The Malaysian Health Authority-National Pharmaceutical Regulatory Agency (NPRA), Ministry of Health Malaysia released the following new drug safety alerts for bringing awareness to health care professionals for a better patient safety.

Drug Safety Alert 1: Risk of priapism with Propofol

Drug Safety Alert 2: Risk of toxic degradations of ingredients of parenteral nutrition (PN) containing amino acids and/or lipids when exposed to light, which may lead to adverse outcomes in paediatric patients less than 2 years of age

 

Drug Safety Alert 1: Risk of priapism with Propofol

Propofol is a sedation inducing agent and anaesthetic medication used intravenously for the induction and maintenance of general anaesthesia (induction of unconsciousness). Propofol may be used prior to diagnostic procedures requiring anaesthesia, in the management of refractory status epilepticus, and for induction and/or maintenance of anaesthesia prior to and during surgeries.

Priapism refers to an abnormal persistent erection of the penis which is a prolonged and painful erection and not associated with any sexual stimulation. An erection which lasts for more than four hours is considered as medical emergency and requires immediate treatment. If not treated, the oxygen-deprived blood in the penis could damage tissue in the penis which can result in damage or destruction of penile tissue and permanent erectile dysfunction.

Drug-induced priapism is caused by a reduced venous drainage from the corpora cavernosa- ‘Low-flow (ischemic) priapism’.

Case Reports:

NPRA received information from Health Canada on the risk of priapism associated with the use of propofol. As per Health Canada’s safety review data, there were 11 case reports pertaining to the risk of priapism with propofol use with the below significant information.

  • Domestic case reports: 01
  • Global Case reports: 10
  • Temporal relationship: “5 minutes to 2 hours” for the symptom’s onset after the propofol administration.

It was reported that 10 patients were recovered after receiving treatment and one patient reported a long-term disability.

NPRA has received a total of 77 case reports comprising of 128 adverse drug events which are suspected to be related to propofol containing products. However, NPRA has not received any case reports locally pertaining to the priapism associated with propofol use.

NPRA has completed a review of this safety issue and asked the product registration holders of propofol products to update the local package inserts by including this safety information in respective sections.

 Advice for Healthcare Professionals

  • To be aware, cautious, and be alert on the risk of priapism associated with the use of propofol products.
  • Drug induced priapism which is a low-flow (ischemic) priapism can cause irreversible damage if not treated immediately. Hence it is considered as a medical emergency and should be treated immediately.
  • Proactive identification of symptoms and early intervention of therapy allows the best chance for functional recovery.

 

Drug Safety Alert 2: Risk of toxic degradations of ingredients of parenteral nutrition (PN) containing amino acids and/or lipids when exposed to light, which may lead to adverse outcomes in paediatric patients less than 2 years of age

Parenteral nutrition (PN) is used during medical conditions such as severe intestinal failure, malabsorption and short bowel syndrome and it is indicated in paediatric (children) and adult patients who cannot be fully fed or are fed enterally due to the above mentioned medical conditions.

Currently, there are 11 registered PN products in Malaysia which are approved for use in paediatric patients less than 2 years of age. These products contain amino acids and/or lipids.

MHRA (Medicines and Healthcare products Regulatory Agency), UK had released a ‘Direct Healthcare Professional Communication” with the below significant information pertaining to this safety alert.

  • Use of PN products containing amino acids and/or lipids which are exposed to light-exposed, might lead to severe adverse effects in premature neonates. This is because exposure of such solutions to light causes formation of peroxides and other degradation products.
  • Premature neonates are considered at high risk of oxidative stress related to multiple risk factors including oxygen therapy, phototherapy, weak immune system and inflammatory response with reduced oxidant defense.
  • As a risk minimization measure, health care professionals are advised to protect the PN products containing amino acids and/or lipids from light (both containers and administration sets) during administration to neonates and children below 2 years of age.

The European Medicines Agency (EMA) has reviewed the risk of toxic degradations of ingredients in PN products exposed to light, which may lead to adverse outcomes in neonates and children below 2 years of age.

It was reported in a study about Oxidative Stress-Related Disease in preterm and new-born infants due to exposure of PN products to ambient light, environmental light and particularly phototherapy which contribute in the formation of peroxides.  New-born and premature neonates are more prone to oxidative stress due to multiple risk factors which included weak (still developing) immune system, oxygen therapy, phototherapy, and inflammatory response with reduced oxidant defense.

Oxidative stress which would result due to high concentrations of photo degradation by-products can disrupts cell structures such as DNA, lipids, and proteins. The neonatal complications of oxidative stress included respiratory distress syndrome, periventribular leukomalacia (PVL), bronchopulmonary dysplasia (BPD), and retinopathy of prematurity (ROP).

NPRA has received seven case reports with 13 adverse drug events which are suspected to be related to PN products containing amino acids and/or lipids which are approved for use in paediatric patients less than 2 years of age. However, no adverse drug events were reported locally which are associated with oxidative stress due to by-products formed by photo degradation of PN.

With the available scientifically evident safety data of PN products, EMA and NPRA has issued a directive for all product registration holders to update their product information documents and local package inserts respectively, by including the recommendations on light protection when the solution is to be used in these population groups.

Advice for Healthcare Professionals:

  • To be aware and alert about light exposure of PN products containing amino acids and/or lipids, especially after admixture with trace elements and/or vitamins which might lead to the formation of high concentration of peroxides in these products.
  • All the PN products containing amino acids and/or lipids (in bags and administration sets) should be protected from light until administration is completed when used in in paediatric patients less than 2 years of age.
  • To know and be informed that exposure of by-products formed by photo degradation of PN could lead to ‘oxidative stress’ related adverse outcomes such as respiratory distress syndrome, bronchopulmonary dysplasia and periventribular leukomalacia particularly in paediatric patients less than 2 years of age.

Voluntary ADR Reporting:

Health care professionals and consumers are advised to report any suspected adverse drug reactions  or suspicious events which are experienced with the use of pharmaceutical medicinal products to the Malaysian health authority (NPRA) by online voluntary reporting facility through ADR web form. This could aid in accumulation of the more evident safety data which could facilitate NPRA in implementing early regulatory actions for a better patient safety.

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