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Safe Pain Management With Opioid Therapy

December 30, 2021

This month, Holly L. Geyer, MD; Halena Gazelka, MD; and Ruben Mesa, MD, provide a case-based discussion of how to manage pain safely with opioid therapy in patients with hematologic malignancies.

This material is repurposed from "How I treat pain in hematologic malignancies safely with opioid therapy," published in the June 25, 2020, edition of Blood.

Pain in Hematologic Malignancies

Since the 1970s, cancer-related death rates have declined and survival rates for several blood cancers have increased. Conditions that were once considered imminently life-threatening are now treated as chronic medical ailments, and such conditions are often accompanied by chronic pain.

  • Fears of addiction and OUD contribute to undertreatment of pain and related symptoms in an estimated 30% of patients with cancer.
  • Standard-of-care treatment of OUD includes initiation of opioid replacement therapy in the form of agonist (buprenorphine, methadone) or antagonist (naltrexone) treatments in conjunction with neuro-behavioral therapies.
  • For mild to moderate pain, non-opioid techniques – including pharmacologic treatments such as acetaminophen or antidepressants and nonpharmacologic treatments such as physical therapy and counseling – should be tried before integrating opioids into the treatment plan.
  • For patients with severe pain and advanced malignancy, it is often appropriate to initiate chronic opioid therapy.
  • Before starting opioids, screening for risk factors of OUD (such as concurrent psychiatric disorders or family history of substance abuse) should be performed.
  • Close monitoring of patients receiving opioids on a chronic basis is essential. This includes assessment of changes in risk factors and patient adherence.

The improvements in cancer survivorship have left many hematologists with the difficult task of managing their patients' chronic opioid therapy. Fear of addiction and opioid use disorder (OUD) contributes to undertreatment of pain in an estimated 30% of patients with cancer.

Considerations Before Starting Opioid Therapy

Screening for pain using a validated tool should be performed routinely throughout the course of treatment. All patients should be educated on the importance of setting realistic goals for symptom management and titrating pain regimens to achieve functionality, as opposed to complete pain resolution.

As a dominant principal in the management of pain in patients with hematologic malignancies, nonopioid techniques should be tried before integrating opioids into the treatment plan. First-line therapies often include:

  • pharmacologic treatments such as acetaminophen, ibuprofen, gabapentin, pregabalin, antidepressants, COX-2 inhibitors, and topical treatments
  • nonpharmacologic treatments such as physical or occupational therapy, tai chi, yoga, community social activities, and counseling

This approach is particularly applicable to nonmalignant pain and mild to moderate malignant pain. For patients with recent surgical interventions, severe pain, advanced malignancy, or who are at end of life, it is often appropriate to initiate chronic opioid therapy.

Case 1

A 54-year-old man with a history of essential thrombocythemia presents to discuss initiating opioids for his abdominal and diffuse bone pain which has persisted over the past year. With no previous history of thrombosis or bleeding events, he is at low risk for thrombosis and has a low disease burden and mild pain scores. He takes aspirin 81 mg/day and has historically avoided acetaminophen and nonsteroidal anti-inflammatory drugs, fearing that they will increase the risk of bleeding. An abdominal CT scan shows splenomegaly and no evidence of portal or mesenteric vein thrombosis. How should this patient be educated on the nature of his pain and the risks, benefits, and expected outcomes of using opioids?

Case 1 Commentary

The patient's pain has been present for more than 3 months and is now deemed to be chronic. Although he has a malignancy, his mild pain suggests that he may benefit from a trial of nonopioid therapies. The patient should be educated on the chronic nature of his pain, and treatment goals need to be established as they relate to functionality. To begin with, we would recommend using acetaminophen on an as-needed basis in combination with physical therapy or yoga. Close follow-up should be scheduled to reassess functional status and the need for therapy adjustment.

Considerations Before Starting Chronic Opioid Therapy

Screening for risks of OUD and patient education about the risks associated with opioids should be conducted before initiating chronic opioid therapy.


Risk factors for developing OUD include:

  • current or previous substance abuse
  • age 18-45 years
  • poor socioeconomic status
  • concurrent psychiatric disorders (depression, anxiety, post-traumatic stress disorder [PTSD], bipolar disorder, schizophrenia)
  • personal history of physical or sexual abuse
  • family history of substance abuse
  • chronic pain
  • unwillingness to participate in multimodal treatment approaches

Prescription drug monitoring programs (PDMPs) play an important role in identifying which controlled substance prescriptions the patient has recently filled and should be reviewed before opioids are prescribed.

For patients identified as moderate to high risk for OUD or overdose, a careful analysis of risks and benefits must be undertaken before prescribing opioids. The review should take into consideration the patient's current life expectancy, response to less aggressive interventions, and access or adherence to adjunctive treatments.

Opioids with high potency or rapid clearance across the blood-brain barrier result in greater dopamine surges and subsequent cravings. Thus, for many patients who have pain refractory to non-opioid interventions, initial treatment with hydrocodone, codeine, tramadol, or low-dose morphine is preferred to fentanyl, hydromorphone, or oxycodone.


All patients and families interested in initiating opioid therapy should be well educated on the multifaceted nature of pain and the risks and benefits of opioids. Clinicians are encouraged to document this discussion and consider developing a standardized handout that includes the discussed content. Topics to address include: the importance of taking opioids only in the manner prescribed, adverse effects, potential drug-drug interactions, risks of addiction and overdose, and practice requirements for patient follow-ups. This document may also double as a controlled substance agreement if patient co-signature is included.


Close monitoring of patients receiving opioids on a chronic basis is essential. Elements included during routine monitoring are based on several factors, including state laws and the condition that opioids are being prescribed for. Follow-up visits should focus on changes in risk factors, patient adherence, and response to therapy. Regardless of the patient's condition, it is recommended that the PDMP be checked regularly to evaluate for drug-drug interactions and patient adherence. Clinicians may also wish to screen for depression, anxiety, and functionality.

Case 2

A 56-year-old man with a history of multiple myeloma, asthma, and PTSD presents to discuss pain management for uncontrolled chronic back pain. As a result of his myeloma, the patient has sustained numerous vertebral compression fractures. Previous treatments, including radiation, chemotherapy, and kyphoplasty, failed to offer significant pain relief. He successfully completed an autologous hematopoietic cell transplantation 1 year ago and remains in complete clinical remission. Despite this, he continues to struggle with debilitating back pain that interferes with daily activities. He has tried using acetaminophen and ibuprofen with minimal relief and, for the past 6 months, has used medical marijuana daily. He has taken leftover oxycodone prescriptions from previous hospitalizations and has found these to provide the greatest symptom relief. He would like to discuss using opioids on a regular basis.

Case 2 Commentary

The patient demonstrates several high-risk features for OUD and overdose, including a history of two psychiatric disorders and a primary pulmonary disease. His ongoing use of cannabis places him at further risk for opioid misuse and other mental health disorders. These risks must be balanced with fact that he has a known severely painful condition and that conservative treatments have failed, along with previous interventional approaches. The patient should be referred to a pain management specialist and, if he is not deemed a candidate for other pharmacologic or interventional treatments, a trial of opioid therapy could be considered. After appropriate screening and education, treatment should begin with low-dose, immediate-release oxycodone or morphine on an as-needed basis with close outpatient monitoring performed quarterly. Each follow-up visit should involve a review of the PDMP and functional status.

Managing Opioid Use Disorder

Patients with cancer have historically been exempt from state, federal, and societal guidelines that govern opioid use, but these exemptions could be reconsidered as improvements in cancer survival continue and new studies demonstrate the prevalence of OUD in this population.

Differentiating Undertreated Pain From OUD

It can be challenging to differentiate OUD from misuse due to uncontrolled pain, chemical coping, and patient misunderstanding of instructions. Behaviors such as increasing the frequency of opioid dosing without authorization from the clinician, seeking pain medications from multiple clinicians, obtaining opioids from family members, and emphatic requests for opioid prescriptions may frequently be misinterpreted as drug-seeking behaviors when in fact they actually represent undertreated pain.

Features more suggestive of OUD include cravings or a strong desire to use opioids, unwillingness to cut down usage, and spending unusual amounts of time or atypical means to obtain opioids.

Standard-of-care treatment of OUD includes initiation of opioid replacement therapy in the form of agonist (buprenorphine, methadone) or antagonist (naltrexone) treatments in conjunction with neurobehavioral therapies. Abrupt discontinuation of opioids is to be avoided, as it may lead to seeking opioids from illicit sources. Opioid tapering is reasonable in patients who have OUD behaviors and who refuse referral assessments. All patients at risk for overdose should be offered a prescription for naloxone. Many clinicians prefer intranasal naloxone because it is easy to administer, and several states now allow this drug to be provided over the counter.

In conversations with patients who have OUD, clinicians are encouraged to discuss and document evidence that supports the condition, reinforce that OUD is a medical disorder, and encourage immediate assessment.

Case 3

A 33-year-old man with a history of chronic myeloid leukemia complicated by thrombosis that resulted in a left below-the-knee amputation just transferred into a practice. Outside records show that he has been taking dasatinib and remains in remission. Records also reveal that he was ultimately dismissed from his previous hematologist's practice for behavioral issues, and he intermittently tested positive for cocaine and heroin on urine drug screens. During today's visit, he says he continues to have severe chronic phantom limb pain and abdominal pain, which he describes as being poorly managed by his previous hematologist and for which he takes as-needed oxycodone. He asks for a higher dose of oxycodone and becomes hostile and demanding when offered referral to a pain management specialist and when discussing alternative non-opioid pain regimens. What are the next best steps for managing this patient?

Case 3 Commentary

This patient demonstrates several concerning features for OUD. Practice policies regarding documentation and referrals should be used and should include reviewing his PDMP results, discussing concerns for OUD with him, making referrals to OUD treatment specialists, and offering him a prescription for naloxone. To avoid withdrawal symptoms and the risk that he may seek opioids from illicit sources, it may be appropriate to provide a short course of oxycodone for him (or preferably buprenorphine if the clinician carries a Drug Enforcement Administration waiver to prescribe certain types of drugs) as a bridge to his OUD assessment appointment. Concurrent referral to palliative care should also be considered.


Safe opioid prescribing in the hematology practice can involve complicated decisions that require a thorough understanding of pain and opioid-related risks and benefits. Baseline patient characteristics play a critical role in determining candidacy for opioid therapy, and clinicians are encouraged to use national and organizational guidelines to assess and monitor patients during treatment.

In the future, there will likely be advanced alternatives to opioids with improved safety profiles and greater effects on chronic pain syndromes. As we await these medical developments, clinicians are encouraged to base their prescribing patterns on available guidelines and adjust practice techniques as knowledge evolves.


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