Cyclosporine Modified 100 mg Capsule, Liquid Filled
🆔 Identity & classification
Where does this data come from?
🏷️ RxNorm drug class
This medicine belongs to the Calcineurin Inhibitor Immunosuppressant class.
Where does this data come from?
🏭 Manufacturer & labeler
Where does this data come from?
🩺 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.
Where does this data come from?
Ask a licensed pharmacist directly — free, answered by our team.
💊 What it looks like
Where does this data come from?
🧪 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.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
-
UNII 7QWA1RIO01
A synthetic form of vitamin E used as an antioxidant in medicines. It prevents oils and fats in the formulation from breaking down, helping the drug remain stable and effective during storage.
-
UNII 3K9958V90M
A liquid solvent derived from fermentation or chemical synthesis. In medicines, alcohol dissolves active ingredients, helps preserve the product, and improves how the body absorbs certain drugs.
-
UNII 1N032N7MFO
A brown-colored mineral form of iron oxide used as a colorant in tablets and capsules. It gives medicines their brown or tan appearance without affecting how the drug works.
-
UNII 2G86QN327L
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.
-
UNII PDC6A3C0OX
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.
-
UNII 4763AXI84L
Glyceryl monolinoleate is a fatty substance derived from linoleic acid, a natural oil component. It acts as an emulsifier and surfactant in medicines, helping blend oil and water-based ingredients together for better mixing and stability.
-
UNII TE7660XO1C
Glycine is an amino acid used in medicines as a buffer to help stabilize pH and improve taste. It may also serve as a filler or binder to give the product proper form and consistency.
-
UNII 9E0S3UM200
A sugar alcohol solution derived from glucose that stays liquid without forming crystals. It functions as a sweetener, humectant (moisture-retaining agent), and solvent in liquid medications and syrups.
-
UNII 7YC686GQ8F
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.
-
UNII 6DC9Q167V3
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.
-
UNII 15FIX9V2JP
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.
11 inactive ingredients listed in the exact product block matched to this NDC.
Where does this data come from?
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
Are inactive ingredients the same for every manufacturer?
Why might an inactive ingredient be missing?
Can inactive ingredients matter?
💲 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 | $1.250 | $37.50 / 30 capsule |
| Medicaid paysCMS SDUD · 12 mo | $1.65 | $49.63 / 30 capsule |
| Medicare drug plans payPart D · Q2 2026 | $2.24 | $67.35 / 30 capsule |
| Medicare Part B allowsASP · J7502 | $1.559 / J7502 unit | — |
Where does this data come from?
🧾 Billing & reimbursement
Where does this data come from?
🔁 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 1% |
| Cyclosporine Modified 100 mgthis 00093-9020-65 | Teva | 1 capsule | $1.250 | AB1 | Availability likely | — |
| Cyclosporine 100 mg 23155-0839-30 | Heritage | 6 capsules | $1.250 | AB1 | Availability likely | — |
| CycloSPORINE, Modfied 100 mg 60505-4632-03 | Apotex | 6 capsules | $1.250 | AB1 | Availability likely | — |
| Cyclosporine 100 mg 60505-0134-00 | Apotex | 30 capsules | $7.291 | AB2 | Availability likely | +483% |
| Cyclosporine 100 mg 68084-0921-25 | American | 1 capsule | $7.291 | AB2 | Availability likely | +483% |
| Gengraf 100 mg 00074-3109-32 | AbbVie | 30 capsules | $7.421 | AB1 | FDA listed | +494% |
| Neoral 100 mg 00078-0248-15 | Novartis | 1 capsule | $11.773 | AB1 | Availability likely | +842% |
| Sandimmune 100 mg 00078-0241-15 | Novartis | 1 capsule | — | AB2 | FDA listed | — |
| Cyclosporine 100 mg 64380-0129-02 | Strides | 6 capsules | — | AB1 | FDA listed | — |
Where does this data come from?
⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
Where does this data come from?
🗺️ Medicaid utilization & spend
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 00093-9020-65 You're viewing this | 30 BLISTER PACK in 1 CARTON (0093-9020-65) / 1 CAPSULE, LIQUID FILLED in 1 BLISTER PACK (0093-9020-19) | 2021-06-08 | Active |
📄 Full prescribing information FDA SPL
🚨 Boxed Warning ▾
WARNING Only physicians experienced in management of systemic immunosuppressive therapy for the indicated disease should prescribe cyclosporine capsules, USP MODIFIED. At doses used in solid organ transplantation, only physicians experienced in immunosuppressive therapy and management of organ transplant recipients should prescribe cyclosporine capsules, USP MODIFIED. 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. Cyclosporine capsules, USP MODIFIED, a systemic immunosuppressant, may increase the susceptibility to infection and the development of neoplasia. In kidney, liver, and heart transplant patients cyclosporine capsules, USP MODIFIED 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. Cyclosporine capsules, USP MODIFIED have increased bioavailability in comparison to Sandimmune ® (cyclosporine capsules, USP). Cyclosporine capsules, USP MODIFIED and Sandimmune (cyclosporine capsules, USP) are not bioequivalent and cannot be used interchangeably without physician supervision.
For a given trough concentration, cyclosporine exposure will be greater with cyclosporine capsules, USP MODIFIED than with Sandimmune (cyclosporine capsules, USP). If a patient who is receiving exceptionally high doses of Sandimmune (cyclosporine capsules, USP) is converted to cyclosporine capsules, USP MODIFIED, particular caution should be exercised. Cyclosporine blood concentrations should be monitored in transplant and rheumatoid arthritis patients taking cyclosporine capsules, USP MODIFIED 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 ).
🎯 Indications and Usage ▾
INDICATIONS AND USAGE Kidney, Liver, and Heart Transplantation Cyclosporine capsules, USP MODIFIED are indicated for the prophylaxis of organ rejection in kidney, liver, and heart allogeneic transplants. Cyclosporine capsules, USP MODIFIED have been used in combination with azathioprine and corticosteroids. Rheumatoid Arthritis Cyclosporine capsules, USP MODIFIED are indicated for the treatment of patients with severe active, rheumatoid arthritis where the disease has not adequately responded to methotrexate.
Cyclosporine capsules, USP MODIFIED can be used in combination with methotrexate in rheumatoid arthritis patients who do not respond adequately to methotrexate alone. Psoriasis Cyclosporine capsules, USP MODIFIED are 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 cyclosporine capsules, USP MODIFIED as with other therapies upon cessation of treatment.
⏱️ Dosage and Administration ▾
DOSAGE AND ADMINISTRATION Cyclosporine capsules, USP MODIFIED, soft gelatin capsules, has increased bioavailability in comparison to Sandimmune (cyclosporine capsules, USP). Cyclosporine capsules, USP MODIFIED and Sandimmune (cyclosporine capsules, USP) are not bioequivalent and cannot be used interchangeably without physician supervision. The daily dose of cyclosporine capsules, USP MODIFIED should always be given in two divided doses (BID).
It is recommended that cyclosporine capsules, USP MODIFIED 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 cyclosporine capsules, USP MODIFIED can be given 4 to 12 hours prior to transplantation or be given postoperatively. The initial dose of cyclosporine capsules, USP MODIFIED 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 cyclosporine capsules, USP MODIFIED is the same as the initial oral dose of Sandimmune (cyclosporine capsules, USP). Suggested initial doses are available from the results of a 1994 survey of the use of Sandimmune (cyclosporine capsules, USP) 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 cyclosporine capsules, USP MODIFIED 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 cyclosporine capsules, USP MODIFIED as for Sandimmune (cyclosporine capsules, USP).
Using the same trough concentration target range for cyclosporine capsules, USP MODIFIED as for Sandimmune (cyclosporine capsules, USP) results in greater cyclosporine exposure when cyclosporine capsules, USP MODIFIED are administered (see Pharmacokinetics, Absorption ). Dosing should be titrated based on clinical assessments of rejection and tolerability. Lower cyclosporine capsules, USP MODIFIED 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 statu…
⛔ Contraindications ▾
CONTRAINDICATIONS General Cyclosporine capsules, USP MODIFIED are 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 cyclosporine capsules, USP MODIFIED. Psoriasis Psoriasis patients who are treated with cyclosporine capsules, USP MODIFIED 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 cyclosporine capsules, USP MODIFIED.
⚠️ Warnings ▾
WARNINGS (See also BOXED WARNING ) All Patients Cyclosporine, the active ingredient of cyclosporine capsules, USP MODIFIED, can cause nephrotoxicity and hepatotoxicity. The risk increases with increasing doses of cyclosporine. Renal dysfunction including structural kidney damage is a potential consequence of cyclosporine capsules, USP MODIFIED and therefore renal function must be monitored during therapy.
Care should be taken in using cyclosporine with nephrotoxic drugs (see PRECAUTIONS ). Patients receiving cyclosporine capsules, USP MODIFIED 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 cyclosporine capsules, USP MODIFIED 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 cyclosporine capsules, USP MODIFIED are not bioequivalent to Sandimmune (cyclosporine capsules, USP), conversion from cyclosporine capsules, USP MODIFIED to Sandimmune (cyclosporine capsules, USP) using a 1:1 ratio (mg/kg/day) may result in lower cyclosporine blood concentrations.
Conversion from cyclosporine capsules, USP MODIFIED to Sandimmune (cyclosporine capsules, USP) should be made with increased monitoring to avoid the potential of underdosing. Kidney, Liver, and Heart Transplant Nephrotoxicity Cyclosporine, the active ingredient of cyclosporine capsules, USP MODIFIED, 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 (cyclosporine capsules, USP) 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.
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 s…
🤒 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 cyclosporine capsules, USP MODIFIED were comparable with those observed in 208 transplanted patients who received Sandimmune (cyclosporine capsules, USP) 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 (cyclosporine capsules, USP), 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 (cyclosporine capsules, USP)) Body System Adverse Reactions Sandimmune (cyclosporine capsules, USP) (N = 227)% Azathioprine (N = 228)% Kidney (N = 705)% Heart (N = 112)% Liver (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 (cyclosporine capsules, USP MODIFIED), 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, i…
👥 Use in Specific Populations ▾
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.
Pediatric Population Pharmacokinetic data from pediatric patients administered cyclosporine capsules, USP MODIFIED or Sandimmune (cyclosporine capsules, USP) are very limited. In 15 renal transplant patients aged 3 to 16 years, cyclosporine whole blood clearance after IV administration of Sandimmune (cyclosporine capsules, USP) was 10.6 ± 3.7 mL/min/kg (assay: Cyclo-trac specific RIA). In a study of 7 renal transplant patients aged 2 to 16, the cyclosporine clearance ranged from 9.8 to 15.5 mL/min/kg.
In 9 liver transplant patients aged 0.6 to 5.6 years, clearance was 9.3 ± 5.4 mL/min/kg (assay: HPLC). In the pediatric population, cyclosporine capsules, USP MODIFIED also demonstrate an increased bioavailability as compared to Sandimmune (cyclosporine capsules, USP). In 7 liver de novo transplant patients aged 1.4 to 10 years, the absolute bioavailability of cyclosporine capsules, USP MODIFIED was 43% (range 30% to 68%) and for Sandimmune (cyclosporine capsules, USP) in the same individuals absolute bioavailability was 28% (range 17% to 42%).
Pediatric Pharmacokinetic Parameters (mean ± SD) Patient Population Dose/day (mg/d) Dose/weight (mg/kg/d) AUC 1 (ng•hr/mL) C max (ng/mL) CL/F (mL/min) CL/F (mL/min/kg) Stable liver transplant 2 Age 2 to 8, Dosed TID (N = 9) 101 ± 25 5.95 ± 1.32 2163 ± 801 629 ± 219 285 ± 94 16.6 ±
4.3Age 8 to 15, Dosed BID (N = 8) 188 ± 55 4.96 ± 2.09 4272 ± 1462 975 ± 281 378 ± 80 10.2 ±
4.0Stable liver transplant 3 Age 3, Dosed BID (N = 1) 120 8.33 5832 1050 171
11.9Age 8 to 15, Dosed BID (N = 5) 158 ± 55 5.51 ± 1.91 4452 ± 2475 1013 ± 635 328 ± 121 11.0 ±
1.9Stable renal transplant 3 Age 7 to 15, Dosed BID (N = 5) 328 ± 83 7.37 ± 4.11 6922 ± 1988 1827 ± 487 418 ± 143 8.7 ± 2.9 1 AUC was measured over one dosing interval. 2 Assay: Cyclo-trac specific monoclonal radioimmunoassay. 3 Assay: TDx specific monoclonal fluorescence polarization immunoassay.
Geriatric Population Comparison of single dose data from both normal elderly volunteers (N = 18, mean age 69 years) and elderly rheumatoid arthritis patients (N = 16, mean age 68 years) to single dose data in young adult volunteers (N = 16, mean age 26 years) showed no significant difference in the pharmacokinetic parameters.
🆘 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 cyclosporine capsules, USP MODIFIED. 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 (6 mg/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 cyclosporine capsules, USP MODIFIED and cyclosporine oral solution, USP MODIFIED are bioequivalent. 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 cyclosporine capsules, USP MODIFIED or Sandimmune (cyclosporine capsules, USP) 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 cyclosporine capsules, USP MODIFIED and 19% to 26% for Sandimmune (cyclosporine capsules, USP).
In the same studies, intrasubject variability of trough concentrations (%CV) was 17% to 30% for cyclosporine capsules, USP MODIFIED and 16% to 38% for Sandimmune (cyclosporine capsules, USP). Absorption Cyclosporine capsules, USP MODIFIED have increased bioavailability compared to Sandimmune (cyclosporine capsules, USP). The absolute bioavailability of cyclosporine administered as Sandimmune (cyclosporine capsules, USP) 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 cyclosporine capsules, USP MODIFIED 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 cyclosporine capsules, USP MODIFIED compared to following administration of Sandimmune (cyclosporine capsules, USP). The dose normalized AUC in de novo liver transplant patients…
📦 How Supplied / Storage and Handling ▾
HOW SUPPLIED Cyclosporine capsules, USP MODIFIED are available as follows: 25 mg: yellow soft gelatin (oval 5) capsules, filled with yellowish to yellow-brown oily liquid, printed “Ivax hourglass logo” and “25 mg”, containing 25 mg cyclosporine, USP MODIFIED and 15.8% v/v (12.4% wt./vol) dehydrated alcohol USP, packaged in unit-dose cartons of 30 capsules (NDC 0093-9018-65). 50 mg: ochre-yellow soft gelatin (oblong 11) capsules, filled with yellowish to yellow-brown oily liquid, printed “Ivax hourglass logo” and “50 mg”, containing 50 mg cyclosporine, USP MODIFIED and 15.8% v/v (12.4% wt./vol) dehydrated alcohol USP, packaged in unit-dose cartons of 30 capsules (NDC 0093-9019-65).
100 mg: brown soft gelatin (oblong 20) capsules, filled with yellowish to yellow-brown oily liquid, printed “Ivax hourglass logo” and “100 mg”, containing 100 mg cyclosporine, USP MODIFIED and 15.8% v/v (12.4% wt./vol) dehydrated alcohol USP, packaged in unit-dose cartons of 30 capsules (NDC 0093-9020-65). Store and Dispense PHARMACIST: Dispense in original unit-dose container. Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].
Keep this and all medications out of the reach of children. Brands listed are the trademarks of their respective owners. Manufactured In Czech Republic By: Teva Czech Industries s.r.o.
Opava-Komarov, Czech Republic Manufactured For: Teva Pharmaceuticals Parsippany, NJ 07054 Rev. M 4/2024
📋 Description ▾
DESCRIPTION Cyclosporine capsules, USP MODIFIED are an oral formulation of cyclosporine, USP that immediately forms an emulsion in an aqueous environment. Cyclosporine, USP, the active principle in cyclosporine capsules, USP MODIFIED, is a cyclic polypeptide immunosuppressant agent consisting of 11 amino acids. It is produced as a metabolite by the fungus species Tolypocladium inflatum .
Chemically, cyclosporine, USP 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) and has the following structural formula: Each soft gelatin capsule for oral administration contains either 25 mg, 50 mg or 100 mg of cyclosporine, USP MODIFIED and 15.8% v/v (12.4% wt./vol) dehydrated alcohol and has the following inactive ingredients: DL-alpha-tocopherol, gelatin, glycine, glycerol 99%, glyceryl monolinoleate, polyoxyl 40 hydrogenated castor oil, propylene glycol, sorbitol solution and titanium dioxide.
In addition, the 25 mg and 50 mg contain ferric oxide (yellow) and the 100 mg contains ferric oxide (brown). structural formula