BlueCross and BlueShield of Montana Medical Policy/Codes
Zinconotide (Prialt)
Chapter: Drugs - Medical Benefit
Current Effective Date: August 27, 2013
Original Effective Date: August 27, 2013
Publish Date: May 27, 2013
Revised Dates: This policy is no longer scheduled for routine literature review and update.
Description

Ziconotide is a non-opioid analgesic, called an N-type calcium channel blocker, that works by targeting and blocking calcium channels on the nerves that transmit pain signals to the brain. On December 28, 2004, the U.S. Food and Drug Administration (FDA) approved Ziconotide for treatment of chronic, severe pain, when administered by intrathecal infusion. The FDA approval specified Ziconotide is for use only in the Medtronic SynchroMed® EL, SynchroMed® II Infusion System and Simms Deltec Cadd Micro® External Microinfusion Device and Catheter. These are programmable pumps that release the drug into the fluid surrounding the spinal cord, through a surgically implanted catheter. In clinical trials, Ziconotide helped alleviate pain in most patients over the long term.

Severe psychiatric symptoms and neurological impairment may occur during treatment with Ziconotide. Patients with a pre-existing history of psychosis should not be treated with Ziconotide. All patients should be monitored frequently for evidence of cognitive impairment, hallucinations, or changes in mood or consciousness. Ziconotide therapy can be interrupted or discontinued abruptly without evidence of withdrawal effects in the event of serious neurological or psychiatric signs or symptoms. Other frequently reported adverse events associated with the drug in clinical trials were asthenia, nausea, vomiting, abnormal gait, ataxia, confusion, dizziness, memory impairment, nystagmus, abnormal vision, and urinary retention.

Policy

Prior authorization is recommended. Call Blue Cross and Blue Shield of Montana (BCBSMT) Customer Service at 1-800-447-7828 or fax your request to the Medical Review Department at 406-441-4624. A retrospective review is performed if services are not prior authorized.

Medically Necessary

BCBSMT may consider Ziconotide intrathecal infusion (Prialt®) medically necessary for management of severe chronic pain in patients for whom intrathecal (IT) therapy is warranted, and who are intolerant of or refractory to other treatment, including systemic analgesics, adjunctive therapies, and IT morphine. 

Investigational

BCBSMT considers Ziconotide intrathecal infusion (Prialt) experimental, investigational and unproven for all other indications.

Federal Mandate

Federal mandate prohibits denial of any drug, device, or biological product fully approved by the FDA as investigational for the Federal Employee Program (FEP). In these instances coverage of these FDA-approved technologies are reviewed on the basis of medical necessity alone. Call the BCBSMT FEP Customer Service Department at 1-800-634-3569 for benefit information.

Rationale for Benefit Administration

This medical policy was developed through consideration of peer reviewed medical literature, FDA approval status, accepted standards of medical practice in Montana, Technology Evaluation Center evaluations, and the concept of medical necessity. BCBSMT reserves the right to make exceptions to policy that benefit the member when advances in technology or new medical information become available.

The purpose of medical policy is to guide coverage decisions and is not intended to influence treatment decisions. Providers are expected to make treatment decisions based on their medical judgment. Blue Cross and Blue Shield of Montana recognizes the rapidly changing nature of technological development and welcomes provider feedback on all medical policies.

When using this policy to determine whether a service, supply or device will be covered, please note that member contract language will take precedence over medical policy when there is a conflict.

Rationale

The safety and efficacy of intrathecal (IT) Ziconotide in the management of severe chronic pain were studied in three double-blind, placebo-controlled, multicenter studies in a total of 457 patients (268 Ziconotide, 189 placebo) using two different titration schedules. The slow titration schedule tested dose increases two to three times per week with a maximum dose of 19.2 mcg/day (0.8 mcg/hr) at 21 days.  The fast titration schedule used daily increases up to a maximum dose of 57.6 mcg/day (2.4 mcg/hr) in five to six days. The safety in chronic use was studied in four additional open-label, long-term studies in 977 patients.

A randomized, double-blind, placebo-controlled study was conducted at 39 centers to evaluate the efficacy of IT Ziconotide administered using a slow titration schedule in 220 patients with severe chronic pain  Patients were randomized 1:1 between Ziconotide (112 patients) and placebo (108 patients). At baseline, 97% of these patients reported that their pain was refractory to treatment including IT morphine, IT bupivacaine (an off-label use for this drug) and/or IT clonidine (an off-label use for this drug) in addition to their systemic analgesics and adjunctive therapy. All IT medications were discontinued over a one- to three-week period and patients were maintained on a stable regimen of non-IT analgesics including opiates, for at least seven days prior to randomization. This period was successfully completed by 93% of the patients screened. Dosing with Ziconotide was started at 2.4 mcg/day (0.1 mcg/hr) and the dose could be increased by 2.4 mcg/day (0.1 mcg/hr) two to three times/week (minimum titration interval 24 hours) to a maximum dose of 19.2 mcg/day (0.8 mcg/hr). The final mean dose at the end of the trial at 21 days was 6.9 mcg/day (0.29 mcg/hr).

Using a 100 mm Visual Analog Scale of Pain Intensity (VASPI) where 100 mm equals the worst possible pain, mean baseline pain scores were 81 in both the Ziconotide and placebo groups. The primary efficacy variable was the mean percent change in the VASPI score from baseline to day 21.  In the intent-to-treat (ITT) efficacy analysis, there was a statistically significant difference between groups in the mean percent change in VASPI score from baseline with the Ziconotide group having a 12% mean improvement at Week 3 compared to a 5% mean improvement in the placebo group (p=0.04). The 95% confidence interval for the treatment difference (Ziconotide – placebo) was 0.4%, 13%. The effect of IT Ziconotide on pain was variable over the time period of treatment for some patients. Some patients had a reduction in VASPI in the first or second week, but did not maintain pain relief by the end of the third week. Other patients, who did not exhibit a reduction in VASPI early in treatment, did have a reduction in VASPI by the third week.

Patients exhibited various degrees of improvement in pain after three weeks of treatment compared with baseline pain assessment. Patients were monitored for their degree of improvement. Patients who did not have a VASPI score recorded at Week 3 (study days 17-23, inclusive) were assigned 0% improvement. The improvement in the proportion of “responders,” defined as having a equals 30% improvement from baseline in VASPI, was 16% in the Ziconotide group compared to 12% in the placebo group, for a net difference of 4%. Non-IT opioid use decreased by 24% in the Ziconotide group and by 17% in the placebo group.

2012 Update

A search of peer reviewed literature through June 2012 identified no new clinical trial publications or any additional information that would change the coverage position of this medical policy.

Coding

Disclaimer for coding information on Medical Policies           

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.           

The presence or absence of procedure, service, supply, device or diagnosis codes in a Medical Policy document has no relevance for determination of benefit coverage for members or reimbursement for providers. Only the written coverage position in a medical policy should be used for such determinations.           

Benefit coverage determinations based on written Medical Policy coverage positions must include review of the member’s benefit contract or Summary Plan Description (SPD) for defined coverage vs. non-coverage, benefit exclusions, and benefit limitations such as dollar or duration caps.

ICD-9 Codes
03.90.  Refer to the ICD-9-CM Manual.
ICD-10 Codes

00HU33Z.  Refer to the ICD-10-CM Manual.

Procedural Codes: J2278
References
  1. FDA Approves Prialt (Ziconotide Intrathecal Infusion) for severe chronic pain.  DGNews (2005).
  2. Available at http://www.docguide.com (Accessed on 2005 June 6).
  3. U.S. Food and Drug Administration, Label and Approval History (2005). Available at http://www.accessdata.fda.gov  (Accessed on 2005 June 6).
  4. Introducing Prialt.  Brought to you by Elan (2004).  Available at http://www.prialt.com  (Accessed on 2005 June 6).
  5. Labeling revision.  U.S. Food and Drug Administration, Label and Approval History.  (2011 September).  Available at http://www.accessdata.fda.gov (Accessed 2012 July 20).
History
April 2013  New 2013 BCBSMT medical policy.  BCBSMT may consider Ziconotide intrathecal infusion (Prialt®) medically necessary for management of severe chronic pain in patients for whom intrathecal (IT) therapy is warranted, and who are intolerant of or refractory to other treatment, including systemic analgesics, adjunctive therapies, and IT morphine.  BCBSMT considers Ziconotide intrathecal infusion (Prialt) experimental, investigational and unproven for all other indications.
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Zinconotide (Prialt)