Questions and Answers Regarding Tacrolimus Oral Capsules (Generic of Prograf), Made by Accord Healthcare Inc.
1. What is tacrolimus?
Tacrolimus oral capsules are drugs approved by FDA for prevention of organ rejection in adult and pediatric patients who received certain types of organ transplants. Prograf is the brand name for tacrolimus oral capsules.
2. Which tacrolimus products does this action affect?
This action only affects generic tacrolimus oral capsules manufactured by Accord Healthcare Inc., including the 0.5 mg, 1 mg, and 5 mg oral capsules. It does not affect other tacrolimus oral capsules, such as Prograf (tacrolimus) oral capsules or other approved generic tacrolimus oral capsules. It does not affect other dosage forms of tacrolimus such as extended-release oral capsules, tacrolimus granules for oral suspension, tacrolimus injection products for intravenous use, or tacrolimus topical ointments.
3. Am I at greater risk of rejection if I am on Accord Healthcare Inc.’s generic tacrolimus oral capsules?
Patients who have been taking Accord Healthcare Inc.’s tacrolimus oral capsules and have tacrolimus trough blood levels at target are not at a greater risk of transplant rejection. FDA did not find that Accord Healthcare Inc.’s tacrolimus oral capsules delivered less drug than Prograf (tacrolimus). The finding that led to this action are data that show a peak blood level that is higher than Prograf (tacrolimus) and may increase the risk for tacrolimus-associated toxicity.
4. Are Accord Healthcare Inc.’s generic tacrolimus oral capsules less effective than Prograf (tacrolimus) oral capsules?
For patients who are stable on an Accord Healthcare Inc. tacrolimus oral capsule product, there is no evidence that it is not effective in preventing organ rejection. Accord Healthcare Inc.’s tacrolimus oral capsules are different from Prograf (tacrolimus) because the peak concentration is higher. That means it is not a generic that can be automatically substituted for Prograf at the pharmacy. While higher concentrations could be associated with adverse events, FDA is not aware of data indicating increased adverse events with Accord Healthcare Inc.’s tacrolimus oral capsules. At this time, FDA is not removing Accord Healthcare Inc.’s tacrolimus oral capsules from the market; they can still be prescribed.
5. Are other generics of Prograf (tacrolimus) oral capsules available on the market?
There are multiple other generics of Prograf (tacrolimus) oral capsules approved by FDA. The Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations database provides information on all approved generic tacrolimus oral capsules that are therapeutically equivalent to Prograf (tacrolimus) capsules. FDA has not identified concerns with Prograf (tacrolimus) oral capsules or the other generics on the market.
6. Do other generics of tacrolimus oral capsules on the market raise similar concerns?
At this time, FDA does not have a concern regarding the bioequivalence of other generics of Prograf (tacrolimus) oral capsules. FDA will continue its monitoring of all generic drugs and all products on the market, and welcomes any information from the public about the performance of drugs and any adverse effects.
7. When was Accord Healthcare Inc.’s generic for tacrolimus oral capsules approved by FDA?
Accord Healthcare Inc. received FDA approval of its abbreviated new drug application (ANDA) on August 31, 2011, for the 0.5 mg, 1 mg, and 5 mg strengths.
8. How can patients find out which company manufactured their tacrolimus oral capsules?
Anyone with questions or concerns about which company manufactured their tacrolimus oral capsules should contact the pharmacy where the prescription was filled.
9. What action is FDA taking?
FDA has changed the therapeutic equivalence (TE) rating for Accord Healthcare Inc.’s tacrolimus oral capsules in the Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations database from AB to BX. This means that the data are insufficient to show that the product provides the same therapeutic effect and safety profile as Prograf (tacrolimus) oral capsules. A drug with a BX rating is still approved and can be prescribed but is not recommended as automatically substitutable at the pharmacy (or by a pharmacist) for the brand-name drug.
10. What are recommendations for patients who are currently taking the Accord Healthcare Inc.’s generic tacrolimus oral capsules?
Patients should not make changes to their treatment, except in consultation with their health care professional. Patients should also inform their health care professional if they have experienced any problems that may be related to taking Accord Healthcare Inc.’s tacrolimus oral capsules.
11. What are recommendations for health care professionals who may have patients taking Accord Healthcare Inc.’s generic tacrolimus oral capsules?
FDA recommends that health care professionals consider these data in deciding the best therapeutic options for patients currently taking Accord Healthcare Inc.’s tacrolimus oral capsules. If health care professionals identify concerns regarding the performance of Accord Healthcare Inc.’s product or adverse events, FDA encourages reporting to FDA’s MedWatch Adverse Event Reporting program.
12. Why did FDA become concerned that Accord Healthcare Inc.’s generic tacrolimus oral capsules may not be therapeutically equivalent to Prograf (tacrolimus) oral capsules?
Members of the transplant community had concerns regarding the substitutability of FDA-approved generic tacrolimus oral capsules to both the brand-name drug and other approved generics. FDA funded a number of studies to investigate these concerns. Multiple post-approval studies signaled there could be a potential issue with the bioequivalence of Accord Healthcare Inc.’s tacrolimus oral capsules and led FDA to further investigate, so FDA funded an additional study by BioPharma Services USA. FDA reviewed the results of the bioequivalence study by BioPharma along with other evidence. FDA is concerned that Accord Healthcare Inc.’s tacrolimus oral capsules may deliver drug to the body at a higher peak concentration compared to Prograf (tacrolimus) oral capsules.
13. Where can I find more information about the BioPharma Services USA study?
The results of the BioPharma study (NCT04725682) will be made available on September 20, 2023 at ClinicalTrials.gov.