[3] Common side effects include gastrointestinal upset, severe allergic reactions, and bone marrow suppression.
[8] When higher doses are used, as in the treatment of toxoplasmosis, pyrimethamine can cause gastrointestinal symptoms such as nausea, vomiting, glossitis, anorexia, and diarrhea.
[17] These mutations decrease the binding affinity between pyrimethamine and dihydrofolate reductase via loss of hydrogen bonds and steric interactions.
[18] Nobel Prize-winning American scientist Gertrude Elion developed the drug at Burroughs-Wellcome (now part of GlaxoSmithKline) to combat malaria.
[23] In the United States in 2015, Turing Pharmaceuticals was criticized for increasing the price 50-fold, from US$13.50 to $750 a tablet,[24] leading to a cost of $75,000 for a course of treatment reported at one hospital.
[27][29] Presentations from Retrophin, a company formerly headed by Martin Shkreli, CEO of Turing, from which Turing acquired the rights to Daraprim, suggested that a closed distribution system could prevent generic competitors from legally obtaining the drugs for the bioequivalence studies required for FDA approval of a generic drug.
"[30][31] As a result of the backlash, Shkreli hired a crisis public relations firm to help explain his fund's move.
[32] Turing Pharmaceuticals announced on 24 November 2015, "that it would not reduce the list price of that drug after all", but they would offer patient assistance programs.
[33] New York Times journalist Andrew Pollack noted that these programs "are standard for companies selling extremely high-priced drugs.
"[33] The price increase was criticized by physician groups such as HIV Medicine Associates and Infectious Diseases Society of America.
[36][37] Nonetheless, the students' work was featured in The Guardian[36] and Time magazine,[38] and on ABC Australia,[35] the BBC,[37] and CNN.
[39] On 22 October 2015, Imprimis Pharmaceuticals announced it had made available compounded and customizable formulations of pyrimethamine and leucovorin in capsules to be taken by mouth starting as low as $99 for a 100-count bottle in the United States.
[7] In January 2020, the FTC filed a case against Vyera "alleging an elaborate anticompetitive scheme to preserve a monopoly for the life-saving drug, Daraprim".
[51] In 2011, researchers discovered that pyrimethamine can increase β-hexosaminidase activity, thus potentially slowing down the progression of late-onset Tay–Sachs disease.