Addressing Concerns about Opioid Use for Cancer Pain

Opioids remain a mainstay of treatment for moderate-tosevere cancer pain. In this interview, Judith A. Paice, PhD, RN, director, Cancer Pain Program, Division of Hematology-Oncology, Northwestern University, Feinberg School of Medicine, Chicago, discusses the issues surrounding the use of opioids for the management of cancer pain and the role of the oncology nurse in assessing pain and addressing patients' fears about use of these agents.

Despite their demonstrated efficacy, there is still some resistance among healthcare providers, patients, and caregivers to use of opioids for cancer pain. What are the concerns?
For those of us working with people who have cancer, the primary barriers from the patients' perspective are the fear of side effects, particularly constipation and cognitive blunting, and the perceived meaning of taking an opioid. For many patients, taking morphine, in particular, means that their disease has advanced. From a professional perspective, we are concerned about the side effects. Also, many prescribers are concerned about the regulatory issues involved in prescribing opioids. They are fearful that the Drug Enforcement Ad ministration is watch ing their practice, especially because there have been several high-profile cases, not in oncology, that have gotten a lot of publicity.

At what point should use of opioids be considered in patients with cancer pain?
According to the World Health Organization's pain ladder, when a patient has moderate-to-severe pain it makes sense to introduce an opioid. That correlates to patient-rated pain, using a 0 to 10 scale, of 4 and above. Also, when patients have milder pain, we might start very low doses of an opioid. This would apply in patients who may not be candidates for a non opioid because of adverse effects or because their pain would not necessarily be responsive to adjuvant analgesics.

What assessments should be done before introduction of opioids?
It's critical that we do a comprehensive pain history, which includes a pain assessment. The pain rating is a small piece of that assessment. We also want to know where all the pain sites are and the quality of the pain, because these factors help in selection of pharmacologic and nonpharmacologic interventions. We determine if the pain is constant, intermittent, or both, and we look at aggravating and alleviating factors. The combined data along with a physical examination and, in some cases, computed tomography scans, xrays, or other tests help clarify the underlying etiology of the pain. If we know the etiology, we can do a better job of identifying pharmacologic and nonpharmacologic therapies, and, in some cases, anticancer therapies that might be helpful. For example, someone with back pain who has a malignancy may have back pain because of an unrelated herniated disc. But a person who has back pain due to vertebral body metastases might benefit from radiotherapy or, in some cases, vertebroplasty or kyphoplasty. By knowing the underlying cause of the pain, we can be much more precise in our management.

Are there medical conditions that are contraindications to use of opioids?
We do want to know about related medical history and diseases, but these are not generally a contraindication for opioid therapy. These conditions are more likely to be contraindications for nonsteroidal anti-inflammatory drugs (NSAIDs). If the patient has chronic renal disease, for instance, then you wouldn't choose an NSAID. If the patient has liver failure or chronic liver disease, you wouldn't want to use anything containing acetaminophen. If the patient has narrow-angle glaucoma, you would be very cautious about using certain tricyclic antidepressants. If the patient is taking a particular chemotherapeutic or hormonal agent, you wouldn't want to use a drug that interferes with the action of that agent; for example, you wouldn't want to use duloxetine in a person who is taking tamoxifen because it might interfere with the metabolism of tamoxifen. It's critical that we have a sense of each patient's current medical diseases and medical history as well as his or her current medication list.

In addition, we like to take a thorough psychosocial history, which includes asking patients about their current and past use of cigarettes, alcohol use, and recreational drug use. Recently, we've begun asking people about the history of addictive diseases in firstorder family members. A history of addictive diseases in any of their family members will make it more challenging in terms of prescribing opioids, but it isn't a contraindication. We also like to ask patients about the things that give them strength, such as family, work, their religious affiliation, or spiritual belief. Often, we can use those to help devise nonpharmacologic approaches to help patients with cancer cope with chronic pain and their other symptoms.

How can constipation and other common side effects of opioids be prevented or managed?
The best strategy is to prevent the constipation, but the measures that are generally useful in preventing constipation are not particularly helpful when it's opioid-induced constipation. We generally encourage patients to take a laxative in combination with a softener. Most patients need to take these agents regularly, so it requires a lot of education. When it has been more than 2 days since their last bowel movement, we become more aggressive and prescribe tablets, liquids, suppositories, or enemas, depending on the patients' preference and whether they have any contraindications.

What about other common side effects?
Cognitive blunting is probably the second most problematic side effect that patients describe. We help people to understand that during the first day or two of opioid therapy they are likely to be sedated, but that for many people sedation dissipates over time. For some, however, it persists, and we will use psychostimulants such as methylphenidate. Nausea also can occur, often early in the course of opioid use in people who are opioid-naïve. We typically have them take an antiemetic around the clock for the first day or two, and then we can wean down the antinausea drug. Most patients become tolerant of the nauseating effect of the opioid by that time.

Other side effects include itching and urinary retention, but for most people, these tend to go away over time. We might switch to a different opioid if they occur. Some of these adverse effects are more common in a postoperative setting or with spinal drug delivery.

Are there any special considerations in treating pain in the elderly?
The elderly tend to have some borderline renal dysfunction, so NSAIDs are dangerous in a certain population of the elderly. In an older cancer patient with cachexia, the patient isn't eating well, which further exacerbates the adverse effects associated with acetaminophen. There is a sense that acetaminophen is safe in lower doses, and yet people who are in a wasting syndrome should not take acetaminophen. So in the elders, it is safest to use opioids. The biggest issue we have found is the need to start very slowly and increase the dose very gradually. Over time, the patients end up at a similar dose to what might be used for a middle-aged person; it just takes longer to get there.

Probably the biggest challenge we face when working with an older patient who has cancer is caregiver issues, such as remembering when to take medication. A caregiver can remind the patient to take a pain medication, but if the patient doesn't have that kind of encouragement or support, he or she may not get good pain relief.

In addition, obtaining schedule II opioids is very difficult. The neighborhood pharmacy may not have that medication, and getting to another pharmacy may be difficult. Again, it comes down to having caregiver support.

Are there issues concerning reimbursement for opioids for cancer pain?
It has gotten very complicated. Even for patients who have insurance, many insurance companies place caps on the numbers of tablets that a patient may obtain, not just for opioids but on any drug/compound used for pain control. For example, a lot of insurance companies have issued refusals for pregabalin, which is newer and slightly more expensive than gabapentin. The insurance companies want the patient to first fail on gabapentin before obtaining pregabalin even though pregabalin has better bioavailability and is easier to titrate. Another example is lidocaine patches. There is very little if any systemic uptake of the drug. So for patients who are having side effects to some of the oral agents, this is a useful addition to their treatment regimen, but some insurance companies are refusing to pay for these unless the patient has postherpetic neuropathy.

In addition, I have found lately that some insurance companies have placed a maximum on how many oxycodone tablets they will pay for. Different insurance companies will allow only a limited number of tablets of oxycodone in any given dose, but they'll allow a patient to order 90 tablets of the 60-mg dose, 90 tablets of the 40-mg dose, and 90 tablets of the 20-mg dose. This becomes very confusing for the patient. What's happening for professionals is we are spending an enormous amount of time on the telephone and filling out paperwork for prior authorization when the insurance companies refuse to pay.

What role can nurses play in overcoming barriers to use of opioids for cancer pain?
Nurses need to be aware of the barriers, the patient's fears in particular because nurses are exquisitely trained to address these fears with their patients and often have the most intimate relationships with their patients. They have the insight to be aware of what might be serving as an obstacle to good pain control.

Studies have demonstrated that patients don't want to talk about symptoms with their oncologist, because they are afraid to distract the oncologist from the cancer care and are concerned that if they report symptoms they won't be a candidate for clinical trials. Through their skills and education, nurses can address these concerns with patients and family members. Pain management really needs to be directed not just to the patient but also to the family. You could have done the best education for the patient, but if the spouse is very anxious about opioids, he or she will send messages to the patient to withhold the drug.