Cyclosporine 100 mg/mL Solution
🆔 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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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.
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UNII 55C81W76DH
A synthetic emulsifier made from glycerin and oleic acid (a plant-based oil). It helps blend water and oil-based ingredients together in formulations and improves how the product spreads or absorbs.
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UNII XRQ165498B
A plant-derived emulsifier made from glycerin and oleic acid. It helps mix oil and water-based ingredients together in the formulation and improves product texture and stability.
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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.
4 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 mL | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $2.124 | $106.20 / 50 ml |
| Medicaid paysCMS SDUD · 12 mo | $2.57 | $128.64 / 50 ml |
| Medicare drug plans payPart D · Q2 2026 | $3.45 | $172.53 / 50 ml |
| 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/mLthis 00172-7313-20 | Teva | 1 bottle | $2.124 | AB1 | Availability likely | — |
| Neoral 100 mg/mL 00078-0274-22 | Novartis | 1 bottle | — | AB1 | FDA listed | — |
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⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
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🗺️ Medicaid utilization & spend
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
🔬 Reported adverse events (FAERS)
Top reported reactions
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Serious outcomes
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 00172-7313-20 You're viewing this | 1 BOTTLE in 1 PACKAGE (0172-7313-20) / 50 mL in 1 BOTTLE | 2005-03-29 | 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 oral solution, USP MODIFIED. At doses used in solid organ transplantation, only physicians experienced in immunosuppressive therapy and management of organ transplant recipients should prescribe cyclosporine oral solution, 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 oral solution, USP MODIFIED, a systemic immunosuppressant, may increase the susceptibility to infection and the development of neoplasia. In kidney, liver, and heart transplant patients cyclosporine oral solution, 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 oral solution, USP MODIFIED has increased bioavailability in comparison to Sandimmune ® (cyclosporine oral solution, USP). Cyclosporine oral solution, USP MODIFIED and Sandimmune (cyclosporine oral solution, USP) are not bioequivalent and cannot be used interchangeably without physician supervision.
For a given trough concentration, cyclosporine exposure will be greater with cyclosporine oral solution, USP MODIFIED than with Sandimmune (cyclosporine oral solution, USP). If a patient who is receiving exceptionally high doses of Sandimmune (cyclosporine oral solution, USP) is converted to cyclosporine oral solution, USP MODIFIED, particular caution should be exercised. Cyclosporine blood concentrations should be monitored in transplant and rheumatoid arthritis patients taking cyclosporine oral solution, 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 ) .
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 cyclosporine oral solution, USP MODIFIED. Cyclosporine, USP the active ingredient in cyclosporine oral solution, USP MODIFIED, 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 Cyclosporine oral solution, USP MODIFIED is indicated for the prophylaxis of organ rejection in kidney, liver, and heart allogeneic transplants. Cyclosporine oral solution, USP MODIFIED has been used in combination with azathioprine and corticosteroids. Rheumatoid Arthritis Cyclosporine oral solution, USP MODIFIED is indicated for the treatment of patients with severe active, rheumatoid arthritis where the disease has not adequately responded to methotrexate.
Cyclosporine oral solution, USP MODIFIED can be used in combination with methotrexate in rheumatoid arthritis patients who do not respond adequately to methotrexate alone. Psoriasis Cyclosporine oral solution, USP MODIFIED 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 cyclosporine oral solution, USP MODIFIED as with other therapies upon cessation of treatment.
⏱️ Dosage and Administration ▾
DOSAGE AND ADMINISTRATION Cyclosporine oral solution, USP MODIFIED has increased bioavailability in comparison to Sandimmune (cyclosporine oral solution, USP). Cyclosporine oral solution, USP MODIFIED and Sandimmune (cyclosporine oral solution, USP) are not bioequivalent and cannot be used interchangeably without physician supervision. The daily dose of cyclosporine oral solution, USP MODIFIED should always be given in two divided doses (BID).
It is recommended that cyclosporine oral solution, 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 oral solution, USP MODIFIED can be given 4 to 12 hours prior to transplantation or be given postoperatively. The initial dose of cyclosporine oral solution, 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 oral solution, MODIFIED is the same as the initial oral dose of Sandimmune (cyclosporine oral solution, USP). Suggested initial doses are available from the results of a 1994 survey of the use of Sandimmune (cyclosporine oral solution, 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 oral solution, 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 oral solution, USP MODIFIED as for Sandimmune (cyclosporine oral solution, USP).
Using the same trough concentration target range for cyclosporine oral solution, USP MODIFIED as for Sandimmune (cyclosporine oral solution, USP) results in greater cyclosporine exposure when cyclosporine oral solution, USP MODIFIED is administered (see Pharmacokinetics, Absorption ) . Dosing should be titrated based on clinical assessments of rejection and tolerability. Lower cyclosporine oral solution, 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…
⛔ Contraindications ▾
CONTRAINDICATIONS General Cyclosporine oral solution, USP MODIFIED 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 cyclosporine oral solution, USP MODIFIED. Psoriasis Psoriasis patients who are treated with cyclosporine oral solution, 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 oral solution, USP MODIFIED.
⚠️ Warnings ▾
WARNINGS (See also BOXED WARNING ) All Patients Cyclosporine, the active ingredient of cyclosporine oral solution, 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 oral solution, 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 oral solution, 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 oral solution, 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 oral solution, USP MODIFIED is not bioequivalent to Sandimmune (cyclosporine oral solution, USP), conversion from cyclosporine oral solution, USP MODIFIED to Sandimmune (cyclosporine oral solution, USP) using a 1:1 ratio (mg/kg/day) may result in lower cyclosporine blood concentrations.
Conversion from cyclosporine oral solution, USP MODIFIED to Sandimmune (cyclosporine oral solution, 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 oral solution, 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 oral solution, 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 Anti-donor immune response Prolonged kidney preservation Retransplant patient Prolonged anastomosis time Concomitant nephrotoxic drugs Clinical Often > 6 weeks postop b Often < 4 weeks postop b Prolonged initial nonfunction Fever >…
🤒 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 oral solution, USP MODIFIED were comparable with those observed in 208 transplanted patients who received Sandimmune (cyclosporine oral solution, 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 oral solution, 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 oral solution, USP)) Body System Adverse Reactions Sandimmune (cyclosporine oral solution, 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 oral solution, 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 i…
🔄 Drug Interactions ▾
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 vancomycin naproxen trimethoprim with sulfamethoxazole 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 cyclosporine oral solution, USP MODIFIED 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 administered concomitantly. Grapefruit Juice Grapefruit and grapefruit juice affect metabolism, increasing blood concentrations of cyclosporine, thus should be avoided. 2.
Drugs/Dietary Supplements That Decrease Cyclosporine Concentrations Antibiotics Anticonvulsants Other Drugs / Dietary Supplements nafcillin carbamazepine bosentan St. John’s Wort rifampin oxcarbazepine octreotide phenobarbital orlistat phenytoin sulfinpyrazone terbinafine ticlopidine Bosentan Coadministration of bosentan (250 to 1000 mg every 12 hours based on tolerability) and cyclosporine (300 mg every 12 hours for 2 days then dosing to achieve a C min of 200 to 250 ng/mL) for 7 days in healthy subjects resulted in decreases in the cyclosporine mean dose-normalized AUC, C max , and trough concentration of approximately 50%, 30%, and 60%, respectively, compared to when cyclosporine was given alone (see Effect of Cyclosporine on the Pharmacokinetics and/or Safety of Other Drugs or Agents ) .
Coadministration of cyclosporine with bosentan should be avoided. Boceprevir Coadministration of boceprevir (800 mg three times daily for 7 days) and cyclosporine (100 mg single dose) in healthy subjects resulted in increases in the mean AUC and C max of cyclosporine approximately 2.7-fold and 2-fold, respectively, compared to when cyclosporin…
🤰 Pregnancy ▾
Pregnancy 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 maximum recommended human dose (MRHD) based on body surface area (BSA). The alcohol content of cyclosporine oral solution, USP MODIFIED 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 18. At 100 mg/kg/day and above, reduction in body weight gain of dams and at 300 mg/kg/day abortions were observed.
Maternal toxicity, embryo-fetotoxicity as indicated by increased pre- and postnatal mortality, reduced fetal weight together with skeletal retardations were observed at 100…
🧒 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 cyclosporine oral solution, USP MODIFIED with no unusual adverse effects. The safety and efficacy of cyclosporine oral solution, USP MODIFIED 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 cyclosporine oral solution, USP MODIFIED 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 cyclosporine oral solution, 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. Cyclosporine oral solution, USP MODIFIED diluted with orange juice or apple juice is bioequivalent to cyclosporine oral solution, USP MODIFIED diluted with water.
The effect of milk on the bioavailability of cyclosporine when administered as cyclosporine oral solution, USP MODIFIED 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 cyclosporine oral solution, USP MODIFIED or Sandimmune (cyclosporine oral solution, 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 oral solution, USP MODIFIED and 19% to 26% for Sandimmune (cyclosporine oral solution, USP). In the same studies, intrasubject variability of trough concentrations (%CV) was 17% to 30% for cyclosporine oral solution, USP MODIFIED and 16% to 38% for Sandimmune (cyclosporine oral solution, USP).
Absorption Cyclosporine oral solution, USP MODIFIED has increased bioavailability compared to Sandimmune (cyclosporine oral solution, USP). The absolute bioavailability of cyclosporine administered as Sandimmune (cyclosporine oral solution, 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 oral solution, USP MODIFIED has not been determined in adults.
In studies of renal transplant, rheumatoid arthritis and psoriasis patients, the mea…
📦 How Supplied / Storage and Handling ▾
HOW SUPPLIED Cyclosporine oral solution, USP MODIFIED is available as a yellowish to yellow-brown oily liquid containing 100 mg/mL cyclosporine, USP in a 50 mL bottle (NDC 0172-7313-20). Store and Dispense PHARMACIST: Store and dispense in the original container at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. Do not store in the refrigerator.
Once opened, the contents must be used within two months. At temperatures below 20°C (68°F) the solution may gel; light flocculation or the formation of a light sediment may also occur. This solution, when mixed with juice, may appear cloudy.
There is no impact on product performance or dosing using the syringe provided. Allow to warm to room temperature 25°C (77°F) to reverse these changes. 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. G 7/2024
📋 Description ▾
DESCRIPTION Cyclosporine oral solution, USP MODIFIED is an oral formulation of cyclosporine, USP that immediately forms an emulsion in an aqueous environment. Cyclosporine, USP, the active principle in cyclosporine oral solution, 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 mL of cyclosporine oral solution, USP MODIFIED contains 100 mg/mL cyclosporine, USP and 15.3% v/v (12.18% wt/vol) dehydrated alcohol, USP and has the following inactive ingredients: polyoxyl 40 hydrogenated castor oil, polyglycerol (3) oleate and polyglycerol (10) oleate.
Cyclosporine Chemical Structure
💬 Information for Patients ▾
Information for Patients: Patients should be advised that any change of cyclosporine formulation should be made cautiously and only under physician supervision because it may result in the need for a change in dosage. Patients should be informed of the necessity of repeated laboratory tests while they are receiving cyclosporine. Patients should be advised of the potential risks during pregnancy and informed of the increased risk of neoplasia.
Patients should also be informed of the risk of hypertension and renal dysfunction. Patients should be advised that during treatment with cyclosporine, vaccination may be less effective and the use of live attenuated vaccines should be avoided. Patients should be given careful dosage instructions.
Cyclosporine oral solution, USP MODIFIED should be diluted, preferably with orange or apple juice that is at room temperature. This solution, when mixed with juice, may appear cloudy. The combination of cyclosporine oral solution, USP MODIFIED with milk can be unpalatable.
Patients should be advised to take cyclosporine oral solution, USP MODIFIED 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. Cyclosporine may impact the ability to drive and use machines.
Patients should be advised to exercise care when driving or using machines if they experience neurological disturbances including confusion, somnolence, or dizziness and discuss with their healthcare provider (see WARNINGS and ADVERSE REACTIONS ).