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). |
| Molecular Weight | 1202.61 |
| 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 | Increased risk of congenital malformations, especially cardiovascular and neural tube defects. Use only if benefit outweighs risk. |
| 2nd trimester | May cause fetal growth restriction and preterm delivery. Monitor fetal growth and amniotic fluid. |
| 3rd trimester | Risk of neonatal immunosuppression, lymphopenia, and infection. Monitor neonate for adverse effects. |
Clinical note
Comprehensive clinical and safety monograph for NEORAL (NEORAL).
| Placental transfer | Cyclosporine crosses the placenta, achieving fetal blood levels approximately 30-50% of maternal levels. |
| Breastfeeding | Cyclosporine is excreted into breast milk in significant amounts. Contraindicated during breastfeeding due to potential for neonatal immunosuppression and growth retardation. |
■ 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 of its excipientsRheumatoid arthritis with abnormal renal function, uncontrolled hypertension, or malignanciesConcurrent use with PUVA or UVB therapy in psoriasisConcurrent use with methotrexate in rheumatoid arthritis
| 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) |
| Food/Dietary |
Loading safety data…
| Lactation Rating |
| L5 (Contraindicated) |
| 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. |
| 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. |
| Avoid grapefruit and grapefruit juice during treatment as they increase cyclosporine levels by inhibiting CYP3A4. High-fat meals may decrease absorption; take with a consistent fat content. Avoid concurrent use with St. John's wort (reduces levels) and potassium-rich foods if hyperkalemia is a concern. |
| Clinical Pearls | Monitor whole blood trough concentrations (target 150-400 ng/mL for renal transplant; lower for other indications). Use grapefruit avoidance to reduce variability. Sublingual administration (placing capsule under tongue) can be used for immediate absorption in noncompliant patients. Convert between Neoral and generic cyclosporine only with close monitoring due to pharmacokinetic differences. Check for drug interactions with CYP3A4 inhibitors (azoles, macrolides) and inducers (rifampin, phenytoin). |
| Patient Advice | Take Neoral consistently with or without meals, but avoid grapefruit and grapefruit juice entirely. · Do not switch between Neoral and other cyclosporine products without your doctor's supervision. · Report any signs of infection (fever, sore throat), tremors, or changes in urine output immediately. · Use reliable contraception during treatment and for 12 weeks after stopping. · Store capsules at room temperature away from moisture and heat; do not use if capsules are discolored or damaged. |