SAHPRA has announced the withdrawal of all pholcodine-containing products from the market. This is due to the risk of severe anaphylactic reactions to neuromuscular blocking agents (NMBAs) used during general anaesthesia and the association with exposure to pholcodine in the preceding year.

Allergic reactions to NMBAs are mostly IgE-mediated, which requires prior sensitisation to the antigen, yet many patients experiencing anaphylaxis have no history of prior exposure to NMBAs. This led to speculation that environmental exposure to other substances containing quaternary ammonium groups was resulting in sensitisation (quaternary ammonium groups are considered to be the primary allergenic structure).

Pholcodine was first hypothesised as the cause in 2005. Subsequently, a multicentre case-control study in France (ALPHO) was commissioned by the EMA. This study found a significantly increased risk of NMBA-associated anaphylaxis with prior pholcodine use or prior occupational exposure to other quaternary ammonium compounds.

Read the SAHPRA press release here.

Read the full ALPHO study here.