Cyclosporine Modified vs. Unmodified: Here’s What Sets Them Apart
Key takeaways:
Cyclosporine (Sandimmune, Gengraf, Neoral) is a prescription medication. It’s most often used to prevent organ transplant rejection, but it can also treat conditions such as rheumatoid arthritis and psoriasis.
Oral cyclosporine comes in two main forms, modified and unmodified. These different versions of cyclosporine contain the same active ingredient but work differently in the body. Cyclosporine eye drops are also available.
Whether you’re taking modified or unmodified cyclosporine, make sure to stick to the same formulation. Don’t switch back and forth between the two without your prescriber’s OK. This will help make sure the medication works consistently.
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If you’re living with a health condition that impacts the way your immune system works, you may be familiar with cyclosporine. It’s a prescription medication that helps calm the immune system, typically following an organ transplant.
There’s a layer of complexity, though. There are two types of cyclosporine: modified and unmodified. These formulations might sound similar, but they aren’t exactly the same. And taking the wrong one could translate to a big difference in how well the medication works for you.
Coming up is a breakdown of the key differences between these two cyclosporine formulations. We’ll look at why the difference matters and help you understand which one might be better for you.
What are modified and unmodified cyclosporine used to treat?
No matter which version of cyclosporine you take, its main purpose is to lower the activity of your immune system.
One of cyclosporine’s key FDA-approved uses is to prevent organ transplant rejection. Both modified and unmodified cyclosporine can be prescribed after a kidney, liver, or heart transplant. When you receive a donor organ — an organ from another person — your body can activate its immune defenses to attack the new organ. Cyclosporine can prevent the new organ from being attacked or rejected.
Both versions have their own additional approved uses as well.
Unmodified cyclosporine can treat chronic rejection. This can happen if other medications don’t effectively manage organ rejection.
Modified cyclosporine can treat certain conditions unrelated to organ transplants. These include rheumatoid arthritis and plaque psoriasis when first-choice medications aren’t enough.
What’s more, cyclosporine has a number of uses that are considered off-label. Although the FDA has not approved these uses, your healthcare professional may still prescribe cyclosporine for conditions such as:
Nephrotic syndrome, a type of kidney disorder
Graft-versus-host disease prevention (following a stem cell transplant)
Uveitis, an eye condition
Ulcerative colitis, an autoimmune condition of the large intestine
Why are there different formulations of cyclosporine?
Cyclosporine comes in different formulations because not everyone absorbs the medication in the same way. Your healthcare professional will make the final call on which version of cyclosporine would be best for you.
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Cyclosporine, unmodified (Sandimmune) is the original version of the medication. It can have relatively unpredictable absorption, meaning some people might get too little or too much of the medication. To keep you on track, your healthcare professional should routinely monitor cyclosporine levels in your blood.
Cyclosporine, modified (Neoral, Gengraf) was made to improve how the medication is absorbed in the body. It works more reliably and predictably for most people. This is especially important since cyclosporine helps keep tabs on your immune system. However, small changes in how much is absorbed could still affect how well it works for you.
Differences between modified and unmodified cyclosporine
There are some key differences between modified and unmodified cyclosporine, such as:
Formulation: Modified and unmodified cyclosporine contain the same active ingredient, but they’re manufactured differently.
Absorption: Modified cyclosporine is absorbed more consistently by the body after you take a dose.
Bioavailability: A higher percentage of modified cyclosporine is usable in the body after you swallow a dose.
Consistency: Unmodified cyclosporine works less predictably in the body and requires more frequent blood tests.
Brand name: Sandimmune is the brand name of unmodified cyclosporine. Modified cyclosporine goes by Neoral and Gengraf.
Always talk to a healthcare professional before switching between modified and unmodified cyclosporine.
What are the side effects of modified and unmodified cyclosporine?
Cyclosporine is a must-have for people living with certain health conditions. But it can also have side effects. Common cyclosporine side effects include swollen gums, more hair growing on your body, and high blood pressure.
A more serious side effect is that cyclosporine can make it more likely to catch an infection. This is because it lowers your immune system's ability to fight germs. It might also cause you to feel tired, shaky, or have headaches. In fact, cyclosporine has a boxed warning for its infection risk.
Another possible side effect is kidney problems. The risk goes up if you take cyclosporine for a long time or at high doses. This can be especially true if you take unmodified cyclosporine after a liver transplant. In these situations, unmodified cyclosporine levels are difficult to predict.
It's important to take cyclosporine regularly. So if you feel bothersome or unexpected side effects, check in with your healthcare professional. They can help you manage side effects to stay consistent with the medication.
Are modified and unmodified cyclosporine interchangeable?
No, modified and unmodified cyclosporine are not interchangeable. Even though they contain the same active ingredient, they’re not exactly the same.
Because of this key difference, cyclosporine has another boxed warning. You can’t freely switch from one type to the other. Switching between the two could mean getting too much or too little of the medication in your body. This increases the chances of side effects or transplant rejection.
If you need to switch cyclosporine formulations, it’s best to follow the advice of a trained healthcare professional. They will closely monitor your health to make sure the new medication is safe and works well for you.
Are cyclosporine eye drops modified or unmodified?
Cyclosporine eye drops (Restasis, Cequa, Verkazia, Vevye) are a special form of cyclosporine. They’re made for treating dry, irritated eyes. They’re not technically classified as "modified" or "unmodified" like oral cyclosporine is.
Cyclosporine eye drops are specially designed to work on the surface of the eyes to reduce inflammation and help your eyes make more tears. These eye drops also don’t go into the bloodstream the way oral cyclosporine does. This means they work differently and have fewer side effects.
How to save on cyclosporine
There are ways to save on cyclosporine modified and unmodified, which are both available as brand-name and generic medications. With a free GoodRx coupon, you may be able to pay as low as:
Generic cyclosporine, unmodified (120 capsules): $360.74
Brand-name Sandimmune (120 capsules): $2138.90
Brand-name Sandimmune (1 bottle of solution): $838.17
Generic cyclosporine, modified (120 capsules): $124.90
Generic cyclosporine, modified (1 bottle of solution): $79.99
Brand-name Neoral (120 capsules): $1245.94
Brand-name Neoral (1 bottle of solution): $644.37
Brand-name Gengraf (120 capsules): $54.11
Brand-name Gengraf (1 bottle of solution): $79.99
You can also save with a copay savings card. If you have commercial insurance, you may be eligible to pay as little as $0 for brand-name Neoral or Sandimmune using a savings card from the manufacturer. Neoral’s manufacturer also offers a 30-day free trial voucher.
Other savings opportunities are also available. For instance, if you’re uninsured or underinsured, you may be eligible for Gengraf’s patient assistance program, which offers the medication free of charge.
The bottom line
Cyclosporine is a life-saving prescription medication that calms the immune system. It’s most often prescribed to prevent organ transplant rejections, and it’s available in both modified (Neoral, Gengraf) and unmodified (Sandimmune) versions. Modified and unmodified cyclosporine contain the same medication, but they’re not interchangeable. Talk to your healthcare professional if you’re interested in switching from one to the other.
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References
AbbVie. (2024). Gengraf- cyclosporine capsule [package insert].
Apotex. (2024). Cyclosporine capsule, gelatin coated [package insert].
Apotex. (2024). Cyclosporine, modified- cyclosporine capsule, liquid filled [package insert].
Cattran, D. C., et al. (2015). Cyclosporin in idiopathic glomerular disease associated with the nephrotic syndrome : Workshop recommendations. Kidney International.
Héritier, J., et al. (2022). Optimized cyclosporine starting dose may reduce risk of acute GvHD after allogeneic hematopoietic cell transplantation: A single-center cohort study. Bone Marrow Transplantation.
MedlinePlus. (2023). Cyclosporine. National Library of Medicine.
Singh, A. K., et al. (2011). Cyclosporine: A commentary on brand versus generic formulation exchange. Journal of Transplantation.
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