Usual Adult Dose for Chronic Pain

Initial dose: 0.1 mcg/hr (2.4 mcg/day) via intrathecal device

• Titrate dose in increments of up to 2.4 mcg/day at intervals of no more than 2 to 3 times per week based on analgesic response and adverse events; adjust pump infusion flow rate as required to achieve new dosing

Maximum dose: 19.2 mcg/day (0.8 mcg/hr)

Comments:

• Administration should be under the direction of a physician experienced in the technique of intrathecal administration and who is familiar with the drug and device labeling.
• This drug is intended for intrathecal delivery using the Medtronic SynchroMed(R) II Infusion System and CADD-Micro Ambulatory Infusion Pump; refer to manufacturer's manual for specific instructions and precautions for programming the microinfusion device and/or refilling the reservoir.

Use: For the management of severe chronic pain in adult patients for whom intrathecal therapy is warranted, and who are intolerant of, or refractory to other treatment, such as systemic analgesics, adjunctive therapies, or intrathecal morphine.

Renal Dose Adjustments

No adjustment recommended

Liver Dose Adjustments

No adjustment recommended

Precautions

US BOXED WARNINGS: NEUROPSYCHIATRIC ADVERSE REACTIONS:

• This drug is contraindicated in patients with a preexisting history of psychosis. Severe psychiatric symptoms and neurological impairment may occur during treatment. Monitor all patients frequently for evidence of cognitive impairment, hallucinations, or changes in mood or consciousness. Discontinue this drug in the event of serious neurological or psychiatric signs or symptoms.

CONTRAINDICATIONS:

• Hypersensitivity to active substance or any product excipients
• Concomitant treatment or medical condition that would render intrathecal administration hazardous such as presence of infection at the microinfusion injection site, uncontrolled bleeding diathesis, and spinal canal obstruction that impairs circulation of CSF
• Preexisting history of psychosis

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• For intrathecal (IT) administration via Medtronic Synchro Med(R) System and CADD-Micro Ambulatory Infusion Pump only; Not for IV administration
• Administration should be under the direction of a physician experienced in the technique of intrathecal administration and familiar with this drug and device labeling

Storage requirements:

• During transit: Refrigerate and protect from light
• Store refrigerated 2C to 8C (36F to 46F); do not freeze; protect from light
• Once solution is prepared for infusion, refrigerate and begin infusion within 24 hours

Reconstitution/preparation techniques:

• May use undiluted or diluted; do not use saline solutions containing preservatives to dilute solution
• Refer to Product Labeling for specific preparation and stability information
• Refer to manufacturer's manuals for specific instructions and precautions for using Medtronic SynchroMed II Infusion System

General:

• During clinical trials, a total of 1254 patients received this drug as a continuous infusion; mean treatment duration was 193 days (14% were treated for at least 1 year); average final dose was 17.6 mcg/day.
• This drug is not an opiate and cannot prevent or relieve symptoms associated with opiate withdrawal.
• Meningitis can occur due to inadvertent contamination of the microinfusion device; vigilance for signs and symptoms of meningitis is necessary.

Monitoring:

• Periodically monitor serum creatine kinase (CK) levels; e.g., every other week for the 1st month, then monthly; increase monitoring if neuromuscular symptoms develop or a reduction in physical activity occurs
• Monitor for cognitive and neuropsychiatric adverse events
• Monitor for meningitis and other infections
• Monitor for reduced level of consciousness

Patient advice:

• Patients should be advised that severe psychiatric symptoms and neurological impairment may occur; changes in mental status, level of alertness/consciousness, mood including depression or suicidal thoughts should be reported to healthcare professional promptly.
• Patients should be advised to avoid hazardous activities such as driving as this drug is associated with cognitive impairment and decreased alertness/unresponsiveness.
• Patients should discuss all concomitant medications, especially CNS-depressant drugs, with their healthcare provider.
• Patients should be instructed to contact their healthcare provider if they experience new or worsening muscle pain, soreness, and/or weakness with or without darkened urine.
• Patients should be instructed to report development of serious skin reactions such as bullous dermatitis, skin ulcers, and skin exfoliation.