TxPharm and PCOP Issue Statement on Tacrolimus Shortage

Dear Transplant Professionals,

The Food and Drug Administration (FDA) and the American Society of Hospital Pharmacists (ASHP) recently published data on shortages of tacrolimus, an anti-rejection medicine used to prevent rejection after organ transplantation.^1-8 At the time this information was published, these shortages apply to some generic versions of tacrolimus, and dates for resolution of the shortages range from July 2019 to April 2020. Generic formulations have been evaluated by the FDA and are equivalent to brand-name (innovator) medicines.⁹  If this shortage affects your patients, we recommend discussing alternative options within your teams to devise a management strategy.  Some alternative options to continue tacrolimus treatment if the formulation used by the patient is on shortage include:

• Changing the current formulation on shortage to a different generic tacrolimus formulation that is not on shortage
  • These can be identified by discussing with your pharmacists and consulting the FDA and ASHP websites
• Changing the current formulation on shortage to a branded tacrolimus formulation, which may not be directly interchangeable with twice-daily tacrolimus products. These formulations include:
  • Prograf® twice-daily capsules¹⁰
  • Astagraf XL® once-daily capsules¹¹
  • Envarsus XR® once-daily tablets¹²
  • Prograf® twice-daily granules for oral suspension¹³

These formulations have been approved to prevent rejection after certain types of organ transplantation and may require dose adjustments depending on the formulation and on clinical situations. In regard to extended-release formulations, Envarsus XR tablets are not currently FDA approved for use in children but clinical trials underway in adolescents 12-18 years of age. Astagraf XL capsules are approved for pediatric use.”.^10-12

Given the importance of maintaining adequate therapy to prevent transplant rejection, transplant patients and caregivers are encouraged to discuss these options with their care teams before being affected by the shortage to minimize the chances of treatment interruption while ensuring safe and effective prevention of organ rejection.

Additional details about the tacrolimus drug shortages can be found on the following websites:

FDA website on drug shortages

ASHP website on drug shortages

Sent on behalf of the Transplant Pharmacy and Pediatric COPs

References

1.            FDA Drug Shortages. 2019. (Accessed July 12, 2019, at https://www.accessdata.fda.gov/scripts/drugshortages/default.cfm.)

2.            Drug Shortages. 2019. (Accessed July 12, 2019, at https://www.ashp.org/Drug-Shortages.)

3.            Colvin M, Smith JM, Hadley N, et al. OPTN/SRTR 2017 Annual Data Report: Heart. American Journal of Transplantation 2019;19:323-403.

4.            Hart A, Smith JM, Skeans MA, et al. OPTN/SRTR 2017 Annual Data Report: Kidney. American Journal of Transplantation 2019;19:19-123.

5.            Kandaswamy R, Stock PG, Gustafson SK, et al. OPTN/SRTR 2017 Annual Data Report: Pancreas. American Journal of Transplantation 2019;19:124-83.

6.            Kim WR, Lake JR, Smith JM, et al. OPTN/SRTR 2017 Annual Data Report: Liver. American Journal of Transplantation 2019;19:184-283.

7.            Smith JM, Weaver T, Skeans MA, et al. OPTN/SRTR 2017 Annual Data Report: Intestine. American Journal of Transplantation 2019;19:284-322.

8.            Valapour M, Lehr CJ, Skeans MA, et al. OPTN/SRTR 2017 Annual Data Report: Lung. American Journal of Transplantation 2019;19:404-84.

9.            Food And Drug Administration. Guidance for Industry - Bioavailability and Bioequivalence Studies Submitted in NDAs or INDs—General Considerations. 2014. (Accessed March 20, 2017, at https://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm389370.pdf.)

10.          Prograf(R) [package insert]. Astellas Pharma US, Inc., Northbrook, IL. June 2019. (Accessed July 22, 2019, at https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/050708s050,050709s042,210115s002lbl.pdf.)

11.          Astagraf XL(R) [package insert]. Astellas Pharma US, Inc., Northbrook, IL. June 2019. (Accessed July 22, 2019, at https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/204096s007lbl.pdf.)

12.          Envarsus XR (R) [package insert]. Veloxis Pharmaceuticals, Edison, NJ. December 2018. (Accessed July 22, 2019, at https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/206406s007lbl.pdf.)

13.          Prograf Granules (R) [package insert]. Astellas Pharma US, Inc., Northbrook, IL. June 2019. (Accessed July 22, 2019, at https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/050708s050,050709s042,210115s002lbl.pdf.)