其 他 安 全 警 示
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| Singapore: Risk of adverse outcomes with light-exposed parenteral nutrition products when used in neonates and children below two years old (English Only) |
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Health Sciences Authority (HSA) announces that the use of light-exposed parenteral nutrition (PN) products containing amino acids and/or lipids might lead to adverse outcomes in neonates, particularly preterm neonates, due to their increased susceptibility to oxidative stress arising from PN photodegradation products. As such, it is important to provide light protection to PN products administered to neonates and children below two years old.
The locally registered PN products indicated for neonates or children below two years old include SMOFlipid, Vaminolact and Intralipid (Fresenius Kabi (Singapore) Pte Ltd); Clinoleic, Primene and Synthamin (Baxter Healthcare (Asia) Pte Ltd); and Lipidem, Lipofundin and Trophamine (B. Braun Singapore Pte Ltd).
In laboratory and clinical studies, light exposure to PN products has been shown to generate peroxides and other photodegradation products in quantifiable amounts, as early as 24 hours after exposure PN products containing vitamins and lipids are the most susceptible, with lipid emulsions being prone to peroxidation due to their high polyunsaturated fatty acid content, and vitamins being prone to stability issues due to photodegradation oxidation (e.g. ascorbic acid, retinol, riboflavin). While intense sunlight is most detrimental, exposure of PN products to ambient light, environmental light and phototherapy can also generate a significant oxidant load in patients.
The presence of high concentrations of photodegradation products in PN products can lead to oxidative stress, which causes damage to cell structures such as DNA, lipids and proteins. Newborns, especially premature neonates, are at a higher risk of oxidative stress compared to children and adults, due to multiple risk factors such as weakened immunity, relative lack of antioxidant and free radical scavenger reserves, and use of oxygen therapy and phototherapy. Oxidative stress has been shown to play a role in many neonatal complications, including respiratory distress syndrome, bronchopulmonary dysplasia (BPD), periventribular leukomalacia (PVL), and retinopathy of prematurity (ROP). In addition, premature neonates have high nutritional needs and require slow intravenous infusion rates, which further increase their risk of exposure to photodegradation products from light-exposed PN products.
Studies have shown that by implementing various light protection measures, the formation of PN photodegradation products can be slowed down or prevented. In a meta-analysis of four randomised trials, a total of 800 newborn premature neonates were evaluated for mortality at 36 weeks’ gestational age or hospital discharge. Mortality in the light-protected group (where there was complete photoprotection of the PN admixture from compounding through delivery to the infant) was half of that in the light-exposed group (odds ratio 0.53; 95% CI 0.32-0.87), suggesting a reduced mortality at 36 weeks' gestational age when light protection for PN products was in place.
In Jul 2019, the European Medicines Agency’s Pharmacovigilance Risk Assessment Committee (PRAC) completed a review of this safety issue, taking into consideration non-clinical and clinical studies which provided evidence on the importance of light protection to reduce the risk of adverse outcomes in premature neonates. While the data on harm primarily concerned premature neonates, the PRAC recommended that light protection of PN products should be extended to neonates and children below two years of age as a precautionary measure.
To date, HSA has not received any local reports of adverse effects in neonates or children treated with PN products not protected from light. HSA is working with companies of affected products to update their local package inserts to reflect this risk. Healthcare professionals are advised to consider the importance of light protection measures when PN products containing amino acids and/or lipids are used in neonates and children below two years of age, to minimise the risk of adverse outcomes in this vulnerable population.
Please refer to the following website in HSA for details:
http://www.hsa.gov.sg/announcements/safety-alert/risk-of-adverse-outcomes-with-light-exposed-parenteral-nutrition-products-when-used-in-neonates-and-children-below-two-years-old
In Hong Kong, there are registered pharmaceutical products which are parenteral nutrition products indicated for neonates and/or infants as mentioned in the above HSA’s announcement: Smoflipid 20% Emulsion For Infusion (HK-53582), Vaminolact I.V. Solution (HK-36470), Intralipid Emulsion 10% For IV Use (HK-35420), Intralipid Inj 20% (HK-35421), Lipidem Emulsion For Infusion (HK-58945), Lipofundin MCT/LCT Emul For IV Inf 10% (HK-28225), Lipofundin MCT/LCT Emul For IV Inf 20% (HK-28226), Trophamine 10% Amino Acid Inj (HK-38154) and Trophamine Amino Acid Inj 6% (HK-50115). All products are prescription-only medicines. So far, the Department of Health (DH) has not received any case of adverse drug reaction related to Smoflipid, Vaminolact, Intralipid , Lipidem, Lipofundin or Trophamine. Safety information on light protection during administration for parenteral nutrition products for neonates and children aged under 2 years to reduce the risk of serious adverse effects is documented in overseas reputable drug references such as the “British National Formulary (BNF) for Children”. The DH will remain vigilant on safety update of the products issued by other overseas drug regulatory authorities.
Ends/Wednesday, May 6, 2020
Issued at HKT 16:00
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