Surfactant- BLES

Pharmacologic Category

Lung Surfactant

Dosing: Pediatric

Respiratory distress: Rescue treatment: Intratracheal: Infants: Administer 5 mL/kg/dose (equals phospholipids 135 mg/kg/dose); may repeat if needed, to a maximum of 4 doses within the first 5 days of life.

Repeat dosing: The manufacturer labeling does not provide recommendations regarding an interval between dosing; however, repeat dosing at least 2 hours to 6 hours after the initial dose has been recommended (Davis 2015); alternatively, it has been recommended that surfactants usually require no more frequent dosing than every 12 hours unless the surfactant is being inactivated by an infectious process, meconium, or blood (AAP [Polin 2014]). According to the manufacturer’s labeling, the need for repeat dosing is based on a positive response to the previous dose and increased respiratory support (ie, Fio2 increased ≥10% than that required after initial response to previous dose). Infants exhibiting deterioration of respiratory function should be evaluated for a patent ductus arteriosus, pneumothorax, and pulmonary hemorrhage prior to retreatment.

Dosing: Renal Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling.

Use: Labeled Indications

Note: Not approved in the US.

Neonatal respiratory distress syndrome: Rescue treatment of neonatal respiratory distress syndrome (NRDS)

Limitations of use: Has not been studied in infants with birth weight <380 g or >4,460 g

Administration: Pediatric

Endotracheal: For intratracheal administration only. Warm to at least room temperature, but no higher than body temperature prior to administration; see product labeling for detailed instructions. Inspect solution to verify complete mixing of the suspension (may swirl gently, but DO NOT SHAKE). Do not filter dose. Suction infant prior to administration. After proper placement of endotracheal tube (ETT) has been established, administer intratracheally by instillation through a #5-French feeding tube inserted into the infant's ETT. Do not instill BLES down the right mainstem bronchus.

Administer as a single bolus dose or administer dose in up to 3 aliquots as tolerated. Each dose or aliquot is instilled over 2 to3 seconds followed by at least 30 seconds of manual ventilation. If surfactant is slow to subside in the ETT during administration, interrupt administration and hand ventilate until the ETT is cleared before continuing; consider the possibility of a mucous plug if surfactant fails to subside. Avoid administering as a slow drip or in small aliquots as this may lead to poor distribution and uneven lung compliance.

Infant should be supine for the first aliquot, than turned to the left and right for subsequent aliquots. Allow 1 to 2 minute recovery periods after each aliquot; oxygen saturation should be ~95% before administration of next aliquot. Following administration of one full dose, withhold suctioning for 2 hours unless clinically necessary. Regimen for repeat dosing is the same as for initial dosing.

Storage/Stability

Store vials frozen at -10°C (14°F) for 36 months. Two excursions at 2°C to 8°C (36°F to 46°F) are permitted for a combined maximum of 2 weeks, and then may return vials to freezer until packaging expiration date. Alternatively, vials may be stored at 2°C to 8°C (36°F to 46°F) for up to 10 months and then discarded. Vials originally stored under refrigeration should not be returned to freezer. Unopened vials kept at room temperature for <6 hours may be returned to original storage conditions (ie, freezer or refrigerator) up to maximum of 2 times. On the vial labeling, record the number of times a vial has been warmed and returned to storage.

Medication Safety Issues

Other safety concerns:

Contraindications

Active pulmonary hemorrhage

Warnings/Precautions

Concerns related to adverse effects:

• Mucous plugs: Marked impairment of ventilation during or shortly after dosing may indicate mucous plugs within the endotracheal tube (ETT); suctioning prior to administration may decrease chance of ETT obstruction. Replace ETT immediately if obstruction is not removed with suctioning.

• Sepsis: Therapy may be associated with increased incidence of sepsis; monitor closely for signs/symptoms of sepsis.

• Transient adverse effects: [Canadian Boxed Warning]: Bovine lipid extract surfactant (BLES) may be associated with transient episodes of bradycardia and decreased oxygen saturation may occur. Discontinue dosing procedure and initiate measures to alleviate the condition; may reinstitute after the patient is stable.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Other warnings/precautions:

• Appropriate use: For intratracheal administration only. Correct any acidosis, hypoglycemia, hypothermia, or hypotension prior to administration.

• Monitoring: [Canadian Boxed Warning]: BLES rapidly affects oxygenation and lung compliance; hyperoxia may occur within minutes of administration. Assess oxygenation closely and adjust ventilator and oxygen delivery as necessary to decrease risk of retinopathy of prematurity, overdistension of chest expansion and pulmonary air leaks.

• Trained personnel: [Canadian Boxed Warning]: Restrict use of BLES to a highly-supervised clinical setting with immediate availability of clinicians experienced in intubation and ventilatory management and general care of premature infants.

Pregnancy Considerations

Bovine lipid extract surfactant is only indicated for use in premature infants.

Breast-Feeding Considerations

Bovine lipid extract surfactant is only indicated for use in premature infants.

Adverse Reactions

>10%:

Cardiovascular: Bradycardia (13%)

Respiratory: Decreased lung function (defined as decreased oxygen saturation or increased CO2) (39%)

Infection: Sepsis (28%)

1% to 10%:

Cardiovascular: Hypotension (2%)

Central nervous system: Brain disease (periventricular leukomalacia: 8%), seizure (2%), hydrocephalus (1%)

Endocrine & metabolic: Respiratory acidosis (4%)

Hematologic & oncologic: Pulmonary hemorrhage (8%)

Respiratory: Pulmonary interstitial emphysema (9%), pneumothorax (8%), apnea (2%), pneumonia (1%)

Miscellaneous: Endotracheal intubation (complications: 6%)

<1%, postmarketing, and/or case reports: Acidosis, hypertension, hypoxia

Metabolism/Transport Effects

None known.

Drug Interactions Open Interactions

Bradycardia-Causing Agents: May enhance the bradycardic effect of other Bradycardia-Causing Agents. Risk C: Monitor therapy

Ceritinib: Bradycardia-Causing Agents may enhance the bradycardic effect of Ceritinib. Management: If this combination cannot be avoided, monitor patients for evidence of symptomatic bradycardia, and closely monitor blood pressure and heart rate during therapy. Exceptions are discussed in separate monographs. Risk D: Consider therapy modification

Fexinidazole [INT]: Bradycardia-Causing Agents may enhance the arrhythmogenic effect of Fexinidazole [INT]. Risk X: Avoid combination

Ivabradine: Bradycardia-Causing Agents may enhance the bradycardic effect of Ivabradine. Risk C: Monitor therapy

Lacosamide: Bradycardia-Causing Agents may enhance the AV-blocking effect of Lacosamide. Risk C: Monitor therapy

Midodrine: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy

Ruxolitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Management: Ruxolitinib Canadian product labeling recommends avoiding use with bradycardia-causing agents to the extent possible. Risk C: Monitor therapy

Siponimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Siponimod. Management: Avoid coadministration of siponimod with drugs that may cause bradycardia. Risk D: Consider therapy modification

Terlipressin: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy

Tofacitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy

Monitoring Parameters

Continuous ECG, transcutaneous O2 saturation, and transcutaneous CO2 should be monitored during administration; after administration, frequent arterial blood gas sampling is necessary to prevent postdosing hyperoxia and hypocarbia; tidal volume after dosing, monitor chest expansion and signs of mucous plugging of ETT.

Product Availability

Not available in the US

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Suspension, Intratracheal:

BLES: 27 mg/mL (3 mL, 4 mL, 5 mL)

Generic Available (US)

May be product dependent

Mechanism of Action

Replaces deficient or ineffective endogenous lung surfactant in neonates with respiratory distress syndrome (RDS). Surfactant prevents the alveoli from collapsing during expiration by lowering surface tension between air and alveolar surfaces.

Pharmacodynamics/Kinetics

Onset of action: 5 to 30 minutes; significant improvement in gas exchange and lung compliance observed within 4 hours

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Effects on Dental Treatment

No significant effects or complications reported

Effects on Bleeding

No information available to require special precautions

References

BLES (bovine lipid extract surfactant) [product monograph]. London, Ontario, Canada: BLES Biochemicals Inc; March 2012.[PubMed 19668609]

Davis DJ, Barrington KJ, Canadian Paediatric Society Fetus and Newborn Committee, “Recommendations for neonatal surfactant therapy,” Paediatric Child Health, 2005 105; 10(2): 109-16. Updated Jan 30 2015. Available at: http://www.cps.ca/en/search-recherche?q=recommendations%20for%20neonatal%20surfactant%20therapy. Accessed December 12, 2015.[PubMed 15558604]

Polin RA, Carlo WA, Committee on Fetus and Newborn, American Academy of Pediatrics. Surfactant replacement therapy for preterm and term neonates with respiratory distress. Pediatrics. 2014;133(1):156-163.[PubMed 24379227]

Last Updated 12/31/19