The ethics of generic immunosuppressive drugs

Generics/Research | Posted 26/09/2014 post-comment0 Post your comment

A literature review of generic immunosuppressive drugs (ISDs) in renal transplant patients concludes that it is ethical to prescribe generic ISDs provided regulatory safeguards are met. Alongside these safeguards, it will be essential to educate patients and to carry out further clinical and health economic studies to inform clinicians, patients and society of the risks and costs of drug substitution [1].

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Certain bioequivalence studies on the kidney transplant population support the safe use of generic ISDs [2, 3], but there are also reports of observed variations in drug concentration following drug substitution. Although generics are widely distributed, ISDs are different because they are so-called ‘critical dose drugs’. A relatively small difference in dose or concentration of a critical dose drug can lead to a serious adverse drug reaction or therapeutic failure.

This review, by Julie Allard and Marie-Chantal Fortin from the University of Montreal Hospital Research Centre, was carried out in Canada where the national healthcare service, Health Canada, has approved nine critical dose drugs, including three ISDs: cyclosporine, tacrolimus and sirolimus.

The ISD cyclosporine A has an effective dose and a toxic dose that are separated by only a small difference in plasma concentration. For such drugs, dosage is adjusted according to measurements of the actual blood levels achieved in the patient. This raises concerns when switching drugs, as even small changes can mean that the drug is no longer effective or can even lead to toxicity [3]. A study in 2005 reported a significantly higher incidence of acute rejection in patients who received generic cyclosporine versus those who received the brand-name drug, which has contributed to an ongoing generic drug controversy [4].

Allard and Fortin examined the various ethical issues involved, including distributive justice, physician duties, risks versus benefits, conflict of interest, informed consent, and logistical and economic issues. Their literature review was limited, they say, by a paucity of clinical data on generic ISDs and the absence of health economics studies in this area. They recommend a comprehensive cost-effectiveness analysis of generic ISDs together with clinical studies in de novo and stable transplant patients for every new generic ISD.

The authors conclude that, with caveats in place, it would be ethical to use generic ISDs, since the benefits to society would be greater than the risks to individual patients. Any risks could be minimized, they say, by implementing new policies such as a law prohibiting non-physicians, e.g. pharmacists, insurance providers, from authorizing substitutions of brand-name ISDs with generic ISDs or substitutions between generic ISDs.

Conflict of interest
The authors of the research paper [1] declared that there were no conflicts of interest.

Editor’s comment
Readers interested to learn more about generics substitution of immunosuppressive drugs are invited to visit to view the following manuscripts published in GaBI Journal:

Commentary on the recommendations of the European Society for Organ Transplantation Advisory Committee on generic substitution of immunosuppressive drugs

Role of hospital clinical pharmacist in transplantation, and generic immunosuppressive therapies

Readers interested in contributing a research or perspective paper to GaBI Journal – an independent, peer reviewed academic journal – please send us your submission here.

Related articles
FDA awards grant to study generic transplant drug tacrolimus

Transplant coordinators’ perception of generic immunosuppressants

1.   Allard J, Fortin M-C. Is it ethical to prescribe generic immunosuppressive drugs to renal transplant patients? Canadian Journal of Kidney Health and Disease. 2014;1(23):2-7.
2.   GaBI Online - Generics and Biosimilars Initiative. FDA grant to study generic versus brand-name transplant drugs []. Mol, Belgium: Pro Pharma Communications International; [cited 2014 Sep 26]. Available from:
3.   GaBI Online - Generics and Biosimilars Initiative. Switching to generic cyclosporine A after heart transplant safe []. Mol, Belgium: Pro Pharma Communications International; [cited 2014 Sep 26]. Available from:
4.   Taber DJ, Baillie GM, Ashcraft EE, et al. Does bioequivalence between modified cyclosporine formulations translate into equal outcomes? Transplantation. 2005;80(11):1633-5.

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