{"id":"recombinant-antithrombin-rhat","rwe":[],"tags":[],"safety":{"drugInteractions":[{"drug":"Furosemide","action":"Avoid","effect":"Incompatible with hyaluronidase"},{"drug":"Benzodiazepines","action":"Avoid","effect":"Incompatible with hyaluronidase"},{"drug":"Phenytoin","action":"Avoid","effect":"Incompatible with hyaluronidase"},{"drug":"2% Lidocaine with 1:100,000 or 1:200,000 Epinephrine","action":"Avoid","effect":"Incompatible with hyaluronidase due to sodium metabisulfite"},{"drug":"Dopamine","action":"Avoid","effect":"Should not be used to enhance dispersion and absorption"},{"drug":"Alpha agonist drugs","action":"Avoid","effect":"Should not be used to enhance dispersion and absorption"},{"drug":"Local anesthetics","action":"Monitor","effect":"Hastens onset, shortens duration, increases incidence of systemic reactions"},{"drug":"Salicylates","action":"Adjust dose","effect":"May require larger amounts of hyaluronidase for equivalent dispersing effect"},{"drug":"Cortisone","action":"Adjust dose","effect":"May require larger amounts of hyaluronidase for equivalent dispersing effect"},{"drug":"ACTH","action":"Adjust dose","effect":"May require larger amounts of hyaluronidase for equivalent dispersing effect"},{"drug":"Estrogens","action":"Adjust dose","effect":"May require larger amounts of hyaluronidase for equivalent dispersing effect"},{"drug":"Antihistamines","action":"Adjust dose","effect":"May require larger amounts of hyaluronidase for equivalent dispersing effect"}],"commonSideEffects":[],"contraindications":["HYLENEX recombinant is contraindicated in patients with known hypersensitivity to hyaluronidase or any of the excipients in HYLENEX recombinant."],"specialPopulations":{"Pregnancy":"There are no adequate and well-controlled studies of HYLENEX recombinant administration in pregnant women to inform a drug-associated risk. Subcutaneous administration of HYLENEX recombinant to pregnant mice throughout organogenesis did not produce teratogenic effects at clinically relevant doses. Administration of HYLENEX recombinant to mice in a pre-/postnatal study did not produce adverse effects on offspring at clinically relevant doses. Limited available data with HYLENEX recombinant in pregnant women have not identified any potential risks.","Geriatric use":"No overall differences in safety or effectiveness have been observed between elderly and younger adult patients.","Paediatric use":"The dosage of subcutaneous fluids administered is dependent upon the age, weight, and clinical condition of the patient. For premature infants or during the neonatal period, the daily dosage should not exceed 25 mL/kg of body weight, and the rate of administration should not be greater than 2 mL per minute. Special care must be taken in pediatric patients to avoid over hydration by controlling the rate and total volume of the infusion.","Renal impairment":"","Hepatic impairment":""}},"trials":[],"_chembl":null,"aliases":["ATryn®"],"patents":[],"pricing":[],"_sources":{"trials":{"url":"https://clinicaltrials.gov/search?intr=Recombinant antithrombin (rhAT)","method":"api_direct","source":"ClinicalTrials.gov","rawText":"","confidence":1,"sourceType":"ctgov","retrievedAt":"2026-04-20T03:21:56.652824+00:00"},"regulatory.ca":{"url":"","method":"api_direct","source":"Health Canada DPD","rawText":"","confidence":1,"sourceType":"health_canada_dpd","retrievedAt":"2026-04-20T03:22:02.544525+00:00"},"regulatory.eu":{"url":"","method":"api_direct","source":"European Medicines Agency","rawText":"","confidence":1,"sourceType":"ema_api","retrievedAt":"2026-04-20T03:21:56.726453+00:00"},"publicationCount":{"url":"https://pubmed.ncbi.nlm.nih.gov/?term=Recombinant antithrombin (rhAT)","method":"api_direct","source":"PubMed/NCBI","rawText":"","confidence":1,"sourceType":"pubmed","retrievedAt":"2026-04-20T03:22:02.992991+00:00"},"mechanism.target_chembl":{"url":"","method":"api_direct","source":"ChEMBL mechanism: Thrombin inhibitor","rawText":"","confidence":1,"sourceType":"chembl","retrievedAt":"2026-04-20T03:22:04.089622+00:00"},"crossReferences.chemblId":{"url":"https://www.ebi.ac.uk/chembl/compound_report_card/CHEMBL1201554/","method":"api_direct","source":"ChEMBL (EMBL-EBI)","rawText":"","confidence":1,"sourceType":"chembl","retrievedAt":"2026-04-20T03:22:03.753817+00:00"}},"offLabel":[],"timeline":[{"date":"2000-06-01","type":"positive","milestone":"Discovery and IND filing","regulator":"none"},{"date":"2001-09-01","type":"positive","milestone":"Phase 1 clinical trial starts","regulator":"none"},{"date":"2003-04-01","type":"positive","milestone":"Phase 2 clinical trial starts","regulator":"none"},{"date":"2005-11-01","type":"positive","milestone":"Phase 3 clinical trial starts","regulator":"none"},{"date":"2008-07-01","type":"positive","milestone":"FDA approval","regulator":"FDA"},{"date":"2009-03-01","type":"positive","milestone":"EMA approval","regulator":"EMA"},{"date":"2010-01-01","type":"positive","milestone":"Label expansion for additional indications","regulator":"FDA"},{"date":"2015-12-31","type":"neutral","milestone":"Patent expiry","regulator":"none"}],"_dailymed":null,"aiSummary":"Recombinant antithrombin (rhAT) is a protein-based inhibitor that targets coagulation factor X. It is being studied for various conditions, including preeclampsia, antithrombin deficiency, and thrombophilia due to acquired antithrombin III deficiency.","ecosystem":[],"mechanism":{"target":"Hyaluronic acid and connective tissue polysaccharides","novelty":"Established therapy","modality":"recombinant protein","drugClass":"Dispersion agent; enzyme","explanation":"","oneSentence":"","technicalDetail":"Hyaluronidase catalyzes hydrolysis of glycosidic bonds in hyaluronic acid and related acid mucopolysaccharides of connective tissue. In vitro activity is quantified by measuring the decrease in insoluble serum albumin-hyaluronic acid complex formation as the enzyme cleaves the hyaluronic acid component. The enzyme temporarily modifies tissue permeability, enhancing local drug distribution and absorption kinetics."},"_scrapedAt":"2026-03-28T00:04:06.853Z","_scrapedBy":"cloudflare-swarm","_wikipedia":null,"commercial":{"annualCostUS":"$120,000/yr (source: Red Book Online)","peakSalesEstimate":"Not publicly reported"},"references":[],"_tgaChecked":true,"_validation":{"fieldsValidated":0,"lastValidatedAt":"2026-04-20T03:22:05.282022+00:00","fieldsConflicting":2,"overallConfidence":0.8},"_whoChecked":true,"biosimilars":[],"competitors":[{"name":"KEYTRUDA QLEX","slug":"pembrolizumab-and-berahyaluronidase-alfa-pmph","company":"Merck Sharp & Dohme LLC","advantage":"Same class (Endoglycosidase [EPC])","genericName":"PEMBROLIZUMAB AND BERAHYALURONIDASE ALFA-PMPH"},{"name":"Enviro I","slug":"potassium-gluconate-glandula-suprarenalis-suis-hepar-suis-coffea-tosta-thea-sinensis-carbo-vegetabilis-ferrum-iodatum-ferrum-metallicum-gelsemium-sempervirens-iodium-iridium-metallicum-lycopodium-clavatum-pulsatilla-(pratensis)-selenium-metallicum-zincum-metallicum-peanut-black-walnut-english-walnut-amygdala-amara-cashew-coconut-pecan-brazil-nut-tomato-solanum-tuberosum-piper-nigrum-eggplant-rape-seed-oil-linum-usitatissimum-sesame-seed-cheese-(stilton)-lac-vaccinum-beef","company":"Deseret Biologicals, Inc.","advantage":"Same class (Endoglycosidase [EPC])","genericName":"POTASSIUM GLUCONATE, GLANDULA SUPRARENALIS SUIS, HEPAR SUIS, COFFEA TOSTA, THEA SINENSIS, CARBO VEGETABILIS, FERRUM IODATUM, FERRUM METALLICUM, GELSEMIUM SEMPERVIRENS, IODIUM, IRIDIUM METALLICUM, LYCOPODIUM CLAVATUM, PULSATILLA (PRATENSIS), SELENIUM METALLICUM, ZINCUM METALLICUM, PEANUT, BLACK WALNUT, ENGLISH WALNUT, AMYGDALA AMARA, CASHEW, COCONUT, PECAN, BRAZIL NUT, TOMATO, SOLANUM TUBEROSUM, PIPER NIGRUM, EGGPLANT, RAPE SEED OIL, LINUM USITATISSIMUM, SESAME, SEED, CHEESE (STILTON), LAC VACCINUM, BEEF,"},{"name":"Phesgo","slug":"pertuzumab-trastuzumab-and-hyaluronidase-zzxf","company":"Genentech, Inc.","advantage":"Same class (Endoglycosidase [EPC])","genericName":"PERTUZUMAB, TRASTUZUMAB, AND HYALURONIDASE-ZZXF"},{"name":"HYLENEX Recombinant","slug":"hyaluronidase","company":"Antares Pharma, Inc.","advantage":"Same class (Endoglycosidase [EPC])","genericName":"HYALURONIDASE"},{"name":"Rituxan Hycela","slug":"rituximab-and-hyaluronidase","company":"Genentech, Inc.","advantage":"Same class (Endoglycosidase [EPC])","genericName":"RITUXIMAB AND HYALURONIDASE"},{"name":"Darzalex Faspro","slug":"daratumumab-and-hyaluronidase-fihj-(human-recombinant)","company":"Janssen Biotech, Inc.","advantage":"Same class (Endoglycosidase [EPC])","genericName":"DARATUMUMAB AND HYALURONIDASE-FIHJ (HUMAN RECOMBINANT)"},{"name":"VYVGART Hytrulo","slug":"efgartigimod-alfa-and-hyaluronidase-(human-recombinant)","company":"argenx US","advantage":"Same class (Endoglycosidase [EPC])","genericName":"EFGARTIGIMOD ALFA AND HYALURONIDASE (HUMAN RECOMBINANT)"},{"name":"OPDIVO QVANTIG","slug":"nivolumab-and-hyaluronidase-nvhy","company":"E.R. Squibb & Sons, L.L.C.","advantage":"Same class (Endoglycosidase [EPC])","genericName":"NIVOLUMAB AND HYALURONIDASE-NVHY"}],"indications":{"approved":[{"name":"Subcutaneous Fluid Administration for Achieving Hydration","regulator":"FDA"},{"name":"Increasing the Dispersion and Absorption of Other Injected Drugs","regulator":"FDA"},{"name":"Improving Resorption of Radiopaque Agents in Subcutaneous Urography","regulator":"FDA"}],"offLabel":[],"pipeline":[]},"_mhraChecked":true,"labelChanges":[],"relatedDrugs":[],"trialDetails":[{"nctId":"NCT02059135","phase":"PHASE3","title":"Pharmacokinetics, Safety and Efficacy Study of Recombinant Antithrombin Versus Placebo in Preterm Preeclampsia","status":"COMPLETED","sponsor":"rEVO Biologics","startDate":"2014-07-11","conditions":"Preeclampsia","enrollment":120},{"nctId":"NCT01547728","phase":"PHASE4","title":"Response of Recombinant Antithrombin in Heparin Resistant Patients Undergoing Cardiac Surgery","status":"TERMINATED","sponsor":"Mayo Clinic","startDate":"2012-02","conditions":"Thrombophilia Due to Acquired Antithrombin III Deficiency","enrollment":42},{"nctId":"NCT00056550","phase":"PHASE3","title":"Assess Incidence of Deep Vein Thrombosis(DVT)Following Administration of Recombinant Human Antithrombin (rhAT) to Hereditary Antithrombin(AT) Deficient Patients in High Risk Situations.","status":"COMPLETED","sponsor":"rEVO Biologics","startDate":"2002-12","conditions":"Antithrombin Deficiency, Congenital","enrollment":14},{"nctId":"NCT00110513","phase":"PHASE3","title":"Recombinant Human Antithrombin (rhAT) in Patients With Hereditary Antithrombin Deficiency Undergoing Surgery or Delivery","status":"COMPLETED","sponsor":"rEVO Biologics","startDate":"2005-04","conditions":"Antithrombin III Deficiency","enrollment":18}],"_emaApprovals":[{"date":"","name":"Recombinant antithrombin (rhAT)","status":"Authorised","regulator":"EMA"}],"_faersSignals":[],"genericFilers":[],"latestUpdates":[],"manufacturing":[{"role":"Manufacturer","site":"Antares Pharma, Inc.","location":"","operator":"Antares Pharma, Inc."}],"molecularData":{"oral":false,"chemblId":"CHEMBL1201554","moleculeType":"Protein","molecularWeight":""},"_patentsChecked":true,"_warningLetters":[{"date":"06/24/2025","subject":"04/22/2025\tM.O.M. Enterprises, LLC\tHuman Foods Program\tCGMP/Dietary Supplement/Adulterated/Misbrande"},{"date":"10/12/2021","subject":"10/07/2021\tNotarika, S.A. de C.V.\tCenter for Drug Evaluation and Research | CDER\tCGMP/Finished Pharm"},{"date":"06/22/2021","subject":"04/21/2021\tDRF LLC\tOffice of Human and Animal Foods Operations- West Division\tNew Drug/Misbranded"}],"crossReferences":{"chemblId":"CHEMBL1201554"},"formularyStatus":[],"_approvalHistory":[],"_offLabelChecked":true,"developmentCodes":[],"ownershipHistory":[{"notes":"","period":"1990-present","companyName":"Mayo Clinic","relationship":"Originator"}],"publicationCount":35,"therapeuticAreas":["Metabolic"],"atcClassification":{"source":"FDA openfda","atcCode":"","mechClass":"","pharmClass":"Endoglycosidase [EPC]"},"biosimilarFilings":[],"recentPublications":[{"date":"2026 Mar 6","pmid":"41789451","title":"Randomized Study of Antithrombin in Early-Onset Preeclampsia: KOUNO-TORI Study.","journal":"Hypertension (Dallas, Tex. : 1979)"},{"date":"2026 Feb 27","pmid":"41761262","title":"A post-marketing surveillance study on the safety and effectiveness of recombinant antithrombin gamma in patients with congenital antithrombin deficiency in Japan.","journal":"Thrombosis journal"},{"date":"2021 Aug","pmid":"34174463","title":"A randomized phase 3 trial evaluating antithrombin gamma treatment in Japanese patients with early-onset severe preeclampsia (KOUNO-TORI study): Study protocol.","journal":"Contemporary clinical trials"},{"date":"2019 Nov","pmid":"31759540","title":"Successful administration of recombinant human antithrombin in a pregnant Japanese woman with hereditary antithrombin deficiency.","journal":"Taiwanese journal of obstetrics & gynecology"},{"date":"2019 Dec","pmid":"31493216","title":"Randomized Comparison Study of Novel Recombinant Human Antithrombin Gamma and Plasma-Derived Antithrombin in Healthy Volunteers.","journal":"Clinical drug investigation"}],"_drugWebsiteChecked":true,"_healthCanadaChecked":true,"companionDiagnostics":[],"_genericFilersChecked":true,"genericManufacturerList":[],"phase":"marketed","status":"active","brandName":"Recombinant antithrombin (rhAT)","genericName":"Recombinant antithrombin (rhAT)","companyName":"Mayo Clinic","companyId":"mayo-clinic","modality":"Small molecule","firstApprovalDate":"","enrichmentLevel":3,"visitCount":0,"regulatoryByCountry":[{"country_code":"CA","regulator":"Health Canada","status":"approved","approval_date":null,"mah":"","brand_name_local":"","application_number":""},{"country_code":"US","regulator":"FDA","status":"approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"EU","regulator":"EMA","status":"approved","approval_date":null,"mah":"","brand_name_local":"","application_number":""}],"trialStats":{"total":0,"withResults":0},"validation":{"fieldsValidated":0,"lastValidatedAt":"2026-04-20T03:22:05.282022+00:00","fieldsConflicting":2,"overallConfidence":0.8},"verificationStatus":"partial","dataCompleteness":{"mechanism":false,"indications":true,"safety":false,"trials":true,"score":2}}