Opioid and Non-Opioid Analgesics
*This policy is managed through the Pharmacy benefit.
COX-II inhibitors, namely celecoxib (Celebrex®), may be considered medically necessary for reducing adenomatous colorectal polyps in familial adenomatous polyposis (FAP), when the patient is at high risk of GI bleed, or in the case of intolerance to traditional NSAIDS.
Use of COX-II inhibitors for the prevention or treatment of cancer or Alzheimer’s disease is considered not medically necessary.
Extended-release hydrocodone (Zohydro ER®) may be considered medically necessary for the labeled indication of the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate.
Extended-release oxycodone (OxyContin®) may be considered medically necessary for the labeled indication of the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate.
Transmucosal fentanyl citrate products (e.g., Abstral, Actiq®, Fentora™, Lazanda, Onsolis, Subsys) may be considered medically necessary for the treatment of breakthrough cancer pain in adult patients with compromised oral intake or absorption.
Celecoxib may not be covered in the presence of concurrent therapy with any NSAID or any dose of daily aspirin.
Extended release oxycodone (OxyContin) therapy should not exceed the following quantity limits:
Extended release hydrocodone bitartrate (Zohydro ER) may be covered when ALL of the following criteria are met:
Transmucosal fentanyl citrate (Actiq®, Fentora™) may be covered for the treatment of breakthrough cancer pain. Therapy should not exceed the following quantity limits:
Analgesics are used to treat a wide variety of pain syndromes. Traditionally, these have been classified in three groups: acute pain, chronic cancer pain and chronic pain in non-cancer patients. Each requires a different approach. In acute pain the goal is to keep the patient comfortable while avoiding respiratory depression and minimzing the potential of opioid dependence. Oncology patients are managed to achieve the best functional balance of analgesia versus sedation. No maximum dose limits exist in this setting, while chronic noncancer pain should be managed with regimens that combine drugs from different pharmacologic classes to minimize opioid use, e.g., antidepressants, NSAIDs or acetaminophen, muscle relaxants and anticonvulsants.
This policy addresses two pharmacologic classes:
Cyclooxygenase (COX) produces metabolic intermediates for three separate pathways that produce prostaglandins, thromboxanes and prostacyclin. Prostaglandins mediate the pain and fever responses (COX-2) and also GI protection (COX-1). Thromboxanes promote platelet aggregation (COX-1) and prostacyclin inhibits it (COX-2). Therefore,selective COX-2 inhibition might leave an unopposed excess of COX-1, which could increase the probability of thrombotic events. This plausible mechanism could explain the increased cardiovascular risk observed with rofecoxib, which was withdrawn from the market due to an excess of heart attacks observed in the clinical trials. To date, no studies have shown an increased cardiovascular risk with celecoxib (Celebrex), which continues to be sold.
It is not clear that the COX-2 selective NSAIDs offer significant clinical advantage for the average patient. The data show that they are no more effective in relieving pain and inflammation than ibuprofen or naproxen, and they may pose risks as yet undiscovered. There is also no conclusive evidence that COX-2 selective agents reduce the risk of renal or other toxicities of nonselective COX inhibitors. The rationale for using celecoxib is an observed reduction in serious gastrointestinal bleeding events. Since these often require hospitalization and can be fatal, it is important to avoid them; however, more recent evidence supports first line use of a nonselective NSAID in combination with a proton pump inhibitor, such as omeprazole.
Abuse of prescription opioid products is a growing concern. The 2006 National Survey on Drug Use and Health (NSDUH) found 4.7 million people used a prescription opioid for non-medical purposes in the month prior to the survey. More than 2 million per year are considered new illicit users of prescription opioids, a 5-fold increase from the 1980s. In 2007, more people > 12 years old began illicitly using opioids than marijuana, cocaine or any other illegal drug. In addition to abuse of opioids, prescriptions of opioids for pain are also increasing. From 1992 to 2002 prescriptions for opioids increased 154% while the US population increased 13%. Along with this increase in legitimate and illicit use of opioids has come an increase in ER visits and deaths due to opioids use.
While it is clear that use and adverse events with opioids are increasing, the data do not differentiate between events due to increased legitimate prescribing for pain and those due to illicit use. Additionally, as the number of total exposures to each drug is unknown, it is difficult to determine the risk associated with each drug due to lack of a meaningful denominator.
In 2010, the Washington State Legislature passed a statute requiring professional boards to draft regulations managing high-dose opioid use, clearly recognized as a serious threat to public health.
Medical policies are systematically developed guidelines that serve as a resource for Company staff when determining coverage for specific medical procedures, drugs or devices. Coverage for medical services is subject to the limits and conditions of the member benefit plan. Members and their providers should consult the member benefit booklet or contact a customer service representative to determine whether there are any benefit limitations applicable to this service or supply. This policy does not apply to Medicare Advantage.
Four years after publication of CLASS and VIGOR trials, we still lack sufficient data to accurately assess incremental risk/benefit of coxibs to the various subgroups of patients. Nonselective NSAIDs have well known and serious toxicities. Merck’s withdrawal of rofecoxib eliminates one choice. Unfortunately, it was the only agent shown to clearly reduce gastrointestinal risk. Since GI risk reduction came at the expense of a significant increase in cardiovascular events, this was not a viable alternative in most cases. Now there is concern that celecoxib and valdecoxib may increase cardiovascular risk as well. Based on the imperfect evidence we currently have, it would seem best to avoid selective COX-2 inhibitors except in patients who are at high risk for major GI bleeding events.
Several trials have demonstrated comparable GI protection using combination therapy with a non-selective NSAID and a proton pump inhibitor (omeprazole or lansoprazole).
The purpose of the OxyContin quantity limit is fourfold:
OxyContin is normally dosed every 12 hours and is designed to be administered as 2 tablets per day. In individuals with more rapid than normal clearance of oxycodone, or other unusual clinical circumstances, it is likely that 3 per day would be required. By setting the limit at 3, we allow for flexibility on the part of practitioners and their patients. OxyContin is available in tablet sizes of 10, 15, 20, 30, 40, 60 and 80 mg. When the 80mg tablet size is reached, the patient should be receiving 160mg/day. For cancer patients needing to go beyond this dose, the 4 tablet limit allows a further escalation to 320mg/day before approval of a quantity override would be needed. Exception for medical necessity will be routinely given when the patient is being treated for cancer pain and has reached the maximum dosage achievable with 4 tablets per day.
Transmucosal fentanyl agents are potent analgesics approved for the treatment of breakthrough pain in opioid-treated and tolerant cancer patients. There is no fully published randomized controlled evidence for use of these products for non-cancer pain at this time.
Availabilty of longer-term safety/tolerability data with Fentora is limited. Because life-threatening respiratory depression could occur at any dose in opioid non-tolerant patients, Fentora and Actiq are contraindicated in the management of acute or postoperative pain, and for use in opioid non-tolerant patients. A unique adverse event issue identified with use of Fentora is application site reactions, including ulceration. Risk is difficult to define, due to the limited number of patients and duration of exposure to this formulation in clinical trials. This side effect has the potential to alter the formulation’s absorption characteristics and may increase risk for serious side effects in some patients. To ensure safety, a cautious approach to use of either transmucosal fentanyl product is warranted.
Management of chronic severe pain in cancer patients requires the effective use of long-acting opioids, supplemented with limited doses of a short-acting opioid (rescue medication). Excessive doses of rescue medication usually indicate suboptimal pain control. This problem can be alleviated by increasing the fraction of the total daily opioid dose given as long-acting opioid.
A literature search from January 2012 through October 2012 did not indicate need to update the criteria in this policy.
Updated with new FDA labeling and stricter FDA indication wording. In 2013, the FDA acted to increased opioid abuse and death by narrowing labeled indications to only severe, around-the-clock pain for which other treatments are inadequate, added post-marketing surveillance requirements on manufacturers, and a block box warning.
Additional criteria for transmucosal fentanyl products added. Criteria for review of Zohydro (hydrocodone ER) added. The proliferation and increasing use of transmucosal fentanyl products for the treatment of breakthrough pain is causing considerable concern. Furthermore, the studies supporting these products are company-sponsored, raising concern for potential bias, and appropriate head-to-head comparisons have not been performed. Measurement of endpoints varies across studies; further confounding attempts to evaluate these agents as a class. Time of onset is usually measured by when there is a statistically significant difference in pain scores, which does not necessarily equate to a clinically meaningful difference. The pharmacokinetics of fentanyl make is an easily abusable opioid.
None of these products are indicated for pediatric use, nor do any of them have randomized controlled trials in pediatric patients. In their recent review of managing breakthrough pain in pediatric patients, Friedrichsdorf and Postier do not recommend their use in pediatric patients.
Zohydro ER is a non-tamper resistant formulation of hydrocodone without acetaminophen. Although FDA approved this product, it has not been launched at this time, and concerns are rising about the abuse potential of this substance, which studies have shown to be among the preferred prescription opioids of abuse in the U.S. Recently, a bipartisan bill was introduced in Congress to prohibit the distribution of non-tamper-resistant forms.
This policy is managed through the Pharmacy benefit
Type of Service
Place of Service
Add to Prescription Drug Section - New Policy.
Replace Policy – Policy updated with additional approval parameters and dosing limitation for OxyContin.
Replace policy. A literature search did not indicate the need to update the criteria in this policy.
Update Related Policies. Add 5.01.542.
Minor Update – Clarification was added to the policy that it is managed through the member’s pharmacy benefit; this is now listed in the header and within the coding section.
Replace policy. Medically necessary policy statement for OxyContin updated with new FDA labeling and stricter FDA indication wording.
Annual review. Policy updated with extended-release hydrocodone (Zohydro ER®) as medically necessary for the labeled indication of the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate.
Disclaimer: This medical policy is a guide in evaluating the medical necessity of a particular service or treatment. The Company adopts policies after careful review of published peer-reviewed scientific literature, national guidelines and local standards of practice. Since medical technology is constantly changing, the Company reserves the right to review and update policies as appropriate. Member contracts differ in their benefits. Always consult the member benefit booklet or contact a member service representative to determine coverage for a specific medical service or supply. CPT codes, descriptions and materials are copyrighted by the American Medical Association (AMA).