WARNING
ANAPHYLAXIS
ANAPHYLAXIS HAS BEEN REPORTED AFTER ADMINISTRATION OF KALBITOR. BECAUSE OF THE RISK OF ANAPHYLAXIS, KALBITOR SHOULD ONLY BE ADMINISTERED BY A HEALTHCARE PROFESSIONAL WITH APPROPRIATE MEDICAL SUPPORT TO MANAGE ANAPHYLAXIS AND HEREDITARY ANGIOEDEMA. HEALTHCARE PROFESSIONALS SHOULD BE AWARE OF THE SIMILARITY OF SYMPTOMS BETWEEN HYPERSENSITIVITY REACTIONS AND HEREDITARY ANGIOEDEMA AND PATIENTS SHOULD BE MONITORED CLOSELY. DO NOT ADMINISTER KALBITOR TO PATIENTS WITH KNOWN CLINICAL HYPERSENSITIVITY TO KALBITOR. [SEE CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS, AND ADVERSE REACTIONS]
INDICATIONS
KALBITOR® (ECALLANTIDE) IS INDICATED FOR TREATMENT OF ACUTE ATTACKS OF HEREDITARY ANGIOEDEMA (HAE) IN PATIENTS 12 YEARS OF AGE AND OLDER.
HOW SUPPLIED
DOSAGE FORMS AND STRENGTHS
KALBITOR IS A CLEAR, COLORLESS LIQUID FREE OF PRESERVATIVES. EACH VIAL OF KALBITOR CONTAINS ECALLANTIDE AT A CONCENTRATION OF 10 MG/ML.
STORAGE AND HANDLING
KALBITOR (ECALLANTIDE) IS SUPPLIED AS THREE 10 MG/ML SINGLE-USE VIALS PACKAGED IN A CARTON. EACH VIAL CONTAINS 10 MG OF ECALLANTIDE. EACH VIAL CONTAINS A SLIGHT OVERFILL.
NDC (47783-101-01): 3 SINGLE-USE VIALS IN 1 CARTON
KALBITOR SHOULD BE KEPT REFRIGERATED (2°C TO 8°C/36°F TO 46°F). VIALS REMOVED FROM REFRIGERATION SHOULD BE STORED BELOW 86°F/30°C AND USED WITHIN 14 DAYS OR RETURNED TO REFRIGERATION UNTIL USE.
PROTECT VIALS FROM LIGHT UNTIL USE.
DO NOT USE BEYOND THE EXPIRATION DATE.
MANUFACTURED FOR: DYAX CORP. 55 NETWORK DRIVE, BURLINGTON, MA 01803. REVISED: 09/2014
DOSAGE AND ADMINISTRATION
RECOMMENDED DOSING
THE RECOMMENDED DOSE OF KALBITOR IS 30 MG (3 ML), ADMINISTERED SUBCUTANEOUSLY IN THREE 10 MG (1 ML) INJECTIONS. IF THE ATTACK PERSISTS, AN ADDITIONAL DOSE OF 30 MG MAY BE ADMINISTERED WITHIN A 24 HOUR PERIOD.
ADMINISTRATION INSTRUCTIONS
KALBITOR SHOULD ONLY BE ADMINISTERED BY A HEALTHCARE PROFESSIONAL WITH APPROPRIATE MEDICAL SUPPORT TO MANAGE ANAPHYLAXIS AND HEREDITARY ANGIOEDEMA.
KALBITOR SHOULD BE REFRIGERATED AND PROTECTED FROM THE LIGHT. KALBITOR IS A CLEAR, COLORLESS LIQUID; VISUALLY INSPECT EACH VIAL FOR PARTICULATE MATTER AND DISCOLORATION PRIOR TO ADMINISTRATION. IF THERE IS PARTICULATE MATTER OR DISCOLORATION, THE VIAL SHOULD NOT BE USED.
USING ASEPTIC TECHNIQUE, WITHDRAW 1 ML (10 MG) OF KALBITOR FROM THE VIAL USING A LARGE BORE NEEDLE. CHANGE THE NEEDLE ON THE SYRINGE TO A NEEDLE SUITABLE FOR SUBCUTANEOUS INJECTION. THE RECOMMENDED NEEDLE SIZE IS 27 GAUGE. INJECT KALBITOR INTO THE SKIN OF THE ABDOMEN, THIGH, OR UPPER ARM. REPEAT THE PROCEDURE FOR EACH OF THE 3 VIALS COMPRISING THE KALBITOR DOSE. THE INJECTION SITE FOR EACH OF THE INJECTIONS MAY BE IN THE SAME OR IN DIFFERENT ANATOMIC LOCATIONS (ABDOMEN, THIGH, UPPER ARM). THERE IS NO NEED FOR SITE ROTATION. INJECTION SITES SHOULD BE SEPARATED BY AT LEAST 2 INCHES (5 CM) AND AWAY FROM THE ANATOMICAL SITE OF ATTACK.
THE SAME INSTRUCTIONS APPLY TO AN ADDITIONAL DOSE ADMINISTERED WITHIN 24 HOURS. DIFFERENT INJECTION SITES OR THE SAME ANATOMICAL LOCATION (AS USED FOR THE FIRST ADMINISTRATION) MAY BE USED.
SIDE EFFECTS
HYPERSENSITIVITY REACTIONS, INCLUDING ANAPHYLAXIS, HAVE OCCURRED IN PATIENTS TREATED WITH KALBITOR [SEE CONTRAINDICATIONS AND WARNINGS AND PRECAUTIONS].
CLINICAL TRIALS EXPERIENCE
BECAUSE CLINICAL TRIALS ARE CONDUCTED UNDER WIDELY VARYING CONDITIONS, ADVERSE REACTION RATES OBSERVED IN THE CLINICAL TRIALS OF A DRUG CANNOT BE DIRECTLY COMPARED TO RATES IN THE CLINICAL TRIALS OF ANOTHER DRUG AND MAY NOT REFLECT THE RATES OBSERVED IN PRACTICE.
THE SAFETY DATA DESCRIBED BELOW REFLECT EXPOSURE TO KALBITOR IN 255 PATIENTS WITH HAE TREATED WITH EITHER INTRAVENOUS OR SUBCUTANEOUS KALBITOR. OF THE 255 PATIENTS, 66% OF PATIENTS WERE FEMALE AND 86% WERE CAUCASIAN. PATIENTS TREATED WITH KALBITOR WERE BETWEEN THE AGES OF 10 AND 78 YEARS.
OVERALL, THE MOST COMMON ADVERSE REACTIONS IN 255 PATIENTS WITH HAE WERE HEADACHE (16%), NAUSEA (13%), FATIGUE (12%), DIARRHEA (11%), UPPER RESPIRATORY TRACT INFECTION (8%), INJECTION SITE REACTIONS (7%), NASOPHARYNGITIS (6%), VOMITING (6%), PRURITUS (5%), UPPER ABDOMINAL PAIN (5%), AND PYREXIA (5%).
ANAPHYLAXIS WAS REPORTED IN 4% OF PATIENTS WITH HAE. INJECTION SITE REACTIONS WERE CHARACTERIZED BY LOCAL PRURITUS, ERYTHEMA, PAIN, IRRITATION, URTICARIA, AND/OR BRUISING.
THE INCIDENCE OF ADVERSE REACTIONS BELOW IS BASED UPON 2 PLACEBO-CONTROLLED, CLINICAL TRIALS (EDEMA3® AND EDEMA4®) IN A TOTAL OF 143 UNIQUE PATIENTS WITH HAE. PATIENTS WERE TREATED WITH KALBITOR 30 MG SUBCUTANEOUS OR PLACEBO. PATIENTS WERE PERMITTED TO PARTICIPATE SEQUENTIALLY IN BOTH PLACEBO-CONTROLLED TRIALS; SAFETY DATA COLLECTED DURING EXPOSURE TO KALBITOR WAS ATTRIBUTED TO TREATMENT WITH KALBITOR, AND SAFETY DATA COLLECTED DURING EXPOSURE TO PLACEBO WAS ATTRIBUTED TO TREATMENT WITH PLACEBO. TABLE 1 SHOWS ADVERSE REACTIONS OCCURRING IN ? 3% OF KALBITOR-TREATED PATIENTS THAT ALSO OCCURRED AT A HIGHER RATE THAN IN THE PLACEBO-TREATED PATIENTS IN THE TWO CONTROLLED TRIALS (EDEMA3 AND EDEMA4) OF THE 30 MG SUBCUTANEOUS DOSE.
TABLE 1: ADVERSE REACTIONS OCCURRING AT ? 3% AND HIGHER THAN PLACEBO IN 2 PLACEBO CONTROLLED CLINICAL TRIALS IN PATIENTS WITH HAE TREATED WITH KALBITOR
ADVERSE REACTIONS KALBITOR
N=100 PLACEBO
N=81
N (%) A N (%)A
HEADACHE 8 (8%) 6 (7%)
NAUSEA 5 (5%) 1 (1%)
DIARRHEA 4 (4%) 3 (4%)
PYREXIA 4 (4%) 0
INJECTION SITE REACTIONS 3 (3%) 1 (1%)
NASOPHARYNGITIS 3 (3%) 0
APATIENTS EXPERIENCING MORE THAN 1 EVENT WITH THE SAME PREFERRED TERM ARE COUNTED ONLY ONCE FOR THAT PREFERRED TERM.
SOME PATIENTS IN EDEMA3 AND EDEMA4 RECEIVED A SECOND, OPEN-LABEL 30 MG SUBCUTANEOUS DOSE OF KALBITOR WITHIN 24 HOURS FOLLOWING THE INITIAL DOSE. ADVERSE REACTIONS REPORTED BY THESE PATIENTS WHO RECEIVED THE ADDITIONAL 30 MG SUBCUTANEOUS DOSE OF KALBITOR WERE CONSISTENT WITH THOSE REPORTED IN THE PATIENTS RECEIVING A SINGLE DOSE.
IMMUNOGENICITY
IN THE KALBITOR HAE PROGRAM, PATIENTS DEVELOPED ANTIBODIES TO KALBITOR. RATES OF SEROCONVERSION INCREASED WITH EXPOSURE TO KALBITOR OVER TIME. OVERALL, 20.2% OF PATIENTS SEROCONVERTED TO ANTI-ECALLANTIDE ANTIBODIES. NEUTRALIZING ANTIBODIES TO ECALLANTIDE WERE DETERMINED IN VITRO TO BE PRESENT IN 8.8% OF PATIENTS AND WERE NOT ASSOCIATED WITH LOSS OF EFFICACY.
ANTI-ECALLANTIDE IGE ANTIBODIES WERE DETECTED AT A RATE OF 4.7% FOR TESTED PATIENTS, AND ANTI-P. PASTORIS IGE ANTIBODIES WERE ALSO DETECTED AT A RATE OF 20.2%. PATIENTS WHO SEROCONVERT MAY BE AT A HIGHER RISK OF A HYPERSENSITIVITY REACTION. THE LONG-TERM EFFECTS OF ANTIBODIES TO KALBITOR ARE NOT KNOWN.
THE TEST RESULTS FOR THE ECALLANTIDE PROGRAM WERE DETERMINED USING ONE OF TWO ASSAY FORMATS: ELISA AND BRIDGING ELECTROCHEMILUMINESCENCE (ECL). AS WITH ALL THERAPEUTIC PROTEINS, THERE IS A POTENTIAL FOR IMMUNOGENICITY WITH THE USE OF KALBITOR. THE INCIDENCE OF ANTIBODY FORMATION IS HIGHLY DEPENDENT ON THE SENSITIVITY AND SPECIFICITY OF THE ASSAY. ADDITIONALLY, THE OBSERVED INCIDENCE OF ANTIBODY (INCLUDING NEUTRALIZING ANTIBODY) POSITIVITY IN AN ASSAY MAY BE INFLUENCED BY SEVERAL FACTORS, INCLUDING ASSAY METHODOLOGY, SAMPLE HANDLING, TIMING OF SAMPLE COLLECTION, CONCOMITANT MEDICATIONS, AND UNDERLYING DISEASE. FOR THESE REASONS, COMPARISON OF THE INCIDENCE OF ANTIBODIES TO KALBITOR WITH THE INCIDENCE OF ANTIBODIES TO OTHER PRODUCTS MAY BE MISLEADING.
POSTMARKETING EXPERIENCE
SIMILAR ADVERSE REACTIONS HAVE BEEN OBSERVED POSTMARKETING AS DESCRIBED FOR CLINICAL TRIAL EXPERIENCE. BECAUSE THESE EVENTS ARE REPORTED VOLUNTARILY FROM A POPULATION OF UNCERTAIN SIZE, IT IS NOT ALWAYS POSSIBLE TO RELIABLY ESTIMATE FREQUENCY OR TO ESTABLISH A CAUSAL RELATIONSHIP WITH DRUG EXPOSURE.
READ THE KALBITOR (ECALLANTIDE INJECTION) SIDE EFFECTS CENTER FOR A COMPLETE GUIDE TO POSSIBLE SIDE EFFECTS
OVERDOSE
THERE HAVE BEEN NO REPORTS OF OVERDOSE WITH KALBITOR. HAE PATIENTS HAVE RECEIVED SINGLE DOSES UP TO 90 MG INTRAVENOUSLY WITHOUT EVIDENCE OF DOSE-RELATED TOXICITY.
CLINICAL PHARMACOLOGY
MECHANISM OF ACTION
HEREDITARY ANGIOEDEMA (HAE) IS A RARE GENETIC DISORDER CAUSED BY MUTATIONS TO C1-ESTERASE-INHIBITOR (C1-INH) LOCATED ON CHROMOSOME 11Q AND INHERITED AS AN AUTOSOMAL DOMINANT TRAIT. HAE IS CHARACTERIZED BY LOW LEVELS OF C1-INH ACTIVITY AND LOW LEVELS OF C4. C1-INH FUNCTIONS TO REGULATE THE ACTIVATION OF THE COMPLEMENT AND INTRINSIC COAGULATION (CONTACT SYSTEM PATHWAY) AND IS A MAJOR ENDOGENOUS INHIBITOR OF PLASMA KALLIKREIN. THE KALLIKREIN-KININ SYSTEM IS A COMPLEX PROTEOLYTIC CASCADE INVOLVED IN THE INITIATION OF BOTH INFLAMMATORY AND COAGULATION PATHWAYS. ONE CRITICAL ASPECT OF THIS PATHWAY IS THE CONVERSION OF HIGH MOLECULAR WEIGHT (HMW) KININOGEN TO BRADYKININ BY THE PROTEASE PLASMA KALLIKREIN. IN HAE, NORMAL REGULATION OF PLASMA KALLIKREIN ACTIVITY AND THE CLASSICAL COMPLEMENT CASCADE IS THEREFORE NOT PRESENT. DURING ATTACKS, UNREGULATED ACTIVITY OF PLASMA KALLIKREIN RESULTS IN EXCESSIVE BRADYKININ GENERATION. BRADYKININ IS A VASODILATOR WHICH IS THOUGHT BY SOME TO BE RESPONSIBLE FOR THE CHARACTERISTIC HAE SYMPTOMS OF LOCALIZED SWELLING, INFLAMMATION, AND PAIN.
KALBITOR IS A POTENT (KI = 25 PM), SELECTIVE, REVERSIBLE INHIBITOR OF PLASMA KALLIKREIN. KALBITOR BINDS TO PLASMA KALLIKREIN AND BLOCKS ITS BINDING SITE, INHIBITING THE CONVERSION OF HMW KININOGEN TO BRADYKININ. BY DIRECTLY INHIBITING PLASMA KALLIKREIN, KALBITOR REDUCES THE CONVERSION OF HMW KININOGEN TO BRADYKININ AND THEREBY TREATS SYMPTOMS OF THE DISEASE DURING ACUTE EPISODIC ATTACKS OF HAE.
PHARMACODYNAMICS
NO EXPOSURE-RESPONSE RELATIONSHIPS FOR KALBITOR TO COMPONENTS OF THE COMPLEMENT OR KALLIKREIN-KININ PATHWAYS HAVE BEEN ESTABLISHED.
THE EFFECT OF KALBITOR ON ACTIVATED PARTIAL THROMBOPLASTIN TIME (APTT) WAS MEASURED BECAUSE OF POTENTIAL EFFECT ON THE INTRINSIC COAGULATION PATHWAY. PROLONGATION OF APTT HAS BEEN OBSERVED FOLLOWING INTRAVENOUS DOSING OF KALBITOR AT DOSES ? 20 MG/M² . AT 80 MG ADMINISTERED INTRAVENOUSLY IN HEALTHY SUBJECTS, APTT VALUES WERE PROLONGED APPROXIMATELY TWO-FOLD OVER BASELINE VALUES AND RETURNED TO NORMAL BY 4 HOURS POST-DOSE.
FOR PATIENTS TAKING KALBITOR, NO SIGNIFICANT QT PROLONGATION HAS BEEN SEEN. IN A RANDOMIZED, PLACEBO-CONTROLLED TRIAL (EDEMA4) STUDYING THE 30 MG SUBCUTANEOUS DOSE VERSUS PLACEBO, 12-LEAD ECGS WERE OBTAINED AT BASELINE, 2 HOURS AND 4 HOURS POST-DOSE (COVERING THE TIME OF EXPECTED CMAX), AND AT FOLLOW-UP (DAY 7). ECGS WERE EVALUATED FOR PR INTERVAL, QRS COMPLEX, AND QTC INTERVAL. KALBITOR HAD NO SIGNIFICANT EFFECT ON THE QTC INTERVAL, HEART RATE, OR ANY OTHER COMPONENTS OF THE ECG.
PHARMACOKINETICS
FOLLOWING THE ADMINISTRATION OF A SINGLE 30 MG SUBCUTANEOUS DOSE OF KALBITOR TO HEALTHY SUBJECTS, A MEAN (± STANDARD DEVIATION) MAXIMUM PLASMA CONCENTRATION OF 586 ± 106 NG/ML WAS OBSERVED APPROXIMATELY 2 TO 3 HOURS POST-DOSE. THE MEAN AREA UNDER THE CONCENTRATION-TIME CURVE WAS 3017 ± 402 NG*HR/ML. FOLLOWING ADMINISTRATION, PLASMA CONCENTRATION DECLINED WITH A MEAN ELIMINATION HALF-LIFE OF 2.0 ± 0.5 HOURS. PLASMA CLEARANCE WAS 153 ± 20 ML/MIN AND THE VOLUME OF DISTRIBUTION WAS 26.4 ± 7.8 L. BASED ON A POPULATION PHARMACOKINETIC ANALYSIS, BODY WEIGHT, AGE, AND GENDER WERE NOT FOUND TO AFFECT KALBITOR EXPOSURE SIGNIFICANTLY. ECALLANTIDE IS A SMALL PROTEIN (7054 DA) AND RENAL ELIMINATION IN THE URINE OF TREATED SUBJECTS HAS BEEN DEMONSTRATED.
NO PHARMACOKINETIC DATA ARE AVAILABLE IN PATIENTS OR SUBJECTS WITH HEPATIC OR RENAL IMPAIRMENT.
CLINICAL STUDIES
THE SAFETY AND EFFICACY OF KALBITOR TO TREAT ACUTE ATTACKS OF HEREDITARY ANGIOEDEMA IN ADOLESCENTS AND ADULTS WERE EVALUATED IN 2 RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIALS (EDEMA4 AND EDEMA3) IN 168 PATIENTS WITH HAE. PATIENTS HAVING AN ATTACK OF HEREDITARY ANGIOEDEMA, AT ANY ANATOMIC LOCATION, WITH AT LEAST 1 MODERATE OR SEVERE SYMPTOM, WERE TREATED WITH 30 MG SUBCUTANEOUS KALBITOR OR PLACEBO. BECAUSE PATIENTS COULD PARTICIPATE IN BOTH TRIALS, A TOTAL OF 143 UNIQUE PATIENTS PARTICIPATED. OF THE 143 PATIENTS, 94 WERE FEMALE, 123 WERE CAUCASIAN, AND THE MEAN AGE WAS 36 YEARS (RANGE 11-77). THERE WERE 64 PATIENTS WITH ABDOMINAL ATTACKS, 55 WITH PERIPHERAL ATTACKS, AND 24 WITH LARYNGEAL ATTACKS.
IN BOTH TRIALS, THE EFFECTS OF KALBITOR WERE EVALUATED USING THE MEAN SYMPTOM COMPLEX SEVERITY (MSCS) SCORE AND THE TREATMENT OUTCOME SCORE (TOS). THESE ENDPOINTS EVALUATED ATTACK SEVERITY (MSCS) AND PATIENT RESPONSE TO TREATMENT (TOS) FOR AN ACUTE HAE ATTACK.
MSCS SCORE IS A POINT-IN-TIME MEASURE OF SYMPTOM SEVERITY. AT BASELINE, AND POST-DOSING AT 4 HOURS AND 24 HOURS, PATIENTS RATED THE SEVERITY OF EACH AFFECTED SYMPTOM ON A CATEGORICAL SCALE (0 = NORMAL, 1 = MILD, 2 = MODERATE, 3 = SEVERE). PATIENT-REPORTED SEVERITY WAS BASED ON EACH PATIENT'S ASSESSMENT OF SYMPTOM IMPACT ON THEIR ABILITY TO PERFORM ROUTINE ACTIVITIES. RATINGS WERE AVERAGED TO OBTAIN THE MSCS SCORE. THE ENDPOINT WAS REPORTED AS THE CHANGE IN MSCS SCORE FROM BASELINE. A DECREASE IN MSCS SCORE REFLECTED AN IMPROVEMENT IN SYMPTOM SEVERITY; THE MAXIMUM POSSIBLE CHANGE TOWARD IMPROVEMENT WAS -3.
TOS IS A MEASURE OF SYMPTOM RESPONSE TO TREATMENT. AT 4 HOURS AND 24 HOURS POST-DOSING, PATIENT ASSESSMENT OF RESPONSE FOR EACH ANATOMIC SITE OF ATTACK INVOLVEMENT WAS RECORDED ON A CATEGORICAL SCALE (SIGNIFICANT IMPROVEMENT [100], IMPROVEMENT [50], SAME [0], WORSENING [-50], SIGNIFICANT WORSENING [-100]). THE RESPONSE AT EACH ANATOMIC SITE WAS WEIGHTED BY BASELINE SEVERITY AND THEN THE WEIGHTED SCORES ACROSS ALL INVOLVED SITES WERE AVERAGED TO CALCULATE THE TOS. A TOS VALUE > 0 REFLECTED AN IMPROVEMENT IN SYMPTOMS FROM BASELINE. THE MAXIMUM POSSIBLE SCORE WAS +100.
EDEMA4
EDEMA4 WAS A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL IN WHICH 96 PATIENTS WERE RANDOMIZED 1:1 TO RECEIVE KALBITOR 30 MG SUBCUTANEOUS OR PLACEBO FOR ACUTE ATTACKS OF HAE. THE PRIMARY ENDPOINT WAS THE CHANGE FROM BASELINE IN MSCS SCORE AT 4 HOURS, AND THE TOS AT 4 HOURS WAS A KEY SECONDARY ENDPOINT. PATIENTS TREATED WITH KALBITOR DEMONSTRATED A GREATER DECREASE FROM BASELINE IN THE MSCS THAN PLACEBO AND A GREATER TOS THAN PATIENTS WITH PLACEBO AND THE RESULTS WERE STATISTICALLY SIGNIFICANT (TABLE 2). AT 24 HOURS, PATIENTS TREATED WITH KALBITOR ALSO DEMONSTRATED A GREATER DECREASE FROM BASELINE IN THE MSCS THAN PLACEBO (-1.5 VS. -1.1; P = 0.04) AND A GREATER TOS (89 VS. 55, P = 0.03).
TABLE 2: CHANGE IN MSCS SCORE AND TOS AT 4 HOURS
EDEMA4 EDEMA3
KALBITOR
(N=48) PLACEBO
(N=48) KALBITOR
(N=36) PLACEBO
(N=36)
CHANGE IN MSCS SCORE AT 4 HOURS
N 47 42 34 35
MEAN -0.8 -0.4 -1.1 -0.6
95% CI 0. - .0, - -0.6, -0.1 -1.4, -0.8, -0.8, -0.4
P-VALUE 0.010 0.041
TOS AT 4 HOURS
N 47 42 34 35
MEAN 53 8 63 36
95% CI 39, 68 -12, 28 49, 76 17, 54
P-VALUE 0.003 0.045
MSCS: MEAN SYMPTOM COMPLEX SEVERITY
TOS: TREATMENT OUTCOME SCORE
CI: CONFIDENCE INTERVAL
MORE PATIENTS IN THE PLACEBO GROUP (24/48, 50%) REQUIRED MEDICAL INTERVENTION TO TREAT UNRESOLVED SYMPTOMS WITHIN 24 HOURS COMPARED TO THE KALBITOR-TREATED GROUP (16/48, 33%).
SOME PATIENTS REPORTED IMPROVEMENT FOLLOWING A SECOND 30 MG SUBCUTANEOUS DOSE OF KALBITOR, ADMINISTERED WITHIN 24 HOURS FOLLOWING THE INITIAL DOSE FOR SYMPTOM PERSISTENCE OR RELAPSE, BUT EFFICACY WAS NOT SYSTEMATICALLY ASSESSED FOR THE SECOND DOSE.
EDEMA3
EDEMA3 WAS A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL IN WHICH 72 PATIENTS WERE RANDOMIZED 1:1 TO RECEIVE KALBITOR OR PLACEBO FOR ACUTE ATTACKS OF HAE. EDEMA3 WAS SIMILAR IN DESIGN TO EDEMA4 WITH THE EXCEPTION OF THE ORDER OF THE PRESPECIFIED EFFICACY ENDPOINTS. IN EDEMA3, THE PRIMARY ENDPOINT WAS THE TOS AT 4 HOURS, AND THE KEY SECONDARY EFFICACY ENDPOINT WAS THE CHANGE FROM BASELINE IN MSCS AT 4 HOURS. AS IN EDEMA4, PATIENTS TREATED WITH KALBITOR DEMONSTRATED A GREATER DECREASE FROM BASELINE IN THE MSCS THAN PLACEBO AND A GREATER TOS THAN PATIENTS TREATED WITH PLACEBO AND THE RESULTS WERE STATISTICALLY SIGNIFICANT (TABLE 2).
IN ADDITION, MORE PATIENTS IN THE PLACEBO GROUP (13/36, 36%) REQUIRED MEDICAL INTERVENTION TO TREAT UNRESOLVED SYMPTOMS WITHIN 24 HOURS COMPARED TO THE KALBITOR-TREATED GROUP (5/36, 14%).
KALBITOR CONSUMER
IMPORTANT: HOW TO USE THIS INFORMATION: THIS IS A SUMMARY AND DOES NOT HAVE ALL POSSIBLE INFORMATION ABOUT THIS PRODUCT. THIS INFORMATION DOES NOT ASSURE THAT THIS PRODUCT IS SAFE, EFFECTIVE, OR APPROPRIATE FOR YOU. THIS INFORMATION IS NOT INDIVIDUAL MEDICAL ADVICE AND DOES NOT SUBSTITUTE FOR THE ADVICE OF YOUR HEALTH CARE PROFESSIONAL. ALWAYS ASK YOUR HEALTH CARE PROFESSIONAL FOR COMPLETE INFORMATION ABOUT THIS PRODUCT AND YOUR SPECIFIC HEALTH NEEDS.
ECALLANTIDE - INJECTION
(E-KAL-LAN-TIDE)
COMMON BRAND NAME(S): KALBITOR
WARNING: ECALLANTIDE MAY INFREQUENTLY CAUSE SERIOUS (RARELY FATAL) ALLERGIC REACTIONS. PATIENTS WHO EXPERIENCE A SEVERE ALLERGIC REACTION WITH THIS DRUG MUST NEVER USE IT AGAIN. BECAUSE THE SYMPTOMS CAN BE THE SAME FOR AN ALLERGIC REACTION AND THE CONDITION WHICH THIS MEDICATION TREATS, YOU WILL BE MONITORED CLOSELY BY YOUR HEALTHCARE PROVIDERS AS YOU RECEIVE THIS MEDICATION IN A CLINIC OR HOSPITAL. IMMEDIATE MEDICAL ATTENTION SHOULD BE PROVIDED IF YOU DEVELOP ANY SIGNS OF AN ALLERGIC REACTION SUCH AS RASH, ITCHING/SWELLING (ESPECIALLY OF THE FACE/TONGUE/THROAT), SEVERE DIZZINESS, TROUBLE BREATHING, OR CHEST PAIN.
USES: THIS MEDICATION IS USED TO TREAT AN ACUTE ATTACK OF A CERTAIN IMMUNE DISEASE PASSED DOWN THROUGH FAMILIES (HEREDITARY ANGIOEDEMA-HAE). ECALLANTIDE BLOCKS A NATURAL SUBSTANCE PRODUCED BY THE BODY (KALLIKREIN) WHICH ACTS TO INCREASE AMOUNTS OF ANOTHER NATURAL SUBSTANCE (BRADYKININ) THOUGHT TO CAUSE THE SYMPTOMS SEEN DURING AN ACUTE ATTACK OF HAE. THIS MEDICATION DOES NOT CURE HAE. ECALLANTIDE MAY LESSEN THE SYMPTOMS DURING AN ACUTE ATTACK OF HAE SUCH AS RAPID SWELLING AND PAIN OF THE HANDS, FEET, LIMBS, FACE, TONGUE, OR THROAT. WHEN ATTACKS INVOLVE THE INTESTINES, SYMPTOMS MAY INCLUDE ABDOMINAL PAIN/CRAMPS, DIARRHEA OR VOMITING. ATTACKS OF SWELLING MAY OCCUR WITHOUT REASON. HOWEVER, ANXIETY, STRESS, SICKNESS, AND SURGERY MAY TRIGGER ATTACKS IN SOME PEOPLE.
HOW TO USE: READ THE MEDICATION GUIDE PROVIDED BY YOUR PHARMACIST BEFORE YOU START USING ECALLANTIDE AND EACH TIME YOU GET A REFILL. IF YOU HAVE ANY QUESTIONS, CONSULT YOUR DOCTOR OR PHARMACIST.
YOUR HEALTHCARE PROVIDER WILL INJECT THIS MEDICATION UNDER YOUR SKIN EITHER IN THE ABDOMEN, THIGH, OR UPPER ARMS AS DIRECTED BY YOUR DOCTOR. YOU WILL RECEIVE THREE SEPARATE SHOTS WHICH SHOULD BE SEPARATED BY AT LEAST 2 INCHES (5 CENTIMETERS). AN ADDITIONAL THREE SHOTS MAY BE GIVEN IN A 24-HOUR PERIOD IF THE HAE ATTACK CONTINUES.
DO NOT RECEIVE AN INJECTION INTO SKIN THAT IS TENDER, RED, OR HARD.
DOSAGE IS BASED ON YOUR MEDICAL CONDITION AND RESPONSE TO TREATMENT.
TELL YOUR DOCTOR IF YOUR CONDITION DOES NOT IMPROVE OR IF IT WORSENS.