HQ Team
September 19, 2023: The USFDA stated that Accord Healthcare Inc.’s generic tacrolimus oral capsules, meant to treat organ rejection, were no longer automatically substitutable at the pharmacy due to increased toxicity.
Accord’s tacrolimus oral capsules can still be sold on prescription and the FDA has changed the therapeutic equivalence rating for the company’s capsules from AB to BX.
A BX rating means that the data are insufficient to show that the Accord’s generic tacrolimus oral capsules provide the same therapeutic effect as other brand-named drug Prograf (tacrolimus) oral capsules.
The drug is indicated for the prevention of organ rejection in adult patients receiving kidney, liver, or heart transplants, and in paediatric patients receiving liver transplants.
FDA-funded study
The FDA funded a bioequivalence study by BioPharma Services and reviewed the results with other evidence.
“These studies indicate that Accord Healthcare Inc.’s tacrolimus oral capsules may deliver drug to the body at a higher maximum concentration compared to Prograf’s tacrolimus oral capsules,” according to an FDA statement.
The increased peak concentration may result in patients having too much tacrolimus in their body compared to Prograf, which may result in signs or symptoms of tacrolimus toxicity, according to the statement.
In 2011, the FDA determined that tacrolimus products qualified as narrow therapeutic index drugs.
In 2012, the regulator updated recommendations for the design of bioequivalence studies to support therapeutic equivalence for tacrolimus generics.
Generic concerns
The transplant community expressed concern regarding the substitutability of FDA-approved generic tacrolimus oral capsules that were approved prior to 2012.
They questioned both their therapeutic equivalence to the brand-name drug, Prograf (tacrolimus) and other approved generics.
Multiple post-approval studies signalled a potential issue with the bioequivalence of Accord Healthcare Inc.’s tacrolimus oral capsules, which led to the BioPharma Services study.
Seizures, tremors
Potential harms to patients from higher concentrations of tacrolimus include kidney damage, high blood pressure, nerve damage, such as seizures, tremors, or headache, and elevated potassium levels.
The FDA is “not aware of post-marketing issues regarding safety or efficacy for Accord Healthcare Inc.’s tacrolimus oral capsules.”
Prograf (tacrolimus) oral capsules and generic tacrolimus oral capsules manufactured by companies other than Accord Healthcare Inc. are not affected by this issue.
