Poractant alfa

Identification

Name
Poractant alfa
Accession Number
DB09113
Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Other protein based therapies
Description

Poractant alfa is a pulmonary surfactant marketed as Curosurf in the United States and Canada. It is used to treat Respiratory Distress Syndrome (RDS) in premature infants with an endogenous pulmonary surfactant deficiency. Poractant alfa is an extract of natural porcine lung surfactant consisting of 99% polar lipids (mainly phospholipids) and 1% hydrophobic low molecular weight proteins (surfactant associated proteins SP-B and SP-C). The phospholipid content of the extract consists primarily of phosphatidylcholine and dipaImitoylphosphatidylcholine. Poractant alfa is a creamy white suspension of this extract in 0.9% sodium chloride solution. It contains no preservatives.

Protein chemical formula
Not Available
Protein average weight
Not Available
Sequences
Not Available
Synonyms
Not Available
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CurosurfSuspension80 mgEndotrachealChiesi Farmaceutici S.P.A.2016-12-19Not applicableCanada
CurosurfSuspension80 mg/mLEndotrachealChiesi Pharmaceuticals Inc.1999-11-18Not applicableUs
Categories
UNII
KE3U2023NP
CAS number
129069-19-8

Pharmacology

Indication

Poractant alfa is indicated for the treatment of Respiratory Distress Syndrome (RDS) in premature infants.

Structured Indications
Pharmacodynamics

Poractant alfa improved lung compliance, pulmonary gas exchange and survival in preterm rabbits.

Mechanism of action

Endogenous pulmonary surfactant reduces surface tension at the air-liquid interface of the alveoli in the lungs, thus stabilizing them against collapse under transpulmonary pressures. A deficiency of pulmonary surfactant in premature infants allows surface tension to increase to the point where sections of lung collapse and respiratory distress syndrome (RDS) develops. Poractant alfa lowers minimum surface tension to less than or equal to 4 mN/m. This compensates for the lack of endogenous surfactant and restores adequate surface activity to the lungs.

Absorption

Poractant alfa is administered directly to the site of action in the lungs via endotracheal tube. It very rapidly adsorbs to the air-liquid interface to form a stable surfactant monolayer. No studies on absorption of poractant alfa have been performed in humans.

Volume of distribution

No studies on the distribution of poractant alfa have been performed in humans.

Protein binding
Not Available
Metabolism

No studies on the metabolism of poractant alfa have been performed in humans. One small study in rabbits did find that poractant alfa may be degraded by macrophages and that it may, in part, be recycled in the alveoli in a similar manner to endogenous lung surfactant.

Route of elimination

No studies on elimination of poractant alfa have been performed in humans.

Half life

The half-life of poractant alfa has only been evaluated in animal studies. When studied in adult and newborn rabbits, the half-life in the lungs was found to be 25 and 67 respectively.

Clearance

No studies on clearance of poractant alfa have been performed in humans.

Toxicity

Studies on the carcinogenicity or reproductive effects of poractant alfa have not been conducted. Mutagenicity assays were negative. In the case of an overdose with poractant alfa where there are clear clinical effects on the infant's respiration, ventilation, or oxygenation, it is recommended that as much of the solution be aspirated as possible and the infant be managed with supportive measures. Fluid and electrolyte balances should be monitored closely in this case.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AcebutololAcebutolol may increase the bradycardic activities of Poractant alfa.Approved
AmiodaroneAmiodarone may increase the bradycardic activities of Poractant alfa.Approved, Investigational
AtenololAtenolol may increase the bradycardic activities of Poractant alfa.Approved
BendroflumethiazideBendroflumethiazide may increase the bradycardic activities of Poractant alfa.Approved
BeractantBeractant may increase the bradycardic activities of Poractant alfa.Approved
BetaxololBetaxolol may increase the bradycardic activities of Poractant alfa.Approved
BisoprololBisoprolol may increase the bradycardic activities of Poractant alfa.Approved
BretyliumBretylium may increase the bradycardic activities of Poractant alfa.Approved
CalfactantCalfactant may increase the bradycardic activities of Poractant alfa.Approved
CarteololCarteolol may increase the bradycardic activities of Poractant alfa.Approved
CarvedilolCarvedilol may increase the bradycardic activities of Poractant alfa.Approved, Investigational
CeritinibPoractant alfa may increase the bradycardic activities of Ceritinib.Approved
ClonidineClonidine may increase the bradycardic activities of Poractant alfa.Approved
CrizotinibCrizotinib may increase the bradycardic activities of Poractant alfa.Approved
DexmedetomidineDexmedetomidine may increase the bradycardic activities of Poractant alfa.Approved, Vet Approved
DigoxinDigoxin may increase the bradycardic activities of Poractant alfa.Approved
DiltiazemDiltiazem may increase the bradycardic activities of Poractant alfa.Approved
DonepezilDonepezil may increase the bradycardic activities of Poractant alfa.Approved
DronedaroneDronedarone may increase the bradycardic activities of Poractant alfa.Approved
EsmololEsmolol may increase the bradycardic activities of Poractant alfa.Approved
FingolimodFingolimod may increase the bradycardic activities of Poractant alfa.Approved, Investigational
GalantamineGalantamine may increase the bradycardic activities of Poractant alfa.Approved
GuanfacineGuanfacine may increase the bradycardic activities of Poractant alfa.Approved, Investigational
IvabradinePoractant alfa may increase the bradycardic activities of Ivabradine.Approved
LabetalolLabetalol may increase the bradycardic activities of Poractant alfa.Approved
LacosamidePoractant alfa may increase the atrioventricular blocking (AV block) activities of Lacosamide.Approved
LanreotideLanreotide may increase the bradycardic activities of Poractant alfa.Approved
LevobunololLevobunolol may increase the bradycardic activities of Poractant alfa.Approved
LucinactantLucinactant may increase the bradycardic activities of Poractant alfa.Approved, Investigational
MethyldopaMethyldopa may increase the bradycardic activities of Poractant alfa.Approved
MetipranololMetipranolol may increase the bradycardic activities of Poractant alfa.Approved
MetoprololMetoprolol may increase the bradycardic activities of Poractant alfa.Approved, Investigational
NadololNadolol may increase the bradycardic activities of Poractant alfa.Approved
NebivololNebivolol may increase the bradycardic activities of Poractant alfa.Approved, Investigational
OctreotideOctreotide may increase the bradycardic activities of Poractant alfa.Approved, Investigational
PasireotidePasireotide may increase the bradycardic activities of Poractant alfa.Approved
PenbutololPenbutolol may increase the bradycardic activities of Poractant alfa.Approved, Investigational
PindololPindolol may increase the bradycardic activities of Poractant alfa.Approved
PropafenonePropafenone may increase the bradycardic activities of Poractant alfa.Approved
PropranololPropranolol may increase the bradycardic activities of Poractant alfa.Approved, Investigational
RivastigmineRivastigmine may increase the bradycardic activities of Poractant alfa.Approved, Investigational
RuxolitinibRuxolitinib may increase the bradycardic activities of Poractant alfa.Approved
SotalolSotalol may increase the bradycardic activities of Poractant alfa.Approved
SufentanilSufentanil may increase the bradycardic activities of Poractant alfa.Approved, Investigational
TimololTimolol may increase the bradycardic activities of Poractant alfa.Approved
TizanidineTizanidine may increase the bradycardic activities of Poractant alfa.Approved
TofacitinibTofacitinib may increase the bradycardic activities of Poractant alfa.Approved, Investigational
VerapamilVerapamil may increase the bradycardic activities of Poractant alfa.Approved
Food Interactions
Not Available

References

Synthesis Reference

Curosurf: Product Monograph. Parma, Italy: Chiesi Farmaceutici S.p.A.; 2008: 25-27.

General References
  1. Fujii AM, Carillo M: Animal-derived surfactant treatment of respiratory distress syndrome in premature neonates: a review. Drugs Today (Barc). 2009 Sep;45(9):697-709. doi: 1396674/dot.2009.45.9.1418185. [PubMed:19956811]
  2. Jeon GW, Oh M, Sin JB: Efficacy of surfactant-TA, calfactant and poractant alfa for preterm infants with respiratory distress syndrome: a retrospective study. Yonsei Med J. 2015 Mar;56(2):433-9. doi: 10.3349/ymj.2015.56.2.433. [PubMed:25683992]
  3. Alberti A, Pettenazzo A, Enzi GB, Palamidese A, Mapp C, Ventura P, Baritussio A: Uptake and degradation of Curosurf after tracheal administration to newborn and adult rabbits. Eur Respir J. 1998 Aug;12(2):294-300. [PubMed:9727777]
  4. Bourbon JR, Chailley-Heu B, Gautier B: The exogenous surfactant Curosurf enhances phosphatidylcholine content in isolated type II cells. Eur Respir J. 1997 Apr;10(4):914-9. [PubMed:9150335]
  5. Calkovska A, Uhliarova B, Joskova M, Franova S, Kolomaznik M, Calkovsky V, Smolarova S: Pulmonary surfactant in the airway physiology: a direct relaxing effect on the smooth muscle. Respir Physiol Neurobiol. 2015 Apr;209:95-105. doi: 10.1016/j.resp.2015.01.004. Epub 2015 Jan 10. [PubMed:25583659]
  6. Cogo PE, Facco M, Simonato M, Verlato G, Rondina C, Baritussio A, Toffolo GM, Carnielli VP: Dosing of porcine surfactant: effect on kinetics and gas exchange in respiratory distress syndrome. Pediatrics. 2009 Nov;124(5):e950-7. doi: 10.1542/peds.2009-0126. Epub 2009 Oct 12. [PubMed:19822594]
  7. Singh N, Halliday HL, Stevens TP, Suresh G, Soll R, Rojas-Reyes MX: Comparison of animal-derived surfactants for the prevention and treatment of respiratory distress syndrome in preterm infants. Cochrane Database Syst Rev. 2015 Dec 21;12:CD010249. doi: 10.1002/14651858.CD010249.pub2. [PubMed:26690260]
  8. Wiseman LR, Bryson HM: Porcine-derived lung surfactant. A review of the therapeutic efficacy and clinical tolerability of a natural surfactant preparation (Curosurf) in neonatal respiratory distress syndrome. Drugs. 1994 Sep;48(3):386-403. [PubMed:7527760]
  9. Sweet D, Bevilacqua G, Carnielli V, Greisen G, Plavka R, Saugstad OD, Simeoni U, Speer CP, Valls-I-Soler A, Halliday H: European consensus guidelines on the management of neonatal respiratory distress syndrome. J Perinat Med. 2007;35(3):175-86. [PubMed:17480144]
  10. Schurch S, Schurch D, Curstedt T, Robertson B: Surface activity of lipid extract surfactant in relation to film area compression and collapse. J Appl Physiol (1985). 1994 Aug;77(2):974-86. [PubMed:8002555]
  11. Malloy CA, Nicoski P, Muraskas JK: A randomized trial comparing beractant and poractant treatment in neonatal respiratory distress syndrome. Acta Paediatr. 2005 Jun;94(6):779-84. [PubMed:16188788]
  12. Ramanathan R, Rasmussen MR, Gerstmann DR, Finer N, Sekar K: A randomized, multicenter masked comparison trial of poractant alfa (Curosurf) versus beractant (Survanta) in the treatment of respiratory distress syndrome in preterm infants. Am J Perinatol. 2004 Apr;21(3):109-19. [PubMed:15085492]
  13. Speer CP, Robertson B, Curstedt T, Halliday HL, Compagnone D, Gefeller O, Harms K, Herting E, McClure G, Reid M, et al.: Randomized European multicenter trial of surfactant replacement therapy for severe neonatal respiratory distress syndrome: single versus multiple doses of Curosurf. Pediatrics. 1992 Jan;89(1):13-20. [PubMed:1727997]
External Links
KEGG Drug
D08402
PubChem Substance
347910412
ChEMBL
CHEMBL1201622
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Poractant_alfa
AHFS Codes
  • 48:36.00 — Pulmonary Surfactants
FDA label
Download (529 KB)
MSDS
Download (60.4 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2RecruitingTreatmentRespiratory Distress Syndrome, Newborn1
3CompletedTreatmentRespiratory Distress Syndrome (RDS)1
4Active Not RecruitingTreatmentChronic Lung Disease of Prematurity / Infant, Premature, Diseases / Respiratory Distress Syndrome, Newborn1
4CompletedPreventionRespiratory Distress Syndrome, Newborn1
4CompletedTreatmentMeconium Aspiration Syndrome1
4TerminatedTreatmentPatent Ductus Arteriosus (PDA) / Premature Babies / Respiratory Distress Syndrome (RDS)1
Not AvailableActive Not RecruitingTreatmentRespiratory Distress Syndrome (RDS) / Surfactant Administration by Aerosolization1
Not AvailableCompletedTreatmentPoor Peripheral Perfusion1
Not AvailableCompletedTreatmentPulmonary Haemorrhage1
Not AvailableCompletedTreatmentRespiratory Distress Syndrome (RDS)1
Not AvailableCompletedTreatmentRespiratory Distress Syndrome, Newborn1
Not AvailableRecruitingTreatmentHyaline Membrane Disease / Respiratory Distress Syndrome (RDS)1
Not AvailableWithdrawnTreatmentRespiratory Distress Syndrome (RDS)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
SuspensionEndotracheal80 mg
SuspensionEndotracheal80 mg/mL
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
PropertyValueSource
water solubilityInsoluble. #MSDS

Taxonomy

Description
Not Available
Kingdom
Organic Compounds
Super Class
Organic Acids
Class
Carboxylic Acids and Derivatives
Sub Class
Amino Acids, Peptides, and Analogues
Direct Parent
Peptides
Alternative Parents
Not Available
Substituents
Not Available
Molecular Framework
Not Available
External Descriptors
Not Available

Drug created on September 22, 2015 10:04 / Updated on December 10, 2017 17:18