The Medicines Control Council has withdrawn the diabetes medicine Avandia from the market because it contains a substance that might increase the likelihood of a heart attack.
The medication, produced by GlaxoSmithKline, is prescribed to some type2 diabetics.
The council made the decision five weeks ago "due to safety risks" attributed to rosiglitazone, a constituent of Avandia.
A statement by the council on Tuesday said: "Rosiglitazone is associated with an increased risk [of] heart failure, myocardial infarction [heart attack] and cardiac arrest".
Avandia was registered in South Africa in October 2004. The EU and the UK have already withdrawn rosiglitazone-containing medicine from their markets.
Spokesman for the department of health Fidel Hadebe could not say how many South Africans take Avandia.
"Given the reality that diabetes is a huge problem in South Africa, it is obvious that quite a number of people are on [Avandia]," he said.
Diabetes nurse educator Razana Allie, of Diabetes SA, said Metformin was one of a few alternative products that could be used in South Africa.
The local representatives of GlaxoSmithKline could not be reached for comment.