In the February 2010 issue of Drug Safety Update, the MHRA discusses the availability of a new formulation of tacrolimus (Modigraf® granules), and warns that the various formulations are not interchangeable.
The MHRA has previously issued advice regarding the prescribing and dispensing of the correct tacrolimus product, following reports of medication errors resulting from unintended switching between Prograf® and Advagraf® (prolonged-release capsules). It now highlights that pharmacists need to be aware of the addition of Modigraf® granules to the product range; this is licensed for the prophylaxis of transplant rejection in adult and paediatric recipients of a kidney, liver, or heart transplant. It is also indicated for treatment of allograft rejection resistant to treatment with other immunosuppressive medicines in adults and children. Modigraf® granules have an approximately 18% higher bioavailability compared to immediate-release Prograf® capsules.
The product information for Modigraf® contains information on converting patients already on Prograf® to this product; switching between Advagraf® and Modigraf® is not however recommended. Oral tacrolimus formulations or regimens should not be altered without careful therapeutic monitoring by a transplant specialist.
The article also notes that patients unable to swallow Prograf® capsules may have either opened the capsules and swallowed the contents with water, or used an unlicensed liquid preparation (‘specials’). Care must be taken when switching patients from these to licensed formulations of tacrolimus, as the bioavailabilities are unknown and may have varied between batches.
Healthcare professionals are given the following advice:
• Prescribers and dispensers should take note of the different bioavailabilities of the available oral formulations of tacrolimus
• Monitor patients carefully when switching between formulations of tacrolimus, or from unlicensed medicines to Modigraf® (the transfer of patients from any unlicensed treatment to Modigraf® should be closely supervised by a transplant specialist)
• Consider use of the Modigraf® for paediatric patients and others with swallowing difficulties (prescribers should satisfy themselves that an alternative, licensed medicine would not meet the patient’s needs before using an unlicensed medicine or a licensed medicine off-label)
• Take care in prescribing or dispensing the correct product/formulation of tacrolimus
• Any suspected adverse reactions to tacrolimus products should be reported on a Yellow Card