Propofol vials had no mention of drug composition: PGI report

Naina Mishra

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Chandigarh, December 7

The propofol (also propoven) injection was found to have extremely hazardous impurities, exposure to which could cause severe skin and respiratory infections, reveals a report of the internal committee of the PGI, a copy of which is with Chandigarh Tribune. It also contained corrosive acids used in chemical reactions, the report said.

An investigation by a team of PGI doctors found the vials of Propoven (Becure), manufactured by Nixi Laboratories Pvt Ltd, Kala Amb, didn’t have relevant information regarding the drug’s composition, which brought the drug under the scanner in the case of death of five patients.

An examination of the propoven label showed it specified only two details – Propofol 10 mg & water for injection (q.s). However, the formulation of the standard Food and Drug Administration (FDA) label of propofol mentions soybean oil (100 mg/ml), glycerol (22.5 mg/ml), egg lecith (12 mg/ml) and disodium edentate (0.005%); with sodium hydroxide to adjust pH, said the report.

The chemical analysis of propoven conducted by PGIMER showed that it contained 26 impurities, including cyclohexylamine (hazardous and exposure above 10 PPM can cause severe skin and respiratory infections), allyloxycarbonyl aminoacetic acid (corrosive acid used in chemical reactions), and protirelin (found to produce coma, hypotension, tachycardia, dyspnea).

After the analysis of eight patients who encountered adverse reactions, it was revealed that all patients were admitted with the Department of Neurosurgery and underwent surgeries for various reasons, of which five died. The patients developed complications that included shock, acute kidney injury, acute liver injury or coagulopathy.

In all cases, hypotension was detected immediately and intraoperative hypotension was more severe in the cases where propofol was also used for the maintenance of anaesthesia.

Propoven (Becure) was compared with Fresofol (Propofol), another brand of the anaesthetic drug. On a close inspection of propoven, it was found that the emulsion appeared to be broken and the consistency was not as smooth and uniform. The pH of both injections was tested to draw a comparison. The pH of fresofol was found to be 7.1 (within FDA range) and of propoven was found to be 5.9. The FDA recommended 7 to 8.5 pH for propofol.

The committee found that the common factor in all cases was the use of propofol as an anaesthetic agent and the brand used in the relevant cases was Propoven (Becure), manufactured by Nixi Laboratories Pvt Ltd, Kala Amb.

The particle size of propoven was heterogeneous and had a very high zeta potential which shows that the sample was not very stable. In contrast, sample of fresofol was stable, homogenous, and had low zeta potential with less variability.

The committee concluded the drug was the “most probable cause of serious adverse reactions, including death of the patients”.

Probable cause of deaths

• Analysis of propoven by the PGI shows it contained 26 impurities
• These include cyclohexylamine that can cause severe skin, respiratory infections
• Vials of Propoven (Becure) of Nixi Lab had no mention of drug composition
• Drug most probable cause of adverse reactions, including deaths, says report