FDA label 81c55696-a04a-49a4-89e3-54f8b080295e

INFUMORPH IS NOT RECOMMENDED FOR SINGLE-DOSE INTRAVENOUS, INTRAMUSCULAR OR SUBCUTANEOUS ADMINISTRATION DUE TO THE VERY LARGE AMOUNT OF MORPHINE IN THE AMPUL AND THE ASSOCIATED RISK OF OVERDOSAGE.

BECAUSE OF THE RISK OF SEVERE ADVERSE EFFECTS, PATIENTS MUST BE OBSERVED IN A FULLY EQUIPPED AND STAFFED ENVIRONMENT FOR AT LEAST 24 HOURS AFTER THE INITIAL (SINGLE) TEST DOSE AND, AS APPROPRIATE, FOR THE FIRST SEVERAL DAYS AFTER CATHETER IMPLANTATION.

IMPROPER OR ERRONEOUS SUBSTITUTION OF INFUMORPH 200 or 500 (10 or 25 mg/mL, respectively) FOR REGULAR DURAMORPH (0.5 or 1 mg/mL) IS LIKELY TO RESULT IN SERIOUS OVERDOSAGE, LEADING TO SEIZURES, RESPIRATORY DEPRESSION AND, POSSIBLY, FATAL OUTCOME.

NALOXONE INJECTION AND RESUSCITATIVE EQUIPMENT SHOULD BE IMMEDIATELY AVAILABLE FOR USE IN CASE OF LIFE-THREATENING OR INTOLERABLE SIDE EFFECTS AND WHENEVER INFUMORPH THERAPY IS BEING INITIATED, THE RESERVOIR IS BEING REFILLED OR ANY MANIPULATION OF THE RESERVOIR SYSTEM IS TAKING PLACE.

WARNINGS Morphine sulfate may be habit forming. Overdoses may cause respiratory depression, coma, and death. THIS PRODUCT WAS DEVELOPED FOR USE (AFTER APPROPRIATE DILUTION, IF NECESSARY) IN CONTINUOUS MICROINFUSION DEVICES FOR INTRATHECAL OR EPIDURAL INFUSION OF NARCOTICS TO CONTROL SEVERE CANCER PAIN. CHRONIC NEURAXIAL OPIOID ANALGESIA IS APPROPRIATE ONLY WHEN LESS INVASIVE MEANS OF CONTROLLING PAIN HAVE FAILED AND SHOULD ONLY BE UNDERTAKEN BY THOSE WHO ARE EXPERIENCED IN APPLYING THIS TREATMENT IN A SETTING WHERE ITS COMPLICATIONS CAN BE ADEQUATELY MANAGED. BECAUSE OF THE RISK OF SEVERE ADVERSE EFFECTS, PATIENTS MUST BE OBSERVED IN A FULLY EQUIPPED AND STAFFED ENVIRONMENT FOR AT LEAST 24 HOURS AFTER THE INITIAL (SINGLE) TEST DOSE AND, AS APPROPRIATE, FOR THE FIRST SEVERAL DAYS AFTER CATHETER IMPLANTATION. THE FACILITY MUST BE EQUIPPED TO RESUSCITATE PATIENTS WITH SEVERE OPIATE OVERDOSAGE, AND THE PERSONNEL MUST BE FAMILIAR WITH THE USE AND LIMITATIONS OF SPECIFIC NARCOTIC ANTAGONISTS (NALOXONE, NALTREXONE) IN SUCH CASES. RESERVOIR FILLING MUST BE PERFORMED BY FULLY TRAINED AND QUALIFIED PERSONNEL, FOLLOWING THE DIRECTIONS PROVIDED BY THE DEVICE MANUFACTURER. CARE SHOULD BE TAKEN IN SELECTING THE PROPER REFILL FREQUENCY TO PREVENT DEPLETION OF THE RESERVOIR, WHICH WOULD RESULT IN EXACERBATION OF SEVERE PAIN AND/OR REFLUX OF CSF INTO SOME DEVICES. STRICT ASEPTIC TECHNIQUE IN FILLING IS REQUIRED TO AVOID BACTERIAL CONTAMINATION AND SERIOUS INFECTION. EXTREME CARE MUST BE TAKEN TO ENSURE THAT THE NEEDLE IS PROPERLY IN THE FILLING PORT OF THE DEVICE BEFORE ATTEMPTING TO REFILL THE RESERVOIR. INJECTING THE SOLUTION INTO THE TISSUE AROUND THE DEVICE OR (IN THE CASE OF DEVICES THAT HAVE MORE THAN ONE PORT) ATTEMPTING TO INJECT THE REFILL DOSE INTO THE DIRECT INJECTION PORT WILL RESULT IN A LARGE, CLINICALLY SIGNIFICANT, OVERDOSAGE TO THE PATIENT. A PERIOD OF OBSERVATION APPROPRIATE TO THE CLINICAL SITUATION SHOULD FOLLOW EACH REFILL OR MANIPULATION OF THE DRUG RESERVOIR. BEFORE DISCHARGE, THE PATIENT AND ATTENDANT(S) SHOULD RECEIVE INSTRUCTION IN THE PROPER HOME CARE OF THE DEVICE AND INSERTION SITE AND IN THE RECOGNITION AND PRACTICAL TREATMENT OF AN OVERDOSE OF NEURAXIAL MORPHINE. Inflammatory Masses INFLAMMATORY MASSES SUCH AS GRANULOMAS, SOME OF WHICH HAVE RESULTED IN SERIOUS NEUROLOGIC IMPAIRMENT INCLUDING PARALYSIS, HAVE BEEN REPORTED TO OCCUR IN PATIENTS RECEIVING CONTINUOUS INFUSION OF OPIOID ANALGESICS INCLUDING INFUMORPH VIA INDWELLING INTRATHECAL CATHETER. PATIENTS RECEIVING CONTINUOUS INFUSION OF INFUMORPH VIA INDWELLING INTRATHECAL CATHETER SHOULD BE CAREFULLY MONITORED FOR NEW NEUROLOGIC SIGNS OR SYMPTOMS. FURTHER ASSESSMENT OR INTERVENTION SHOULD BE BASED ON THE CLINICAL CONDITION OF THE INDIVIDUAL PATIENT. Tolerance and Myoclonic Activity PATIENTS SOMETIMES MANIFEST UNUSUAL ACCELERATION OF NEURAXIAL MORPHINE REQUIREMENTS, WHICH MAY CAUSE CONCERN REGARDING SYSTEMIC ABSORPTION AND THE HAZARDS OF LARGE DOSES; THESE PATIENTS MAY BENEFIT FROM HOSPITALIZATION AND DETOXIFICATION. TWO CASES OF MYOCLONIC-LIKE SPASM OF THE LOWER EXTREMITIES HAVE BEEN REPORTED IN PATIENTS RECEIVING MORE THAN 20 MG/DAY OF INTRATHECAL MORPHINE. AFTER DETOXIFICATION, IT MIGHT BE POSSIBLE TO RESUME TREATMENT AT LOWER DOSES, AND SOME PATIENTS HAVE BEEN SUCCESSFULLY CHANGED FROM CONTINUOUS EPIDURAL MORPHINE TO CONTINUOUS INTRATHECAL MORPHINE. REPEAT DETOXIFICATION MAY BE INDICATED AT A LATER DATE. THE UPPER DAILY DOSAGE LIMIT FOR EACH PATIENT DURING CONTINUING TREATMENT MUST BE INDIVIDUALIZED.

ADVERSE REACTIONS IMPROPER OR ERRONEOUS SUBSTITUTION OF INFUMORPH 200 or 500 (10 or 25 mg/mL, respectively) FOR REGULAR DURAMORPH (0.5 or 1 mg/mL) IS LIKELY TO RESULT IN SERIOUS OVERDOSAGE, LEADING TO SEIZURES, RESPIRATORY DEPRESSION AND, POSSIBLY, FATAL OUTCOME. The most serious adverse experiences encountered during continuous intrathecal or epidural infusion of INFUMORPH are respiratory depression, myoclonus, and formation of inflammatory masses. 1. Single-dose neuraxial administration may result in acute or delayed respiratory depression for periods at least as long as 24 hours. Severe respiratory depression, potentially life-threatening, can result from technical errors during refill, e.g., injection of INFUMORPH outside the filling port, unintentional injection into the direct bypass-dosing port featured on some devices or local infiltration. 2. Tolerance and myoclonus : See WARNINGS for discussion of these and related hazards. 3. Inflammatory masses : See WARNINGS . While low doses of intravenously administered morphine have little effect on cardiovascular stability, high doses are excitatory, resulting from sympathetic hyperactivity and increase in circulating catecholamines. Excitation of the central nervous system, resulting in convulsions , may accompany high doses of morphine given intravenously. Dysphoric reactions may occur after any size dose and toxic psychoses have been reported. Pruritus Single-dose epidural or intrathecal administration is accompanied by a high incidence of pruritus that is dose-related but not confined to the site of administration. Pruritus, following continuous infusion of epidural or intrathecal morphine, is occasionally reported in the literature; these reactions are poorly understood as to their cause. Urinary Retention Urinary retention, which may persist 10 to 20 hours following single epidural or intrathecal administration, is a frequent side effect and must be anticipated primarily in male patients, with a somewhat lower incidence in females. Also frequently reported in the literature is the occurrence of urinary retention during the first several days of hospitalization for the initiation of continuous intrathecal or epidural morphine therapy. Patients who develop urinary retention have responded to cholinomimetic treatment and/or judicious use of catheters (see PRECAUTIONS ). Constipation Constipation is frequently encountered during continuous infusion of morphine; this can usually be managed by conventional therapy. Headache Lumbar puncture-type headache is encountered in a significant minority of cases for several days following intrathecal catheter implantation; this, generally, responds to bed rest and/or other conventional therapy. Peripheral Edema There are several reports of peripheral edema, including unexplained genital swelling in male patients, following infusion-device implant surgery. Other Other adverse experiences reported following morphine therapy include — Dizziness, euphoria, anxiety, depression of cough reflex, interference with thermal regulation and oliguria . Evidence of histamine release such as urticaria, wheals and/or local tissue irritation may occur. Pruritus, nausea/vomiting and urinary retention, if associated with continuous infusion therapy, may respond to intravenous administration of a low dose of naloxone (0.2 mg). The risks of using narcotic antagonists in patients chronically receiving narcotic therapy should be considered. NALOXONE INJECTION AND RESUSCITATIVE EQUIPMENT SHOULD BE IMMEDIATELY AVAILABLE FOR USE IN CASE OF LIFE-THREATENING OR INTOLERABLE SIDE EFFECTS AND WHENEVER INFUMORPH THERAPY IS BEING INITIATED, THE RESERVOIR IS BEING REFILLED OR ANY MANIPULATION OF THE RESERVOIR SYSTEM IS TAKING PLACE.