Neoral cyclosporine 100 mg Capsule, Liquid Filled
Past resolved recalls for this product (1)
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Calcineurin Inhibitor Immunosuppressant class.
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🏭 Manufacturer & labeler
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🩺 Clinical
Cyclosporine and cyclosporine (modified) are used with other medications to prevent transplant rejection (attack of the transplanted organ by the immune system of the person who received the organ) in people who have received kidney, liver, and heart transplants. Cyclosporine (modified) is also used alone or with methotrexate (Rheumatrex) to treat the symptoms of rheumatoid arthritis (arthritis caused by swelling of the lining of the joints) in patients whose symptoms were not relieved by methotrexate alone. Cyclosporine (modified) is also used to treat psoriasis (a skin disease in which red,...
Read the full MedlinePlus article ↗- Cyclosporine levels in your blood can vary quite a bit, and both too much and too little can cause real problems — too high raises the risk of kidney damage, and too low means the...
- Why do I need blood tests so often while taking cyclosporine?
- No — grapefruit and grapefruit juice are a hard no with cyclosporine. They block a key enzyme in your body that normally clears cyclosporine, which can cause your blood levels to c...
- Can I eat grapefruit while taking cyclosporine?
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Cyclosporine — tap one for details:
Cyclosporine may be associated with lower levels of 1 nutrient — worth a chat with your pharmacist, not a cause for alarm.
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💊 What it looks like
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
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Cochineal is a natural red colorant derived from insects, used to give medicines and supplements their red or pink appearance. It helps make tablets and capsules visually identifiable.
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Corn oil is a vegetable oil extracted from corn kernels. It's used in medicines as a solvent to dissolve active ingredients and help the body absorb them, and sometimes as a lubricant in capsules.
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A dark iron oxide compound that gives medicines their black or dark color. It's used as a colorant in tablets and capsules to help identify the product and make it visually distinctive.
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Gelatin is a protein derived from animal collagen, commonly used in medicines as a gelling agent and capsule material. It helps create soft or hard capsule shells that hold and release medication, and can also thicken liquid formulations.
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Glycerin is a clear, thick liquid derived from plant oils or fats. It acts as a humectant to retain moisture, a sweetener, and a solvent in medications.
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A synthetic oily substance made from castor oil. It works as a solubilizer and emulsifier to help mix oily and water-based ingredients together in the medicine.
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Propylene glycol is a clear liquid derived from petroleum or vegetable sources. It acts as a solvent, humectant, and preservative in medicines, helping dissolve active ingredients and maintain product stability.
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Titanium dioxide is a bright white mineral powder commonly used as a colorant and opacifying agent. It makes pills and tablets white or lighter in color and helps make coatings non-transparent.
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Tocopherol is a form of vitamin E derived from plant oils. It acts as an antioxidant in medicines to prevent oils and fats from breaking down and spoiling during storage.
9 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per ea | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $11.773 | $353.19 / 30 capsule |
| Medicaid paysCMS SDUD · 12 mo | $10.48 | $314.29 / 30 capsule |
| Medicare drug plans payPart D · Q2 2026 | $11.31 | $339.38 / 30 capsule |
| Medicare Part B allowsASP · J7502 | $1.559 / J7502 unit | — |
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🧾 Billing & reimbursement
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Cyclosporine 100 mg 75907-0048-30 | Dr. | 1 capsule | $1.240 | AB1 | Availability likely | save 89% |
| Cyclosporine Modified 100 mg 00093-9020-65 | Teva | 1 capsule | $1.250 | AB1 | Availability likely | save 89% |
| Cyclosporine 100 mg 23155-0839-30 | Heritage | 6 capsules | $1.250 | AB1 | Availability likely | save 89% |
| CycloSPORINE, Modfied 100 mg 60505-4632-03 | Apotex | 6 capsules | $1.250 | AB1 | Availability likely | save 89% |
| Cyclosporine 100 mg 60505-0134-00 | Apotex | 30 capsules | $7.291 | AB2 | Availability likely | save 38% |
| Cyclosporine 100 mg 68084-0921-25 | American | 1 capsule | $7.291 | AB2 | Availability likely | save 38% |
| Gengraf 100 mg 00074-3109-32 | AbbVie | 30 capsules | $7.421 | AB1 | FDA listed | save 37% |
| Neoral 100 mgthis 00078-0248-15 | Novartis | 1 capsule | $11.773 | AB1 | Availability likely | — |
| Sandimmune 100 mg 00078-0241-15 | Novartis | 1 capsule | — | AB2 | FDA listed | — |
| Cyclosporine 100 mg 64380-0129-02 | Strides | 6 capsules | — | AB1 | FDA listed | — |
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⏳ Availability & generic status
FDA-approved generic versions are listed, and recent pricing/market data suggests they may be available — see Therapeutic equivalents.
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🗺️ Medicaid utilization & spend
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
🔬 Reported adverse events (FAERS)
Top reported reactions
Age at onset
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Serious outcomes
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 00078-0248-15 You're viewing this | 30 BLISTER PACK in 1 CARTON (0078-0248-15) / 1 CAPSULE, LIQUID FILLED in 1 BLISTER PACK (0078-0248-61) | 1995-07-14 | Active |
📄 Full prescribing information FDA SPL
🚨 Boxed Warning ▾
WARNING Only physicians experienced in management of systemic immunosuppressive therapy for the indicated disease should prescribe Neoral. At doses used in solid organ transplantation, only physicians experienced in immunosuppressive therapy and management of organ transplant recipients should prescribe Neoral. Patients receiving the drug should be managed in facilities equipped and staffed with adequate laboratory and supportive medical resources.
The physician responsible for maintenance therapy should have complete information requisite for the follow-up of the patient. Neoral, a systemic immunosuppressant, may increase the susceptibility to infection and the development of neoplasia. In kidney, liver, and heart transplant patients Neoral may be administered with other immunosuppressive agents.
Increased susceptibility to infection and the possible development of lymphoma and other neoplasms may result from the increase in the degree of immunosuppression in transplant patients. Neoral Soft Gelatin Capsules (cyclosporine capsules, USP) MODIFIED and Neoral Oral Solution (cyclosporine oral solution, USP) MODIFIED have increased bioavailability in comparison to Sandimmune Soft Gelatin Capsules (cyclosporine capsules, USP) and Sandimmune Oral Solution (cyclosporine oral solution, USP). Neoral and Sandimmune are not bioequivalent and cannot be used interchangeably without physician supervision.
For a given trough concentration, cyclosporine exposure will be greater with Neoral than with Sandimmune. If a patient who is receiving exceptionally high doses of Sandimmune is converted to Neoral, particular caution should be exercised. Cyclosporine blood concentrations should be monitored in transplant and rheumatoid arthritis patients taking Neoral to avoid toxicity due to high concentrations.
Dose adjustments should be made in transplant patients to minimize possible organ rejection due to low concentrations. Comparison of blood concentrations in the published literature with blood concentrations obtained using current assays must be done with detailed knowledge of the assay methods employed (see DOSAGE AND ADMINISTRATION) .
For Psoriasis Patients (see also BOXED WARNING above) Psoriasis patients previously treated with PUVA and to a lesser extent, methotrexate or other immunosuppressive agents, UVB, coal tar, or radiation therapy, are at an increased risk of developing skin malignancies when taking Neoral. Cyclosporine, the active ingredient in Neoral, in recommended dosages, can cause systemic hypertension and nephrotoxicity. The risk increases with increasing dose and duration of cyclosporine therapy.
Renal dysfunction, including structural kidney damage, is a potential consequence of cyclosporine, and therefore, renal function must be monitored during therapy.
🎯 Indications and Usage ▾
INDICATIONS AND USAGE Kidney, Liver, and Heart Transplantation Neoral is indicated for the prophylaxis of organ rejection in kidney, liver, and heart allogeneic transplants. Neoral has been used in combination with azathioprine and corticosteroids. Rheumatoid Arthritis Neoral is indicated for the treatment of patients with severe active, rheumatoid arthritis where the disease has not adequately responded to methotrexate.
Neoral can be used in combination with methotrexate in rheumatoid arthritis patients who do not respond adequately to methotrexate alone. Psoriasis Neoral is indicated for the treatment of adult, nonimmunocompromised patients with severe (i.e., extensive and/or disabling), recalcitrant, plaque psoriasis who have failed to respond to at least one systemic therapy (e.g., PUVA, retinoids, or methotrexate) or in patients for whom other systemic therapies are contraindicated or cannot be tolerated. While rebound rarely occurs, most patients will experience relapse with Neoral as with other therapies upon cessation of treatment.
⏱️ Dosage and Administration ▾
DOSAGE AND ADMINISTRATION Neoral Soft Gelatin Capsules (cyclosporine capsules, USP) MODIFIED and Neoral Oral Solution (cyclosporine oral solution, USP) MODIFIED Neoral has increased bioavailability in comparison to Sandimmune. Neoral and Sandimmune are not bioequivalent and cannot be used interchangeably without physician supervision. The daily dose of Neoral should always be given in two divided doses (BID).
It is recommended that Neoral be administered on a consistent schedule with regard to time of day and relation to meals. Grapefruit and grapefruit juice affect metabolism, increasing blood concentration of cyclosporine, thus should be avoided. Specific Populations Renal Impairment in Kidney, Liver, and Heart Transplantation Cyclosporine undergoes minimal renal elimination and its pharmacokinetics do not appear to be significantly altered in patients with end-stage renal disease who receive routine hemodialysis treatments (see CLINICAL PHARMACOLOGY) .
However, due to its nephrotoxic potential (see WARNINGS) , careful monitoring of renal function is recommended; cyclosporine dosage should be reduced if indicated (see WARNINGS and PRECAUTIONS) . Renal Impairment in Rheumatoid Arthritis and Psoriasis Patients with impaired renal function should not receive cyclosporine (see CONTRAINDICATIONS, WARNINGS and PRECAUTIONS) . Hepatic Impairment The clearance of cyclosporine may be significantly reduced in severe liver disease patients (see CLINICAL PHARMACOLOGY) .
Dose reduction may be necessary in patients with severe liver impairment to maintain blood concentrations within the recommended target range (see WARNINGS and PRECAUTIONS) . Newly Transplanted Patients The initial oral dose of Neoral can be given 4 to 12 hours prior to transplantation or be given postoperatively. The initial dose of Neoral varies depending on the transplanted organ and the other immunosuppressive agents included in the immunosuppressive protocol.
In newly transplanted patients, the initial oral dose of Neoral is the same as the initial oral dose of Sandimmune. Suggested initial doses are available from the results of a 1994 survey of the use of Sandimmune in US transplant centers. The mean ± SD initial doses were 9 ± 3 mg/kg/day for renal transplant patients (75 centers), 8 ± 4 mg/kg/day for liver transplant patients (30 centers), and 7 ± 3 mg/kg/day for heart transplant patients (24 centers).
Total daily doses were divided into two equal daily doses. The Neoral dose is subsequently adjusted to achieve a pre-defined cyclosporine blood concentration (see Blood Concentration Monitoring in Transplant Patients , below). If cyclosporine trough blood concentrations are used, the target range is the same for Neoral as for Sandimmune.
Using the same trough concentration target range for Neoral as for Sandimmune results in greater cyclosporine exposure when Neoral is administered (see Pharmacokinetics, Absorption) . Dosing should be titrated based on clinical assessments of rejection and tolerability. Lower Neoral doses may be sufficient as maintenance therapy.
Adjunct therapy with adrenal corticosteroids is recommended initially. Different tapering dosage schedules of prednisone appear to achieve similar results. A representative dosage schedule based on the patient’s weight started with 2.0 mg/kg/day for the first 4 days tapered to 1.0 mg/kg/day by 1 week, 0.6 mg/kg/day by 2 weeks, 0.3 mg/kg/day by 1 month, and 0.15 mg/kg/day by 2 months and thereafter as a maintenance dose.
Steroid doses may be further tapered on an individualized basis depending on status of patient and function of graft. Adjustments in dosage of prednisone must be made according to the clinical situation. Conversion from Sandimmune to Neoral in Transplant Patients In transplanted patients who are considered for conversion to Neoral from Sandimmune, Neoral should be started with the same daily dose as was previously used with Sandimmune (1:1 dose conversion).
The Neoral dose should subsequent…
⛔ Contraindications ▾
CONTRAINDICATIONS General Neoral is contraindicated in patients with a hypersensitivity to cyclosporine or to any of the ingredients of the formulation. Rheumatoid Arthritis Rheumatoid arthritis patients with abnormal renal function, uncontrolled hypertension, or malignancies should not receive Neoral. Psoriasis Psoriasis patients who are treated with Neoral should not receive concomitant PUVA or UVB therapy, methotrexate or other immunosuppressive agents, coal tar or radiation therapy.
Psoriasis patients with abnormal renal function, uncontrolled hypertension, or malignancies should not receive Neoral.
⚠️ Warnings ▾
WARNINGS (See also BOXED WARNING.) All Patients Cyclosporine, the active ingredient of Neoral, can cause nephrotoxicity and hepatotoxicity. The risk increases with increasing doses of cyclosporine. Renal dysfunction, including structural kidney damage, is a potential consequence of Neoral and therefore renal function must be monitored during therapy.
Care should be taken in using cyclosporine with nephrotoxic drugs (see PRECAUTIONS) . Patients receiving Neoral require frequent monitoring of serum creatinine (see Special Monitoring under DOSAGE AND ADMINISTRATION) . Elderly patients should be monitored with particular care, since decreases in renal function also occur with age.
If patients are not properly monitored and doses are not properly adjusted, cyclosporine therapy can be associated with the occurrence of structural kidney damage and persistent renal dysfunction. An increase in serum creatinine and BUN may occur during Neoral therapy and reflect a reduction in the glomerular filtration rate. Impaired renal function at any time requires close monitoring, and frequent dosage adjustment may be indicated.
The frequency and severity of serum creatinine elevations increase with dose and duration of cyclosporine therapy. These elevations are likely to become more pronounced without dose reduction or discontinuation. 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.
Conversion from Neoral to Sandimmune should be made with increased monitoring to avoid the potential of underdosing. Kidney, Liver, and Heart Transplant Nephrotoxicity Cyclosporine, the active ingredient of Neoral, can cause nephrotoxicity and hepatotoxicity when used in high doses. It is not unusual for serum creatinine and BUN levels to be elevated during cyclosporine therapy.
These elevations in renal transplant patients do not necessarily indicate rejection, and each patient must be fully evaluated before dosage adjustment is initiated. Based on the historical Sandimmune experience with oral solution, nephrotoxicity associated with cyclosporine had been noted in 25% of cases of renal transplantation, 38% of cases of cardiac transplantation, and 37% of cases of liver transplantation. Mild nephrotoxicity was generally noted 2 to 3 months after renal transplant and consisted of an arrest in the fall of the pre-operative elevations of BUN and creatinine at a range of 35 to 45 mg/dL and 2.0 to 2.5 mg/dL, respectively.
These elevations were often responsive to cyclosporine dosage reduction. More overt nephrotoxicity was seen early after transplantation and was characterized by a rapidly rising BUN and creatinine. Since these events are similar to renal rejection episodes, care must be taken to differentiate between them.
This form of nephrotoxicity is usually responsive to cyclosporine dosage reduction. Although specific diagnostic criteria which reliably differentiate renal graft rejection from drug toxicity have not been found, a number of parameters have been significantly associated with one or the other. It should be noted however, that up to 20% of patients may have simultaneous nephrotoxicity and rejection. a p < 0.05, b p < 0.01, c p < 0.001, d p < 0.0001 Nephrotoxicity vs.
Rejection Parameter Nephrotoxicity Rejection History Donor > 50 years old or hypotensive Prolonged kidney preservation Prolonged anastomosis time Concomitant nephrotoxic drugs Anti-donor immune response Retransplant patient Clinical Often > 6 weeks postop b Prolonged initial nonfunction (acute tubular necrosis) Often < 4 weeks postop b Fever > 37.5°C Weight gain > 0.5 kg Graft swelling and tenderness Decrease in daily urine volume > 500 mL (or 50%) Laboratory CyA serum trough level > 200 ng/mL Gradual rise in Cr (< 0.15 mg/dL/day) a Cr plateau < 25% above baseline BUN/Cr ≥ 20 CyA serum trough level < 150 ng/mL Rapid rise in Cr (> 0.3 mg/dL/day) a Cr > 25% above baseline…
🤒 Adverse Reactions ▾
ADVERSE REACTIONS Kidney, Liver, and Heart Transplantation The principal adverse reactions of cyclosporine therapy are renal dysfunction, tremor, hirsutism, hypertension, and gum hyperplasia. Hypertension Hypertension, which is usually mild to moderate, may occur in approximately 50% of patients following renal transplantation and in most cardiac transplant patients. Glomerular Capillary Thrombosis Glomerular capillary thrombosis has been found in patients treated with cyclosporine and may progress to graft failure.
The pathologic changes resembled those seen in the hemolytic-uremic syndrome and included thrombosis of the renal microvasculature, with platelet-fibrin thrombi occluding glomerular capillaries and afferent arterioles, microangiopathic hemolytic anemia, thrombocytopenia, and decreased renal function. Similar findings have been observed when other immunosuppressives have been employed post-transplantation. Hypomagnesemia Hypomagnesemia has been reported in some, but not all, patients exhibiting convulsions while on cyclosporine therapy.
Although magnesium-depletion studies in normal subjects suggest that hypomagnesemia is associated with neurologic disorders, multiple factors, including hypertension, high dose methylprednisolone, hypocholesterolemia, and nephrotoxicity associated with high plasma concentrations of cyclosporine appear to be related to the neurological manifestations of cyclosporine toxicity. Clinical Studies In controlled studies, the nature, severity, and incidence of the adverse events that were observed in 493 transplanted patients treated with Neoral were comparable with those observed in 208 transplanted patients who received Sandimmune in these same studies when the dosage of the two drugs was adjusted to achieve the same cyclosporine blood trough concentrations.
Based on the historical experience with Sandimmune, the following reactions occurred in 3% or greater of 892 patients involved in clinical trials of kidney, heart, and liver transplants. Randomized Kidney Patients Cyclosporine Patients (Sandimmune) Sandimmune Azathioprine Kidney Heart Liver Body System Adverse Reactions (N = 227)% (N = 228)% (N = 705)% (N = 112)% (N = 75)% Genitourinary Renal Dysfunction 32 6 25 38 37 Cardiovascular Hypertension 26 18 13 53 27 Cramps 4 < 1 2 < 1 0 Skin Hirsutism 21 < 1 21 28 45 Acne 6 8 2 2 1 Central Nervous System Tremor 12 0 21 31 55 Convulsions 3 1 1 4 5 Headache 2 < 1 2 15 4 Gastrointestinal Gum Hyperplasia 4 0 9 5 16 Diarrhea 3 < 1 3 4 8 Nausea/Vomiting 2 < 1 4 10 4 Hepatotoxicity < 1 < 1 4 7 4 Abdominal Discomfort < 1 0 < 1 7 0 Autonomic Nervous System Paresthesia 3 0 1 2 1 Flushing < 1 0 4 0 4 Hematopoietic Leukopenia 2 19 < 1 6 0 Lymphoma < 1 0 1 6 1 Respiratory Sinusitis < 1 0 4 3 7 Miscellaneous Gynecomastia < 1 0 < 1 4 3 Among 705 kidney transplant patients treated with cyclosporine oral solution (Sandimmune) in clinical trials, the reason for treatment discontinuation was renal toxicity in 5.4%, infection in 0.9%, lack of efficacy in 1.4%, acute tubular necrosis in 1.0%, lymphoproliferative disorders in 0.3%, hypertension in 0.3%, and other reasons in 0.7% of the patients.
The following reactions occurred in 2% or less of cyclosporine-treated patients: allergic reactions, anemia, anorexia, confusion, conjunctivitis, edema, fever, brittle fingernails, gastritis, hearing loss, hiccups, hyperglycemia, migraine (Neoral), muscle pain, peptic ulcer, thrombocytopenia, tinnitus. The following reactions occurred rarely: anxiety, chest pain, constipation, depression, hair breaking, hematuria, joint pain, lethargy, mouth sores, myocardial infarction, night sweats, pancreatitis, pruritus, swallowing difficulty, tingling, upper GI bleeding, visual disturbance, weakness, weight loss.
Patients receiving immunosuppressive therapies, including cyclosporine and cyclosporine-containing regimens, are at increased risk of infections (viral, bacterial, fungal, parasitic). Both generalized and localized infection…
🔄 Drug Interactions ▾
Drug Interactions When diclofenac or methotrexate was coadministered with cyclosporine in rheumatoid arthritis patients, the AUC of diclofenac and methotrexate, each was significantly increased (see PRECAUTIONS, Drug Interactions) . No clinically significant pharmacokinetic interactions occurred between cyclosporine and aspirin, ketoprofen, piroxicam, or indomethacin. Specific Populations Renal Impairment In a study performed in 4 subjects with end-stage renal disease (creatinine clearance < 5 mL/min), an intravenous infusion of 3.5 mg/kg of cyclosporine over 4 hours administered at the end of a hemodialysis session resulted in a mean volume of distribution (Vdss) of
3.49L/kg and systemic clearance (CL) of 0.369 L/hr/kg. This systemic CL (0.369 L/hr/kg) was approximately two thirds of the mean systemic CL (0.56 L/hr/kg) of cyclosporine in historical control subjects with normal renal function. In 5 liver transplant patients, the mean clearance of cyclosporine on and off hemodialysis was 463 mL/min and 398 mL/min, respectively.
Less than 1% of the dose of cyclosporine was recovered in the dialysate. Hepatic Impairment Cyclosporine is extensively metabolized by the liver. Since severe hepatic impairment may result in significantly increased cyclosporine exposures, the dosage of cyclosporine may need to be reduced in these patients.
Drug Interactions A. Effect of Drugs and Other Agents on Cyclosporine Pharmacokinetics and/or Safety All of the individual drugs cited below are well substantiated to interact with cyclosporine. In addition, concomitant use of NSAIDs with cyclosporine, particularly in the setting of dehydration, may potentiate renal dysfunction.
Caution should be exercised when using other drugs which are known to impair renal function (see WARNINGS, Nephrotoxicity) . Drugs That May Potentiate Renal Dysfunction Antibiotics Antineoplastics Antifungals Anti-inflammatory Drugs Gastrointestinal Agents Immunosuppressives Other Drugs ciprofloxacin melphalan amphotericin B azapropazon cimetidine tacrolimus fibric acid derivatives (e.g., bezafibrate, fenofibrate) gentamicin ketoconazole colchicine ranitidine methotrexate tobramycin diclofenac trimethoprim with sulfamethoxazole naproxen vancomycin sulindac During the concomitant use of a drug that may exhibit additive or synergistic renal impairment with cyclosporine, close monitoring of renal function (in particular serum creatinine) should be performed.
If a significant impairment of renal function occurs, the dosage of the coadministered drug should be reduced or an alternative treatment considered. Cyclosporine is extensively metabolized by CYP 3A isoenzymes, in particular CYP3A4, and is a substrate of the multidrug efflux transporter P-glycoprotein. Various agents are known to either increase or decrease plasma or whole blood concentrations of cyclosporine usually by inhibition or induction of CYP3A4 or P-glycoprotein transporter or both.
Compounds that decrease cyclosporine absorption, such as orlistat, should be avoided. Appropriate Neoral dosage adjustment to achieve the desired cyclosporine concentrations is essential when drugs that significantly alter cyclosporine concentrations are used concomitantly (see Blood Concentration Monitoring) . 1.
Drugs That Increase Cyclosporine Concentrations Calcium Channel Blockers Antifungals Antibiotics Glucocorticoids Other Drugs diltiazem fluconazole azithromycin methylprednisolone Allopurinol nicardipine itraconazole clarithromycin Amiodarone verapamil ketoconazole erythromycin Bromocriptine voriconazole quinupristin/ dalfopristin colchicine danazol imatinib metoclopramide nefazodone oral contraceptives HIV Protease Inhibitors The HIV protease inhibitors (e.g., indinavir, nelfinavir, ritonavir, and saquinavir) are known to inhibit cytochrome P-450 3A and thus could potentially increase the concentrations of cyclosporine, however no formal studies of the interaction are available.
Care should be exercised when these drugs are a…
🤰 Pregnancy ▾
Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to cyclosporine, including Neoral, during pregnancy. Encourage women who are taking Neoral during pregnancy to enroll in the Transplant Pregnancy Registry International (TPRI) by calling 1-877-955-8677 or visiting https://www.transplantpregnancyregistry.org . Risk Summary Available data from published literature, including the Transplant Pregnancy Registry International, observational cohort studies, case-controlled studies, meta-analysis, case series, and case reports, over decades of use with cyclosporine in pregnancy have not identified a drug associated risk of major birth defects, or miscarriage.
Adverse maternal or fetal outcomes including hypertension, preeclampsia, preterm birth, and low birth weight are increased in patients treated with cyclosporine. However, patients receiving cyclosporine during pregnancy have underlying medical conditions and may be treated with concomitant medications that limit the interpretability of these findings (see Data) . Embryo-fetal developmental (EFD) studies in rats and rabbits with cyclosporine have shown embryo-fetal toxicity at dose levels below the MRHD based on BSA.
The alcohol content of Neoral should be taken into account when given to pregnant women (see WARNINGS, Special Excipients) . The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Human Data Available data from the National Transplantation Pregnancy Registry (NTPR) including 622 pregnancies in renal, liver, and heart transplant recipients exposed to cyclosporine during pregnancy found that the overall rate of major birth defects, live birth rates, and miscarriage rates were comparable to the general population.
Maternal and fetal adverse outcomes, including the rate of hypertension, preeclampsia, premature births, and low birth weight infants appear to be increased in transplant recipients treated with cyclosporine compared to the general population. However, these patients have underlying medical conditions that confound the above findings. Animal Data Animal studies have shown reproductive toxicity in rats and rabbits.
Three EFD studies (two oral and one intravenous) are available in rats. In two EFD studies, pregnant rats were orally administered with cyclosporine either at doses of 10, 17, 30, 100 and 300 mg/kg/day or 4, 10 and 25 mg/kg/day from gestation day (GD) 6 to 15 or from GD 7 to 17, respectively. Maternal toxicity characterized by mortality, clinical signs of toxicity and impaired body weight gain were observed at 30 mg/kg/day and above.
Cyclosporine was embryo- and fetotoxic as indicated by increased embryonic mortality and reduced fetal weight together with skeletal retardations in rats at 25 mg/kg/day and above. In addition, ventricular septal defect was observed at 25 mg/kg/day in fetuses. In the first study, the oral no observed effect level (NOEL) for both dams and fetuses was 17 mg/kg/day (0.2 times the MRHD based on BSA).
In the other oral study, the NOEL for dams and fetuses were 10 and 4 mg/kg/day (0.13 and 0.05 times the MRHD based on BSA), respectively. In the IV EFD study, rats were administered with 3, 6 and 12 mg/kg/day of cyclosporine from GD 7 to 17. An increase in post implantation loss was observed at 12 mg/kg/day; ventricular septal defect was observed at ≥ 6 mg/kg/day in fetuses.
The IV NOEL for dams and fetus were 6 and 3 mg/kg/day (0.08 and 0.04 times the MRHD, respectively, based on BSA), respectively, after IV administration. In rabbits, cyclosporine was orally administered at dose levels of 10, 30, 100 or 300 mg/kg/day from GD 6 to…
🧒 Pediatric Use ▾
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.
🧓 Geriatric Use ▾
Geriatric Use In rheumatoid arthritis clinical trials with cyclosporine, 17.5% of patients were age 65 or older. These patients were more likely to develop systolic hypertension on therapy, and more likely to show serum creatinine rises ≥ 50% above the baseline after 3 to 4 months of therapy. Clinical studies of Neoral in transplant and psoriasis patients did not include a sufficient number of subjects aged 65 and over to determine whether they respond differently from younger subjects.
Other reported clinical experiences have not identified differences in response between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
🆘 Overdosage ▾
OVERDOSAGE There is a minimal experience with cyclosporine overdosage. Forced emesis and gastric lavage can be of value up to 2 hours after administration of Neoral. Transient hepatotoxicity and nephrotoxicity may occur which should resolve following drug withdrawal.
Oral doses of cyclosporine up to 10 g (about 150 mg/kg) have been tolerated with relatively minor clinical consequences, such as vomiting, drowsiness, headache, tachycardia and, in a few patients, moderately severe, reversible impairment of renal function. However, serious symptoms of intoxication have been reported following accidental parenteral overdosage with cyclosporine in premature neonates. General supportive measures and symptomatic treatment should be followed in all cases of overdosage.
Cyclosporine is not dialyzable to any great extent, nor is it cleared well by charcoal hemoperfusion. The oral dosage at which half of experimental animals are estimated to die is 31 times, 39 times, and > 54 times the human maintenance dose for transplant patients (6mg/kg; corrections based on body surface area) in mice, rats, and rabbits.
🧬 Clinical Pharmacology ▾
CLINICAL PHARMACOLOGY 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. Cyclosporine has been demonstrated to suppress some humoral immunity and to a greater extent, cell-mediated immune reactions such as allograft rejection, delayed hypersensitivity, experimental allergic encephalomyelitis, Freund’s adjuvant arthritis, and graft versus host disease in many animal species for a variety of organs.
The effectiveness of cyclosporine results from specific and reversible inhibition of immunocompetent lymphocytes in the G 0 - and G 1 -phase of the cell cycle. T-lymphocytes are preferentially inhibited. The T-helper cell is the main target, although the T-suppressor cell may also be suppressed.
Cyclosporine also inhibits lymphokine production and release, including interleukin-2. No effects on phagocytic function (changes in enzyme secretions, chemotactic migration of granulocytes, macrophage migration, carbon clearance in vivo) have been detected in animals. Cyclosporine does not cause bone marrow suppression in animal models or man.
Pharmacokinetics The immunosuppressive activity of cyclosporine is primarily due to parent drug. Following oral administration, absorption of cyclosporine is incomplete. The extent of absorption of cyclosporine is dependent on the individual patient, the patient population, and the formulation.
Elimination of cyclosporine is primarily biliary with only 6% of the dose (parent drug and metabolites) excreted in urine. The disposition of cyclosporine from blood is generally biphasic, with a terminal half-life of approximately 8.4 hours (range, 5 to 18 hours). Following intravenous administration, the blood clearance of cyclosporine (assay: HPLC) is approximately 5 to 7 mL/min/kg in adult recipients of renal or liver allografts.
Blood cyclosporine clearance appears to be slightly slower in cardiac transplant patients. The Neoral Soft Gelatin Capsules (cyclosporine capsules, USP) MODIFIED and Neoral Oral Solution (cyclosporine oral solution, USP) MODIFIED are bioequivalent. Neoral Oral Solution diluted with orange juice or apple juice is bioequivalent to Neoral Oral Solution diluted with water.
The effect of milk on the bioavailability of cyclosporine when administered as Neoral Oral Solution has not been evaluated. The relationship between administered dose and exposure (area under the concentration versus time curve, AUC) is linear within the therapeutic dose range. The intersubject variability (total, %CV) of cyclosporine exposure (AUC) when Neoral or Sandimmune is administered ranges from approximately 20% to 50% in renal transplant patients.
This intersubject variability contributes to the need for individualization of the dosing regimen for optimal therapy (see DOSAGE AND ADMINISTRATION) . Intrasubject variability of AUC in renal transplant recipients (%CV) was 9% to 21% for Neoral and 19% to 26% for Sandimmune. In the same studies, intrasubject variability of trough concentrations (%CV) was 17% to 30% for Neoral and 16% to 38% for Sandimmune.
Absorption Neoral has increased bioavailability compared to Sandimmune. The absolute bioavailability of cyclosporine administered as Sandimmune is dependent on the patient population, estimated to be less than 10% in liver transplant patients and as great as 89% in some renal transplant patients. The absolute bioavailability of cyclosporine administered as Neoral has not been determined in adults.
In studies of renal transplant, rheumatoid arthritis and psoriasis patients, the mean cyclosporine AUC was approximately 20% to 50% greater and the peak blood cyclosporine concentration (C max ) was approximately 40% to 106% greater following administration of Neoral compared to following administration of Sandimmune. The dose normalized AUC in de novo liver transplant patients administered Neoral 28 days after transplantation…
📦 How Supplied / Storage and Handling ▾
HOW SUPPLIED Neoral ® Soft Gelatin Capsules (cyclosporine capsules, USP) MODIFIED 25 mg Oval, blue-gray imprinted in red, “Neoral” over “25 mg.” Packages of 30 unit-dose blisters (NDC 0078-0246-15). 100 mg Oblong, blue-gray imprinted in red, “NEORAL” over “100 mg.” Packages of 30 unit-dose blisters (NDC 0078-0248-15). Store and Dispense In the original unit-dose container at controlled room temperature 68°F to 77°F (20°C to 25°C).
Neoral ® Oral Solution (cyclosporine oral solution, USP) MODIFIED A clear, yellow liquid supplied in 50 mL bottles containing 100 mg/mL (NDC 0078-0274-22). Store and Dispense In the original container at controlled room temperature 68°F to 77°F (20° to 25°C). Do not store in the refrigerator.
Once opened, the contents must be used within two months. At temperatures below 68°F (20°C) the solution may gel; light flocculation or the formation of a light sediment may also occur. There is no impact on product performance or dosing using the syringe provided.
Allow to warm to room temperature 77°F (25°C) to reverse these changes. Neoral ® Soft Gelatin Capsules (cyclosporine capsules, USP) MODIFIED Neoral ® Oral Solution (cyclosporine oral solution, USP) MODIFIED Distributed by: Novartis Pharmaceuticals Corporation, East Hanover, New Jersey 07936 © Novartis Revised: September 2023 T2023-70
📋 Description ▾
DESCRIPTION Neoral is an oral formulation of cyclosporine that immediately forms a microemulsion in an aqueous environment. Cyclosporine, the active principle in Neoral, is a cyclic polypeptide immunosuppressant agent consisting of 11 amino acids. It is produced as a metabolite by the fungus species Beauveria nivea.
Chemically, cyclosporine is designated as [ R -[ R* , R * -( E )]]-cyclic-(L-alanyl-D-alanyl- N -methyl-L-leucyl- N -methyl-L-leucyl- N -methyl-L-valyl-3-hydroxy- N ,4-dimethyl-L-2-amino-6-octenoyl-L-α -amino-butyryl- N -methylglycyl- N -methyl-L-leucyl-L-valyl- N -methyl-L-leucyl). chemical structure of cyclosporine Neoral Soft Gelatin Capsules (cyclosporine capsules, USP) MODIFIED are available in 25 mg and 100 mg strengths. Each 25 mg capsule contains: cyclosporine………………………………………………………………………………25 mg alcohol, USP dehydrated......................................................................11.9% v/v (9.5% wt/vol.) Each 100 mg capsule contains: cyclosporine……………………………………………………………………………...100 mg alcohol, USP dehydrated.......................................................................11.9% v/v (9.5% wt/vol.) Inactive ingredients: Carmine, corn oil-mono-di-triglycerides, DL-α-tocopherol USP, gelatin NF, glycerol, iron oxide black, polyoxyl 40 hydrogenated castor oil NF, propylene glycol USP, titanium dioxide USP, and other ingredients.
Neoral Oral Solution (cyclosporine oral solution, USP) MODIFIED is available in 50 mL bottles. Each mL contains: cyclosporine……………………...............................................................................100 mg/mL alcohol, USP dehydrated.....................................................................11.9% v/v (9.5% wt/vol.) Inactive ingredients: Corn oil-mono-di-triglycerides, DL-α -tocopherol USP, polyoxyl 40 hydrogenated castor oil NF, and propylene glycol USP. The chemical structure of cyclosporine (also known as cyclosporin A) is: