The following is a discussion of ziconotide’s efficacy, appropriate dosage, and interaction with other drugs. Ziconotide, or Prialt, is the newest pain treatment drug approved by the FDA for intraspinal administration. Its introduction into the health care market was an occasion for much fanfare and drama. Having extensively researched ziconotide, I find it very effective in treating neuropathic pain and reflex sympathetic dystrophy (RSD). A unique agent, the drug is a synthetic version of the conopeptide derived from a marine snail. To review the pharmacology, ziconotide is an N-type calcium channel blocker within the dorsal horn of the spinal cord. From a clinical standpoint, I consider Prialt to be a viable option for patients who are intolerant or refractory from previous oral or intraspinal drug treatments.
The proper dosing of ziconotide requires a cautious approach. While Elan Pharmaceuticals recommends that initial dosing begins at 1.2 to 2.4 mcg per day (with dosing changes to occur two to three times per week), the original studies set a patient’s average daily dose at 17.6 mcg/day. At these doses, physicians observed many adverse effects of ziconotide.
Despite the manufacturer’s guidelines, I have cautiously urged my practitioners to begin dosing at 0.25 to 0.5 micrograms per day, with dosing change intervals at four weeks or next pump refill. The four week interval is prudent to achieve an optimal treatment dose and avoid adverse effects. Frequent changes in the dose may create a result analogous to the tsunami effect: as the drug begins to bind to the appropriate site, the adverse effects could become more pronounced each day until the wave crashes and the impact becomes intolerable. It is important to note that while the adverse psychological effects recede upon drug withdrawal, the climax of adverse effects can be taxing to all involved. Hence the recommended slogan for ziconotide dosing is, start low, go slow.
Ziconotide has a strong reputation as a safe and effective drug. According to the literature, no cases of granuloma or meningitis have been reported. One case of inadvertent parenteral systemic administering did arise in which a patient received 500 mcg parenterally and recovered with no sequela. However, the patient experienced significant somnolence for approximately two days and then recovered without any notable cardiac or central nervous system effects.
David Shields, PhD, of Elan Pharmaceuticals, has extensively studied ziconotide and its interaction with other drugs. Some stability studies have also been published. In my conversations with Dr. Shields, he stated that ziconotide’s greatest stability occurs when combined with drugs at the concentrations recommended by the Polyanalgesic Consensus Conference 2003. Significant ziconotide degradation occurs when combined with morphine, hydromorphone and bupivacaine at concentrations exceeding Conference recommendations or when combined with drugs within the pump for more than four weeks. Other studies show ziconotide to be very stable with baclofen and fentanyl. For patients treated with ziconotide, I suggest performing pump refills every four weeks to optimize therapy and maintain drug stability.
Ziconotide: Reimbursement Issues
Reimbursement for ziconotide requires significant attention by all parties within the pain practice. Currently, Medicare covers ziconotide treatment. However, the reimbursement rates vary according to Medicare carrier. It is my understanding that as of this date, the California Medicare carrier NHIC is reimbursing ziconotide at 95 percent of average wholesale price in California, which equates to $6.95 per mcg. In other states, the regional carriers are reimbursing ziconotide at approximately $6.40/mcg.
As reimbursement for ziconotide may fall short of your pharmacy charges, pain practices will want to be informed of applicable reimbursement.
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