Ziconotide (Prialt): uses, how it works and side effects

Ziconotide is an option for severe chronic pain when other treatments do not help enough or are not tolerated, and when treatment delivered directly into the spinal fluid is needed. The drug is not an opioid. Pain specialists give it through a pump and monitor the treatment closely. Severe psychiatric and neurological side effects are possible, so the dose has to be adjusted carefully.

What is ziconotide?

Ziconotide is available under the brand name Prialt. It is the synthetic version of a peptide found in the venom of the marine cone snail Conus magus. This potent painkiller is given for severe chronic pain directly into the cerebrospinal fluid, or CSF. This fluid surrounds the brain and the spinal cord.

During development, ziconotide carried the code SNX-111; its natural counterpart is called omega-conotoxin MVIIA. It was approved in the US in 2004.

How does ziconotide work?

Ziconotide blocks certain calcium channels at the endings of pain-carrying nerves in the dorsal horn of the spinal cord. These voltage-gated N-type channels control whether the nerves release the messenger chemicals that pass pain signals on toward the brain. By blocking the channels, ziconotide prevents these messengers from being released and interrupts the pain signal right there in the spinal cord.

Because it is a peptide, ziconotide has a hard time getting from the bloodstream into the brain. That is why it is infused through a pump directly into the CSF. It must never be given intravenously, that is, into a vein.

Ziconotide works differently from opioids. It does not cause respiratory depression (a slowing of breathing), and it does not lead to comparable tolerance: its effect does not fade over time the way opioid effects do. These properties make it a treatment option for pain that is hard to control.

In a controlled trial, people with treatment-resistant pain related to cancer or AIDS received either ziconotide or placebo. Pain scores fell considerably more with ziconotide. 1 However, the doses that work and the doses that can no longer be tolerated lie close together. Specialists call this a narrow therapeutic window. That is why they adjust the dose slowly and carefully.

Is ziconotide FDA-approved?

Yes. The US Food and Drug Administration (FDA) approved ziconotide (Prialt) in 2004 to treat severe chronic pain. The approval covers people who need intrathecal therapy and who either do not tolerate other treatments or do not respond well enough to them. “Intrathecal” means that a drug is delivered directly into the space that holds the CSF. 2

The US prescribing information carries a prominent warning about severe psychiatric symptoms and neurological impairment. This warning is called a “Boxed Warning.” Ziconotide must not be used in people who have had psychosis in the past.

What is ziconotide prescribed for?

Before prescribing it, pain specialists carefully check whether ziconotide is suitable for the individual patient. It is an option for severe chronic pain when intrathecal treatment is required and other therapies, including intrathecal morphine, have not helped enough or are not tolerated. An implanted or external microinfusion pump delivers the drug, and pain specialists oversee the treatment.

What are the side effects?

The prescribing information lists common side effects that include:

• Dizziness and nausea
• Confusion and memory problems
• Walking difficulties, sleepiness and involuntary eye movements

Serious side effects need particular attention:

• Severe psychiatric symptoms such as depression, suicidal thoughts and hallucinations, as well as neurological impairment, can occur. The “Boxed Warning” draws attention to this. Close monitoring is therefore needed throughout treatment.
• If serious neurological or psychiatric signs appear, the drug must be stopped.
• If the pump or catheter becomes contaminated, meningitis (inflammation of the membranes around the brain) or other infections can occur.