Pharmacodynamics of LIORESAL INTRATHECAL:

Adult Patients: The onset of action is generally one-half hour to one hour after an intrathecal bolus. Peak spasmolytic effect is seen at approximately four hours after dosing and effects may last four to eight hours. Onset, peak response, and duration of action may vary with individual patients depending on the dose and severity of symptoms.

Pediatric Patients: The onset, peak response and duration of action is similar to those seen in adult patients.

LIORESAL INTRATHECAL’S antispastic action is first seen at 6 to 8 hours after initiation of continuous infusion. Maximum activity is observed in 24 to 48 hours.

Continuous Infusion: No additional information is available for pediatric patients.

Pharmacokinetics of LIORESAL INTRATHECAL:

The pharmacokinetics of CSF clearance of LIORESAL INTRATHECAL calculated from intrathecal bolus or continuous infusion studies approximates CSF turnover, suggesting elimination is by bulk-flow removal of CSF.

Intrathecal Bolus: After a bolus lumbar injection of 50 or 100 mcg LIORESAL INTRATHECAL in seven patients, the average CSF elimination half-life was 1.51 hours over the first four hours and the average CSF clearance was approximately 30 mL/hour.

Continuous Infusion: The mean CSF clearance for LIORESAL INTRATHECAL (baclofen injection) was approximately 30 mL/hour in a study involving ten patients on continuous intrathecal infusion. Concurrent plasma concentrations of baclofen during intrathecal administration are expected to be low (0-5 ng/mL).

Limited pharmacokinetic data suggest that a lumbar-cisternal concentration gradient of about 4:1 is established along the neuroaxis during baclofen infusion. This is based upon simultaneous CSF sampling via cisternal and lumbar tap in 5 patients receiving continuous baclofen infusion at the lumbar level at doses associated with therapeutic efficacy; the interpatient variability was great. The gradient was not altered by position.

Six pediatric patients (age 8-18 years) receiving continuous intrathecal baclofen infusion at doses of 77-400 mcg/day had plasma baclofen levels near or below 10 ng/mL.

LABORATORY TESTS

No specific laboratory tests are deemed essential for the management of patients on LIORESAL INTRATHECAL.

DRUG INTERACTIONS

There is inadequate systematic experience with the use of LIORESAL INTRATHECAL in combination with other medications to predict specific drug-drug interactions. Interactions attributed to the combined use of LIORESAL INTRATHECAL and epidural morphine include hypotension and dyspnea.

CARCINOGENESIS, MUTAGENESIS, AND IMPAIRMENT OF FERTILITY

No increase in tumors was seen in rats receiving baclofen orally for two years. Adequate genotoxicity assays of baclofen have not been performed.

PREGNANCY

There are no adequate and well-controlled studies in pregnant women. In animal studies, baclofen had adverse effects on embryofetal development when administered orally to pregnant rats. LIORESAL INTRATHECAL should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Baclofen given orally increased the incidence of fetal structural abnormalities (omphaloceles) in rats. Reductions in food intake and body weight gain were observed in the dams. Fetal structural abnormalities were not observed in mice or rabbits

NURSING MOTHERS

In mothers treated with oral LIORESAL (baclofen USP) in therapeutic doses, the active substance passes into the milk. It is not known whether detectable levels of drug are present in milk of nursing mothers receiving LIORESAL INTRATHECAL. As a general rule, nursing should be undertaken while a patient is receiving LIORESAL INTRATHECAL only if the potential benefit justifies the potential risks to the infant.

PEDIATRIC USE

Children should be of sufficient body mass to accommodate the implantable pump for chronic infusion. Please consult pump manufacturer's manual for specific recommendations.

Safety and effectiveness in pediatric patients below the age of 4 have not been established. Considerations based on experience with oral LIORESAL (baclofen USP)

A dose-related increase in incidence of ovarian cysts was observed in female rats treated chronically with oral LIORESAL. Ovarian cysts have been found by palpation in about 4% of the multiple sclerosis patients who were treated with oral LIORESAL for up to one year. In most cases these cysts disappeared spontaneously while patients continued to receive the drug. Ovarian cysts are estimated to occur spontaneously in approximately 1% to 5% of the normal female population.

Spasticity of Spinal Cord Origin – Clinical Studies:

Commonly Observed in Patients with Spasticity of Spinal Origin — In pre- and post-marketing clinical trials, the most commonly observed adverse events associated with use of LIORESAL INTRATHECAL (baclofen injection) which were not seen at an equivalent incidence among placebo-treated patients were: somnolence, dizziness, nausea, hypotension, headache, convulsions and hypotonia.

Associated with Discontinuation of Treatment — 8/474 patients with spasticity of spinal cord origin receiving long term infusion of LIORESAL INTRATHECAL in pre- and post-marketing clinical studies in the U.S. discontinued treatment due to adverse events. These include: pump pocket infections (3), meningitis (2), wound dehiscence (1), gynecological fibroids (1) and pump overpressurization (1) with unknown, if any, sequela. Eleven patients who developed coma secondary to overdose had their treatment temporarily suspended, but all were subsequently re-started and were not, therefore, considered to be true discontinuations.

Fatalities — See Warnings.

Incidence in Controlled Trials — Experience with LIORESAL INTRATHECAL (baclofen injection) obtained in parallel, placebo-controlled, randomized studies provides only a limited basis for estimating the incidence of adverse events because the studies were of very brief duration (up to three days of infusion) and involved only a total of 63 patients. The following events occurred among the 31 patients receiving LIORESAL INTRATHECAL (baclofen injection) in two randomized, placebo-controlled trials: hypotension (2), dizziness (2), headache (2), dyspnea (1). No adverse events were reported among the 32 patients receiving placebo in these studies.

Events Observed during the Pre- and Post-marketing Evaluation of LIORESAL INTRATHECAL — Adverse events associated with the use of LIORESAL INTRATHECAL reflect experience gained with 576 patients followed prospectively in the United States. They received LIORESAL INTRATHECAL for periods of one day (screening) (N = 576) to over eight years (maintenance) (N = 10). The usual screening bolus dose administered prior to pump implantation in these studies was typically 50 mcg. The maintenance dose ranged from 12 mcg to 2003 mcg per day. Because of the open, uncontrolled nature of the experience, a causal linkage between events observed and the administration of LIORESAL INTRATHECAL cannot be reliably assessed in many cases and many of the adverse events reported are known to occur in association with the underlying conditions being treated. Nonetheless, many of the more commonly reported reactions—hypotonia, somnolence, dizziness, paresthesia, nausea/vomiting and headache—appear clearly drug-related.

Adverse experiences reported during all U.S. studies (both controlled and uncontrolled) are shown in the following table. Eight of 474 patients who received chronic infusion via implanted pumps had adverse experiences which led to a discontinuation of long term treatment in the pre- and post-marketing studies.

In addition to the more common (1% or more) adverse events reported in the prospectively followed 576 domestic patients in pre- and post-marketing studies, experience from an additional 194 patients exposed to LIORESAL INTRATHECAL (baclofen injection) from foreign studies has been reported. The following adverse events, not described in the table, and arranged in decreasing order of frequency, and classified by body system, were reported:

Nervous System: Abnormal gait, thinking abnormal, tremor, amnesia, twitching, vasodilitation, cerebrovascular accident, nystagmus, personality disorder, psychotic depression, cerebral ischemia, emotional lability, euphoria, hypertonia, ileus, drug dependence, incoordination, paranoid reaction and ptosis.

Digestive System: Flatulence, dysphagia, dyspepsia and gastroenteritis.

Cardiovascular: Postural hypotension, bradycardia, palpitations, syncope, arrhythmia ventricular, deep thrombophlebitis, pallor and tachycardia.

Respiratory: Respiratory disorder, aspiration pneumonia, hyperventilation, pulmonary embolus and rhinitis.

Urogenital: Hematuria and kidney failure.

Skin and Appendages: Alopecia and sweating.

Metabolic and Nutritional Disorders: Weight loss, albuminuria, dehydration and hyperglycemia.

Special Senses: Abnormal vision, abnormality of accommodation, photophobia, taste loss and tinnitus.

Body as a Whole: Suicide, lack of drug effect, abdominal pain, hypothermia, neck rigidity, chest pain, chills, face edema, flu syndrome and overdose.

Hemic and Lymphatic System: Anemia.

Spasticity of Cerebral Origin – Clinical Studies:

Commonly Observed — In pre-marketing clinical trials, the most commonly observed adverse events associated with use of LIORESAL INTRATHECAL (baclofen injection) which were not seen at an equivalent incidence among placebo-treated patients included: agitation, constipation, somnolence, leukocytosis, chills, urinary retention and hypotonia.

Associated with Discontinuation of Treatment — Nine of 211 patients receiving LIORESAL INTRATHECAL in pre-marketing clinical studies in the U.S. discontinued long term infusion due to adverse events associated with intrathecal therapy.

The nine adverse events leading to discontinuation were: infection (3), CSF leaks (2), meningitis (2), drainage (1), and unmanageable trunk control (1).

Fatalities — Three deaths, none of which were attributed to LIORESAL INTRATHECAL, were reported in patients in clinical trials involving patients with spasticity of cerebral origin. See Warnings on other deaths reported in spinal spasticity patients.

Incidence in Controlled Trials — Experience with LIORESAL INTRATHECAL (baclofen injection) obtained in parallel, placebo-controlled, randomized studies provides only a limited basis for estimating the incidence of adverse events because the studies involved a total of 62 patients exposed to a single 50 mcg intrathecal bolus. The following events occurred among the 62 patients receiving LIORESAL INTRATHECAL in two randomized, placebo-controlled trials involving cerebral palsy and head injury patients, respectively: agitation, constipation, somnolence, leukocytosis, nausea, vomiting, nystagmus, chills, urinary retention, and hypotonia.

Events Observed during the Pre-marketing Evaluation of LIORESAL INTRATHECAL — Adverse events associated with the use of LIORESAL INTRATHECAL reflect experience gained with a total of 211 U.S. patients with spasticity of cerebral origin, of whom 112 were pediatric patients (under age 16 at enrollment). They received LIORESAL INTRATHECAL for periods of one day (screening) (N=211) to 84 months (maintenance) (N=1). The usual screening bolus dose administered prior to pump implantation in these studies was 50-75 mcg. The maintenance dose ranged from 22 mcg to 1400 mcg per day. Doses used in this patient population for long term infusion are generally lower than those required for patients with spasticity of spinal cord origin.

Because of the open, uncontrolled nature of the experience, a causal linkage between events observed and the administration of LIORESAL INTRATHECAL cannot be reliably assessed in many cases. Nonetheless, many of the more commonly reported reactions—somnolence, dizziness, headache, nausea, hypotension, hypotonia and coma—appear clearly drug-related.

The most frequent (≥1%) adverse events reported during all clinical trials are shown in the following table. Nine patients discontinued long term treatment due to adverse events.

The more common (1% or more) adverse events reported in the prospectively followed 211 patients exposed to LIORESAL INTRATHECAL (baclofen injection) have been reported. In the total cohort, the following adverse events, not described in the table, and arranged in decreasing order of frequency, and classified by body system, were reported:

Nervous System: Akathisia, ataxia, confusion, depression, opisthotonos, amnesia, anxiety, hallucinations, hysteria, insomnia, nystagmus, personality disorder, reflexes decreased, and vasodilitation.

Digestive System: Dysphagia, fecal incontinence, gastrointestinal hemorrhage and tongue disorder.

Cardiovascular: Bradycardia.

Respiratory: Apnea, dyspnea and hyperventilation.

Urogenital: Abnormal ejaculation, kidney calculus, oliguria and vaginitis.

Skin and Appendages: Rash, sweating, alopecia, contact dermatitis and skin ulcer.

Special Senses: Abnormality of accommodation.

Body as a Whole: Death, fever, abdominal pain, carcinoma, malaise and hypothermia.

Hemic and Lymphatic System: Leukocytosis and petechial rash.

Postmarketing Experience:

The following adverse events have been reported during post-approval use of LIORESAL INTRATHECAL. Because these events are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency.

Musculoskeletal: The onset of scoliosis or worsening of a pre-existing scoliosis has been reported.
Urogenital: Sexual dysfunction in men and women, including decreased libido and orgasm dysfunction, have been reported. Erectile dysfunction in men has also been reported. Priapism has been reported following baclofen withdrawal.

Treatment Suggestions for Overdose:

There is no specific antidote for treating overdoses of LIORESAL INTRATHECAL (baclofen injection); however, the following steps should ordinarily be undertaken:

1. Residual LIORESAL INTRATHECAL solution should be removed from the pump as soon as possible.
2. Patients with respiratory depression should be intubated if necessary, until the drug is eliminated.

If lumbar puncture is not contraindicated, consideration should be given to withdrawing 30-40 mL of CSF to reduce CSF baclofen concentration.

Maintenance Therapy:

Spasticity of Spinal Cord Origin Patients: The clinical goal is to maintain muscle tone as close to normal as possible, and to minimize the frequency and severity of spasms to the extent possible, without inducing intolerable side effects. Very often, the maintenance dose needs to be adjusted during the first few months of therapy while patients adjust to changes in life style due to the alleviation of spasticity. During periodic refills of the pump, the daily dose may be increased by 10-40%, but no more than 40%, to maintain adequate symptom control. The daily dose may be reduced by 10-20% if patients experience side effects. Most patients require gradual increases in dose over time to maintain optimal response during chronic therapy. A sudden large requirement for dose escalation suggests a catheter complication (i.e., catheter kink or dislodgement).

Maintenance dosage for long term continuous infusion of LIORESAL INTRATHECAL (baclofen injection) has ranged from 12 mcg/day to 2003 mcg/day, with most patients adequately maintained on 300 micrograms to 800 micrograms per day. There is limited experience with daily doses greater than 1000 mcg/day. Determination of the optimal LIORESAL INTRATHECAL dose requires individual titration. The lowest dose with an optimal response should be used.

Spasticity of Cerebral Origin Patients: The clinical goal is to maintain muscle tone as close to normal as possible and to minimize the frequency and severity of spasms to the extent possible, without inducing intolerable side effects, or to titrate the dose to the desired degree of muscle tone for optimal functions. Very often the maintenance dose needs to be adjusted during the first few months of therapy while patients adjust to changes in life style due to the alleviation of spasticity. During periodic refills of the pump, the daily dose may be increased by 5-20%, but no more than 20%, to maintain adequate symptom control. The daily dose may be reduced by 10-20% if patients experience side effects. Many patients require gradual increases in dose over time to maintain optimal response during chronic therapy. A sudden large requirement for dose escalation suggests a catheter complication (i.e., catheter kink or dislodgement).

Maintenance dosage for long term continuous infusion of LIORESAL INTRATHECAL (baclofen injection) has ranged from 22 mcg/day to 1400 mcg/day, with most patients adequately maintained on 90 micrograms to 703 micrograms per day. In clinical trials, only 3 of 150 patients required daily doses greater than 1000 mcg/day.

Pediatric Patients: Use same dosing recommendations for patients with spasticity of cerebral origin. Pediatric patients under 12 years seemed to require a lower daily dose in clinical trials. Average daily dose for patients under 12 years was 274 mcg/day, with a range of 24 to 1199 mcg/day. Dosage requirement for pediatric patients over 12 years does not seem to be different from that of adult patients. Determination of the optimal LIORESAL INTRATHECAL dose requires individual titration. The lowest dose with an optimal response should be used.

Potential need for dose adjustments in chronic use : During long term treatment, approximately 5% (28/627) of patients become refractory to increasing doses. There is not sufficient experience to make firm recommendations for tolerance treatment; however, this “tolerance” has been treated on occasion, in hospital, by a “drug holiday” consisting of the gradual reduction of LIORESAL INTRATHECAL over a 2 to 4 week period and switching to alternative methods of spasticity management. After the “drug holiday,” LIORESAL INTRATHECAL may be restarted at the initial continuous infusion dose.

Stability

Parenteral drug products should be inspected for particulate matter and discoloration prior to administration, whenever solution and container permit.

Delivery Specifications

The specific concentration that should be used depends upon the total daily dose required as well as the delivery rate of the pump. LIORESAL INTRATHECAL may require dilution when used with certain implantable pumps. Please consult manufacturer's manual for specific recommendations.

Preparation Instruction:

Screening

Use the 1 mL screening ampule only (50 mcg/mL) for bolus injection into the subarachnoid space. For a 50 mcg bolus dose, use 1 mL of the screening ampule. Use 1.5 mL of 50 mcg/mL baclofen injection for a 75 mcg bolus dose. For the maximum screening dose of 100 mcg, use 2 mL of 50 mcg/mL baclofen injection (2 screening ampules).

Maintenance

For patients who require concentrations other than 500 mcg/mL or 2000 mcg/mL, LIORESAL INTRATHECAL must be diluted.

LIORESAL INTRATHECAL must be diluted with sterile preservative free Sodium Chloride for Injection, U.S.P.

Delivery Regimen:

LIORESAL INTRATHECAL is most often administered in a continuous infusion mode immediately following implant. For those patients implanted with programmable pumps who have achieved relatively satisfactory control on continuous infusion, further benefit may be attained using more complex schedules of LIORESAL INTRATHECAL delivery. For example, patients who have increased spasms at night may require a 20% increase in their hourly infusion rate. Changes in flow rate should be programmed to start two hours before the time of desired clinical effect.

Storage:

Does not require refrigeration.

Do not store above 86°F (30°C).

Do not freeze.

Do not heat sterilize.

Manufactured by Novartis Pharma Stein AG, Stein, Switzerland, for
Medtronic, Inc., Minneapolis, Minnesota 55432-5604 USA.

Lioresal® is a registered trademark of Saol
SynchroMed® is a registered trademark of Medtronic, Inc.

Medtronic, Inc.
710 Medtronic Parkway NE
Minneapolis, MN 55432-5604
USA
www.medtronic.com
Tel. 763-505-5000
Toll-free 1-800-328-0810
Fax 763-505-1000

Rev. 09/2016

Table of contents

Introduction

Package contents

Indications

Contraindications

Warnings

Precautions

Adverse events

Instructions for use
        Sterilization
        Preliminary procedures
        Emptying the SynchroMed pump
        Refilling the SynchroMed pump
        Programming the SynchroMed pump
        After the refill procedure

Reservoir rinse procedure
        Performing a reservoir rinse

Technical support

Emergency procedures
        Lioresal Intrathecal (baclofen injection) overdose
        Lioresal Intrathecal (baclofen injection) underdose/withdrawal
        Emergency procedure to empty pump reservoir

Special notice

Limited Warranty
        Medtronic® Neuromodulation MODEL 856X REFILL KIT LIMITED WARRANTY

Introduction

These instructions include only the procedure for refilling the pump reservoir with Lioresal Intrathecal (baclofen injection). Refer to the appropriate pump technical manual for implanting instructions.

Package contents

The Model 856X Refill Kit contains the following sterile components that are not made with natural rubber latex:

• 20-mL syringe
• Extension set with a clamp
• Template
• 0.22-micron filter
• Two 22-gauge noncoring needles
• Fenestrated drape
• Accessories (povidone iodine swabs, gauze pads, alcohol pads, gloves)

Indications

The Model 856X Refill Kit is intended for use in refilling Medtronic implantable programmable infusion pumps with the exception of Medtronic MiniMed infusion pumps.

Contraindications

Medtronic refill kits are contraindicated for all catheter access port procedures.

Warnings

Withdrawal - Abrupt discontinuation of intrathecal baclofen, regardless of the cause, has resulted in sequelae that include high fever, altered mental status, exaggerated rebound spasticity, and muscle rigidity, that in rare cases has advanced to rhabdomyolysis, multiple organ-system failure and death.

Prevention of abrupt discontinuation of intrathecal baclofen requires careful attention to programming and monitoring of the infusion system, refill scheduling and procedures, and pump alarms. Patients and caregivers should be advised of the importance of keeping scheduled refill visits and should be educated on the early symptoms of baclofen withdrawal. Special attention should be given to patients at apparent risk (e.g. spinal cord injuries at T-6 or above, communication difficulties, history of withdrawal symptoms from oral or intrathecal baclofen). Consult the technical manual of the implantable infusion system for additional postimplant clinician and patient information.

User instructions - Comply with all product instructions for initial preparation and filling, implantation, programming, refilling, and accessing the catheter access port (if present) of the pump. Failure to comply with all instructions can lead to technical errors or improper use of implanted infusion pumps and result in additional surgical procedures, a return of underlying symptoms, drug withdrawal symptoms, or a clinically significant or fatal drug underdose or overdose.

Implantation and system management - Implantation and ongoing system management must be performed by individuals trained in the operation and handling of the infusion system and must be in compliance with procedures described in the appropriate technical instructions. Inadequate training or failure to follow instructions can require surgical revision or replacement, and result in a clinically significant or fatal drug underdose or overdose.

Calculating catheter volume - Use the catheter length recorded at implant or catheter revision when calculating catheter volume. The actual implanted catheter length and catheter model number are required to accurately calculate catheter volume. A universal value does not exist that can be used as a substitute for this knowledge. An inaccurate catheter volume calculation can result in a clinically significant or fatal drug underdose or overdose.

Contrast medium (pumps with a catheter access port) - Do not inject any contrast medium into the pump reservoir. Injecting contrast medium into the pump reservoir can impair pump operation.

Refill - Patients must return to the clinic for refills at the prescribed times. Failure to return to the clinic for refills at the prescribed times can result in the actual flow rate of the pump being less than expected, resulting in a loss of or change in therapy, which may lead to a return of underlying symptoms, drug withdrawal symptoms, or a clinically significant or fatal drug underdose. Failure to return at the prescribed times can also damage the pump, requiring surgical replacement.

Refill kit components – Use the appropriate Medtronic refill kit during all refill procedures for Medtronic implantable infusion pumps. Using components other than Medtronic components or a kit other than the appropriate refill kit can damage Medtronic components, requiring surgical revision or replacement, and allow drug leakage into surrounding tissue, resulting in loss of or change in therapy, which may lead to a return of underlying symptoms, drug withdrawal symptoms, or a clinically significant or fatal drug underdose or overdose.

Injection error during a pump refill procedure - Be certain you are accessing the reservoir fill port when injecting fluids into an implanted pump. ALWAYS:

• identify the pump model and reservoir volume.
• identify the location of the reservoir fill port.
  • Avoid pocket fill, i.e. improper injection of medication into the subcutaneous tissue (see below)
  • Avoid inadvertent injection into the catheter access port (see below)
• use the instructions, noncoring needles, appropriate template edge, and other accessories provided in the appropriate kit.
• verify the location of the reservoir fill port during needle insertion according to the instructions provided AND using other medical procedures as appropriate.
• refer to the drug labeling for indications, contraindications, warnings, precautions, adverse events, and dosage and administration information.

Pocket fill is the improper injection of refill medication into the subcutaneous tissue, which includes the pump pocket. The injection of drug into the subcutaneous tissue can lead to an acute systemic overdose, which can be fatal. After a pocket fill, the pump reservoir will become empty sooner than anticipated, and this may cause underdose symptoms and/or baclofen withdrawal syndrome, which can be fatal. If it is suspected or known that all or part of the drug was injected into the pocket during the refill procedure, monitor the patient closely for signs and symptoms of overdose in an appropriate facility for a sufficient amount of time or until the symptoms have resolved. Refer to the refill kit manual or the Indications, Drug Stability, and Emergency Procedures for SynchroMed and IsoMed Implantable Infusion Systems Reference Manual for emergency procedures associated with drug underdose and overdose. Refer to the drug product information label for specific drug underdose and overdose symptoms and methods of management.

Inadvertent injection into the catheter access port may result in a clinically significant or fatal drug overdose. If it is suspected or known that all or part of the drug was injected into the catheter access port during the refill procedure, monitor the patient closely for signs and symptoms of overdose in an appropriate facility for a sufficient amount of time or until the symptoms have resolved. Refer to the catheter access port kit manual or the Indications, Drug Stability, and Emergency Procedures for SynchroMed and IsoMed Implantable Infusion Systems Reference Manual for emergency procedures associated with drug overdose. Refer to the drug labeling for specific drug overdose symptoms and methods of management.

Changing drug or decreasing drug concentrations - Rinse the reservoir twice between solutions when changing drug or decreasing drug concentrations in the pump reservoir. A significant amount of drug may be present in the pump reservoir after emptying the pump. This residual volume cannot be removed by emptying the pump. Rinsing the reservoir between solutions minimizes the amount of drug in this residual volume but does not eliminate it. Failure to account for residual drug in the pump reservoir can result in a concentration that is different than intended and a clinically significant or fatal drug underdose or overdose. Program a bridge bolus after rinsing the reservoir twice. The bridge bolus advances the remaining old drug (the drug left in the pump tubing, catheter access port, and catheter after emptying and refilling the pump) to the catheter tip at the prior flow rate.

Refer to "Performing a reservoir rinse" on page 18 of this manual. Refer to the programming guide for bridge bolus procedures.

Connections - Firmly secure all connections. Failure to secure connections can allow drug to leak onto the surrounding skin and may result in inadequate therapy or infection.

Reservoir fill port injections - Do not use excessive force when accessing the reservoir fill port. Excessive force can result in damage to the needle or pump requiring surgical revision or replacement, and leakage into surrounding tissue, resulting in loss of or change in therapy, which may lead to a return of underlying symptoms, drug withdrawal symptoms, or a clinically significant or fatal drug underdose or overdose.

Intrathecal therapy - For intrathecal therapy, use ONLY a preservative-free sterile solution indicated for intrathecal use. Nonindicated fluids containing preservatives or endotoxins can be neurotoxic in intrathecal applications. Using nonindicated fluids can result in adverse events including, but not limited to, extreme pain, cramps, seizures, and death.

Drug information - Refer to the drug labeling for indications, contraindications, warnings, precautions, dosage and administration information, and screening procedures. Refer to the drug labeling for specific drug underdose or overdose symptoms and methods of management. Failure to refer to the drug labeling can result in inappropriate patient selection and management, inadequate therapy, intolerable side effects, or a clinically significant or fatal drug underdose or overdose. Consider the possibility of a drug error if the patient experiences unusual side effects. Failure to do so can result in misdiagnosis of patient symptoms.

Mixing drugs - The effects that drug mixtures have on pump operation are unknown. Drugs can precipitate when mixed. These precipitates can inhibit pump flow or block the catheter, resulting in loss of therapy or a clinically significant or fatal drug underdose.

Drug interaction and side effects - Inform patients of the appropriate warnings and precautions regarding drug interactions, potential side effects, and signs and symptoms that require medical attention, including prodromal signs and symptoms of inflammatory mass. Failure to recognize the signs and symptoms and to seek appropriate medical intervention can result in serious patient injury or death.

Drug overdose symptoms and management - Refer to the emergency procedures included at the end of this manual and the drug labeling for specific drug overdose symptoms and methods of management.

Drug underdose/overdose - Inform patients and caregivers of the signs and symptoms of a drug underdose and overdose. Inform patients and caregivers:

• to be aware and report any unusual signs or symptoms at anytime during or after a refill or catheter access port procedure.
• to be alert for any burning sensations in the area of the pump pocket during their refill or catheter access port procedure.
• to especially watch for signs of underdose and overdose.
• to stay alert for signs or symptoms that may indicate changes to their prescribed drug concentration or programmed dose.
• to seek emergency assistance as necessary. Refer to the refill kit or catheter access port kit manual or the Indications, Drug Stability and Emergency Procedures for SynchroMed and IsoMed Implantable Infusion Systems Reference Manual for emergency procedures associated with drug underdose and overdose.

Failure to recognize these signs and symptoms and to seek appropriate medical intervention can result in serious patient injury or death.

Patient travel - Patients should notify their clinicians of any travel plans. Clinicians need this information to coordinate patient care and pump refills and help prevent a loss of or change in therapy, which may lead to a return of underlying symptoms, drug withdrawal symptoms, or a clinically significant or fatal drug underdose.

Precautions

Compatibility, all components - Follow these guidelines when selecting system components:

• Medtronic components: For proper therapy, use only components that are compatible with the appropriate indication.
• Non-Medtronic components: No claims of safety, efficacy, or compatibility are made with regard to the use of non-Medtronic components with Medtronic components. Refer to the non-Medtronic documentation for information.

Component packaging - Before shipment the components in the sterile package were sterilized by the process indicated on the package label. Do not use or implant a component if the following circumstances have occurred:

• The storage package or sterile seal has been pierced or altered because component sterility cannot be guaranteed and infection may occur.
• The component shows signs of damage because the component may not function properly.
• The use-by date has expired because component sterility cannot be guaranteed and infection may occur; also, device battery longevity may be reduced and may require early replacement.

Storage temperature: kits and accessories - Do not store or transport the kit device components or accessories above 57 °C (135 °F) or below –34 °C (–30 °F). Temperatures outside this range can damage device components.

Aseptic technique - Use strict aseptic technique when accessing the reservoir fill port or the catheter access port of an implanted pump. Failure to use aseptic technique can contaminate fluids or tissues and result in local or systemic infection.

Infection - Use extreme caution when accessing the reservoir fill port or catheter access port of the implanted pump if local or systemic infection is suspected. Avoid contaminating the system or further spreading the infection. Local or systemic infection may require pump revision or removal.

Therapy discontinuance - If therapy is discontinued for an extended period, fill the pump reservoir with preservative-free saline. Program the pump to infuse at the minimum flow rate. Refill the pump as needed to ensure the pump always contains fluid in the reservoir and fluid pathway. Stopping the pump for extended periods or allowing the pump reservoir to empty completely can damage the system and require surgical replacement.

Single use only - Do not reuse any component. Components are intended for single use only. Reusing components can result in inadequate therapy and an increased risk of infection.

Reservoir valve activation - Do not prematurely activate the pump reservoir valve. Activation of the pump reservoir valve seals the pump reservoir valve closed. Unusual resistance or the inability to inject the entire fill volume may indicate activation of the pump reservoir valve. If the valve closes, a portion of the reservoir contents must be delivered or removed before filling can be completed, and procedural delays can occur. To prevent activation of the pump reservoir valve during emptying and filling procedures:

• completely aspirate all contents of the pump reservoir before filling;
• do not allow air into the pump reservoir through an open needle in the septum or an unclamped extension; and
• do not exceed the maximum reservoir volume indicated in the pump labeling.

Adverse events

The adverse events associated with the use of this device may include, but may not be limited to, the following:

• Meningitis
• Infection
• Reservoir contamination
• Overpressurization of the reservoir
• Injection into pocket or subcutaneous tissue
• Activation of reservoir valve

Instructions for use

Become thoroughly familiar with all product literature before using this refill kit.

Reservoir rinse procedure

Technical support

A toll-free technical support service is available 24 hours a day for clinicians managing patients with Medtronic implantable infusion pumps. Telephone Customer Service at: 1-800-707-0933.

Emergency procedures

Special notice

The Medtronic 856X Refill Kit is designed to be used for refilling Medtronic implantable programmable infusion pumps with the exception of Medtronic MiniMed infusion pumps. Medtronic cannot warrant or guarantee the refill kit because, despite the exercise of all due care in design, component selection, manufacture, and testing prior to sale, the components of the refill kit may be easily damaged before or during use by improper handling or other intervening acts.