Date Issued: November 14, 2018
- Patients who have an implanted pump that delivers medicine into the spinal fluid to treat or manage pain
- Caregivers of these patients
- Health care providers who manage the care of these patients
Anesthesiologists, General Surgeons, Neurosurgeons, Neurologists, Nurses and Nurse Practitioners, Orthopaedic Surgeons, Pain Management Specialists, Pharmacists, Physician Assistants, Primary Care Physicians, Outsourcing Facilities, Compounders
Implanted pumps are medical devices that are surgically implanted under the skin, typically in the abdomen. They are connected to an implanted catheter and are used to deliver prescription medicines and fluids within the body, including the intrathecal space (into the spinal fluid), to treat pain, muscle spasticity, and other diseases or conditions. Implanted pumps are periodically refilled with medicines or fluids by a health care provider.
They are often used to treat or manage pain after other treatments, such as oral medicines, physical therapy, or surgery, are unsuccessful.
The FDA is providing recommendations and sharing important information with health care providers, pharmacists, compounders, patients and caregivers about the risks of using medications delivered into the spinal fluid to treat or manage pain that are not approved for use with the implanted pumps.
Summary of Problem and Scope:
The FDA is aware that patients undergoing treatment or management of pain are commonly given pain medicines in the spinal fluid (intrathecal administration) that are not FDA approved for use with the implanted pump. While individual patients may experience some relief from using pain medicines not approved for intrathecal administration in their implanted pumps, such use may create additional risks including dosing errors, pump failures, and other safety concerns. The FDA wants to ensure that patients, caregivers, compounders, pharmacists, and health care providers are aware of these risks to make informed treatment decisions.
The FDA-approved implanted pump labeling identifies which pain medicines are approved for use with each pump. Pain medicines approved by FDA for delivery into the spinal fluid must meet additional safety standards because the spinal cord and brain tissue are highly sensitive to preservatives or infectious organisms such as bacteria or viruses. The implanted pump’s current labeling should be reviewed to determine which pain medicines are approved for use in each pump. The table below includes examples of medicines approved and not approved for intrathecal use with implanted pumps to treat or manage pain.
The only approved medicines identified in implanted pump labeling for intrathecal infusion to treat or manage pain
Examples of medicines not identified in the implanted pump labeling for intrathecal infusion to treat or manage pain
INFUMORPH® (morphine sulfate), preservative free, injectable solution
*PRIALT® (preservative free ziconotide sterile solution)
Medicines not FDA approved for intrathecal administration or intrathecal implanted pump use (for example, hydromorphone, bupivacaine, fentanyl, clonidine)
ANY mixture of two or more different kinds of medicines
Any compounded medicine (for example, to achieve higher concentration or different formulation of an FDA approved medicine)
* The current labeling (Instructions for Use) of the implanted pump should be reviewed because not all pumps are currently approved for use with PRIALT.
The FDA has received numerous Medical Device Reports (MDRs) describing adverse events with implanted pumps. These reports describe pump failures, dosing errors, and other potential safety issues. Patients’ symptoms described in these reports include pain, opioid withdrawal, fever, vomiting, muscle spasm, cognitive changes, weakness, cardiac and respiratory distress. In addition to MDRs, the FDA reviewed available data from other sources including premarket device applications, mandated FDA postapproval studies, publicly available scientific literature, current device labeling, information from health care providers, and device manufacturers. Based on this analysis, the FDA is sharing information about pump failures, dosing errors, and other safety information so that patients and providers can make informed treatment decisions.
While pump failure can occur independently of the type of medicine used, the data reviewed by FDA indicates that the implanted pump failure rate may more than double when medicines not approved for intrathecal administration with the pump are infused. Because not all medicines (such as compounded drugs) have been evaluated for compatibility with the components of the pump, there is an increased risk for part failure that may lead to earlier than expected surgical removal or replacement of the pump. For example, some medicines or fluids may contain preservatives or other characteristics that can damage the pump tubing, or lead to corrosion of the pumping mechanism. This may cause the implanted pump to perform in unexpected ways including pump motor stalls, which ultimately stops the medication delivery, leading to potential medicine withdrawal symptoms.
In addition to dose errors from pump failure, the dose accuracy of the pump operation was reviewed by the FDA based on data using medicines approved for use in the pump. These medicines were determined to be compatible with the implanted pump. The compatibility or incompatibility of other medicines with a specific pump is unknown.
Programmable implanted pumps also have dose calculation software that provides options for users to select pre-programmed medicines and concentrations identified in the approved pump labeling to help prevent unintended dosing errors. The accuracy of the software calculations are dependent on using the approved medicine, medicine concentration, and medicine characteristics. For example, if there is more than one medicine in the pump reservoir, the pump software can only calculate the dose based on a single infusion rate.
Additionally, using a higher concentration of a medicine to fill a pump may prolong the amount of time between pump refills. However, it is known that due to technological limitations of these pumps, the lower the infusion rate, the greater the risk of flow rate inaccuracy. Therefore, the patient may not receive the intended dose at very low flow rates, potentially leading to symptoms associated with under or over-dose.
Other Potential Safety Issues
The spinal cord and brain tissue are highly susceptible to the effects of medicines given intrathecally. Medicines approved by FDA for intrathecal injection must meet additional safety standards to ensure they do not damage these sensitive tissues. These standards are greater than those for medicines approved for different routes of administration such as an injection into a vein or muscle. If the implanted pump is filled with a medicine that is not approved for intrathecal injection, the medicine itself may be toxic to the spinal cord and brain tissue or there may be infectious agents present. In addition, the interaction of the materials between the pump system and medicines not approved for use in the pump is unknown, and could also be toxic to the spinal cord and brain tissue.
Lastly, the use of some highly concentrated medicines are associated with granuloma formation (inflammatory mass) at the tip of the catheter or infusion site. Granuloma formation may lead to pain and neurological deficits due to compression of the spinal cord or nerves.
Intrathecal delivery of medication with an implanted pump for pain management is often reserved for patients who fail other treatment options. Several clinical factors are considered when selecting medicines for intrathecal use with the implanted pump such as the severity, type, and location of the pain as well as individual patient factors including diagnosis, projected life span, comorbidities, and individual response to different medicines. FDA acknowledges that some patients being treated for pain may not be adequately managed by medicines approved for use with these pumps; however, the use of medicines not approved with the implanted pumps are associated with additional risks such as pump failures, dosing errors, and other potential safety issues. Therefore, the FDA is sharing information and providing recommendations so that patients, caregivers, compounders, pharmacists, and health care providers can make informed treatment decisions.
When considering a medicine for use in an implanted pump:
- Review the implanted pump labeling to identify the medicines and medicine concentrations approved for use with that specific pump.
- Be aware that the following medicines are NOT currently approved for use with implanted pumps for intrathecal infusion of pain medications:
- Medicines not FDA approved for intrathecal administration or intrathecal implanted pump use (for example, hydromorphone, bupivacaine, fentanyl, clonidine)
- ANY mixture of two or more different kinds of medicines
- Any compounded medicine (for example, to achieve higher concentration or different formulation of an FDA approved medicine)
- Be aware that while individual patients may experience some relief from using medicines not approved for intrathecal administration in their implanted pumps for pain management, such use may pose additional risks including pump failures, dosing errors, and other potential safety issues.
- Healthcare providers generally may prescribe a drug for an unapproved use when they determine that it is medically appropriate for their patient, however, providers and patients should be aware that such unapproved uses have not been reviewed by FDA for safety or effectiveness.
- Health care providers, patients, and caregivers are encouraged to consider and discuss both the benefits and risks of using implanted pumps for the intrathecal infusion of medications for pain management in order to make informed treatment decisions.
- Report adverse events to the FDA if you suspect an implanted pump is having problems:
- Patients, caregivers, and physicians may file a voluntary report through MedWatch, the FDA Safety Information and Adverse Event Reporting program.
- User facilities must comply with the applicable Medical Device Reporting (MDR) regulations.
- Health care providers employed by facilities that are subject to the FDA's user facility reporting requirements should follow the reporting procedures established by their facilities.
The FDA conducted the analysis above and will update this communication if significant new information becomes available.
Deer T.R., Pope J.E., Hayek S.M., Bux A., Buchser E., Eldabe S., De Andres J.A., Erdek M., Patin D., Grider J.S., Doleys D.M., Jacobs M.S., Yaksh T.L., Poree L., Wallace M.S., Prager J., Rauck R., DeLeon O., Diwan S., Falowski S.M., Gazelka H.M., Kim P., Leong M., Levy R.M., McDowell II G., McRoberts P., Naidu R., Narouze S., Perruchoud C., Rosen S.M., Rosenberg W.S., Saulino M., Staats P., Stearns L.J., Willis D., Krames E., Huntoon M., Mekhail N. 2017. The Polyanalgesic Consensus Conference (PACC): Recommendations on Intrathecal Drug Infusion Systems Best Practices and Guidelines. Neuromodulation 2017; 20: 96–132
If you have questions about this communication, please contact the Division of Industry and Consumer Education (DICE) at DICE@FDA.HHS.GOV, 800-638-2041 or 301-796-7100.