Transcription
Dosing andAdministration Guidefor REMICADE INDICATIONSDOSAGE ON, IONSPATIENTASSESSMENTSELECTED IMPORTANT SAFETY INFORMATIONSerious and sometimes fatal side effects have been reported with REMICADE (infliximab). Infections dueto bacterial, mycobacterial, invasive fungal, viral, or other opportunistic pathogens (eg, TB, histoplasmosis)have been reported. Lymphoma, including cases of fatal hepatosplenic T-cell lymphoma (HSTCL), and othermalignancies have been reported, including in children and young adult patients. Due to the risk of HSTCL,mostly reported in Crohn’s disease and ulcerative colitis, assess the risk/benefit, especially if the patient ismale and is receiving azathioprine or 6-mercaptopurine treatment. REMICADE is contraindicated at doses 5 mg/kg in patients with moderate or severe heart failure and in patients with severe hypersensitivityreactions to REMICADE . Other serious side effects reported include melanoma, Merkel cell carcinoma,invasive cervical cancer, hepatitis B reactivation, hepatotoxicity, hematological events, hypersensitivity,cardiovascular and cerebrovascular reactions during and after infusion, neurological events, and lupus-likesyndrome. Please see related and other Important Safety Information on pages 17-20 of this guide.1
IndicationsCrohn’s DiseaseREMICADE is indicated for reducing signs and symptoms and inducing and maintaining clinical remission in adult patients withmoderately to severely active Crohn’s disease (CD) who have had an inadequate response toconventional therapy. reducing the number of draining enterocutaneous and rectovaginal fistulas and maintaining fistula closurein adult patients with fistulizing CD.Pediatric Crohn’s DiseaseREMICADE is indicated for reducing signs and symptoms and inducing and maintaining clinical remissionin pediatric patients 6 years of age and older with moderately to severely active CD who have had aninadequate response to conventional therapy.Ulcerative ColitisREMICADE is indicated for reducing signs and symptoms, inducing and maintaining clinical remission andmucosal healing, and eliminating corticosteroid use in adult patients with moderately to severely activeulcerative colitis (UC) who have had an inadequate response to conventional therapy.Pediatric Ulcerative ColitisREMICADE is indicated for reducing signs and symptoms and inducing and maintaining clinical remissionin pediatric patients 6 years of age and older with moderately to severely active UC who have had aninadequate response to conventional therapy.Rheumatoid ArthritisREMICADE , in combination with methotrexate, is indicated for reducing signs and symptoms, inhibitingthe progression of structural damage, and improving physical function in adult patients with moderately toseverely active rheumatoid arthritis (RA).Ankylosing SpondylitisREMICADE is indicated for reducing signs and symptoms in adult patients with active ankylosing spondylitis (AS).Psoriatic ArthritisREMICADE is indicated for reducing signs and symptoms of active arthritis, inhibiting the progression ofstructural damage, and improving physical function in adult patients with psoriatic arthritis (PsA).Plaque PsoriasisREMICADE is indicated for treatment of adult patients with chronic severe (i.e., extensive and/or disabling)plaque psoriasis (Ps) who are candidates for systemic therapy and when other systemic therapies aremedically less appropriate. REMICADE should only be administered to patients who will be closelymonitored and have regular follow-up visits with a physician.SELECTED IMPORTANT SAFETY INFORMATIONSerious and sometimes fatal side effects have been reported with REMICADE (infliximab). Infections dueto bacterial, mycobacterial, invasive fungal, viral, or other opportunistic pathogens (eg, TB, histoplasmosis)have been reported. Lymphoma, including cases of fatal hepatosplenic T-cell lymphoma (HSTCL), and othermalignancies have been reported, including in children and young adult patients. Due to the risk of HSTCL,mostly reported in Crohn’s disease and ulcerative colitis, assess the risk/benefit, especially if the patient ismale and is receiving azathioprine or 6-mercaptopurine treatment. REMICADE is contraindicated at doses 5 mg/kg in patients with moderate or severe heart failure and in patients with severe hypersensitivityreactions to REMICADE . Other serious side effects reported include melanoma, Merkel cell carcinoma,invasive cervical cancer, hepatitis B reactivation, hepatotoxicity, hematological events, hypersensitivity,cardiovascular and cerebrovascular reactions during and after infusion, neurological events, and lupus-likesyndrome. Please see related and other Important Safety Information on pages 17-20 of this guide.2
Recommended Dosing1Adult Crohn’s DiseaseREMICADE is administered by intravenous (IV) infusion for at least 2 hours. Infusions occur every 8weeks after 3 induction doses.INDUCTION DOSING5 mg/kg IV given at 0, 2, and 6 weeksas an induction regimenMAINTENANCE DOSING*5 mg/kg IV given every 8 weeksthereafter as a maintenance regimen*If response is lost, consider treatment with 10 mg/kg every 8 weeks.Patients who do not respond by Week 14 are unlikely to respond with continueddosing and consideration should be given to discontinuing treatment.Pediatric Crohn’s Disease (6 years of age and older)REMICADE is administered by IV infusion for at least 2 hours. Infusions occur every 8 weeks after 3induction doses.INDUCTION DOSING5 mg/kg IV given at 0, 2, and 6 weeksas an induction regimenMAINTENANCE DOSING5 mg/kg IV given every 8 weeksthereafter as a maintenance regimenSELECTED IMPORTANT SAFETY INFORMATIONSerious and sometimes fatal side effects have been reported with REMICADE (infliximab). Infections dueto bacterial, mycobacterial, invasive fungal, viral, or other opportunistic pathogens (eg, TB, histoplasmosis)have been reported. Lymphoma, including cases of fatal hepatosplenic T-cell lymphoma (HSTCL), and othermalignancies have been reported, including in children and young adult patients. Due to the risk of HSTCL,mostly reported in Crohn’s disease and ulcerative colitis, assess the risk/benefit, especially if the patient ismale and is receiving azathioprine or 6-mercaptopurine treatment. REMICADE is contraindicated at doses 5 mg/kg in patients with moderate or severe heart failure and in patients with severe hypersensitivityreactions to REMICADE . Other serious side effects reported include melanoma, Merkel cell carcinoma,invasive cervical cancer, hepatitis B reactivation, hepatotoxicity, hematological events, hypersensitivity,cardiovascular and cerebrovascular reactions during and after infusion, neurological events, and lupus-likesyndrome. Please see related and other Important Safety Information on pages 17-20 of this guide.3
Recommended Dosing1 (cont)Adult Ulcerative ColitisREMICADE is administered by IV infusion for at least 2 hours. Infusions occur every 8 weeks after 3induction doses.MAINTENANCE DOSING5 mg/kg IV given every 8 weeksthereafter as a maintenance regimenINDUCTION DOSING5 mg/kg IV given at 0, 2, and 6 weeksas an induction regimenPediatric Ulcerative Colitis (6 years of age and older)REMICADE is administered by IV infusion for at least 2 hours. Infusions occur every 8 weeks after 3induction doses.INDUCTION DOSING5 mg/kg IV given at 0, 2, and 6 weeksas an induction regimenMAINTENANCE DOSING5 mg/kg IV given every 8 weeksthereafter as a maintenance regimenRheumatoid ArthritisREMICADE is administered by IV infusion for at least 2 hours. Infusions occur every 8 weeks after 3induction doses.INDUCTION DOSING3 mg/kg IV given at 0, 2, and 6 weeksas an induction regimenMAINTENANCE DOSING*3 mg/kg IV given every 8 weeksthereafter as a maintenance regimenREMICADE should be given in combination with methotrexate.*If the response is incomplete, consider adjusting the dosage up to 10 mg/kg IV every 8 weeksor treating as often as every 4 weeks. Note that risk of serious infections is increasedat higher doses per infusion or more frequent dosing.SELECTED IMPORTANT SAFETY INFORMATIONSerious and sometimes fatal side effects have been reported with REMICADE (infliximab). Infections dueto bacterial, mycobacterial, invasive fungal, viral, or other opportunistic pathogens (eg, TB, histoplasmosis)have been reported. Lymphoma, including cases of fatal hepatosplenic T-cell lymphoma (HSTCL), and othermalignancies have been reported, including in children and young adult patients. Due to the risk of HSTCL,mostly reported in Crohn’s disease and ulcerative colitis, assess the risk/benefit, especially if the patient ismale and is receiving azathioprine or 6-mercaptopurine treatment. REMICADE is contraindicated at doses 5 mg/kg in patients with moderate or severe heart failure and in patients with severe hypersensitivityreactions to REMICADE . Other serious side effects reported include melanoma, Merkel cell carcinoma,invasive cervical cancer, hepatitis B reactivation, hepatotoxicity, hematological events, hypersensitivity,cardiovascular and cerebrovascular reactions during and after infusion, neurological events, and lupus-likesyndrome. Please see related and other Important Safety Information on pages 17-20 of this guide.4
Recommended Dosing1 (cont)Ankylosing SpondylitisREMICADE is administered by IV infusion for at least 2 hours. Infusions occur every 6 weeks after 3induction doses.INDUCTION DOSING5 mg/kg IV given at 0, 2, and 6 weeksas an induction regimen6MAINTENANCE DOSING5 mg/kg IV given every 6 weeksthereafter as a maintenance regimenPsoriatic ArthritisREMICADE is administered by IV infusion for at least 2 hours. Infusions occur every 8 weeks after 3induction doses.INDUCTION DOSING5 mg/kg IV given at 0, 2, and 6 weeksas an induction regimenMAINTENANCE DOSING5 mg/kg IV given every 8 weeksthereafter as a maintenance regimenREMICADE can be used with or without methotrexate in patients with PsA.Plaque PsoriasisREMICADE is administered by IV infusion for at least 2 hours. Infusions occur every 8 weeks after 3induction doses.INDUCTION DOSING5 mg/kg IV given at 0, 2, and 6 weeksas an induction regimenMAINTENANCE DOSING5 mg/kg IV given every 8 weeksthereafter as a maintenance regimenSELECTED IMPORTANT SAFETY INFORMATIONSerious and sometimes fatal side effects have been reported with REMICADE (infliximab). Infections dueto bacterial, mycobacterial, invasive fungal, viral, or other opportunistic pathogens (eg, TB, histoplasmosis)have been reported. Lymphoma, including cases of fatal hepatosplenic T-cell lymphoma (HSTCL), and othermalignancies have been reported, including in children and young adult patients. Due to the risk of HSTCL,mostly reported in Crohn’s disease and ulcerative colitis, assess the risk/benefit, especially if the patient ismale and is receiving azathioprine or 6-mercaptopurine treatment. REMICADE is contraindicated at doses 5 mg/kg in patients with moderate or severe heart failure and in patients with severe hypersensitivityreactions to REMICADE . Other serious side effects reported include melanoma, Merkel cell carcinoma,invasive cervical cancer, hepatitis B reactivation, hepatotoxicity, hematological events, hypersensitivity,cardiovascular and cerebrovascular reactions during and after infusion, neurological events, and lupus-likesyndrome. Please see related and other Important Safety Information on pages 17-20 of this guide.5
Dosing Calculator for Adult Patients3 mg/kg1,24 mg/kg1,2For patients with rheumatoid arthritisFor patients with rheumatoid se ofREMICADE 402408VolumeNumber of ReconstitutedREMICADE REMICADE Vialsto .436.036.937.538.139.039.640.240.8TotalDose ofREMICADE 464472480492500508520528536544VolumeNumber of ReconstitutedREMICADE REMICADE Vialsto 5555555555566666*After reconstituting with 10 mL of Sterile Water for Injection, USP, the final concentration is 10 250.050.852.052.853.654.4Calculate the dose, totalvolume of reconstitutedREMICADE solutionrequired, and the numberof REMICADE vials needed.1Prior to reconstitution anduse, vials of REMICADE mustbe stored in a refrigerator at atemperature between2 C to 8 C (36 F to 46 F).1If needed, unopenedREMICADE vials may bestored at room temperatureup to a maximum of 30 C(86 F) for a single periodof up to 6 months but notexceeding the originalexpiration date. The newexpiration date must bewritten in the space providedon the carton. Once removedfrom the refrigerator,REMICADE cannot bereturned to the refrigerator.1The infusion of REMICADE should begin within 3 hours ofreconstitution and dilution.1Prior to initiatingREMICADE , bring pediatricand adult patients up todate with all vaccinations.Live vaccines or therapeuticinfectious agents should notbe given with REMICADE .At least a 6-month waitingperiod following birthis recommended beforethe administration of livevaccines to infants exposedin utero to infliximab.1
Dosing Calculator for Adult Patients (cont)6 mg/kg1,25 e ofREMICADE 670680For patients with rheumatoid arthritisVolumeNumber of ReconstitutedREMICADE REMICADE Vialsto .060.061.562.563.565.066.067.068.0TotalDose ofREMICADE 696708720738750762780792804816VolumeNumber of ReconstitutedREMICADE REMICADE Vialsto 7777777888888899*After reconstituting with 10 mL of Sterile Water for Injection, USP, the final concentration is 10 875.076.278.079.280.481.6Calculate the dose, total volumeof reconstituted REMICADE solution required, and the numberof REMICADE vials needed.1Prior to reconstitution and use,vials of REMICADE must be storedin a refrigerator at a temperaturebetween 2 C to 8 C (36 F to 46 F).1If needed, unopenedREMICADE vials may be storedat room temperature up to amaximum of 30 C (86 F) for asingle period of up to 6 monthsbut not exceeding the originalexpiration date. The newexpiration date must be writtenin the space provided on thecarton. Once removed from therefrigerator, REMICADE cannotbe returned to the refrigerator.Calculate the dose, total volumeof reconstituted REMICADE solution required, and the numberof REMICADE vials needed.1The infusion of REMICADE should begin within 3 hours ofreconstitution and dilution.1Calculate the dose, total volumeof reconstituted REMICADE solution required, and the numberof REMICADE vials needed.1Prior to initiating REMICADE ,bring pediatric and adultpatients up to date with allvaccinations. Live vaccines ortherapeutic infectious agentsshould not be given withREMICADE . At least a 6-monthwaiting period following birthis recommended before theadministration of live vaccinesto infants exposed in utero toinfliximab. Calculate the dose,total volume of reconstitutedREMICADE solution required,and the number of REMICADE vials needed.1
Dosing Calculator for Adult Patients (cont)7 mg/kg1,28 mg/kg1,2For patients with rheumatoid arthritisFor patients with rheumatoid se ofREMICADE 938952VolumeNumber of ReconstitutedREMICADE REMICADE Vialsto .282.684.086.187.588.991.092.493.895.2TotalDose ofREMICADE 928944960984100010161040105610721088VolumeNumber of ReconstitutedREMICADE REMICADE Vialsto 999991010101010101111111111*After reconstituting with 10 mL of Sterile Water for Injection, USP, the final concentration is 10 4100.0101.6104.0105.6107.2108.8Calculate the dose, totalvolume of reconstitutedREMICADE solutionrequired, and the numberof REMICADE vials needed.1Prior to reconstitution anduse, vials of REMICADE mustbe stored in a refrigerator at atemperature between2 C to 8 C (36 F to 46 F).1If needed, unopenedREMICADE vials may bestored at room temperatureup to a maximum of 30 C(86 F) for a single periodof up to 6 months but notexceeding the originalexpiration date. The newexpiration date must bewritten in the space providedon the carton. Once removedfrom the refrigerator,REMICADE cannot bereturned to the refrigerator.1The infusion of REMICADE should begin within 3 hours ofreconstitution and dilution.1Prior to initiatingREMICADE , bring pediatricand adult patients up todate with all vaccinations.Live vaccines or therapeuticinfectious agents should notbe given with REMICADE .At least a 6-month waitingperiod following birthis recommended beforethe administration of livevaccines to infants exposedin utero to infliximab.1
Dosing Calculator for Adult Patients (cont)10 mg/kg1,29 mg/kg1,2For patients with rheumatoid se ofREMICADE 31170118812061224VolumeNumber of ReconstitutedREMICADE REMICADE Vialsto 8120.6122.4For patients with rheumatoidarthritis or Crohn’s diseaseTotalDose ofREMICADE umeNumber of ReconstitutedREMICADE REMICADE Vialsto 0101011111111121212121213131313141414*After reconstituting with 10 mL of Sterile Water for Injection, USP, the final concentration is 10 e the dose, totalvolume of reconstitutedREMICADE solutionrequired, and the numberof REMICADE vials needed.1Prior to reconstitution anduse, vials of REMICADE mustbe stored in a refrigerator at atemperature between2 C to 8 C (36 F to 46 F).1If needed, unopenedREMICADE vials may bestored at room temperatureup to a maximum of 30 C(86 F) for a single periodof up to 6 months but notexceeding the originalexpiration date. The newexpiration date must bewritten in the space providedon the carton. Once removedfrom the refrigerator,REMICADE cannot bereturned to the refrigerator.1The infusion of REMICADE should begin within 3 hours ofreconstitution and dilution.1Prior to initiatingREMICADE , bring pediatricand adult patients up todate with all vaccinations.Live vaccines or therapeuticinfectious agents should notbe given with REMICADE .At least a 6-month waitingperiod following birthis recommended beforethe administration of livevaccines to infants exposedin utero to infliximab.
Dosing Calculator for Pediatric Patients5 mg/kg1,2For pediatric patients with ulcerative colitis orCrohn’s diseasePatientWeight (lb)PatientWeight (kg)Total Dose ofREMICADE olumeNumber ofReconstitutedREMICADE REMICADE toVials Required Be 40.041.042.043.044.545.5*After reconstituting with 10 mL of Sterile Water for Injection, USP, the final concentration is 10 mg/mL.10Calculate the dose, total volume ofreconstituted REMICADE solutionrequired, and the numberof REMICADE vials needed.1Prior to reconstitution and use, vialsof REMICADE must be stored in arefrigerator at a temperature between2 C to 8 C (36 F to 46 F).1If needed, unopened REMICADE vialsmay be stored at room temperatureup to a maximum of 30 C (86 F) for asingle period of up to 6 months butnot exceeding the original expirationdate. The new expiration date mustbe written in the space provided onthe carton. Once removed from therefrigerator, REMICADE cannot bereturned to the refrigerator.1The infusion of REMICADE shouldbegin within 3 hours of reconstitutionand dilution.1Prior to initiating REMICADE ,bring pediatric and adult patientsup to date with all vaccinations.Live vaccines or therapeuticinfectious agents should not begiven with REMICADE . At least a6-month waiting period followingbirth is recommended before theadministration of live vaccines toinfants exposed in utero to infliximab.
Reconstitution, Dilution, andAdministration Instructions1REMICADE is intended for use under the guidance and supervision of a healthcare provider. The suppliedlyophilized powder must be reconstituted and diluted prior to administration. The infusion solution shouldbe prepared and administered by a trained medical professional using aseptic technique by thefollowing procedure:Calculate the dose, total volume of reconstituted REMICADE solution required, and thenumber of REMICADE vials needed. More than one vial may be needed for a full dose.Reconstitute each 100-mg REMICADE vial with 10 mL of Sterile Water for Injection, USP,to obtain a concentration of 10 mg/mL, using a syringe equipped with a 21-gauge orsmaller needle as follows: Remove the flip-top from the vial and wipe the top with an alcohol swab Insert the syringe needle into the vial through the center of the rubber stopper anddirect the stream of Sterile Water for Injection, USP, to the glass wall of the vial. Gentlyswirl the solution by rotating the vial to dissolve the lyophilized powder, which has acake-like appearance. Avoid prolonged or vigorous agitation. DO NOT SHAKE.Foaming of the solution on reconstitution is not unusual Allow the reconstituted solution to stand for 5 minutes. Visually inspect thereconstituted solution for particulate matter and discoloration. The reconstitutedsolution should be colorless to light yellow and opalescent, and the solution maydevelop a few translucent particles as infliximab is a protein. Do not use if the lyophilizedpowder has not fully dissolved or if opaque particles, discoloration, or other foreignparticles are present. Do not store unused reconstituted REMICADE solutionSELECTED IMPORTANT SAFETY INFORMATIONSerious and sometimes fatal side effects have been reported with REMICADE (infliximab). Infections dueto bacterial, mycobacterial, invasive fungal, viral, or other opportunistic pathogens (eg, TB, histoplasmosis)have been reported. Lymphoma, including cases of fatal hepatosplenic T-cell lymphoma (HSTCL), and othermalignancies have been reported, including in children and young adult patients. Due to the risk of HSTCL,mostly reported in Crohn’s disease and ulcerative colitis, assess the risk/benefit, especially if the patient ismale and is receiving azathioprine or 6-mercaptopurine treatment. REMICADE is contraindicated at doses 5 mg/kg in patients with moderate or severe heart failure and in patients with severe hypersensitivityreactions to REMICADE . Other serious side effects reported include melanoma, Merkel cell carcinoma,invasive cervical cancer, hepatitis B reactivation, hepatotoxicity, hematological events, hypersensitivity,cardiovascular and cerebrovascular reactions during and after infusion, neurological events, and lupus-likesyndrome. Please see related and other Important Safety Information on pages 17-20 of this guide.11
Reconstitution, Dilution, andAdministration Instructions1 (cont)Dilute the total volume of the reconstituted REMICADE solution to 250 mL* with sterile0.9% Sodium Chloride Injection, USP (do not dilute with any other diluent) as follows: Withdraw a volume from the 0.9% Sodium Chloride Injection, USP, 250-mL bottle or bagequal to the total volume of reconstituted REMICADE required for a dose. Slowly addthe total volume of reconstituted REMICADE solution from the vial(s) to the 250-mLinfusion bottle or bag Discard any unused portion of the reconstituted REMICADE solution remaining inthe vial(s) Gently invert the bag to mix the solution. The resulting infusion concentration shouldrange between 0.4 mg/mL (minimum recommended concentration) and 4 mg/mL(maximum recommended concentration) of infliximab*For volumes greater than 250 mL, either use a larger infusion bag (eg, 500 mL) ormultiple 250-mL infusion bags to ensure that the concentration of the infusion solutiondoes not exceed 4 mg/mL.The REMICADE infusion should begin within 3 hours of reconstitution and dilution. Theinfusion must be administered intravenously for at least 2 hours with an infusion set withan in-line, sterile, nonpyrogenic, low-protein–binding filter (pore size 1.2 µm or less).Given that the vials do not contain antibacterial preservatives, discard any unused portionof the infusion solution (do not store for reuse).No physical biochemical compatibility studies have been conducted to evaluate the coadministration ofREMICADE with other agents. REMICADE should not be infused concomitantly in the same IV line withother agents.SELECTED IMPORTANT SAFETY INFORMATIONSerious and sometimes fatal side effects have been reported with REMICADE (infliximab). Infections dueto bacterial, mycobacterial, invasive fungal, viral, or other opportunistic pathogens (eg, TB, histoplasmosis)have been reported. Lymphoma, including cases of fatal hepatosplenic T-cell lymphoma (HSTCL), and othermalignancies have been reported, including in children and young adult patients. Due to the risk of HSTCL,mostly reported in Crohn’s disease and ulcerative colitis, assess the risk/benefit, especially if the patient ismale and is receiving azathioprine or 6-mercaptopurine treatment. REMICADE is contraindicated at doses 5 mg/kg in patients with moderate or severe heart failure and in patients with severe hypersensitivityreactions to REMICADE . Other serious side effects reported include melanoma, Merkel cell carcinoma,invasive cervical cancer, hepatitis B reactivation, hepatotoxicity, hematological events, hypersensitivity,cardiovascular and cerebrovascular reactions during and after infusion, neurological events, and lupus-likesyndrome. Please see related and other Important Safety Information on pages 17-20 of this guide.12
Reconstitution, Dilution, andAdministration Instructions1 (cont)INFUSION-RELATED REACTIONSAdverse Reactions During or Shortly After InfusionAn infusion reaction was defined in clinical trials as any adverse event occurring during an infusion orwithin 1 hour after an infusion. In all the clinical studies, approximately 20% of REMICADE -treated patientsexperienced an infusion reaction compared with 10% of placebo-treated patients. Of REMICADE -treatedpatients who had an infusion reaction during the induction period, 27% experienced an infusion reactionduring the maintenance period. Of patients who did not have an infusion reaction during the inductionperiod, 9% experienced an infusion reaction during the maintenance period.Among all REMICADE infusions, 3% were accompanied by nonspecific symptoms such as fever or chills,1% were accompanied by cardiopulmonary reactions (primarily chest pain, hypotension, hypertensionor dyspnea), and 1% were accompanied by prur
ulcerative colitis (UC) who have had an inadequate response to conventional therapy. Pediatric Ulcerative Colitis REMICADE is indicated for reducing signs and symptoms and inducing and maintaining clinical remission in pediatric patients 6 years of age and older with moderately to severely active UC who have had an
