death have led health professionals to look for other viable pain management options when possible.  Recently, an emergency department in New York successfully attempted to run a whole shift without giving opioids to patients (http://www.ashpintersections.org/2016/02/pharm-d-m-d-team-successfully-enacts-opioid-free-ed-shift/).

Personally, I am excited to see the results of this clinical trial.  I believe we will need to begin looking for other viable methods of pain management following surgery or injury to combat the growing opioid epidemic in the US.  Hospitals can begin to use this kind of data to try prescribing alternative medications such as NSAIDs when safe.  Although NSAIDs come with their own set of problems and are especially unsafe in older patients, there are many cases in which it could be a superior option to opioids.

Do you think it is feasible to significantly reduce prescription and usage of opioids for pain management, or do you believe will it be near impossible to make this transition in the near future?

Rahman NM, Pepperell J, Rehal S, et al. Effect of Opioids vs NSAIDs and Larger vs Smaller Chest Tube Size on Pain Control and Pleurodesis Efficacy Among Patients With Malignant Pleural Effusion: The TIME1 Randomized Clinical Trial. JAMA. 2015;314:2641-2653.