1. Use of the Personal Therapy Manager With Prialt® (Ziconotide Intrathecal Infusion) for Patient-controlled Analgesia: Case Series
Gladstone C. McDowell, II, MD Integrated Pain Solutions, Columbus, Ohio

2. Personal Therapy Manager (PTM) and Prialt® (ziconotide intrathecal infusion)
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)
1. PRIALT® (ziconotide intrathecal infusion) [package insert]. South San Francisco, CA: Elan Pharmaceuticals, Inc; 2008.
2. McGivern JG. Ziconotide: a review of its pharmacology and use in the treatment of pain. Neuropsychiatr Dis Treat. 2007;3(1):69-85.
1. PRIALT® (ziconotide intrathecal infusion) [package insert]
2. McGivern JG. Neuropsychiatr Dis Treat. 2007;3(1):69-85.

3. PTM is Contraindicated for Use With Ziconotide
“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
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
1. Personal Therapy Manager for Synchromed II [PI]. Minneapolis, MN: Medtronic; 2007.
2. Baumgartl WH. Pilot study results on the safety of high dose intrathecal bolusing of ziconotide. Poster presented at: 10th Annual Meeting of the North American Neuromodulation Society; December 7-10, 2006; Las Vegas, NV.
3. Rosenblum SM. Intrathecal bolus injection of ziconotide for severe chronic pain: evaluation of analgesic response. Poster presented at: The American Society of Anesthesiologists Annual Meeting; October 18-22, 2008; Orlando, FL.
4. Grigsby E, McGlothlen G, Michiels W. Single-shot Trialing to Assess Patient Response to Intrathecal Ziconotide. American Society of Regional Pain and Anesthesia 2010 Annual Pain Meeting and Workshops; November 18-21, 2010; Phoenix, AZ.
5. Charapata S, Ellis D. Unintentional overdose with intrathecal ziconotide. American Academy of Pain Medicine 18th Annual Meeting: San Francisco, CA; Pain Med. 2002;3:
1. Personal Therapy Manager for Synchromed II [Product Insert]
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):

4. 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)

5. 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

6. 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

7. Ziconotide (IT) Monotherapy Cases (1)
Arachnoiditis
Simple continuous dose
Ziconotide mcg/d
PTM dose
Ziconotide 0.25 mcg q4h
Status
Pain 4/10, maintains active lifestyle
Minimal contact, generally seen only for pump refills
Rheumatoid arthritis and osteoarthritis
Ziconotide 4.8 mcg/d
Ziconotide 0.20 mcg q3h
(Oral) oxymorphone ER 5 mg q12h
Pain 4–5/10, more functional
Seen only for pump refills

8. Ziconotide (IT) Monotherapy Cases (2)
Chronic pancreatitis (failed SCS)
Simple continuous dose
Ziconotide 1.5 mcg/d
PTM dose
Ziconotide 0.15 mcg q2h
Status
Pain 5/10, functional
Phone calls reduced, seen only for pump refills and titration

9. Combination Therapy Cases (1)
Metastatic breast cancer – lumbar spine metastases
Simple continuous dose
Ziconotide mcg/d + hydromorphone 6.7 mg/d
PTM dose
Ziconotide 0.25 mcg + hydromorphone 0.25 mg q8h
Status
Pain 6/10, now fully ambulatory and more active
Minimal unscheduled contact, generally seen only for pump refills
Metastatic breast cancer – thoracic/lumbar spine, bilateral femur, and extensive pelvis metastases with fractures
Ziconotide mcg/d + hydromorphone 3.0 mg/d
Ziconotide 0.10 mcg + hydromorphone 0.02 mg q3h
Pain remains high, but she is functional despite continued tumor spread
No hospital admissions or ER visits, seen monthly for pump refills and occasional dose increases

10. Combination Therapy Cases (2)
Metastatic pancreatic cancer – L5 metastasis
Simple continuous dose
Ziconotide 1.0 mcg/d + hydromorphone 1.5 mg/d
PTM dose
Ziconotide 0.10 mcg + hydromorphone 0.15 mg q8h
Status
Pain 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)
Ziconotide mcg/d + hydromorphone 1.33 mg/d
Ziconotide 0.20 mcg + hydromorphone mg q3h
Pain 4–5/10, young patient remains active
Generally seen only for pump refills

11. Combination Therapy Cases (3)
Diabetic peripheral neuropathy
Simple continuous dose
Ziconotide 6.0 mcg/d
Hydromorphone 1.2 mg/d
PTM dose
Ziconotide 0.25 mcg q3h
Hydromorphone 0.05 mg q3h
Status
More active, less neuropathy pain, less frequent anxiety flares
Minimal unscheduled contact, generally seen only for pump refills

12. 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 for
Efficacy, safety, tolerability
Dosing parameters
Guidelines for physicians