Peptide education
Cyclosporine
Ciclosporin · Cyclosporin A · Neoral · Sandimmune · Restasis
Cyclosporine is an immunosuppressant made from a cyclic peptide. Systemic products help prevent rejection after certain organ transplants and treat some severe inflammatory diseases. A separate eye emulsion is used for a specific form of dry eye.
The formulation matters. Systemic cyclosporine requires monitoring for kidney injury, high blood pressure, infections, and drug interactions. RESTASIS has its own eye-specific instructions and precautions.
Overview
Quick answer
NEORAL is modified oral cyclosporine; SANDIMMUNE includes non-modified capsules and an intravenous product. The oral forms are not bioequivalent. RESTASIS is an ophthalmic emulsion with a different indication and dose.
How does cyclosporine work?
Cyclosporine binds a protein called cyclophilin. Together they inhibit calcineurin, reducing signals involved in T-cell activation. The systemic label also describes reduced interleukin-2 production.
What is oral NEORAL used for?
Its US label covers rejection prevention in kidney, liver, and heart allografts; severe active rheumatoid arthritis after inadequate response to methotrexate; and selected adults who are not immunocompromised and have severe, recalcitrant plaque psoriasis.
What is RESTASIS used for?
RESTASIS is an eye emulsion intended to increase tear production when it is presumed to be reduced by ocular inflammation associated with keratoconjunctivitis sicca.
Can NEORAL and SANDIMMUNE be switched without monitoring?
No. They are not bioequivalent. Their labels call for physician supervision and monitoring when changing formulations.
What are the main systemic risks?
Systemic treatment can cause kidney injury and high blood pressure and can increase susceptibility to infection and malignancy. Other medicines can change cyclosporine concentrations or add toxicity.
Evidence
Evidence snapshot
In 209 recipients, predicted one-year graft survival was 80.4% with cyclosporine plus prednisone and 64.0% with an azathioprine-based regimen that also included prednisone.
NEORAL's label covers certain transplants, severe active rheumatoid arthritis after inadequate methotrexate response, and selected severe plaque psoriasis.
RESTASIS is an eye emulsion for patients whose tear production is presumed to be suppressed by inflammation associated with keratoconjunctivitis sicca.
The labels describe different absorption and say switching requires physician supervision and monitoring.
Claims
Common claims vs evidence
| Claim | Human evidence | Verdict |
|---|---|---|
| All cyclosporine products can be exchanged at the same dose. | Modified NEORAL and non-modified SANDIMMUNE have different bioavailability. Their labels describe supervised conversion and monitoring of concentrations and safety measures. | A change in formulation requires the treating clinician's supervision. |
| Cyclosporine eye drops have the same indications as oral cyclosporine. | RESTASIS is labeled to increase tear production in specified inflammatory dry eye. NEORAL is labeled for selected systemic transplant and inflammatory conditions. | The products have different routes, doses, and indications. |
| The transplant trial tested cyclosporine without other immunosuppression. | Both randomized groups received prednisone. The comparator also included azathioprine. | The outcomes compare regimens, not cyclosporine alone against no treatment. |
Bottom line
Main takeaway
Cyclosporine reduces immune activity. The prescribed product determines whether it is being used systemically or in the eye.
Modified and non-modified oral products are not bioequivalent. Systemic treatment calls for monitoring, including kidney function and blood pressure, with blood concentrations checked as directed for the indication.
The kidney-transplant trial compared cyclosporine plus prednisone with an azathioprine-based regimen. Its predicted graft-survival estimates belong to that historical transplant setting.
Identity
What it is
Cyclosporine is an 11-amino-acid cyclic polypeptide. NEORAL's modified oral formulation and SANDIMMUNE's non-modified formulation deliver the same named active medicine with different absorption.
RESTASIS is a 0.05% cyclosporine eye emulsion. Its labeled use and administration differ from systemic immunosuppression.
Use context
Routes, doses, and cycle patterns
Systemic dosing depends on the indication, formulation, clinical response, and monitoring. RESTASIS has a separate ophthalmic schedule.
Human studies and product labels
NEORAL for transplant rejection prevention
- Purpose
- Kidney, liver, and heart allograft rejection prevention
- Context
- Modified oral product label
- Route
- Oral
- Amount
- Individualized to the transplanted organ and accompanying immunosuppression
- Frequency
- Daily amount divided into two doses
The label describes adjustment using cyclosporine blood concentrations, rejection assessment, and tolerability.
NEORAL for severe active rheumatoid arthritis
- Purpose
- Disease inadequately responsive to methotrexate
- Context
- Modified oral product label
- Route
- Oral
- Amount
- 2.5 mg/kg per day initially, with labeled adjustments up to 4 mg/kg per day
- Frequency
- Daily amount divided into two doses
The label calls for monitoring of kidney function and blood pressure, and directs dose changes according to response and toxicity.
NEORAL for severe plaque psoriasis
- Purpose
- Selected adults without immunocompromise who have severe recalcitrant plaque psoriasis
- Context
- Modified oral product label
- Route
- Oral
- Amount
- 2.5 mg/kg per day initially, with labeled adjustments up to 4 mg/kg per day
- Frequency
- Daily amount divided into two doses
The indication applies when specified systemic treatments have failed, are contraindicated, or cannot be tolerated. The label sets monitoring requirements and contraindications for this population.
RESTASIS eye emulsion
- Purpose
- Increase tear production in specified inflammatory dry eye
- Context
- Ophthalmic product label
- Route
- Ophthalmic
- Amount
- One drop of 0.05% emulsion in each eye
- Frequency
- Twice daily, approximately 12 hours apart
Eye burning was the most common adverse reaction in the product label.
What varies
- Transplant teams use cyclosporine blood concentrations and clinical assessment to guide systemic doses. NEORAL and SANDIMMUNE differ in bioavailability.
- The NEORAL label describes interactions with many medicines and says grapefruit can increase cyclosporine concentrations.
Research
Research evidence
A randomized kidney-transplant trial compared cyclosporine and prednisone with an azathioprine-based regimen. Product labels also describe evidence for selected systemic and ophthalmic indications.
| Study / evidence area | Population | Design | Product context | Main outcome | Limitations | Weight |
|---|---|---|---|---|---|---|
| Kidney-transplant immunosuppression trial | 209 deceased-donor kidney transplant recipients | Randomized multicenter comparison | Cyclosporine plus prednisone versus an azathioprine-based regimen | Predicted one-year graft survival was 80.4% with cyclosporine and 64.0% with the comparator regimen. | The comparison used historical transplant regimens, and the reported survival figures are predicted estimates. | Controlled human evidence |
| RESTASIS prescribing information | Patients with the labeled inflammatory tear-production condition | US prescribing information describing clinical studies | Cyclosporine ophthalmic emulsion 0.05% | At six months, approximately 15% of RESTASIS recipients versus 5% receiving vehicle had at least a 10 mm increase from baseline in Schirmer tear-test wetting. Ocular burning was the most common adverse reaction. | Increased tear production was not seen in patients using topical anti-inflammatory drugs or punctal plugs in the labeled studies. | Product-specific clinical evidence |
Cautions
Safety and unknowns
- Systemic cyclosporine can damage the kidneys and raise blood pressure. Kidney function and blood pressure are monitored during treatment.
- Immunosuppression can increase infection and malignancy risk. The systemic labels also describe interactions that can change drug exposure or toxicity.
- RESTASIS can cause eye burning. Its label also addresses the risk of contaminating the vial and precautions with contact lenses.
Product quality
Product identity and quality
The modified oral, non-modified oral, intravenous, and ophthalmic products have different labels and administration requirements.
Formulation
Modified NEORAL and non-modified SANDIMMUNE are not bioequivalent.
Eye formulation
RESTASIS is labeled for ophthalmic use and has its own handling instructions.
Mechanism
How it is proposed to work
Systemic cyclosporine reduces signals that activate T cells, which helps suppress immune responses involved in organ rejection and inflammatory disease. The RESTASIS label says its exact ocular mechanism is unknown.
A laboratory study found that the cyclosporine-cyclophilin complex binds and inhibits calcineurin. The systemic label describes reduced production of interleukin-2 and other lymphocyte signals.
FAQ
Common questions
Can NEORAL and SANDIMMUNE be swapped directly?
They are not bioequivalent. Switching requires physician supervision and monitoring.
Does RESTASIS have the same use as oral cyclosporine?
No. RESTASIS is an eye emulsion for a specified tear-production indication; oral NEORAL has different systemic indications.
Details
Technical details
Sources
References
- 1.
- 2.
- 3.
- 4.
FDA. FDA statistical review of OTX-101 and the RESTASIS tear-production endpoint
An FDA review of a different cyclosporine product describes the RESTASIS approval endpoint as the same threshold of at least 10 mm improvement from baseline.
- 5.
PubMed. A randomized clinical trial of cyclosporine in cadaveric renal transplantation
doi:10.1056/NEJM198310063091401 PMID:6350878
- 6.
PubMed. Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes
doi:10.1016/0092-8674(91)90124-h PMID:1715244