NEORAL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for NEORAL (NEORAL).
Cyclosporine, the active ingredient in Neoral, is a calcineurin inhibitor. It binds to cyclophilin, forming a complex that inhibits calcineurin, thereby preventing dephosphorylation and nuclear translocation of NF-AT (nuclear factor of activated T-cells). This inhibits transcription of interleukin-2 and other cytokines, reducing T-cell activation and proliferation.
| Metabolism | Primarily metabolized by CYP3A4 (and to a lesser extent CYP3A5) in the liver and intestine. Undergoes extensive first-pass metabolism. Metabolites are excreted mainly via bile into feces. |
| Excretion | Primarily biliary/fecal (94%): 94% of dose eliminated in feces via bile, 6% in urine (0.1% unchanged). Minimal renal elimination of parent drug. |
| Half-life | Terminal elimination half-life: 8.4 hours (range 6–24 hours) in healthy volunteers; prolonged in hepatic impairment (up to 20 hours). |
| Protein binding | 90%–98% bound to plasma proteins (primarily lipoproteins, albumin, and globulins). |
| Volume of Distribution | 4.5 L/kg (range 3–5 L/kg). Indicates extensive distribution into tissues, including erythrocytes (50–60% in blood). |
| Bioavailability | Oral (Neoral): 30% (range 10%–89%) due to variable absorption; dependent on bile flow and food. IV: 100%. |
| Onset of Action | Oral: 2–6 hours (peak immunosuppressive effect); IV: minutes (with continuous infusion). |
| Duration of Action | Dosing interval: 12–24 hours. Clinical effect persists for drug concentration above trough target (e.g., 100–400 ng/mL whole blood). |
| Action Class | Immunosuppressant- Calcineurin inhibitors |
| Brand Substitutes | DavaIndia Ciclosporin 100mg Capsule, C Psorin 100mg Capsule, Imusporin 100 Capsule, Panimun Bioral 100mg Capsule, Cyclophil 100mg Capsule, DavaIndia Ciclosporin 50mg Capsule, Cyclosorin 50mg Capsule, Grafotas 50mg Capsule, Arpimune-O 50mg Capsule, Imusporin 50mg Capsule, Imunet 25mg Capsule, Zymmune 25mg Capsule, Grafotas 25mg Capsule, Imusporin 25mg Capsule, Iminoral 25mg Capsule |
Initial dose 10-15 mg/kg/day orally divided q12h, then taper by 5% weekly to maintenance of 3-5 mg/kg/day divided q12h. For psoriasis: 2.5 mg/kg/day orally divided q12h. For rheumatoid arthritis: 2.5-5 mg/kg/day orally divided q12h. Administer consistently with or without food.
| Dosage form | CAPSULE |
| Renal impairment | For CrCl <30 mL/min: avoid use; for CrCl 30-50 mL/min: reduce dose by 25%; for CrCl 50-80 mL/min: no adjustment needed. Monitor serum creatinine and cyclosporine levels. |
| Liver impairment | Child-Pugh A: reduce dose by 25%; Child-Pugh B: reduce dose by 50%; Child-Pugh C: contraindicated. Monitor liver function and cyclosporine trough levels. |
| Pediatric use | For nephrotic syndrome: 5-6 mg/kg/day orally divided q12h; for transplant: 10-15 mg/kg/day orally divided q12h based on weight. Use ideal body weight for obese children. Adjust to target trough levels of 150-300 ng/mL for initial therapy. |
| Geriatric use | Start at lower end of dosing range (e.g., 2.5 mg/kg/day) due to decreased renal function; monitor renal function and blood pressure closely; adjust based on trough levels and creatinine clearance. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for NEORAL (NEORAL).
| Breastfeeding | Cyclosporine is excreted into breast milk. The milk-to-plasma ratio is approximately 0.2-0.6. Limited data indicate that infant serum levels are low, but caution is advised due to potential for immunosuppression and growth retardation. The American Academy of Pediatrics considers cyclosporine to be compatible with breastfeeding, but monitoring of infant serum levels and toxicity is recommended. |
| Teratogenic Risk | Neoral (cyclosporine) is classified as FDA Pregnancy Category C. Animal studies have shown embryotoxic and fetotoxic effects at doses 2-5 times the human dose. In humans, use during pregnancy has been associated with increased risks of prematurity, low birth weight, and intrauterine growth restriction. Limited data suggest a possible increased risk of congenital malformations, but no consistent pattern has been identified. First trimester exposure carries the highest risk for major malformations. |
■ FDA Black Box Warning
Neoral is a systemic immunosuppressant that increases susceptibility to infection and development of lymphoma and other malignancies, particularly of the skin. Only physicians experienced in immunosuppressive therapy and management of organ transplant patients should prescribe Neoral. Patients receiving the drug should be managed in facilities equipped and staffed with adequate laboratory and supportive medical resources.
| Serious Effects |
["Hypersensitivity to cyclosporine or any component of the formulation","Uncontrolled hypertension","Uncontrolled infections","Malignancies (except non-melanoma skin cancer) in patients with rheumatoid arthritis or psoriasis","Concurrent use with PUVA or UVB therapy, methotrexate, other immunosuppressive agents, or coal tar in psoriasis patients (relative contraindication)"]
| Precautions | ["Nephrotoxicity (monitor renal function)","Hypertension (monitor blood pressure)","Increased risk of infections and malignancies","Neurotoxicity (e.g., tremor, headache, seizures)","Hyperkalemia (monitor serum potassium)","Hepatotoxicity (monitor liver function)","Anaphylactic reactions (rare, with IV formulation)","Drug interactions (e.g., with other nephrotoxic agents, CYP3A4 inhibitors/inducers)"] |
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| Fetal Monitoring | Maternal: Monitor blood pressure, renal function (serum creatinine, BUN), liver function tests, cyclosporine trough levels, and signs of infection. Fetal/neonatal: Serial ultrasound for fetal growth and amniotic fluid volume; monitor for preterm labor and low birth weight. Neonatal monitoring includes renal function and blood pressure. |
| Fertility Effects | Cyclosporine does not appear to have a direct negative impact on female fertility. In animal studies, high doses caused impaired fertility in male rats (decreased sperm motility and count). In humans, limited data suggest no significant effect on male or female fertility, but caution is warranted in cases of severe renal or hepatic impairment which may indirectly affect fertility. |