Tagraxofusp-erzs: Difference between revisions
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{{DrugProjectFormSinglePage | {{DrugProjectFormSinglePage | ||
|authorTag= {{Uma}} | |authorTag= {{Uma}} | ||
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|genericName=generic name | |genericName=generic name | ||
|aOrAn=a | |aOrAn=a | ||
|drugClass= | |drugClass= antineoplastic biologic response modulator | ||
|indicationType= treatment | |indicationType= treatment | ||
|indication= | |indication= | ||
|hasBlackBoxWarning=Yes | |hasBlackBoxWarning=Yes | ||
|adverseReactions= Some adverse reactions that occur in patients undergoing treatment with Tagraxofusp-erzs are | |adverseReactions=Some adverse reactions that occur in patients undergoing treatment with Tagraxofusp-erzs are capillary leak syndrome, nausea, fatigue, peripheral edema, pyrexia, and weight gain. Some lab abnormalities that occur include decreases in [[albumin]], [[platelets]], [[hemoglobin]], [[calcium]], sodium, and increases in glucose,[[ALT]], and [[AST]]. | ||
|blackBoxWarningTitle= CAPILLARY LEAK SYNDROME | |||
|blackBoxWarningTitle= WARNING: CAPILLARY LEAK SYNDROME | |||
|blackBoxWarningBody=<i><span style="color:#FF0000;"></span></i> | |blackBoxWarningBody=<i><span style="color:#FF0000;"></span></i> | ||
*There have been fatal and life-threatening cases of Capillary Leak Syndrome | *There have been fatal and life-threatening cases of [[Capillary Leak Syndrome]] | ||
*Before initiating treatment, check patient to ensure proper cardiac function and that serum albumin is greater than 3.2 g/dL | *Before initiating treatment, check patient to ensure proper cardiac function and that serum albumin is greater than 3.2 g/dL | ||
*Measure Albumin levels periodically during treatment, and monitor closely after ending treatment for a period of time that is clinically instructed | *Measure Albumin levels periodically during treatment, and monitor closely after ending treatment for a period of time that is clinically instructed | ||
*Additionally, assess patients periodically and monitor carefully for signs or symptoms of CLS. Some signs and symptoms include weight gain, [[edema] (new or progressively deteriorating), [[pulmonary edema]], [[hypotension]], or[[ hemodynamic instability]] | *Additionally, assess patients periodically and monitor carefully for signs or symptoms of CLS. Some signs and symptoms include weight gain, [[edema]] (new or progressively deteriorating), [[pulmonary edema]], [[hypotension]], or[[ hemodynamic instability]] | ||
|fdaLIADAdult= | |fdaLIADAdult= | ||
==== | ====ELZONRIS is indicated for:==== | ||
*ELZONRIS is indicated for the treatment of [[blastic plasmacytoid dendritic cell neoplasm]] | |||
*It is a CD123-directed cytotoxin for the treatment of the specific cancer | |||
*This medication is administered to adult patients and pediatric patients 2 years and older with this type of cancer | |||
====Dosing Considerations==== | ====Dosing Considerations==== | ||
*Before initiating treatment of ELZONRIS, guarantee that the [[serum albumin]] is greater than or equal to 3.2 g/dL | |||
*Patients with [[H1- histamine antagonist]], [[H2- histamine antagonist]], [[corticosteroids]], and [[acetaminophen]] should be premedicated about 1 hour before initiating the ELZONRIS dose | |||
*The patients should be monitored after the first cycle of administration in an in person setting for up to 24 hours after initiation of the last infusion | |||
*The following cycles should be administered in an inpatient setting as well, or in a setting containing the equipment needed to treat and monitor the patients [[hematopoietic malignancies]]. Patients should be monitored for 4 hours following the previous infusion. | |||
====Preparation of | ====Preparation of ELZONRIS==== | ||
Before initiating dosage, make sure the following components are available to provide the patient treatment safely and successfully: 1 empty 10 mL sterile vial, 0.9% of sodium chloride injection, 3 10 mL sterile syringes, 1 mini-bifuse Y-connector, microbore tubing, and 1 0.2 [[micron polyethersulfone]] in-line filter | |||
Elzonris should be thawed in a room with the temperature ranging from 15°C and 25°C (59°F and 77°F), for 15-30 minutes in its original container and carton. The thawed medication is permitted to be exposed to room temperature for 1 hour prior to dosage preparation. THE VIAL SHOULD NOT BE REFROZEN AFTER IT HAS BEEN THAWED. | |||
The presentation of thawed Elzonris should be clear and colorless liquid that might consist of a few white to translucent particles. | |||
Preparation should be done using aseptic techniques. The steps of preparation are as follows: | |||
Prepare 10 mL of 100 mcg/mL Elzonris: | |||
*Use the sterile 10 mL syringe to transfer 9 mL of 0.9% sodium chloride injection, | |||
*Gently swirl the vial to make sure all the contents have been mixed properly. Then, remove the cap from the vial to use the sterile 1 mL syringe to 1 mL of the thawed Elzonris | |||
*Then transfer the 1 mL of Elzonris to the 10-mL vial that contains the sodium chloride injection. To mix the contents, slowly flip it back and forth. The final concentration is 100 mdg/mL. | |||
Prepare the Elzonris infusion set to initiate treatment | |||
*Calculate the weight-based required volume of the patient for the required volume of the diluted Elzonris (100 mcg/mL) | |||
*Repeat all of step one if the required weight-based dosage is above 10 mL of diluted ELZONRIS (100 mcg/mL). | |||
*Fill the syringes with at least 3 mL of the 0.9% sodium chloride injection. This will be used to flush the administration set after the dose has been administered to the patient. | |||
*Connect the saline flush syringe to an arm of the Y-connecter (see above for required materials). Make sure the clamp is close, and then connect the product syringe to the other arm of the Y-connecter. Finally, connect the final end of the Y-connecter to the microbore tube. | |||
*Use the supply side of the 0.2 micron filter and put it to the side. | |||
*Now, unclamp the arm of the Y-connector that contains the product syringe, and prepare the entire infusion set. Cap the filter and reclamp the Y-connector line on the product side. | |||
====Administration of | ====Administration of ELZONRIS==== | ||
*The recommended dose for patients is 12 mcg/kg that is administered intravenously for a period of 15 minutes daily once. The medication should be administered on days 1 and 5 of a 21-day cycle. | |||
*Patients should continue the treatment until the disease progresses, stops, or the patient suffers from unacceptable toxicity | |||
|offLabelAdultGuideSupport= | |offLabelAdultGuideSupport= | ||
There is limited information regarding ELZONRIS Off-Label Guideline-Supported Use and Dosage (Adult) in the drug label. | |||
There is limited information regarding | |||
|offLabelAdultNoGuideSupport= | |offLabelAdultNoGuideSupport= | ||
There is limited information regarding ELZONRIS Off-Label Non-Guideline-Supported Use and Dosage (Adult) in the drug label. | |||
There is limited information regarding | |||
|fdaLIADPed= | |fdaLIADPed= | ||
Elzonris reactions in pediatric patients above the age of 2 have been established. The pediatric patients respond to Elzonris similar to adult patients. To understand dose recommendations for pediatric patients, their guardian should talk to their healthcare provider. | |||
|offLabelPedGuideSupport= | |offLabelPedGuideSupport= | ||
There is limited information regarding | There is limited information regarding ELZONRIS Off-Label Guideline-Supported Use and Dosage (Pediatric) in the drug label. | ||
|offLabelPedNoGuideSupport= | |offLabelPedNoGuideSupport= | ||
There is limited information regarding ELZONRIS Off-Label Non-Guideline-Supported Use and Dosage (Pediatric) in the drug label. | |||
There is limited information regarding | |||
|contraindications= | |contraindications= | ||
*There are no contraindications for administration of Elzonris. | |||
|warnings = | |warnings = | ||
==== | ====Capillary Leak Syndrome==== | ||
*In the Clinical Trial of 94 patients, the total reported incidence cases for Capillary Leak Syndrome is 55% or 52/94 patients. Patients that experienced Grade 1 or 2 CLS was 46%, Grade 3 6%, and Grade 4 1%. There were two reported deaths (2%). | |||
*Some signs and symptoms that occur in patients treated with Elzonris include hypoalbuminemia, edema, weight gain, and hypotension | |||
====== | *Patients should be tested before initiating treatment to check for proper cardiac function and make sure the serum albumin is greater than or equal to 3.2 g/dL. | ||
*Additionally, assess patients periodically and monitor carefully for signs or symptoms of CLS. Some signs and symptoms include weight gain, [[edema]] (new or progressively deteriorating), [[pulmonary edema]], [[hypotension]], or [[ hemodynamic instability]] | |||
======Hypersensitivity Reactions====== | |||
====== | *Patients may suffer severe hypersensitivity reactions while undergoing treatment with Elzonris. In Clinical Trials, there were 46% or 43/94 patients who suffered hypersensitivity reactions. About 10% or 9/94 of the patients suffered from Grade 3 hypersensitivity reactions. | ||
*Some hypersensitivity reactions that were reported with the clinical trial include: rash, [[pruritus]], [[stomatitis]], and [[wheezing]]. | |||
*Patients should be monitored carefully for manifestation of hypersensitivity reactions, and if any arise immediately discontinue Elzonris treatment and care for the specific reaction present. | |||
*Patients should talk with their medical practitioner to understand the side effects of the medication, and when to reduce the dose or discontinue forever. | |||
====Hepatotoxicity==== | |||
*Trials showed that elevated liver enzymes were related to Elzonris infusions. | |||
*Clinical trials showed that about 88% or 83/94 patients showed an increase in liver enzymes. About 48% of the patients showed signs of Grade 1 or 2 elevation levels, 36% showed Grade 3 in elevation levels, and about 4% showed Grade 4 in elevation levels of liver enzymes. | |||
*Patients liver enzymes such as [[alanine aminotransferase (ALT)]] and [[aspartate aminotransferase (AST)]] should be monitored regularly and prior to every infusion. | |||
*Temporarily discontinue treatment and daily dosage if the levels of the enzymes rises to greater than 5 times the upper limit of the normal levels, and recommence treatment once the levels have gone back to normal. Patients should talk to their doctor if they have any concerns about the levels of their liver enzymes and/or if the enzyme levels are consistently above normal. | |||
====Infusion Reactions==== | ====Infusion Reactions==== | ||
Some infusion reaction are capillary leak syndrome, nausea, fatigue, peripheral edema, pyrexia, and weight increase | |||
|clinicalTrials = | |clinicalTrials = | ||
The safety of Elzonris was tested in Study STML-401-0114 which was a single-arm clinical trial. It was conducted among 94 adults with newly-diagnosed or relapsed/refractory myeloid malignancies, which included 58 patients with BPDCN, that were treated with ELZONRIS 12 mcg/kg daily for 5 days of a 21-day cycle. | |||
About 2% of the patients had a fatal adverse reaction, which was the Capillary Leak Syndrome. About 11% or 10 patients discontinued treatment with Elzonris because of an adverse reaction. The most common adverse reactions that became severe enough for discontinuation were hepatic toxicities and Capillary Leak Syndrome. | |||
|postmarketing= There is limited information regarding | |postmarketing= There is limited information regarding Alpelisib Postmarketing Experience in the drug label. | ||
|drugInteractions= There | |drugInteractions= | ||
There have been no drug interaction studies conducted with Elzonris. | |||
|useInPregnancyFDA= | |useInPregnancyFDA= Elzonris has shown to have embryo-fetal adverse effects for its development. Animal reproduction or developmental toxicity studies have not been conducted with tagraxofusp-erzs. Counsel pregnant women of the potential risk to the fetus. | ||
|useInLaborDelivery= The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. | |useInLaborDelivery= The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. | ||
|useInNursing= | |useInNursing= Women should not breastfeed while undergoing treatment with this medication and for 1 week after the last dose. | ||
|useInPed= The | |useInPed= A trial conducted with adults in a well-controlled study with 1 child (2 years to < 12 years old) and 2 adolescents (12 years to < 17 years old), treated with ELZONRIS at the recommended dosage. The efficacy of Elzonris in Pediatric patients is similar to that in adults. | ||
|useInGeri= | |useInGeri= There were 94 patients who received ELZONRIS at the labeled dose in STML-401-0114, and of that, 23% were 75 years of age and older. The older patients showed more tendencies for an altered mental status like confusional state, delirium, mental status changes, dementia, and encephalopathy, compared to the younger patients. | ||
|useInGender= There is no FDA guidance on the use of | |useInGender= There is no FDA guidance on the use of ALPELISIB with respect to specific gender populations. | ||
|useInRace= There is no FDA guidance on the use of | |useInRace= There is no FDA guidance on the use of ALPELISIB with respect to specific racial populations. | ||
|useInRenalImpair= There is no FDA guidance on the use of | |useInRenalImpair= There is no FDA guidance on the use of ALPELISIB in patients with renal impairment. | ||
|useInHepaticImpair= There is no FDA guidance on the use of | |useInHepaticImpair= There is no FDA guidance on the use of ALPELISIB in patients with hepatic impairment. | ||
|useInReproPotential= | |useInReproPotential= FDA guidance suggests healthcare providers should advise and counsel all patients with reproductive potential that ELZONRIS may impair fertility. Advise females to use acceptable contraceptive methods during ELZONRIS treatment and for at least 1 week after the last dose of ELZONRIS. | ||
|useInImmunocomp= There is no FDA guidance one the use of | |useInImmunocomp= There is no FDA guidance one the use of ALPELISIB in patients who are immunocompromised. | ||
|useInOthers=(Description) | |useInOthers=(Description) | ||
|administration= | |administration= | ||
Elzonris is administered intravenously | |||
|overdose = | |overdose = | ||
In cases of overdosage with Elzonris, patients showed a similar set of adverse reactions as indicated in Elzonris’s profile. These include capillary leak syndrome, nausea, fatigue, peripheral edema, pyrexia, and weight gain. | |||
There are no established protocols to entail an Elzonris overdose. As in all cases of overdose with every drug, “Initiate general symptomatic and supportive measures in all cases” | |||
If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately. | |||
|drugBox={{Drugbox2 | |drugBox={{Drugbox2 | ||
| verifiedrevid = | | verifiedrevid = | ||
| IUPAC_name = | | IUPAC_name = (2S)-1-N-[4-methyl-5-[2-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridin-4-yl]-1,3-thiazol-2-yl]pyrrolidine-1,2-dicarboxamide | ||
| image = | | image = | ||
| drug_name = | | drug_name = Tagrxofusp-erzs | ||
<!--Clinical data--> | <!--Clinical data--> | ||
| Line 123: | Line 131: | ||
| pregnancy_US = | | pregnancy_US = | ||
| legal_status = | | legal_status = | ||
| routes_of_administration = | | routes_of_administration = Intravenous use | ||
<!--Pharmacokinetic data--> | <!--Pharmacokinetic data--> | ||
| bioavailability = | | bioavailability = intravenously | ||
| metabolism = | | metabolism = hydrolysis reactions and CYP3A4 | ||
| elimination_half-life = | | elimination_half-life = 0.7 hours | ||
| excretion = | | excretion = 7.1 L/hr | ||
<!--Identifiers--> | <!--Identifiers--> | ||
| CAS_number_Ref = | | CAS_number_Ref = | ||
| CAS_number = | | CAS_number = 1217486-61-7 | ||
| ATC_prefix = | | ATC_prefix = | ||
| ATC_suffix = | | ATC_suffix = | ||
| Line 153: | Line 161: | ||
<!--Chemical data--> | <!--Chemical data--> | ||
| C= | H= | N= | O= | | C= | H= | N= | O= | ||
| molecular_weight = | | molecular_weight = 441.5 g/mol | ||
| smiles = | | smiles = | ||
| InChI = | | InChI = 1S/C19H22F3N5O2S/c1-10-14(11-6-7-24-13(9-11)18(2,3)19(20,21)22)30-16(25-10)26-17(29)27-8-4-5-12(27)15(23)28/h6-7,9,12H,4-5,8H2,1-3H3,(H2,23,28)(H,25,26,29)/t12-/m0/s1 | ||
| InChIKey = | | InChIKey = STUWGJZDJHPWGZ-LBPRGKRZSA-N | ||
| StdInChI_Ref = | | StdInChI_Ref = | ||
| StdInChI = | | StdInChI = | ||
| Line 163: | Line 171: | ||
| melting_point = | | melting_point = | ||
}} | }} | ||
|mechAction= | |mechAction= *Elzonris a CD123-directed cytotoxin that is composed of [[ interleukin-3 (IL-3)]] and [[truncated diphtheria toxin (DT)]]. It is a fusion protein that interrupts and stops protein synthesis that will cause cell death in CD123- expressing cells. | ||
|structure= There is limited information regarding | |structure= There is limited information regarding ELZONRIS Structure in the drug label. | ||
|PD= | |PD= | ||
|PK= | |||
|PK= The mean area under of the plasma plasma drug concentration over time curve 231 hr times mcg/liter and the maximum plasma concentration 162 mcg/L, resulting from the administration of Elzonris with a dose of 12 mcg/kg via 15-min infusion in patients. | |||
=====Distribution===== | =====Distribution===== | ||
The mean volume of distribution is 5.1 (1.9) L | |||
=====Elimination===== | =====Elimination===== | ||
The mean SD clearance is 7.1 L/hr and the mean SD terminal half-life 0.7 hours. | |||
=====Specific Populations===== | =====Specific Populations===== | ||
There were no major changes that occurred in the efficacy of Elzonris after adjusting the dosage by the body weight. There were no significant effects based on gender, age (22-84), mild-moderate renal impairment, mild-moderate hepatic impairment, or drastic changes in body weight after changing up the dosage. | |||
The effects of severe hepatic impairment or severe renal impairment have not been established. | |||
Patients are advised to not breastfeed during treatment, and for 1 week after the last dose. | |||
|nonClinToxic= | |nonClinToxic= | ||
====Carcinogenesis, Mutagenesis, Impairment of Fertility==== | ====Carcinogenesis, Mutagenesis, Impairment of Fertility==== | ||
*Studies of carcinogenicity and mutagenicity have not yet been performed. There are no studies conducted on animal fertility. | |||
|clinicalStudies= | |clinicalStudies= | ||
====Study STML-401-0114 (NCT 02113982; Study 0114)==== | |||
==== | *This clinical trial was held in multiple centers, and was an open label, single-arm trial that additionally included a cohort of 13 patients administered treatment-naive BPDCN. | ||
*The treatment in the trial consisted of patients receiving a daily dosage of 12 mcg/kg Elzonris that was administered intravenously over 15 minutes. This round of administration occurred on Days 1 and 5 of a 21-day cycle. | |||
*The demographics of the patients were as follows: | |||
*With a total of 13 patients, 2 were female and 11 were male. The median age for those 13 patients was 65 years with the minimum age being 22 and the maximum age being 84. | |||
*The efficacy was measured based on the rate of complete response or clinical complete response (CR/CRc). The CR/CRc Rate was measured as 7 and the Duration of CR/CRc was measured as a minimum of 3.9 months and a maximum of 12.2 months. The duration of follow up was a minimum of 0.2 months and a maximum of 12.7 months. | |||
*With 15 patients in relapsed/refractory BPDCN, one patient reached CR duration of 111 days and one person reached CRc duration of 424 days. | |||
|howSupplied= | |howSupplied= | ||
Elzonris is supplied as an injection that is preservative free, sterile, clear, and colorless. | |||
It is a 1000 mcg in mL solution. It is supplied in a single-dose glass vial. Each of the cartons that it comes in contains one vial. | |||
|storage= | |storage= | ||
Elzonris should be stored in a freezer under temperatures ranging from -25°C and -15°C (-13°F and 5°F). Elzonris should be protected from the light, so leave it in its original packaging until its ready to be administered. The vials should be thawed at room temperature, 15°C and 25°C (59°F and 77°F), right before preparation. DO NOT REFREEZE THE VIAL AFTER IT HAS BEEN THAWED. Check the label for an expiration date, and do not use it beyond that date. | |||
|packLabel= | |||
|fdaPatientInfo= | |fdaPatientInfo= | ||
===== | ====Capillary Leak Syndrome==== | ||
*Patients should be aware of the seriousness of CLS and learn the side effect prior to initiating treatment. Some of the side effects include new or worsening edema, weight gain, shortness of breath, and/or hypotension after infusion. | |||
==== | *Patients should contact their healthcare provider immediately if any of these signs and symptoms arise. | ||
*Patients are advised to weight themselves daily because CLS can cause a sudden increase in body weight. | |||
======Hypersensitivity Reactions====== | |||
*Patients are advised to know the effects of hypersensitivity reactions and what they are. Contact their medical professional immediately when any of these signs or symptoms arise: | |||
*Rash, flushing, wheezing and swelling of the face | |||
====Hepatotoxicity==== | |||
*Patients should call their healthcare provider immediately if any signs and/or symptoms of Hepatotoxicity arise. | |||
*Some of the signs and symptoms include fatigue, anorexia and/or right upper abdominal discomfort. | |||
*Patients may be required to temporarily discontinue treatment with Elzonris if these symptoms pose harsh threats to the liver enzyme levels. | |||
====Infusion Reactions==== | |||
Some infusion reaction are capillary leak syndrome, nausea, fatigue, peripheral edema, pyrexia, and weight increase | |||
====Discontinuation==== | ====Discontinuation==== | ||
*Patients will be advised to temporarily or permanently discontinue the medication if adverse reactions become severe or persist. | |||
====Infusion reactions==== | ====Infusion reactions==== | ||
*Advise patients that administration of | *Advise patients that administration of ELZONRIS may result in infusion reactions. | ||
|nlmPatientInfo=(Link to patient information page) | |nlmPatientInfo=(Link to patient information page) | ||
|lookAlike= There is limited information regarding | |lookAlike= There is limited information regarding ELZONRIS Look-Alike Drug Names in the drug label. | ||
|brandNames= | |brandNames= | ||
ELZONRIS | |||
|drugShortage= | |drugShortage= | ||
Drug Shortage | Drug Shortage | ||
}} | }} | ||
Latest revision as of 22:55, 14 December 2020
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Uma Maveli[2]
Disclaimer
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Black Box Warning
|
WARNING: CAPILLARY LEAK SYNDROME
See full prescribing information for complete Boxed Warning.
|
Overview
Tagraxofusp-erzs is a antineoplastic biologic response modulator that is FDA approved for the treatment of . There is a Black Box Warning for this drug as shown here. Common adverse reactions include Some adverse reactions that occur in patients undergoing treatment with Tagraxofusp-erzs are capillary leak syndrome, nausea, fatigue, peripheral edema, pyrexia, and weight gain. Some lab abnormalities that occur include decreases in albumin, platelets, hemoglobin, calcium, sodium, and increases in glucose,ALT, and AST..
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
ELZONRIS is indicated for:
- ELZONRIS is indicated for the treatment of blastic plasmacytoid dendritic cell neoplasm
- It is a CD123-directed cytotoxin for the treatment of the specific cancer
- This medication is administered to adult patients and pediatric patients 2 years and older with this type of cancer
Dosing Considerations
- Before initiating treatment of ELZONRIS, guarantee that the serum albumin is greater than or equal to 3.2 g/dL
- Patients with H1- histamine antagonist, H2- histamine antagonist, corticosteroids, and acetaminophen should be premedicated about 1 hour before initiating the ELZONRIS dose
- The patients should be monitored after the first cycle of administration in an in person setting for up to 24 hours after initiation of the last infusion
- The following cycles should be administered in an inpatient setting as well, or in a setting containing the equipment needed to treat and monitor the patients hematopoietic malignancies. Patients should be monitored for 4 hours following the previous infusion.
Preparation of ELZONRIS
Before initiating dosage, make sure the following components are available to provide the patient treatment safely and successfully: 1 empty 10 mL sterile vial, 0.9% of sodium chloride injection, 3 10 mL sterile syringes, 1 mini-bifuse Y-connector, microbore tubing, and 1 0.2 micron polyethersulfone in-line filter Elzonris should be thawed in a room with the temperature ranging from 15°C and 25°C (59°F and 77°F), for 15-30 minutes in its original container and carton. The thawed medication is permitted to be exposed to room temperature for 1 hour prior to dosage preparation. THE VIAL SHOULD NOT BE REFROZEN AFTER IT HAS BEEN THAWED. The presentation of thawed Elzonris should be clear and colorless liquid that might consist of a few white to translucent particles. Preparation should be done using aseptic techniques. The steps of preparation are as follows: Prepare 10 mL of 100 mcg/mL Elzonris:
- Use the sterile 10 mL syringe to transfer 9 mL of 0.9% sodium chloride injection,
- Gently swirl the vial to make sure all the contents have been mixed properly. Then, remove the cap from the vial to use the sterile 1 mL syringe to 1 mL of the thawed Elzonris
- Then transfer the 1 mL of Elzonris to the 10-mL vial that contains the sodium chloride injection. To mix the contents, slowly flip it back and forth. The final concentration is 100 mdg/mL.
Prepare the Elzonris infusion set to initiate treatment
- Calculate the weight-based required volume of the patient for the required volume of the diluted Elzonris (100 mcg/mL)
- Repeat all of step one if the required weight-based dosage is above 10 mL of diluted ELZONRIS (100 mcg/mL).
- Fill the syringes with at least 3 mL of the 0.9% sodium chloride injection. This will be used to flush the administration set after the dose has been administered to the patient.
- Connect the saline flush syringe to an arm of the Y-connecter (see above for required materials). Make sure the clamp is close, and then connect the product syringe to the other arm of the Y-connecter. Finally, connect the final end of the Y-connecter to the microbore tube.
- Use the supply side of the 0.2 micron filter and put it to the side.
- Now, unclamp the arm of the Y-connector that contains the product syringe, and prepare the entire infusion set. Cap the filter and reclamp the Y-connector line on the product side.
Administration of ELZONRIS
- The recommended dose for patients is 12 mcg/kg that is administered intravenously for a period of 15 minutes daily once. The medication should be administered on days 1 and 5 of a 21-day cycle.
- Patients should continue the treatment until the disease progresses, stops, or the patient suffers from unacceptable toxicity
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding ELZONRIS Off-Label Guideline-Supported Use and Dosage (Adult) in the drug label.
Non–Guideline-Supported Use
There is limited information regarding ELZONRIS Off-Label Non-Guideline-Supported Use and Dosage (Adult) in the drug label.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
Elzonris reactions in pediatric patients above the age of 2 have been established. The pediatric patients respond to Elzonris similar to adult patients. To understand dose recommendations for pediatric patients, their guardian should talk to their healthcare provider.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding ELZONRIS Off-Label Guideline-Supported Use and Dosage (Pediatric) in the drug label.
Non–Guideline-Supported Use
There is limited information regarding ELZONRIS Off-Label Non-Guideline-Supported Use and Dosage (Pediatric) in the drug label.
Contraindications
- There are no contraindications for administration of Elzonris.
Warnings
|
WARNING: CAPILLARY LEAK SYNDROME
See full prescribing information for complete Boxed Warning.
|
Capillary Leak Syndrome
- In the Clinical Trial of 94 patients, the total reported incidence cases for Capillary Leak Syndrome is 55% or 52/94 patients. Patients that experienced Grade 1 or 2 CLS was 46%, Grade 3 6%, and Grade 4 1%. There were two reported deaths (2%).
- Some signs and symptoms that occur in patients treated with Elzonris include hypoalbuminemia, edema, weight gain, and hypotension
- Patients should be tested before initiating treatment to check for proper cardiac function and make sure the serum albumin is greater than or equal to 3.2 g/dL.
- Additionally, assess patients periodically and monitor carefully for signs or symptoms of CLS. Some signs and symptoms include weight gain, edema (new or progressively deteriorating), pulmonary edema, hypotension, or hemodynamic instability
Hypersensitivity Reactions
- Patients may suffer severe hypersensitivity reactions while undergoing treatment with Elzonris. In Clinical Trials, there were 46% or 43/94 patients who suffered hypersensitivity reactions. About 10% or 9/94 of the patients suffered from Grade 3 hypersensitivity reactions.
- Some hypersensitivity reactions that were reported with the clinical trial include: rash, pruritus, stomatitis, and wheezing.
- Patients should be monitored carefully for manifestation of hypersensitivity reactions, and if any arise immediately discontinue Elzonris treatment and care for the specific reaction present.
- Patients should talk with their medical practitioner to understand the side effects of the medication, and when to reduce the dose or discontinue forever.
Hepatotoxicity
- Trials showed that elevated liver enzymes were related to Elzonris infusions.
- Clinical trials showed that about 88% or 83/94 patients showed an increase in liver enzymes. About 48% of the patients showed signs of Grade 1 or 2 elevation levels, 36% showed Grade 3 in elevation levels, and about 4% showed Grade 4 in elevation levels of liver enzymes.
- Patients liver enzymes such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST) should be monitored regularly and prior to every infusion.
- Temporarily discontinue treatment and daily dosage if the levels of the enzymes rises to greater than 5 times the upper limit of the normal levels, and recommence treatment once the levels have gone back to normal. Patients should talk to their doctor if they have any concerns about the levels of their liver enzymes and/or if the enzyme levels are consistently above normal.
Infusion Reactions
Some infusion reaction are capillary leak syndrome, nausea, fatigue, peripheral edema, pyrexia, and weight increase
Adverse Reactions
Clinical Trials Experience
The safety of Elzonris was tested in Study STML-401-0114 which was a single-arm clinical trial. It was conducted among 94 adults with newly-diagnosed or relapsed/refractory myeloid malignancies, which included 58 patients with BPDCN, that were treated with ELZONRIS 12 mcg/kg daily for 5 days of a 21-day cycle. About 2% of the patients had a fatal adverse reaction, which was the Capillary Leak Syndrome. About 11% or 10 patients discontinued treatment with Elzonris because of an adverse reaction. The most common adverse reactions that became severe enough for discontinuation were hepatic toxicities and Capillary Leak Syndrome.
Postmarketing Experience
There is limited information regarding Alpelisib Postmarketing Experience in the drug label.
Drug Interactions
There have been no drug interaction studies conducted with Elzonris.
Use in Specific Populations
Pregnancy
Pregnancy Category (FDA):
Elzonris has shown to have embryo-fetal adverse effects for its development. Animal reproduction or developmental toxicity studies have not been conducted with tagraxofusp-erzs. Counsel pregnant women of the potential risk to the fetus.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Tagraxofusp-erzs in women who are pregnant.
Labor and Delivery
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
Nursing Mothers
Women should not breastfeed while undergoing treatment with this medication and for 1 week after the last dose.
Pediatric Use
A trial conducted with adults in a well-controlled study with 1 child (2 years to < 12 years old) and 2 adolescents (12 years to < 17 years old), treated with ELZONRIS at the recommended dosage. The efficacy of Elzonris in Pediatric patients is similar to that in adults.
Geriatic Use
There were 94 patients who received ELZONRIS at the labeled dose in STML-401-0114, and of that, 23% were 75 years of age and older. The older patients showed more tendencies for an altered mental status like confusional state, delirium, mental status changes, dementia, and encephalopathy, compared to the younger patients.
Gender
There is no FDA guidance on the use of ALPELISIB with respect to specific gender populations.
Race
There is no FDA guidance on the use of ALPELISIB with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of ALPELISIB in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of ALPELISIB in patients with hepatic impairment.
Females of Reproductive Potential and Males
FDA guidance suggests healthcare providers should advise and counsel all patients with reproductive potential that ELZONRIS may impair fertility. Advise females to use acceptable contraceptive methods during ELZONRIS treatment and for at least 1 week after the last dose of ELZONRIS.
Immunocompromised Patients
There is no FDA guidance one the use of ALPELISIB in patients who are immunocompromised.
Administration and Monitoring
Administration
Elzonris is administered intravenously
Monitoring
There is limited information regarding Tagraxofusp-erzs Monitoring in the drug label.
IV Compatibility
There is limited information regarding the compatibility of Tagraxofusp-erzs and IV administrations.
Overdosage
In cases of overdosage with Elzonris, patients showed a similar set of adverse reactions as indicated in Elzonris’s profile. These include capillary leak syndrome, nausea, fatigue, peripheral edema, pyrexia, and weight gain. There are no established protocols to entail an Elzonris overdose. As in all cases of overdose with every drug, “Initiate general symptomatic and supportive measures in all cases” If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.
Pharmacology
Tagrxofusp-erzs
| |
| Systematic (IUPAC) name | |
| (2S)-1-N-[4-methyl-5-[2-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridin-4-yl]-1,3-thiazol-2-yl]pyrrolidine-1,2-dicarboxamide | |
| Identifiers | |
| CAS number | |
| ATC code | ? |
| PubChem | ? |
| Chemical data | |
| Formula | ? |
| Mol. mass | 441.5 g/mol |
| Pharmacokinetic data | |
| Bioavailability | intravenously |
| Metabolism | hydrolysis reactions and CYP3A4 |
| Half life | 0.7 hours |
| Excretion | 7.1 L/hr |
| Therapeutic considerations | |
| Pregnancy cat. |
? |
| Legal status | |
| Routes | Intravenous use |
Mechanism of Action
- Elzonris a CD123-directed cytotoxin that is composed of interleukin-3 (IL-3) and truncated diphtheria toxin (DT). It is a fusion protein that interrupts and stops protein synthesis that will cause cell death in CD123- expressing cells.
Structure
There is limited information regarding ELZONRIS Structure in the drug label.
Pharmacodynamics
There is limited information regarding Tagraxofusp-erzs Pharmacodynamics in the drug label.
Pharmacokinetics
The mean area under of the plasma plasma drug concentration over time curve 231 hr times mcg/liter and the maximum plasma concentration 162 mcg/L, resulting from the administration of Elzonris with a dose of 12 mcg/kg via 15-min infusion in patients.
Distribution
The mean volume of distribution is 5.1 (1.9) L
Elimination
The mean SD clearance is 7.1 L/hr and the mean SD terminal half-life 0.7 hours.
Specific Populations
There were no major changes that occurred in the efficacy of Elzonris after adjusting the dosage by the body weight. There were no significant effects based on gender, age (22-84), mild-moderate renal impairment, mild-moderate hepatic impairment, or drastic changes in body weight after changing up the dosage. The effects of severe hepatic impairment or severe renal impairment have not been established. Patients are advised to not breastfeed during treatment, and for 1 week after the last dose.
Nonclinical Toxicology
Carcinogenesis, Mutagenesis, Impairment of Fertility
- Studies of carcinogenicity and mutagenicity have not yet been performed. There are no studies conducted on animal fertility.
Clinical Studies
Study STML-401-0114 (NCT 02113982; Study 0114)
- This clinical trial was held in multiple centers, and was an open label, single-arm trial that additionally included a cohort of 13 patients administered treatment-naive BPDCN.
- The treatment in the trial consisted of patients receiving a daily dosage of 12 mcg/kg Elzonris that was administered intravenously over 15 minutes. This round of administration occurred on Days 1 and 5 of a 21-day cycle.
- The demographics of the patients were as follows:
- With a total of 13 patients, 2 were female and 11 were male. The median age for those 13 patients was 65 years with the minimum age being 22 and the maximum age being 84.
- The efficacy was measured based on the rate of complete response or clinical complete response (CR/CRc). The CR/CRc Rate was measured as 7 and the Duration of CR/CRc was measured as a minimum of 3.9 months and a maximum of 12.2 months. The duration of follow up was a minimum of 0.2 months and a maximum of 12.7 months.
- With 15 patients in relapsed/refractory BPDCN, one patient reached CR duration of 111 days and one person reached CRc duration of 424 days.
How Supplied
Elzonris is supplied as an injection that is preservative free, sterile, clear, and colorless. It is a 1000 mcg in mL solution. It is supplied in a single-dose glass vial. Each of the cartons that it comes in contains one vial.
Storage
Elzonris should be stored in a freezer under temperatures ranging from -25°C and -15°C (-13°F and 5°F). Elzonris should be protected from the light, so leave it in its original packaging until its ready to be administered. The vials should be thawed at room temperature, 15°C and 25°C (59°F and 77°F), right before preparation. DO NOT REFREEZE THE VIAL AFTER IT HAS BEEN THAWED. Check the label for an expiration date, and do not use it beyond that date.
Images
Drug Images
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Package and Label Display Panel
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Patient Counseling Information
Capillary Leak Syndrome
- Patients should be aware of the seriousness of CLS and learn the side effect prior to initiating treatment. Some of the side effects include new or worsening edema, weight gain, shortness of breath, and/or hypotension after infusion.
- Patients should contact their healthcare provider immediately if any of these signs and symptoms arise.
- Patients are advised to weight themselves daily because CLS can cause a sudden increase in body weight.
Hypersensitivity Reactions
- Patients are advised to know the effects of hypersensitivity reactions and what they are. Contact their medical professional immediately when any of these signs or symptoms arise:
- Rash, flushing, wheezing and swelling of the face
Hepatotoxicity
- Patients should call their healthcare provider immediately if any signs and/or symptoms of Hepatotoxicity arise.
- Some of the signs and symptoms include fatigue, anorexia and/or right upper abdominal discomfort.
- Patients may be required to temporarily discontinue treatment with Elzonris if these symptoms pose harsh threats to the liver enzyme levels.
Infusion Reactions
Some infusion reaction are capillary leak syndrome, nausea, fatigue, peripheral edema, pyrexia, and weight increase
Discontinuation
- Patients will be advised to temporarily or permanently discontinue the medication if adverse reactions become severe or persist.
Infusion reactions
- Advise patients that administration of ELZONRIS may result in infusion reactions.
Precautions with Alcohol
Alcohol-Tagraxofusp-erzs interaction has not been established. Talk to your doctor regarding the effects of taking alcohol with this medication.
Brand Names
ELZONRIS
Look-Alike Drug Names
There is limited information regarding ELZONRIS Look-Alike Drug Names in the drug label.
Drug Shortage Status
Drug Shortage
Price
References
The contents of this FDA label are provided by the National Library of Medicine.