MEDICAL POLICY

POLICY
RELATED POLICIES
POLICY GUIDELINES
DESCRIPTION
SCOPE
BENEFIT APPLICATION
RATIONALE
REFERENCES
CODING
APPENDIX
HISTORY

Opioid and Non-Opioid Analgesics

Number 5.01.529*

Effective Date October 14, 2013

Revision Date(s) 10/14/13, 11/13/12; 12/13/11

Replaces N/A

*This policy is managed through the Pharmacy benefit.

Policy

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 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 (Actiq®, Fentora™) may be considered medically necessary for the treatment of breakthrough cancer pain.

Related Policies

5.01.521

Pharmacologic Treatment of Neuropathy, Fibromyalgia and Seizure Disorders

5.01.542

Medical Necessity Criteria for Medication Safety: Controlled Substances Utilization Service Program

5.01.605

Medical Necessity Criteria for Pharmacy Edits

Policy Guidelines

Celecoxib may be covered in the following cases:

  • Adenomatous colorectal polyps in familial adenomatous polyposis (FAP);
  • Where the patient is at high risk of NSAID induced adverse GI events as evidenced by any of the following:
  • Patient has a history of peptic ulcer disease,
  • Patient has a history of NSAID related ulcer,
  • Patient has a history of clinically significant gastrointestinal bleeding, or
  • Patient is 65 years of age;
  • Presence of any of the following concomitant drug therapy:
  • Anticoagulants (e.g., warfarin, heparin, or LMW heparin), or
  • Chronic use of oral corticosteroids;
  • Where the prescriber indicates that the patient has previously been unable to tolerate therapy with at least two different traditional NSAIDs.

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:

  • Three tablets per day of Oxycontin 10 mg, 15 mg, 20 mg, 30 mg, 40 mg OR four tablets per day of Oxycontin 60 mg and 80 mg.
  • In the event that a request is received that does not meet criteria for approval but is of a sufficiently high dose that would require tapering, a 3 month approval may be authorized to allow the provider time to reduce the dose to the allowed quantities above. These requests may be approved on a case by case basis and are subject to a clinical review for medical necessity.
  • In addition, short term approvals may be given on a case by case basis when clinical rationale has been submitted by a provider indicating that a tapering dose is being attempted. These requests are subject to a clinical review for medical necessity.
  • Quantity limit requests that are the result of a lower strength tablet being used in multiples that could be achieved with a higher dose tablet (i.e., three 20mg tablets versus one 60mg tablet) will not be approved. In certain circumstances, an approval may be given based on clinical rationale submitted and would be subject to a review for medical necessity.

Transmucosal fentanyl citriate (Actiq®, Fentora™) may be covered for the treatment of breakthrough cancer pain. Therapy should not exceed the following quantity limits:

  • Actiq® lozenges (any strength) – four doses per day (120 per 30 days)
  • Fentora™ buccal tablets, 100mcg, 200mcg – eight doses per day (240 per 30 days)
  • Fentora™ buccal tablets, 300mcg and higher – four doses per day (120 per 30 days)

Description

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:

  • COX-2 inhibitors
  • Opioids
  • Long-acting opioids (OxyContin®)
  • Immediate acting rescue medications: Transmucosal fentanyl citrate (Actiq®, Fentora™)

COX-2 Inhibitors

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.

Opioid Abuse

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.

  • The public health surveillance system, Drug Abuse Warning System (DAWN), last published data on drug related emergency visits from 2008 and found the largest number of ER visits occurred with oxycodone combinations (105,214) followed by hydrocodone combinations (89,051) then methadone (63,629). These numbers have increased dramatically from 2004 with a 152% increase for oxycodone, 123% with hydrocodone and 73% with methadone (all p<0.05). The rationale for the ER visit (drug abuse, side effects etc.) was not included.
  • An analysis of serious events from the FDA’s adverse event reporting system found oxycodone was suspected in the largest number of deaths and serious nonfatal outcomes with 5,548 reports. The cause of the adverse event (drug abuse, side effects etc.) was not included.
  • An analysis of deaths among Medicaid enrollees from overdose in Washington state from 2004-2007 found methadone was involved in the most deaths (64%), followed by oxycodone (22.9%) and hydrocodone (13.9%).
  • Adverse events related to methadone have increased 1800% from 1997 to 2004 with a 390% increase in fatalities during the same period. Most methadone deaths appear to be the result of accidental exposures, although more data is needed.

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.

2013 Update

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.

Scope

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.

Benefit Application

Applies to all pharmacy benefit contracts that include Pharmacy Prior Authorization Edits.

Rationale

COX-II Inhibitors

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).

Extended-release Oxycodone

The purpose of the OxyContin quantity limit is fourfold:

  1. Reduce unnecessarily large quantities from being dispensed, thereby decreasing the likelihood of unnecessary tablets remaining in medicine cabinets where relatives and other visitors to the home could pilfer them.
  2. Remind prescribers to select a larger tablet size when increasing the dose, rather than ordering two tablets to be taken at one time.
  3. Serve as a warning signal is cases where a patient may be using part of the prescription nonmedically, or may be diverting pills for use by others for whom they were not prescribed.

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

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.

2012 Update

A literature search from January 2012 through October 2012 did not indicate need to update the criteria in this policy.

2013 Update

Updated with new FDA labeling and stricter FDA indication wording.

References

  1. Silverstein FE, Faich G, Goldstein JL et al. Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: The CLASS study: A randomized controlled trial. Celecoxib Long-term Arthritis Safety Study. JAMA 2000; 284:1247-55.
  2. Bombardier C, Laine L, Reicin A et al. Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. (VIGOR) NEJM 2000; 343:1520-28.
  3. Lai KC, Chu KM, Hui WM, et al. Celecoxib compared with lansoprazole and naproxen to prevent gastrointestinal ulcer complications. Am J Med. 2005 Nov;118(11):1271-8.
  4. Chan FK, Hung LC, Suen BY, et al. Celecoxib versus diclofenac and omeprazole in reducing the risk of recurrent ulcer bleeding in patients with arthritis. NEJM. 2002 Dec 26;347(26):2104-10.
  5. Celecoxib plus aspirin versus naproxen and lansoprazole plus aspirin: a randomized, double-blind, endoscopic trial. Clin Gastroenterol Hepatol. 2007 Oct;5(10):1167-74.
  6. Coluzzi PH, Schwartzberg L, Conroy JD et al. Breakthrough cancer pain: a randomized trail comparing oral transmucosal fentanyl citrate (OFTC®) and morphine sulfate immediate release (MSIR®). Pain. 2001;91:123-130.
  7. Payne R, Coluzzi P, Hart L et al. Long-term safety of oral transmucosal fentanyl citrate for breakthrough cancer pain. J Pain Symptom Manage. 2001;22:575-583.
  8. Farrar JT, Cleary J, Rauck R et al. Oral transmucosal fentanyl citrate: randomized, double-blind, placebo controlled trial for treatment of breakthrough pain in cancer patients. J Natl Cancer Inst. 1998;90:611-616.
  9. SAMHSA. Results from the 2006 National Survey on Drug Use and Health: national findings. Rockville, MD: Substance Abuse and Mental Health Services Administration; 2007b.
  10. US Department of Health and Human Services, substance abuse and mental health services administration. Results from the 2007 national survey on drug use and health: national findings. NSDUH Series H-34, DSHS Publication No. SMA 08-4343. Rockville, MD: Office of Applied Studies, 2008.
  11. Webster, L. Update on Abuse-resistant and abuse-deterrent approaches to opioid formulations. Pain Med 2009;10 Suppl 2:S124-S133.
  12. Drug Abuse Warning Network (DAWN): Drug-related emergency department visits for 2004-2009 [online]. Available online: http://www.samhsa.gov/data/DAWN.aspx. Last accessed on October 1, 2013.
  13. Moore TJ, Cohen MR and Furberg CD. Serious adverse drug events reported to the Food and Drug Administration, 1998-2005. Arch Intern Med 2007;167 (16):1752-1759.
  14. Coolen P, Best S, Lima A, et al. Overdose deaths involving prescription opioids among Medicaid enrollees – Washington, 2004-2007. MMWR 2009;58(42):1171-1175.
  15. US Department of Health and Human Services, Substance Abuse and Mental Health Services. Summary report of the meeting: methadone mortality – a reassessment [online]. Available online: http://www.dpt.samhsa.gov/pdf/Methadone_Mortality_Data_2010.pdf Last accessed on October 1, 2013.
  16. Walsh SL, Nuzzo PA, Lofwall MR and Holtman JR. The relative abuse liability of oral oxycodone, hydrocodone, and hydromorphone assessed in prescription opioid abusers. Drug Alcohol Depend 2008;98(3):191-202.

Coding

Codes

Number

Description

CPT

 

This policy is managed through the Pharmacy benefit

ICD-9 Procedure

   

ICD-9 Diagnosis

   

HCPCS

   

Type of Service

Prescription Drug

 

Place of Service

Inpatient/
Physician's Office

 

Appendix

N/A

History

Date

Reason

02/08/11

Add to Prescription Drug Section - New Policy.

12/13/11

Replace Policy – Policy updated with additional approval parameters and dosing limitation for OxyContin.

11/13/12

Replace policy. A literature search did not indicate the need to update the criteria in this policy.

03/15/13

Update Related Policies. Add 5.01.542.

07/08/13

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.

10/14/13

Replace policy. Medically necessary policy statement for OxyContin updated with new FDA labeling and stricter FDA indication wording.


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).
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