Neoral®

GoodRx

Cyclosporine, Modified · oral capsule

Misc.

OFF-LABELNot in the FDA label for this product

Non-infectious intermediate or posterior uveitis

Oral, dosed to effect and to renal tolerance; the trial used doses high enough to raise creatinine and blood pressure

RCT · n=56 · only 46% each

A randomised double-masked trial compared cyclosporine with prednisolone in 56 patients with bilateral sight-threatening non-infectious intermediate or posterior uveitis. Visual acuity or vitreous haze improved in only 13 of 28 patients (46%) in each arm, and macular oedema resolved in 7 of 15 on cyclosporine against 10 of 16 on prednisolone (p=0.376). Twenty-eight patients per arm cannot exclude a real difference, so this is a failure to detect one rather than a demonstration that the two are equal, and the authors' own word is that only 46% improved: two mediocre options, not two good ones. Patients who failed both drugs alone improved on the combination. The notable adverse effects were rises in serum creatinine and hypertension. Formulation caveat, which comes from the dates rather than from the paper: this trial published in 1991 and the Neoral microemulsion reached the market in 1995, so it necessarily used the original oil-based formulation. The two are not interchangeable without blood-level monitoring, and Neoral gives higher exposure per milligram, so neither the response rate nor the creatinine and blood-pressure signal transfers dose for dose.

Nussenblatt RB, Palestine AG, Chan CC, Stevens G, Mellow SD, Green SB. Randomized, double-masked study of cyclosporine compared to prednisolone in the treatment of endogenous uveitis. Am J Ophthalmol. 1991;112(2):138-46

Non-infectious ocular inflammation, as a corticosteroid-sparing agent

151 to 250 mg daily in adults; the cohort found lower doses less successful and higher doses no better

Cohort · n=373 · 52% at 1 yr

The Systemic Immunosuppressive Therapy for Eye Diseases cohort followed 373 patients starting cyclosporine as their single non-corticosteroid agent. Sustained complete control of inflammation was reached by 33.4% at 6 months and 51.9% at 1 year, and corticosteroid-sparing success, meaning controlled inflammation on prednisone of 10 mg a day or less, by 22.1% and 36.1%. Toxicity ended treatment within a year in 10.7%, and patients over 55 were more than three times as likely to stop for toxicity as those aged 18 to 39, so an alternative agent may suit older patients better. The authors describe the drug as modestly effective. The cohort spans 1979 to 2007 and so straddles both the oil-based and microemulsion formulations.

Kaçmaz RO, Kempen JH, Newcomb C, et al. Cyclosporine for ocular inflammatory diseases. Ophthalmology. 2010;117(3):576-84

Contraindications

Neoral is contraindicated in patients with a hypersensitivity to cyclosporine or to any of the ingredients of the formulation.

Available Forms

25 mg unit-dose blisters, 100 mg unit-dose blisters, 50 mL bottles, 100 mg/mL

Mechanism of Action

Cyclosporine is a potent immunosuppressive agent that in animals prolongs survival of allogeneic transplants involving skin, kidney, liver, heart, pancreas, bone marrow, small intestine, and lung.

Warnings & Precautions

All Patients: Cyclosporine, the active ingredient of Neoral, can cause nephrotoxicity and hepatotoxicity. The risk increases with increasing doses of cyclosporine.
Because: Neoral is not bioequivalent to Sandimmune, conversion from Neoral to Sandimmune using a 1:1 ratio (mg/kg/day) may result in lower cyclosporine blood concentrations.

Common Side Effects

The principal adverse reactions of cyclosporine therapy are renal dysfunction, tremor, hirsutism, hypertension, and gum hyperplasia. Hypertension, which is usually mild to moderate, may occur in approximately 50% of patients following renal transplantation and in most cardiac transplant patients.

Pregnancy & Lactation

Pregnancy: There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to cyclosporine, including Neoral, during pregnancy.

Lactation: Cyclosporine and its metabolites are present in human milk following oral and intravenous administration. Adverse effects on the breastfed infant have not been reported.

Pediatric Use

Although no adequate and well-controlled studies have been completed in children, transplant recipients as young as one year of age have received Neoral with no unusual adverse effects. The safety and efficacy of Neoral treatment in children with juvenile rheumatoid arthritis or psoriasis below the age of 18 have not been established.