Use of the Personal Therapy Manager With

Prialt® (Ziconotide Intrathecal Infusion) for Patient-controlled

Analgesia:Case Series

Gladstone C. McDowell, II, MDIntegrated Pain Solutions, Columbus, Ohio

Personal Therapy Manager (PTM) and Prialt® (ziconotide intrathecal infusion)

PTM Patient-activated delivery of physician-

programmed supplemental dose of intrathecal (IT) medication as needed

Ziconotide IT analgesic for chronic severe pain1

Inhibits N-type calcium channels, believed to reduce signaling along the spinal pain pathways2

We have used the PTM in patients receiving continuous infusion of IT ziconotide (monotherapy or combination)

21. PRIALT® (ziconotide intrathecal infusion) [package insert]. 2008.2. McGivern JG. Neuropsychiatr Dis Treat. 2007;3(1):69-85.

PTM is Contraindicated for Use With Ziconotide

However, Bolus trials are routinely used to test

effectiveness of ziconotide for individuals2-4

Ziconotide overdose does not lead to respiratory depression or death5

Formal study is needed to define usage criteria to ensure efficacy and safety and minimize side effects

3

“Contraindications

… Do not prescribe or use the Personal Therapy Manager for administration of an intrathecal infusion of ziconotide, because ziconotide has a defined titration scheme.”1

1. Personal Therapy Manager for Synchromed II [Product Insert]. 2007.2. Baumgartl WH. (poster) 10th Annual Meeting of NANS; 2006.3. Rosenblum SM. (Abstract A1566) ASA Annual Meeting; 2008.

4. Grigsby E, et al. (Abstract 14) ASRA 2010 Annual Pain Meeting and Workshops; 2010.

5. Charapata S and Ellis D. Pain Medicine. 2002;3(2):189-190.

Dosing considerations

PTM with ziconotide monotherapy Simpler, safer than combination therapy

PTM with ziconotide in combination with opioid Calculate programmed dose based on ziconotide

infusion dose (minding opioid overdose) Bolus doses equivalent to ~10% of daily

continuous dose– Ziconotide bolus dose range, 0.15 to 0.25 mcg

Intervals of 1−2 hours (cancer patients) to 4−6 hours (nonmalignant disease patients)

4

Tolerability and Pain Relief

This treatment strategy was well tolerated No severe adverse effects A few patients experienced nausea or dizziness

with PTM doses that exceeded 60% of their simple continuous ziconotide dose

The addition of PTM increased patient satisfaction and decreased office visits

Patient compliance was related directly to proper and adequate education regarding the utility and beneficial effects of the PTM device

5

PTM Cases

Ziconotide monotherapy, 3 patients: 1 patient with arachnoiditis 1 patient with rheumatoid arthritis and osteoarthritis 1 patient with chronic pancreatitis

Ziconotide + hydromorphone, 11 patients: 4 patients with metastatic breast cancer 1 patient with large anal cancer 1 patient with metastatic pancreatic cancer 3 patients with lumbar postlaminectomy syndrome 1 patient with diabetic peripheral neuropathy 1 patient with interstitial cystitis and lumbar

postlaminectomy syndrome

6

Ziconotide (IT) Monotherapy Cases (1) Arachnoiditis

Simple continuous dose Ziconotide 14.983 mcg/dPTM doseZiconotide 0.25 mcg q4hStatusPain 4/10, maintains active lifestyleMinimal contact, generally seen only for pump refills

Rheumatoid arthritis and osteoarthritisSimple continuous dose Ziconotide 4.8 mcg/dPTM doseZiconotide 0.20 mcg q3hStatus(Oral) oxymorphone ER 5 mg q12hPain 4–5/10, more functionalSeen only for pump refills

7

Ziconotide (IT) Monotherapy Cases (2) Chronic pancreatitis (failed SCS)

Simple continuous dose Ziconotide 1.5 mcg/dPTM doseZiconotide 0.15 mcg q2hStatusPain 5/10, functionalPhone calls reduced, seen only for pump refills and titration

8

Combination Therapy Cases (1) Metastatic breast cancer – lumbar spine metastases

Simple continuous dose Ziconotide 6.701 mcg/d + hydromorphone 6.7 mg/dPTM doseZiconotide 0.25 mcg + hydromorphone 0.25 mg q8hStatusPain 6/10, now fully ambulatory and more activeMinimal unscheduled contact, generally seen only for pump refills

Metastatic breast cancer – thoracic/lumbar spine, bilateral femur, and extensive pelvis metastases with fractures

Simple continuous dose Ziconotide 14.408 mcg/d + hydromorphone 3.0 mg/dPTM doseZiconotide 0.10 mcg + hydromorphone 0.02 mg q3hStatusPain remains high, but she is functional despite continued tumor

spreadNo hospital admissions or ER visits, seen monthly for pump refills

and occasional dose increases9

Combination Therapy Cases (2) Metastatic pancreatic cancer – L5 metastasis

Simple continuous dose Ziconotide 1.0 mcg/d + hydromorphone 1.5 mg/dPTM doseZiconotide 0.10 mcg + hydromorphone 0.15 mg q8hStatusPain 1/10 within 1 month, rare PTM use, doses reduced by 5%Minimal phone contact, receiving home pump refills

Lumbar post-laminectomy syndrome (failed SCS)Simple continuous dose Ziconotide 3.994 mcg/d + hydromorphone 1.33 mg/dPTM doseZiconotide 0.20 mcg + hydromorphone 0.067 mg q3hStatusPain 4–5/10, young patient remains activeGenerally seen only for pump refills

10

Combination Therapy Cases (3) Diabetic peripheral neuropathy

Simple continuous dose Ziconotide 6.0 mcg/dHydromorphone 1.2 mg/dPTM doseZiconotide 0.25 mcg q3hHydromorphone 0.05 mg q3hStatusMore active, less neuropathy pain, less frequent anxiety

flaresMinimal unscheduled contact, generally seen only for pump

refills

11

Conclusions

The PTM can be used with ziconotide monotherapy or with ziconotide in combination with an opioid with acceptable tolerability and improved pain relief outcomes

Individualization of therapy and communication with patient are essential for successful PTM use

Formal study is needed to provide evidence for1)Efficacy, safety, tolerability2)Dosing parameters3)Guidelines for physicians

12