INDICATIONS
EXTRANEAL (ICODEXTRIN PERITONEAL DIALYSIS SOLUTION) IS INDICATED FOR A SINGLE DAILY EXCHANGE FOR THE LONG (8- TO 16- HOUR) DWELL DURING CONTINUOUS AMBULATORY PERITONEAL DIALYSIS (CAPD) OR AUTOMATED PERITONEAL DIALYSIS (APD) FOR THE MANAGEMENT OF END-STAGE RENAL DISEASE. EXTRANEAL (ICODEXTRIN PERITONEAL DIALYSIS SOLUTION) IS ALSO INDICATED TO IMPROVE (COMPARED TO 4.25% DEXTROSE) LONG-DWELL ULTRAFILTRATION AND CLEARANCE OF CREATININE AND UREA NITROGEN IN PATIENTS WITH HIGH AVERAGE OR GREATER TRANSPORT CHARACTERISTICS, AS DEFINED USING THE PERITONEAL EQUILIBRATION TEST (PET) (SEE CLINICAL PHARMACOLOGY, CLINICAL STUDIES).
HOW SUPPLIED
EXTRANEAL (ICODEXTRIN) PERITONEAL DIALYSIS SOLUTION IS AVAILABLE IN THE FOLLOWING CONTAINERS AND FILL VOLUMES:
CONTAINER FILL VOLUME NDC
ULTRABAG 1.5 L NDC 094 1-0679-51
ULTRABAG 2.0 L NDC 0941-0679-52
ULTRABAG 2.5 L NDC 0941-0679-53
AMBU-FLEX III 1.5 L NDC 0941-0679-45
AMBU-FLEX III 2.0 L NDC 0941-0679-47
AMBU-FLEX III 2.5 L NDC 0941-0679-48
AMBU-FLEX II 2.0 L NDC 0941-0679-06
AMBU-FLEX II 2.5 L NDC 0941-0679-05
EACH 100 ML OF EXTRANEAL CONTAINS 7.5 GRAMS OF ICODEXTRIN IN AN ELECTROLYTE SOLUTION WITH 40 MEQ/L LACTATE.
STORE AT 20-25°C (68-77°F). EXCURSIONS PERMITTED TO 15-30°C (59-86°F) [SEE USP CONTROLLED ROOM TEMPERATURE]. STORE IN MOISTURE BARRIER OVERWRAP IN CARTON UNTIL READY TO USE. PROTECT FROM FREEZING.
BAXTER HEALTHCARE CORPORATION, DEERFIELD, IL 60015 USA. REVISED: NOV 2010
DOSAGE AND ADMINISTRATION
EXTRANEAL (ICODEXTRIN PERITONEAL DIALYSIS SOLUTION) IS INTENDED FOR INTRAPERITONEAL ADMINISTRATION ONLY. IT SHOULD BE ADMINISTERED ONLY AS A SINGLE DAILY EXCHANGE FOR THE LONG DWELL IN CONTINUOUS AMBULATORY PERITONEAL DIALYSIS OR AUTOMATED PERITONEAL DIALYSIS. THE RECOMMENDED DWELL TIME IS 8- TO 16- HOURS.
NOT FOR INTRAVENOUS INJECTION.
PATIENTS SHOULD BE CAREFULLY MONITORED TO AVOID UNDER- OR OVER-HYDRATION. AN ACCURATE FLUID BALANCE RECORD MUST BE KEPT AND THE PATIENT'S BODY WEIGHT MONITORED TO AVOID POTENTIALLY SEVERE CONSEQUENCES INCLUDING CONGESTIVE HEART FAILURE, VOLUME DEPLETION, AND HYPOVOLEMIC SHOCK.
ASEPTIC TECHNIQUE SHOULD BE USED THROUGHOUT THE PERITONEAL DIALYSIS PROCEDURE.
TO REDUCE POSSIBLE DISCOMFORT DURING ADMINISTRATION, SOLUTIONS MAY BE WARMED PRIOR TO USE (SEE DIRECTIONS FOR USE).
EXTRANEAL (ICODEXTRIN PERITONEAL DIALYSIS SOLUTION) SHOULD BE ADMINISTERED OVER A PERIOD OF 10-20 MINUTES AT A RATE THAT IS COMFORTABLE FOR THE PATIENT.
DO NOT USE EXTRANEAL (ICODEXTRIN PERITONEAL DIALYSIS SOLUTION) IF IT IS CLOUDY OR DISCOLORED, IF IT CONTAINS PARTICULATE MATTER, OR IF THE CONTAINER IS LEAKY.
FOLLOWING USE, THE DRAINED FLUID SHOULD BE INSPECTED FOR THE PRESENCE OF FIBRIN OR CLOUDINESS, WHICH MAY INDICATE THE PRESENCE OF PERITONITIS.
FOR SINGLE USE ONLY. DISCARD UNUSED PORTION.
ADDITION OF POTASSIUM
POTASSIUM IS OMITTED FROM EXTRANEAL (ICODEXTRIN PERITONEAL DIALYSIS SOLUTION) SOLUTIONS BECAUSE DIALYSIS MAY BE PERFORMED TO CORRECT HYPERKALEMIA. IN SITUATIONS WHERE THERE IS A NORMAL SERUM POTASSIUM LEVEL OR HYPOKALEMIA, THE ADDITION OF POTASSIUM CHLORIDE (UP TO A CONCENTRATION OF 4 MEQ/L) MAY BE INDICATED TO PREVENT SEVERE HYPOKALEMIA. THE DECISION TO ADD POTASSIUM CHLORIDE SHOULD BE MADE BY THE PHYSICIAN AFTER CAREFUL EVALUATION OF SERUM POTASSIUM.
ADDITION OF INSULIN
ADDITION OF INSULIN TO EXTRANEAL (ICODEXTRIN PERITONEAL DIALYSIS SOLUTION) WAS EVALUATED IN 6 INSULIN-DEPENDENT DIABETIC PATIENTS UNDERGOING CAPD FOR END STAGE RENAL DISEASE. NO INTERFERENCE OF EXTRANEAL (ICODEXTRIN PERITONEAL DIALYSIS SOLUTION) WITH INSULIN ABSORPTION FROM THE PERITONEAL CAVITY OR WITH INSULIN'S ABILITY TO CONTROL BLOOD GLUCOSE WAS OBSERVED (SEE DRUG/LABORATORY TEST INTERACTIONS). APPROPRIATE MONITORING OF BLOOD GLUCOSE SHOULD BE PERFORMED WHEN INITIATING EXTRANEAL (ICODEXTRIN PERITONEAL DIALYSIS SOLUTION) IN DIABETIC PATIENTS AND INSULIN DOSAGE ADJUSTED IF NEEDED (SEE PRECAUTIONS).
ADDITION OFHEPARIN
NO HUMAN DRUG INTERACTION STUDIES WITH HEPARIN WERE CONDUCTED. IN VITRO STUDIES DEMONSTRATED NO EVIDENCE OF INCOMPATIBILITY OF HEPARIN WITH EXTRANEAL (ICODEXTRIN PERITONEAL DIALYSIS SOLUTION) .
ADDITION OF ANTIBIOTICS
NO FORMAL CLINICAL DRUG INTERACTION STUDIES HAVE BEEN PERFORMED. IN VITRO COMPATIBILITY STUDIES WITH EXTRANEAL (ICODEXTRIN) AND THE FOLLOWING ANTIBIOTICS HAVE DEMONSTRATED NO EFFECTS WITH REGARD TO MINIMUM INHIBITORY CONCENTRATION (MIC): VANCOMYCIN, CEFAZOLIN, AMPICILLIN, AMPICILLIN/FLUCOXACILLIN, CEFTAZIDIME, GENTAMICIN, AND AMPHOTERICIN. HOWEVER, AMINOGLYCOSIDES SHOULD NOT BE MIXED WITH PENICILLINS DUE TO CHEMICAL INCOMPATIBILITY.
PATIENTS UNDERGOING PERITONEAL DIALYSIS SHOULD BE UNDER CAREFUL SUPERVISION OF A PHYSICIAN EXPERIENCED IN THE TREATMENT OF END-STAGE RENAL DISEASE WITH PERITONEAL DIALYSIS. IT IS RECOMMENDED THAT PATIENTS BEING PLACED ON PERITONEAL DIALYSIS SHOULD BE APPROPRIATELY TRAINED IN A PROGRAM THAT IS UNDER SUPERVISION OF A PHYSICIAN.
DIRECTIONS FOR USE
FOR COMPLETE CAPD AND APD SYSTEM PREPARATION, SEE DIRECTIONS ACCOMPANYING ANCILLARY EQUIPMENT.
ASEPTIC TECHNIQUE SHOULD BE USED.
WARMING
FOR PATIENT COMFORT, EXTRANEAL (ICODEXTRIN PERITONEAL DIALYSIS SOLUTION) L CAN BE WARMED TO 37°C (98°F). ONLY DRY HEAT SHOULD BE USED. IT IS BEST TO WARM SOLUTIONS WITHIN THE OVERWRAP USING A HEATING PAD. DO NOT IMMERSE EXTRANEAL (ICODEXTRIN PERITONEAL DIALYSIS SOLUTION) IN WATER FOR WARMING. DO NOT USE A MICROWAVE OVEN TO WARM EXTRANEAL (ICODEXTRIN PERITONEAL DIALYSIS SOLUTION) . HEATING ABOVE 40°C (104°F) MAY BE DETRIMENTAL TO THE SOLUTION.
TO OPEN
TO OPEN, TEAR THE OVERWRAP DOWN AT THE SLIT AND REMOVE THE SOLUTION CONTAINER. SOME OPACITY OF THE PLASTIC, DUE TO MOISTURE ABSORPTION DURING THE STERILIZATION PROCESS, MAY BE OBSERVED. THIS DOES NOT AFFECT THE SOLUTION QUALITY OR SAFETY AND MAY OFTEN LEAVE A SLIGHT AMOUNT OF MOISTURE WITHIN THE OVERWRAP.
INSPECT FOR CONTAINER INTEGRITY
INSPECT THE CONTAINER FOR SIGNS OF LEAKAGE AND CHECK FOR MINUTE LEAKS BY SQUEEZING THE CONTAINER FIRMLY.
ADDING MEDICATIONS
SOME DRUG ADDITIVES MAY BE INCOMPATIBLE WITH EXTRANEAL (ICODEXTRIN PERITONEAL DIALYSIS SOLUTION) . SEE DOSAGE AND ADMINISTRATION SECTION FOR ADDITIONAL INFORMATION. IF THE RE-SEALABLE RUBBER PLUG ON THE MEDICATION PORT IS MISSING OR PARTLY REMOVED, DO NOT USE THE PRODUCT IF MEDICATION IS TO BE ADDED.
1. PUT ON MASK. CLEAN AND/OR DISINFECT HANDS.
2. PREPARE MEDICATION PORT SITE USING ASEPTIC TECHNIQUE.
3. USING A SYRINGE WITH A 1-INCH LONG, 25- TO 19-GAUGE NEEDLE, PUNCTURE THE MEDICATION PORT AND INJECT ADDITIVE.
4. REPOSITION CONTAINER WITH CONTAINER PORTS UP AND EVACUATE MEDICATION PORT BY SQUEEZING AND TAPPING IT.
5. MIX SOLUTION AND ADDITIVE THOROUGHLY.
PREPARATION FOR ADMINISTRATION
1. PUT ON MASK. CLEAN AND/OR DISINFECT HANDS.
2. PLACE EXTRANEAL (ICODEXTRIN PERITONEAL DIALYSIS SOLUTION) ON WORK SURFACE.
3. REMOVE PULL RING FROM CONNECTOR OF SOLUTION CONTAINER. IF CONTINUOUS FLUID FLOW FROM CONNECTOR IS OBSERVED, DISCARD SOLUTION CONTAINER.
4. REMOVE TIP PROTECTOR FROM TUBING SET AND IMMEDIATELY ATTACH TO CONNECTOR OF SOLUTION CONTAINER.
5. CONTINUE WITH THERAPY SET-UP AS INSTRUCTED IN USER MANUAL OR DIRECTIONS ACCOMPANYING TUBING SETS.
6. UPON COMPLETION OF THERAPY, DISCARD ANY UNUSED PORTION.
SIDE EFFECTS
CLINICAL TRIALS
BECAUSE CLINICAL TRIALS ARE CONDUCTED UNDER WIDELY VARYING CONDITIONS, ADVERSE REACTION RATES OBSERVED IN CLINICAL TRIALS OF A DRUG CANNOT BE COMPARED TO RATES IN THE CLINICAL TRIALS OF ANOTHER DRUG AND MAY NOT REFLECT THE RATES OBSERVED IN PRACTICE. THE ADVERSE REACTION INFORMATION FROM CLINICAL TRIALS DOES, HOWEVER, PROVIDE A BASIS FOR IDENTIFYING THE ADVERSE EVENTS THAT APPEAR TO BE RELATED TO DRUG USE AND FOR APPROXIMATING RATES.
EXTRANEAL (ICODEXTRIN PERITONEAL DIALYSIS SOLUTION) WAS ORIGINALLY STUDIED IN CONTROLLED CLINICAL TRIALS OF 493 PATIENTS WITH END-STAGE RENAL DISEASE WHO RECEIVED A SINGLE DAILY EXCHANGE OF EXTRANEAL (ICODEXTRIN PERITONEAL DIALYSIS SOLUTION) FOR THE LONG DWELL (8-TO 16- HOURS). THERE WERE 215 PATIENTS EXPOSED FOR AT LEAST 6 MONTHS AND 155 PATIENTS EXPOSED FOR AT LEAST ONE YEAR. THE POPULATION WAS 18-83 YEARS OF AGE, 56% MALE AND 44% FEMALE, 73% CAUCASIAN, 18% BLACK, 4% ASIAN, 3% HISPANIC, AND IT INCLUDED PATIENTS WITH THE FOLLOWING COMORBID CONDITIONS: 27% DIABETES, 49% HYPERTENSION AND 23% HYPERTENSIVE NEPHROPATHY.
RASH WAS THE MOST FREQUENTLY OCCURRING EXTRANEAL (ICODEXTRIN PERITONEAL DIALYSIS SOLUTION) -RELATED ADVERSE EVENT (5.5%, EXTRANEAL (ICODEXTRIN PERITONEAL DIALYSIS SOLUTION) ; 1.7% CONTROL). SEVEN PATIENTS ON EXTRANEAL (ICODEXTRIN PERITONEAL DIALYSIS SOLUTION) DISCONTINUED TREATMENT DUE TO RASH, AND ONE PATIENT ON EXTRANEAL (ICODEXTRIN PERITONEAL DIALYSIS SOLUTION) DISCONTINUED DUE TO EXFOLIATIVE DERMATITIS. THE RASH TYPICALLY APPEARED WITHIN THE FIRST THREE WEEKS OF TREATMENT AND RESOLVED WITH TREATMENT DISCONTINUATION OR, IN SOME PATIENTS, WITH CONTINUED TREATMENT.
FEMALE PATIENTS REPORTED A HIGHER INCIDENCE OF SKIN EVENTS, INCLUDING RASH, IN BOTH EXTRANEAL (ICODEXTRIN PERITONEAL DIALYSIS SOLUTION) AND DEXTROSE CONTROL TREATMENT GROUPS.
TABLE 1 SHOWS THE ADVERSE EVENTS REPORTED IN THESE CLINICAL STUDIES, REGARDLESS OF CAUSALITY, OCCURRING IN ? 5% OF PATIENTS AND MORE COMMON ON EXTRANEAL (ICODEXTRIN PERITONEAL DIALYSIS SOLUTION) THAN CONTROL.
TABLE 1 - ADVERSE EXPERIENCES IN ? 5 % OF PATIENTS AND MORE COMMON ON EXTRANEAL (ICODEXTRIN PERITONEAL DIALYSIS SOLUTION)
EXTRANEAL CONTROL
N = 493 N = 347
PERITONITIS 26% 25%
UPPER RESPIRATORY INFECTION 15% 13%
HYPERTENSION 13% 8%
RASH 10% 5%
HEADACHE 9% 7%
ABDOMINAL PAIN 8% 6%
FLU SYNDROME 7% 6%
NAUSEA 7% 5%
COUGH INCREASE 7% 4%
EDEMA 6% 5%
ACCIDENTAL INJURY 6% 4%
CHEST PAIN 5% 4%
DYSPEPSIA 5% 4%
HYPERGLYCEMIA 5% 4%
ADVERSE REACTIONS REPORTED WITH AN INCIDENCE OF > 5% AND AT LEAST AS COMMON ON DEXTROSE CONTROL INCLUDED PAIN, ASTHENIA, EXIT SITE INFECTION, INFECTION, BACK PAIN, HYPOTENSION, DIARRHEA, VOMITING, NAUSEA/VOMITING, ANEMIA, PERIPHERAL EDEMA, HYPOKALEMIA, HYPERPHOSPHATEMIA, HYPOPROTEINEMIA, HYPERVOLEMIA, ARTHRALGIA, DIZZINESS, DYSPNEA, SKIN DISORDER, PRURITIS.
ADDITIONAL ADVERSE EVENTS OCCURRING AT AN INCIDENCE OF < 5% AND THAT MAY OR MAY NOT HAVE BEEN RELATED TO EXTRANEAL (ICODEXTRIN PERITONEAL DIALYSIS SOLUTION) INCLUDE: PAIN ON INFUSION, ABDOMINAL ENLARGEMENT, CLOUDY EFFLUENT, ULTRAFILTRATION DECREASE, POSTURAL HYPOTENSION, HEART FAILURE, HYPONATREMIA, HYPOCHLOREMIA, HYPERCALCEMIA, HYPOGLYCEMIA, ALKALINE PHOSPHATASE INCREASE, SGPT INCREASE, SGOT INCREASE, CRAMPING, CONFUSION, LUNG EDEMA, FACIAL EDEMA, EXFOLIATIVE DERMATITIS, ECZEMA, VESICOBULLOUS RASH, MACULOPAPULAR RASH, ERYTHEMA MULTIFORME. ALL REPORTED EVENTS ARE INCLUDED IN THE LIST EXCEPT THOSE ALREADY LISTED IN TABLE 1 OR THE FOLLOWING TWO PARAGRAPHS, THOSE NOT PLAUSIBLY ASSOCIATED WITH EXTRANEAL (ICODEXTRIN PERITONEAL DIALYSIS SOLUTION) , AND THOSE THAT WERE ASSOCIATED WITH THE CONDITION BEING TREATED OR RELATED TO THE DIALYSIS PROCEDURE.
EXTRANEAL (ICODEXTRIN PERITONEAL DIALYSIS SOLUTION) WAS ADDITIONALLY STUDIED IN A SUBPOPULATION OF 92 HIGH AVERAGE/HIGH TRANSPORTER APD PATIENTS IN A TWO-WEEK CONTROLLED CLINICAL TRIAL WHERE PATIENTS RECEIVED A SINGLE DAILY EXCHANGE OF EXTRANEAL (ICODEXTRIN PERITONEAL DIALYSIS SOLUTION) (N=47) OR DEXTROSE CONTROL (N=45) FOR THE LONG DWELL (14 ±2 HOURS). CONSISTENT WITH THE DATA REPORTED IN THE ORIGINAL TRIALS OF EXTRANEAL (ICODEXTRIN PERITONEAL DIALYSIS SOLUTION) , RASH WAS THE MOST FREQUENTLY OCCURRING EVENT.
PERITONEAL DIALYSIS-RELATED
ADVERSE EVENTS COMMON TO THE PERITONEAL DIALYSIS, INCLUDING PERITONITIS, INFECTION AROUND THE CATHETER, FLUID AND ELECTROLYTE IMBALANCE, AND PAIN, WERE OBSERVED AT A SIMILAR FREQUENCY WITH EXTRANEAL AND CONTROLS (SEE PRECAUTIONS).
CHANGES IN ALKALINE PHOSPHATASE AND SERUM ELECTROLYTES
AN INCREASE IN MEAN SERUM ALKALINE PHOSPHATASE HAS BEEN OBSERVED IN CLINICAL STUDIES OF ESRD PATIENTS RECEIVING EXTRANEAL (ICODEXTRIN PERITONEAL DIALYSIS SOLUTION) . NO ASSOCIATED INCREASES IN OTHER LIVER CHEMISTRY TESTS WERE OBSERVED. SERUM ALKALINE PHOSPHATASE LEVELS DID NOT SHOW PROGRESSIVE INCREASE OVER A 12-MONTH STUDY PERIOD. LEVELS RETURNED TO NORMAL APPROXIMATELY TWO WEEKS AFTER DISCONTINUATION OF EXTRANEAL (ICODEXTRIN PERITONEAL DIALYSIS SOLUTION) .
DECREASES IN SERUM SODIUM AND CHLORIDE HAVE BEEN OBSERVED IN PATIENTS USING EXTRANEAL (ICODEXTRIN PERITONEAL DIALYSIS SOLUTION) . THE DECLINES IN SERUM SODIUM AND CHLORIDE MAY BE RELATED TO DILUTION RESULTING FROM THE PRESENCE OF ICODEXTRIN METABOLITES IN PLASMA. ALTHOUGH THESE DECREASES HAVE BEEN SMALL AND CLINICALLY UNIMPORTANT, MONITORING OF PATIENTS' SERUM ELECTROLYTE LEVELS AS PART OF ROUTINE BLOOD CHEMISTRY TESTING IS RECOMMENDED.
POST-MARKETING
THE FOLLOWING ADVERSE REACTIONS HAVE BEEN IDENTIFIED DURING POST-APPROVAL USE OF EXTRANEAL (ICODEXTRIN PERITONEAL DIALYSIS SOLUTION) . BECAUSE THESE REACTIONS ARE REPORTED VOLUNTARILY FROM A POPULATION OF UNCERTAIN SIZE, IT IS NOT POSSIBLE TO ESTIMATE THEIR FREQUENCY RELIABLY OR TO ESTABLISH A CAUSAL RELATIONSHIP TO DRUG EXPOSURE. ADVERSE REACTIONS ARE LISTED BY MEDDRA SYSTEM ORDER CLASS (SOC), FOLLOWED BY PREFERRED TERM IN ORDER OF SEVERITY.
INFECTIONS AND INFESTATIONS: FUNGAL PERITONITIS, PERITONITIS BACTERIAL, CATHETER SITE INFECTION, CATHETER RELATED INFECTION
BLOOD AND LYMPHATIC SYSTEM DISORDERS: THROMBOCYTOPENIA, LEUKOPENIA, LEUKOCYTOSIS
IMMUNE SYSTEM DISORDERS: LEUKOCYTOCLASTIC VASCULITIS, SERUM SICKNESS, HYPERSENSITIVITY
METABOLISM AND NUTRITION DISORDERS: SHOCK HYPOGLYCEMIA, FLUID OVERLOAD, DEHYDRATION, FLUID IMBALANCE
NERVOUS SYSTEM DISORDERS: HYPOGLYCEMIC COMA, BURNING SENSATION
EYE DISORDERS: VISION BLURRED
RESPIRATORY, THORACIC, AND MEDIASTINAL DISORDERS: BRONCHOSPASM, STRIDOR
GASTROINTESTINAL DISORDERS: SCLEROSING ENCAPSULATING PERITONITIS, ASEPTIC PERITONITIS, PERITONEAL CLOUDY EFFLUENT, ILEUS, ASCITES, INGUINAL HERNIA, ABDOMINAL DISCOMFORT
SKIN AND SUBCUTANEOUS DISORDERS: TOXIC EPIDERMAL NECROLYSIS, ERYTHEMA MULTIFORME, ANGIOEDEMA, URTICARIA GENERALIZED, TOXIC SKIN ERUPTION, SWELLING FACE, PERIORBITAL EDEMA, EXFOLIATIVE RASH, SKIN EXFOLIATION, PRURIGO, RASH (INCLUDING MACULAR, PAPULAR, ERYTHEMATOUS, EXFOLIATIVE), DERMATITIS (INCLUDING ALLERGIC AND CONTACT), DRUG ERUPTION, ERYTHEMA, ONYCHOMADESIS, DRY SKIN, SKIN CHAPPED, BLISTER
MUSCULOSKELETAL, CONNECTIVE TISSUE DISORDERS: ARTHRALGIA, BACK PAIN, MUSCULOSKELETAL PAIN
REPRODUCTIVE SYSTEM AND BREAST DISORDERS: PENILE EDEMA, SCROTAL EDEMA
GENERAL DISORDERS AND ADMINISTRATIVE SITE CONDITIONS: DISCOMFORT, PYREXIA, CHILLS, MALAISE, DRUG EFFECT DECREASED, DRUG INEFFECTIVE, CATHETER SITE ERYTHEMA, CATHETER SITE INFLAMMATION, INFUSION RELATED REACTION (INCLUDING INFUSION SITE PAIN, INSTILLATION SITE PAIN)
DRUG ABUSE AND DEPENDENCE
THERE HAS BEEN NO OBSERVED POTENTIAL OF DRUG ABUSE OR DEPENDENCE WITH EXTRANEAL (ICODEXTRIN PERITONEAL DIALYSIS SOLUTION) .
READ THE EXTRANEAL (ICODEXTRIN PERITONEAL DIALYSIS SOLUTION) SIDE EFFECTS CENTER FOR A COMPLETE GUIDE TO POSSIBLE SIDE EFFECTS
WARNINGS
DANGEROUS DRUG-DEVICE INTERACTION
(SEE BOXED WARNING)
ONLY USE GLUCOSE-SPECIFIC MONITORS AND TEST STRIPS TO MEASURE BLOOD GLUCOSE LEVELS IN PATIENTS USING EXTRANEAL (ICODEXTRIN) PERITONEAL DIALYSIS SOLUTION. BLOOD GLUCOSE MONITORING DEVICES USING GLUCOSE DEHYDROGENASE PYRROLOQUINOLINEQUINONE (GDH-PQQ) OR GLUCOSE-DYE-OXIDOREDUCTASE (GDO)-BASED METHODS MUST NOT BE USED. IN ADDITION, SOME BLOOD GLUCOSE MONITORING SYSTEMS USING GLUCOSE DEHYDROGENASE FLAVIN-ADENINE DINUCLEOTIDE (GDH-FAD)-BASED METHODS MUST NOT BE USED. USE OF GDH-PQQ, GDO, AND GDH-FAD-BASED GLUCOSE MONITORS AND TEST STRIPS HAS RESULTED IN FALSELY ELEVATED GLUCOSE READINGS (DUE TO THE PRESENCE OF MALTOSE, SEE DRUG/LABORATORY TEST INTERACTIONS). FALSELY ELEVATED GLUCOSE READINGS HAVE LED PATIENTS OR HEALTH CARE PROVIDERS TO WITHHOLD TREATMENT OF HYPOGLYCEMIA OR TO ADMINISTER INSULIN INAPPROPRIATELY. BOTH OF THESE SITUATIONS HAVE RESULTED IN UNRECOGNIZED HYPOGLYCEMIA, WHICH HAS LED TO LOSS OF CONSCIOUSNESS, COMA, PERMANENT NEUROLOGICAL DAMAGE, AND DEATH. PLASMA LEVELS OF EXTRANEAL (ICODEXTRIN) AND ITS METABOLITES RETURN TO BASELINE WITHIN APPROXIMATELY 14 DAYS FOLLOWING CESSATION OF EXTRANEAL (ICODEXTRIN) ADMINISTRATION. THEREFORE FALSELY ELEVATED GLUCOSE LEVELS MAY BE MEASURED UP TO TWO WEEKS FOLLOWING CESSATION OF EXTRANEAL (ICODEXTRIN) THERAPY WHEN GDH-PQQ, GDO, AND GDH-FAD-BASED BLOOD GLUCOSE MONITORS AND TEST STRIPS ARE USED.
BECAUSE GDH-PQQ, GDO, AND GDH-FAD-BASED BLOOD GLUCOSE MONITORS MAY BE USED IN HOSPITAL SETTINGS, IT IS IMPORTANT THAT THE HEALTH CARE PROVIDERS OF PERITONEAL DIALYSIS PATIENTS USING EXTRANEAL (ICODEXTRIN) CAREFULLY REVIEW THE PRODUCT INFORMATION OF THE BLOOD GLUCOSE TESTING SYSTEM, INCLUDING THAT OF TEST STRIPS, TO DETERMINE IF THE SYSTEM IS APPROPRIATE FOR USE WITH EXTRANEAL (ICODEXTRIN).
TO AVOID IMPROPER INSULIN ADMINISTRATION, EDUCATE PATIENTS TO ALERT HEALTH CARE PROVIDERS OF THIS INTERACTION WHENEVER THEY ARE ADMITTED TO THE HOSPITAL.
THE MANUFACTURERS) OF THE MONITOR AND TEST STRIPS SHOULD BE CONTACTED TO DETERMINE IF ICODEXTRIN OR MALTOSE CAUSES INTERFERENCE OR FALSELY ELEVATED GLUCOSE READINGS. FOR A LIST OF TOLL FREE NUMBERS FOR GLUCOSE MONITOR AND TEST STRIP MANUFACTURERS, PLEASE CONTACT THE BAXTER RENAL CLINICAL HELP LINE 1-888-RENAL-HELP OR VISIT WWW.GLUCOSESAFETY.COM.
EXTRANEAL (ICODEXTRIN PERITONEAL DIALYSIS SOLUTION) IS INTENDED FOR INTRAPERITONEAL ADMINISTRATION ONLY. NOT FOR INTRAVENOUS INJECTION.
ENCAPSULATING PERITONEAL SCLEROSIS (EPS) IS A KNOWN, RARE COMPLICATION OF PERITONEAL DIALYSIS THERAPY. EPS HAS BEEN REPORTED IN PATIENTS USING PERITONEAL DIALYSIS SOLUTIONS INCLUDING EXTRANEAL (ICODEXTRIN). INFREQUENT BUT FATAL OUTCOMES HAVE BEEN REPORTED.
IF PERITONITIS OCCURS, THE CHOICE AND DOSAGE OF ANTIBIOTICS SHOULD BE BASED UPON THE RESULTS OF IDENTIFICATION AND SENSITIVITY STUDIES OF THE ISOLATED ORGANISM(S) WHEN POSSIBLE. PRIOR TO THE IDENTIFICATION OF THE INVOLVED ORGANISM(S), BROAD-SPECTRUM ANTIBIOTICS MAY BE INDICATED.
RARELY, SERIOUS HYPERSENSITIVITY REACTIONS TO EXTRANEAL (ICODEXTRIN PERITONEAL DIALYSIS SOLUTION) HAVE BEEN REPORTED SUCH AS TOXIC EPIDERMAL NECROLYSIS, ANGIOEDEMA, SERUM SICKNESS, ERYTHEMA MULTIFORME AND LEUKOCYTOCLASTIC VASCULITIS. IF A SERIOUS REACTION IS SUSPECTED, DISCONTINUE EXTRANEAL (ICODEXTRIN PERITONEAL DIALYSIS SOLUTION) AND INSTITUTE APPROPRIATE TREATMENT AS CLINICALLY INDICATED.
PATIENTS WITH SEVERE LACTIC ACIDOSIS SHOULD NOT BE TREATED WITH LACTATE-BASED PERITONEAL DIALYSIS SOLUTIONS (SEE CONTRAINDICATIONS). IT IS RECOMMENDED THAT PATIENTS WITH CONDITIONS KNOWN TO INCREASE THE RISK OF LACTIC ACIDOSIS [E.G., ACUTE RENAL FAILURE, INBORN ERRORS OF METABOLISM, TREATMENT WITH DRUGS SUCH AS METFORMIN AND NUCLEOSIDE/NUCLEOTIDE REVERSE TRANSCRIPTASE INHIBITORS (NRTIS)] MUST BE MONITORED FOR OCCURRENCE OF LACTIC ACIDOSIS BEFORE THE START OF TREATMENT AND DURING TREATMENT WITH LACTATE-BASED PERITONEAL DIALYSIS SOLUTIONS.
WHEN PRESCRIBING THE SOLUTION TO BE USED FOR AN INDIVIDUAL PATIENT, CONSIDERATION SHOULD BE GIVEN TO THE POTENTIAL INTERACTION BETWEEN THE DIALYSIS TREATMENT AND THERAPY DIRECTED AT OTHER EXISTING ILLNESSES. SERUM POTASSIUM LEVELS SHOULD BE MONITORED CAREFULLY IN PATIENTS TREATED WITH CARDIAC GLYCOSIDES. FOR EXAMPLE, RAPID POTASSIUM REMOVAL MAY CREATE ARRHYTHMIAS IN CARDIAC PATIENTS USING DIGITALIS OR SIMILAR DRUGS; DIGITALIS TOXICITY MAY BE MASKED BY HYPERKALEMIA, HYPERMAGNESEMIA, OR HYPOCALCEMIA. CORRECTION OF ELECTROLYTES BY DIALYSIS MAY PRECIPITATE SIGNS AND SYMPTOMS OF DIGITALIS EXCESS. CONVERSELY, TOXICITY MAY OCCUR AT SUBOPTIMAL DOSAGES OF DIGITALIS IF POTASSIUM IS LOW OR CALCIUM HIGH.
OVERDOSE
NO DATA ARE AVAILABLE ON EXPERIENCES OF OVERDOSAGE WITH EXTRANEAL (ICODEXTRIN PERITONEAL DIALYSIS SOLUTION) . OVERDOSAGE OF EXTRANEAL WOULD BE EXPECTED TO RESULT IN HIGHER LEVELS OF SERUM ICODEXTRIN AND METABOLITES, BUT IT IS NOT KNOWN WHAT SIGNS OR SYMPTOMS MIGHT BE CAUSED BY EXPOSURE IN EXCESS OF THE EXPOSURES USED IN CLINICAL TRIALS. IN THE EVENT OF OVERDOSAGE WITH EXTRANEAL (ICODEXTRIN PERITONEAL DIALYSIS SOLUTION) , CONTINUED PERITONEAL DIALYSIS WITH GLUCOSE-BASED SOLUTIONS SHOULD BE PROVIDED.
CLINICAL PHARMACOLOGY
MECHANISM OF ACTION
EXTRANEAL (ICODEXTRIN PERITONEAL DIALYSIS SOLUTION) IS AN ISOSMOTIC PERITONEAL DIALYSIS SOLUTION CONTAINING GLUCOSE POLYMERS (ICODEXTRIN) AS THE PRIMARY OSMOTIC AGENT. ICODEXTRIN FUNCTIONS AS A COLLOID OSMOTIC AGENT TO ACHIEVE
ULTRAFILTRATION DURING LONG PERITONEAL DIALYSIS DWELLS. ICODEXTRIN ACTS IN THE PERITONEAL CAVITY BY EXERTING OSMOTIC PRESSURE ACROSS SMALL INTERCELLULAR PORES RESULTING IN TRANSCAPILLARY ULTRAFILTRATION THROUGHOUT THE DWELL. LIKE OTHER PERITONEAL DIALYSIS SOLUTIONS, EXTRANEAL (ICODEXTRIN PERITONEAL DIALYSIS SOLUTION) ALSO CONTAINS ELECTROLYTES TO HELP NORMALIZE ELECTROLYTE BALANCE AND LACTATE TO HELP NORMALIZE ACID-BASE STATUS.
PHARMACOKINETICS OF ICODEXTRIN
ABSORPTION
ABSORPTION OF ICODEXTRIN FROM THE PERITONEAL CAVITY FOLLOWS ZERO-ORDER KINETICS CONSISTENT WITH CONVECTIVE TRANSPORT VIA PERITONEAL LYMPHATIC PATHWAYS. IN A SINGLE-DOSE PHARMACOKINETIC STUDY USING EXTRANEAL (ICODEXTRIN), A MEDIAN OF 40% (60 G) OF THE INSTILLED ICODEXTRIN WAS ABSORBED FROM THE PERITONEAL SOLUTION DURING A 12-HOUR DWELL. PLASMA LEVELS OF ICODEXTRIN ROSE DURING THE DWELL AND DECLINED AFTER THE DWELL WAS DRAINED. PEAK PLASMA LEVELS OF ICODEXTRIN PLUS ITS METABOLITES (MEDIAN CPEAK 2.2G/L) WERE OBSERVED AT THE END OF THE LONG DWELL EXCHANGE (MEDIAN T^ = 13 HOURS).
AT STEADY-STATE, THE MEAN PLASMA LEVEL OF ICODEXTRIN PLUS ITS METABOLITES WAS ABOUT 5 G/L. IN MULTIDOSE STUDIES, STEADY-STATE LEVELS OF ICODEXTRIN WERE ACHIEVED WITHIN ONE WEEK. PLASMA LEVELS OF ICODEXTRIN AND METABOLITES RETURN TO BASELINE VALUES WITHIN APPROXIMATELY TWO WEEKS FOLLOWING CESSATION OF ICODEXTRIN ADMINISTRATION.
METABOLISM
ICODEXTRIN IS METABOLIZED BY ALPHA-AMYLASE INTO OLIGOSACCHARIDES WITH A LOWER DEGREE OF POLYMERIZATION (DP), INCLUDING MALTOSE (DP2), MALTOTRIOSE (DPS), MALTOTETRAOSE (DP4), AND HIGHER MOLECULAR WEIGHT SPECIES. IN A SINGLE DOSE STUDY, DP2, DPS AND DP4 SHOWED A PROGRESSIVE RISE IN PLASMA CONCENTRATIONS WITH A PROFILE SIMILAR TO THAT FOR TOTAL ICODEXTRIN, WITH PEAK VALUES REACHED BY THE END OF THE DWELL AND DECLINING THEREAFTER. ONLY VERY SMALL INCREASES IN BLOOD LEVELS OF LARGER POLYMERS WERE OBSERVED. STEADY-STATE PLASMA LEVELS OF ICODEXTRIN METABOLITES WERE ACHIEVED WITHIN ONE WEEK AND STABLE PLASMA LEVELS WERE OBSERVED DURING LONG-TERM ADMINISTRATION.
SOME DEGREE OF METABOLISM OF ICODEXTRIN OCCURS INTRAPERITONEALLY WITH A PROGRESSIVE RISE IN THE CONCENTRATION OF THE SMALLER POLYMERS IN THE DIALYSATE DURING THE 12-HOUR DWELL.
ELIMINATION
ICODEXTRIN UNDERGOES RENAL ELIMINATION IN DIRECT PROPORTION TO THE LEVEL OF RESIDUAL RENAL FUNCTION. DIFFUSION OF THE SMALLER ICODEXTRIN METABOLITES FROM PLASMA INTO THE PERITONEAL CAVITY IS ALSO POSSIBLE AFTER SYSTEMIC ABSORPTION AND METABOLISM OF ICODEXTRIN.
SPECIAL POPULATIONS
GERIATRICS
THE INFLUENCE OF AGE ON THE PHARMACOKINETICS OF ICODEXTRIN AND ITS METABOLITES WAS NOT ASSESSED.
GENDER AND RACE
THE INFLUENCE OF GENDER AND RACE ON THE PHARMACOKINETICS OF ICODEXTRIN AND ITS METABOLITES WAS NOT ASSESSED.
CLINICAL STUDIES
EXTRANEAL (ICODEXTRIN PERITONEAL DIALYSIS SOLUTION) HAS DEMONSTRATED EFFICACY AS A PERITONEAL DIALYSIS SOLUTION IN CLINICAL TRIALS OF APPROXIMATELY 480 PATIENTS STUDIED WITH END-STAGE RENAL DISEASE (ESRD).
ULTRAFILTRATION, UREA AND CREATININE CLEARANCE
IN THE ACTIVE-CONTROLLED TRIALS OF ONE TO SIX MONTHS IN DURATION, DESCRIBED BELOW, EXTRANEAL (ICODEXTRIN PERITONEAL DIALYSIS SOLUTION) USED ONCE-DAILY FOR THE LONG DWELL IN EITHER CONTINUOUS AMBULATORY PERITONEAL DIALYSIS (CAPD) OR AUTOMATED PERITONEAL DIALYSIS (APD) THERAPY RESULTED IN HIGHER NET ULTRAFILTRATION THAN 1.5% AND 2.5% DEXTROSE SOLUTIONS, AND HIGHER CREATININE AND UREA NITROGEN CLEARANCES THAN 2.5% DEXTROSE. NET ULTRAFILTRATION WAS SIMILAR TO 4.25% DEXTROSE ACROSS ALL PATIENTS IN THESE STUDIES. EFFECTS WERE GENERALLY SIMILAR IN CAPD AND APD.
IN AN ADDITIONAL RANDOMIZED, MULTICENTER, ACTIVE-CONTROLLED TWO-WEEK STUDY IN HIGH AVERAGE/HIGH TRANSPORTER APD PATIENTS, EXTRANEAL (ICODEXTRIN PERITONEAL DIALYSIS SOLUTION) USED ONCE DAILY FOR THE LONG DWELL PRODUCED HIGHER NET ULTRAFILTRATION COMPARED TO 4.25% DEXTROSE. MEAN CREATININE AND UREA NITROGEN CLEARANCES WERE ALSO GREATER WITH EXTRANEAL (ICODEXTRIN PERITONEAL DIALYSIS SOLUTION) AND ULTRAFILTRATION EFFICIENCY WAS IMPROVED.
IN 175 CAPD PATIENTS RANDOMIZED TO EXTRANEAL (ICODEXTRIN PERITONEAL DIALYSIS SOLUTION) (N=90) OR 2.5% DEXTROSE SOLUTION (N=85) FOR THE 8-15 HOUR OVERNIGHT DWELL FOR ONE MONTH, MEAN NET ULTRAFILTRATION FOR THE OVERNIGHT DWELL WAS SIGNIFICANTLY GREATER IN THE EXTRANEAL (ICODEXTRIN PERITONEAL DIALYSIS SOLUTION) GROUP AT WEEKS 2 AND 4 (FIGURE 1). MEAN CREATININE AND UREA NITROGEN CLEARANCES WERE ALSO GREATER WITH EXTRANEAL (ICODEXTRIN PERITONEAL DIALYSIS SOLUTION) (FIGURE 2).
FIGURE 1 - MEAN NET ULTRAFILTRATION FOR THE OVERNIGHT DWELL
FIGURE 2 - MEAN CREATININE AND UREA NITROGEN CLEARANCE FOR THE OVERNIGHT DWELL
IN ANOTHER STUDY OF 39 APD PATIENTS RANDOMIZED TO EXTRANEAL (ICODEXTRIN PERITONEAL DIALYSIS SOLUTION) OR 2.5% DEXTROSE SOLUTION FOR THE LONG, DAYTIME DWELL (10-17 HOURS) FOR THREE MONTHS, THE NET ULTRAFILTRATION REPORTED DURING THE TREATMENT PERIOD WAS (MEAN ± SD) 278 ± 192 ML FOR THE EXTRANEAL (ICODEXTRIN PERITONEAL DIALYSIS SOLUTION) GROUP AND -138 ± 352 ML FOR THE DEXTROSE GROUP (P < 0.001). MEAN CREATININE AND UREA NITROGEN CLEARANCES WERE SIGNIFICANTLY GREATER FOR EXTRANEAL (ICODEXTRIN PERITONEAL DIALYSIS SOLUTION) THAN 2.5% DEXTROSE AT WEEKS 6 AND 12 (P < 0.001).
IN A SIX-MONTH STUDY IN CAPD PATIENTS COMPARING EXTRANEAL (ICODEXTRIN PERITONEAL DIALYSIS SOLUTION) (N=28) WITH 4.25% DEXTROSE (N=31), NET ULTRAFILTRATION ACHIEVED DURING AN 8-HOUR DWELL AVERAGED 510 ML FOR EXTRANEAL (ICODEXTRIN PERITONEAL DIALYSIS SOLUTION) AND 556 ML FOR 4.25% DEXTROSE. FOR 12-HOUR DWELLS, NET ULTRAFILTRATION AVERAGED 575 ML FOR EXTRANEAL (ICODEXTRIN PERITONEAL DIALYSIS SOLUTION) (N=29) AND 476 ML FOR 4.25% DEXTROSE (N=31). THERE WAS NO SIGNIFICANT DIFFERENCE BETWEEN THE TWO GROUPS WITH RESPECT TO ULTRAFILTRATION.
IN A TWO WEEK STUDY IN HIGH AVERAGE/HIGH TRANSPORTER APD PATIENTS (4-HOUR D/P CREATININE RATIO > 0.70 AND A 4-HOUR D/D0 RATIO < 0.34, AS DEFINED BY THE PERITONEAL EQUILIBRATION TEST (PET)), COMPARING EXTRANEAL (ICODEXTRIN PERITONEAL DIALYSIS SOLUTION) (N=47) TO 4.25% DEXTROSE (N=45), AFTER ADJUSTING FOR BASELINE, THE MEAN NET ULTRAFILTRATION ACHIEVED DURING A 14 ± 2 HOUR DWELL WAS SIGNIFICANTLY GREATER IN THE EXTRANEAL (ICODEXTRIN PERITONEAL DIALYSIS SOLUTION) GROUP THAN THE 4.25% DEXTROSE GROUP AT WEEKS 1 AND 2 (P < 0.001, SEE FIGURE 3). CONSISTENT WITH INCREASES IN NET ULTRAFILTRATION, THERE WERE ALSO SIGNIFICANTLY GREATER CREATININE AND UREA NITROGEN CLEARANCES AND ULTRAFILTRATION EFFICIENCY IN THE EXTRANEAL (ICODEXTRIN PERITONEAL DIALYSIS SOLUTION) GROUP (P < 0.001, SEE FIGURE 3).
FIGURE 3 - MEAN NET ULTRAFILTRATION, CREATININE AND UREA NITROGEN CLEARANCES AND ULTRAFILTRATION EFFICIENCY FOR THE LONG DWELL IN HIGH AVERAGE/HIGH TRANSPORTER PATIENTS
PERITONEAL MEMBRANE TRANSPORT CHARACTERISTICS: AFTER ONE YEAR OF TREATMENT WITH EXTRANEAL (ICODEXTRIN PERITONEAL DIALYSIS SOLUTION) DURING THE LONG DWELL EXCHANGE, THERE WERE NO DIFFERENCES IN MEMBRANE TRANSPORT CHARACTERISTICS FOR UREA AND CREATININE. THE MASS TRANSFER AREA COEFFICIENTS (MTAC) FOR UREA, CREATININE, AND GLUCOSE AT ONE YEAR WERE NOT DIFFERENT IN PATIENTS RECEIVING TREATMENT WITH EXTRANEAL (ICODEXTRIN PERITONEAL DIALYSIS SOLUTION) OR 2.5% DEXTROSE SOLUTION FOR THE LONG DWELL.