Pronunciation:

(SYE kloe spor een)

U.S. Brand Names:

Synonyms:

Generic Available:

Canadian Brand Names:

Use:

Ophthalmic emulsion (Restasis™): Increase tear production when suppressed tear production is presumed to be due to keratoconjunctivitis sicca-associated ocular inflammation (in patients not already using topical anti-inflammatory drugs or punctal plugs)

Use - Unlabeled/Investigational:

Pregnancy Risk Factor:

Pregnancy Implications:

Lactation:

Contraindications:

Warnings/Precautions:

Transplant patients: May cause significant hyperkalemia and hyperuricemia. May cause seizures, particularly if used with high-dose corticosteroids. Encephalopathy has been reported, predisposing factors include hypertension, hypomagnesemia, hypocholesterolemia, high-dose corticosteroids, high cyclosporine serum concentration, and graft-versus-host disease; may be more common in patients with liver transplant. To avoid toxicity or possible organ rejection, make dose adjustments based on cyclosporine blood concentrations. Adjustment of dose should only be made under the direct supervision of an experienced physician. Anaphylaxis has been reported with I.V. use; reserve for patients who cannot take oral form.

Psoriasis: Patients should avoid excessive sun exposure; safety and efficacy in children <18 have not been established

Rheumatoid arthritis: Safety and efficacy for use in juvenile rheumatoid arthritis have not been established. If receiving other immunosuppressive agents, radiation or UV therapy, concurrent use of cyclosporine is not recommended.

Ophthalmic emulsion: Has not been studied in patients with a history of herpes keratitis. Safety and efficacy have not been established in patients <16 years of age.

Products may contain corn oil, castor oil, ethanol, or propylene glycol; injection also contains Cremophor® EL (polyoxyethylated castor oil).

Adverse Reactions:

>10%:

Cardiovascular: Hypertension (13% to 53%; psoriasis 25% to 27%)

Central nervous system: Headache (2% to 15%; RA 17%, psoriasis 14% to 16%)

Dermatologic: Hirsutism (21% to 45%), hypertrichosis (RA 19%)

Endocrine & metabolic: Increased triglycerides (psoriasis 15%), female reproductive disorder (psoriasis 8% to 11%)

Gastrointestinal: Nausea (RA 23%), diarrhea (RA 12%), gum hyperplasia (4% to 16%), abdominal discomfort (RA 15%), dyspepsia (RA 12%)

Neuromuscular & skeletal: Tremor (12% to 55%)

Renal: Renal dysfunction/nephropathy (25% to 38%; RA 10%, psoriasis 21%), creatinine elevation 50% (RA 24%), increased creatinine (psoriasis 16% to 20%)

Respiratory: Upper respiratory infection (psoriasis 8% to 11%)

Miscellaneous: Infection (psoriasis 24% to 25%)

Kidney, liver, and heart transplant only (2% unless otherwise noted):

Cardiovascular: Flushes (<1% to 4%), MI

Central nervous system: Convulsions (1% to 5%), anxiety, confusion, fever, lethargy

Dermatologic: Acne (1% to 6%), brittle fingernails, hair breaking, pruritus

Endocrine & metabolic: Gynecomastia (<1% to 4%), hyperglycemia

Gastrointestinal: Nausea (2% to 10%), vomiting (2% to 10%), diarrhea (3% to 8%), abdominal discomfort (<1% to 7%), cramps (0% to 4%), anorexia, constipation, gastritis, mouth sores, pancreatitis, swallowing difficulty, upper GI bleed, weight loss

Hematologic: Leukopenia (<1% to 6%), anemia, thrombocytopenia

Hepatic: Hepatotoxicity (<1% to 7%)

Neuromuscular & skeletal: Paresthesia (1% to 3%), joint pain, muscle pain, tingling, weakness

Ocular: Conjunctivitis, visual disturbance

Otic: Hearing loss, tinnitus

Renal: Hematuria

Respiratory: Sinusitis (<1% to 7%)

Miscellaneous: Lymphoma (<1% to 6%), allergic reactions, hiccups, night sweats

Rheumatoid arthritis only (1% to <3% unless otherwise noted):

Cardiovascular: Hypertension (8%), edema (5%), chest pain (4%), arrhythmia (2%), abnormal heart sounds, cardiac failure, MI, peripheral ischemia

Central nervous system: Dizziness (8%), pain (6%), insomnia (4%), depression (3%), migraine (2%), anxiety, hypoesthesia, emotional lability, impaired concentration, malaise, nervousness, paranoia, somnolence, vertigo

Dermatologic: Purpura (3%), abnormal pigmentation, angioedema, cellulitis, dermatitis, dry skin, eczema, folliculitis, nail disorder, pruritus, skin disorder, urticaria

Endocrine & metabolic: Menstrual disorder (3%), breast fibroadenosis, breast pain, diabetes mellitus, goiter, hot flashes, hyperkalemia, hyperuricemia, hypoglycemia, libido increased/decreased

Gastrointestinal: Vomiting (9%), flatulence (5%), gingivitis (4%), gum hyperplasia (2%), constipation, dry mouth, dysphagia, enanthema, eructation, esophagitis, gastric ulcer, gastritis, gastroenteritis, gingival bleeding, glossitis, peptic ulcer, salivary gland enlargement, taste perversion, tongue disorder, tooth disorder, weight loss/gain

Genitourinary: Leukorrhea (1%), abnormal urine, micturition urgency, nocturia, polyuria, pyelonephritis, urinary incontinence, uterine hemorrhage

Hematologic: Anemia, leukopenia

Hepatic: Bilirubinemia

Neuromuscular & skeletal: Paresthesia (8%), tremor (8%), leg cramps/muscle contractions (2%), arthralgia, bone fracture, joint dislocation, myalgia, neuropathy, stiffness, synovial cyst, tendon disorder, weakness

Ocular: Abnormal vision, cataract, conjunctivitis, eye pain

Otic: Tinnitus, deafness, vestibular disorder

Renal: Increased BUN, hematuria, renal abscess

Respiratory: Cough (5%), dyspnea (5%), sinusitis (4%), abnormal chest sounds, bronchospasm, epistaxis

Miscellaneous: Infection (9%), abscess, allergy, bacterial infection, carcinoma, fungal infection, herpes simplex, herpes zoster, lymphadenopathy, moniliasis, diaphoresis increased, tonsillitis, viral infection

Psoriasis only (1% to <3% unless otherwise noted):

Cardiovascular: Chest pain, flushes

Central nervous system: Psychiatric events (4% to 5%), pain (3% to 4%), dizziness, fever, insomnia, nervousness, vertigo

Dermatologic: Hypertrichosis (5% to 7%), acne, dry skin, folliculitis, keratosis, pruritus, rash, skin malignancies

Endocrine & metabolic: Hot flashes

Gastrointestinal: Nausea (5% to 6%), diarrhea (5% to 6%), gum hyperplasia (4% to 6%), abdominal discomfort (3% to 6%), dyspepsia (2% to 3%), abdominal distention, appetite increased, constipation, gingival bleeding

Genitourinary: Micturition increased

Hematologic: Bleeding disorder, clotting disorder, platelet disorder, red blood cell disorder

Hepatic: Hyperbilirubinemia

Neuromuscular & skeletal: Paresthesia (5% to 7%), arthralgia (1% to 6%)

Ocular: Abnormal vision

Respiratory: Bronchospasm (5%), cough (5%), dyspnea (5%), rhinitis (5%), respiratory infection

Miscellaneous: Flu-like symptoms (8% to 10%)

Postmarketing and/or case reports (any indication): Death (due to renal deterioration), mild hypomagnesemia, hyperkalemia, increased uric acid, gout, hyperbilirubinemia, increased cholesterol, encephalopathy, impaired consciousness, neurotoxicity

Ophthalmic emulsion (Restasis™):

>10%: Ocular: Burning (17%)

1% to 10%: Ocular: Hyperemia (conjunctival 5%), eye pain, pruritus, stinging

Overdosage/Toxicology:

Drug Interactions:

Allopurinol: Increases cyclosporine concentrations by inhibiting cyclosporine metabolism

Antibiotics: Concomitant use may potentiate renal dysfunction (seen with gentamicin, tobramycin, vancomycin, trimethoprim and sulfamethoxazole); increased cyclosporine concentrations by inhibiting cyclosporine metabolism (seen with clarithromycin, erythromycin, and norfloxacin); may decrease cyclosporine concentrations by inducing cyclosporine metabolism (seen with nafcillin, and rifampin); may decrease immunosuppressant effects (seen with ciprofloxacin); CNS disturbances, seizures (seen with imipenem)

Anticonvulsants: May decrease cyclosporine concentrations by inducing cyclosporine metabolism (seen with carbamazepine, phenobarbital, and phenytoin)

Antineoplastics: Concomitant use may potentiate renal dysfunction (seen with melphalan)

Antifungals: Concomitant use may potentiate renal dysfunction (seen with amphotericin B, ketoconazole); increase cyclosporine concentrations by inhibiting cyclosporine metabolism (seen with fluconazole, itraconazole, and ketoconazole)

Bromocriptine: Increases cyclosporine concentrations by inhibiting cyclosporine metabolism

Calcium channel blockers (diltiazem, nicardipine, verapamil): Increase cyclosporine concentrations by inhibiting cyclosporine metabolism. Nifedipine has been reported to increase the risk of gingival hyperplasia.

Colchicine: May potentiate renal dysfunction.

CYP3A4 inducers: CYP3A4 inducers may decrease the levels/effects of cyclosporine. Example inducers include aminoglutethimide, carbamazepine, nafcillin, nevirapine, phenobarbital, phenytoin, and rifamycins.

CYP3A4 inhibitors: May increase the levels/effects of cyclosporine. Example inhibitors include azole antifungals, ciprofloxacin, clarithromycin, diclofenac, doxycycline, erythromycin, imatinib, isoniazid, nefazodone, nicardipine, propofol, protease inhibitors, quinidine, and verapamil.

CYP3A4 substrates: Cyclosporine may increase the levels/effects of CYP3A4 substrates. Example substrates include benzodiazepines, calcium channel blockers, cyclosporine, mirtazapine, nateglinide, nefazodone, sildenafil (and other PDE-5 inhibitors), tacrolimus, and venlafaxine. Selected benzodiazepines (midazolam and triazolam), cisapride, ergot alkaloids, selected HMG-CoA reductase inhibitors (lovastatin and simvastatin), and pimozide are generally contraindicated with strong CYP3A4 inhibitors.

Danazol: Increases cyclosporine concentrations by inhibiting cyclosporine metabolism

Digoxin: Decreased clearance and decreased volume of distribution of digoxin; severe digitalis toxicity has been observed

Diuretics, potassium-sparing: Concomitant use may lead to hyperkalemia

Glucocorticoids: Increase cyclosporine concentrations by inhibiting cyclosporine metabolism, seen with methylprednisolone. Decreased clearance of prednisolone and convulsions observed when used with cyclosporine.

H2 blockers: Concomitant use may potentiate renal dysfunction (seen with cimetidine, ranitidine)

HMG-CoA reductase inhibitors: Cyclosporine may increase levels/effects of HMG-CoA reductase inhibitors, resulting in myalgias, rhabdomyolysis, acute renal failure; dosage adjustments of HMG-CoA reductase inhibitors are recommended.

Immunosuppressives: Concomitant use may potentiate renal dysfunction (seen with tacrolimus, muromonab-CD3)

Metoclopramide: Increases cyclosporine concentrations by inhibiting cyclosporine metabolism

Methotrexate: Cyclosporine increases plasma levels of methotrexate and decreases plasma levels of its metabolite; monitor closely for signs of toxicity

Minoxidil: Concomitant use may lead to severe hypertrichosis

NSAIDs: Concomitant use may potentiate renal dysfunction, especially in dehydrated patients (seen with diclofenac, naproxen, sulindac). In addition, diclofenac plasma levels are doubled when given with cyclosporine; the lowest possible dose of diclofenac should be used. Monitor serum creatinine.

Octreotide: May decrease cyclosporine concentrations by inducing cyclosporine metabolism

Oral contraceptives: May increase serum levels of cyclosporine; monitor for signs of toxicity

Orlistat: May decrease absorption of cyclosporine; avoid concomitant use.

Prednisolone: Cyclosporine may increase serum levels/effects of prednisolone.

Protease inhibitors: Formal interaction studies have not been done; protease inhibitors are known to induce CYP3A4; use caution when using cyclosporine with indinavir, nelfinavir, ritonavir, or saquinavir

Rifabutin: Formal interaction studies have not been done; rifabutin is known to increase the metabolism of medications via CYP3A4.

Ticlopidine: May decrease cyclosporine concentrations by inducing cyclosporine metabolism

Vaccines: Vaccination may be less effective; avoid use of live vaccines during therapy.

Voriconazole: Cyclosporine serum concentrations may be increased; monitor serum concentrations and renal function. Decrease cyclosporine dosage by 50% when initiating voriconazole.

Ethanol/Nutrition/Herb Interactions:

Food: Grapefruit juice increases absorption; unsupervised use should be avoided.

Herb/Nutraceutical: Avoid St John's wort; as an enzyme inducer, it may increase the metabolism of and decrease plasma levels of cyclosporine; organ rejection and graft loss have been reported. Avoid cat's claw, echinacea (have immunostimulant properties).

Stability:

Capsule: Store at controlled room temperature

Injection: Store at controlled room temperature; do not refrigerate. Ampuls should be protected from light.

Ophthalmic emulsion: Store at 15°C to 25°C (59°F to 77°F). Vials are single-use; discard immediately following administration.

Oral solution: Store at controlled room temperature; do not refrigerate. Use within 2 months after opening; should be mixed in glass containers

Reconstitution:

Sandimmune® injection: Injection should be further diluted [1 mL (50 mg) of concentrate in 20-100 mL of D5W or NS] for administration by intravenous infusion. Light protection is not required for intravenous admixtures of cyclosporine.

Stability of injection of parenteral admixture at room temperature (25°C) is 6 hours in PVC; 24 hours in Excel®, PAB® containers, or glass.

Polyoxyethylated castor oil (Cremophor® EL) surfactant in cyclosporine injection may leach phthalate from PVC containers such as bags and tubing. The actual amount of diethylhexyl phthalate (DEHP) plasticizer leached from PVC containers and administration sets may vary in clinical situations, depending on surfactant concentration, bag size, and contact time.

Compatibility:

Neoral® oral solution: Orange juice, apple juice; avoid changing diluents frequently; mix thoroughly and drink at once

Sandimmune® oral solution: Milk, chocolate milk, orange juice; avoid changing diluents frequently; mix thoroughly and drink at once

Compatibility:

Y-site administration: Compatible: Alatrofloxacin, gatifloxacin, linezolid, propofol, sargramostim. Incompatible: Amphotericin B cholesteryl sulfate complex

Compatibility when admixed: Compatible: Ciprofloxacin. Incompatible: Magnesium sulfate

Mechanism of Action:

Pharmacodynamics/Kinetics:

Absorption:

Ophthalmic emulsion: Serum concentrations not detectable.

Oral:

Cyclosporine (non-modified): Erratic and incomplete; dependent on presence of food, bile acids, and GI motility; larger oral doses are needed in pediatrics due to shorter bowel length and limited intestinal absorption

Cyclosporine (modified): Erratic and incomplete; increased absorption, up to 30% when compared to cyclosporine (non-modified); less dependent on food, bile acids, or GI motility when compared to cyclosporine (non-modified)

Distribution: Widely in tissues and body fluids including the liver, pancreas, and lungs; crosses placenta; enters breast milk

Vdss: 4-6 L/kg in renal, liver, and marrow transplant recipients (slightly lower values in cardiac transplant patients; children <10 years have higher values)

Protein binding: 90% to 98% to lipoproteins

Metabolism: Extensively hepatic via CYP; forms at least 25 metabolites; extensive first-pass effect following oral administration

Bioavailability: Oral:

Cyclosporine (non-modified): Dependent on patient population and transplant type (<10% in adult liver transplant patients and as high as 89% in renal transplant patients); bioavailability of Sandimmune® capsules and oral solution are equivalent; bioavailability of oral solution is ~30% of the I.V. solution

Children: 28% (range: 17% to 42%); gut dysfunction common in BMT patients and oral bioavailability is further reduced

Cyclosporine (modified): Bioavailability of Neoral® capsules and oral solution are equivalent:

Children: 43% (range: 30% to 68%)

Adults: 23% greater than with cyclosporine (non-modified) in renal transplant patients; 50% greater in liver transplant patients

Half-life elimination: Oral: May be prolonged in patients with hepatic impairment and shorter in pediatric patients due to the higher metabolism rate

Cyclosporine (non-modified): Biphasic: Alpha: 1.4 hours; Terminal: 19 hours (range: 10-27 hours)

Cyclosporine (modified): Biphasic: Terminal: 8.4 hours (range: 5-18 hours)

Time to peak, serum: Oral:

Cyclosporine (non-modified): 2-6 hours; some patients have a second peak at 5-6 hours

Cyclosporine (modified): Renal transplant: 1.5-2 hours

Excretion: Primarily feces; urine (6%, 0.1% as unchanged drug and metabolites)

Dosage:

Children: Transplant: Refer to adult dosing; children may require, and are able to tolerate, larger doses than adults.

Adults:

Newly-transplanted patients: Adjunct therapy with corticosteroids is recommended. Initial dose should be given 4-12 hours prior to transplant or may be given postoperatively; adjust initial dose to achieve desired plasma concentration

Oral: Dose is dependent upon type of transplant and formulation:

Cyclosporine (modified):

Renal: 9 ± 3 mg/kg/day, divided twice daily

Liver: 8 ± 4 mg/kg/day, divided twice daily

Heart: 7 ± 3 mg/kg/day, divided twice daily

Cyclosporine (non-modified): Initial dose: 15 mg/kg/day as a single dose (range 14-18 mg/kg); lower doses of 10-14 mg/kg/day have been used for renal transplants. Continue initial dose daily for 1-2 weeks; taper by 5% per week to a maintenance dose of 5-10 mg/kg/day; some renal transplant patients may be dosed as low as 3 mg/kg/day

Note: When using the non-modified formulation, cyclosporine levels may increase in liver transplant patients when the T-tube is closed; dose may need decreased

I.V.: Cyclosporine (non-modified): Initial dose: 5-6 mg/kg/day as a single dose (¹/3 the oral dose), infused over 2-6 hours; use should be limited to patients unable to take capsules or oral solution; patients should be switched to an oral dosage form as soon as possible

Conversion to cyclosporine (modified) from cyclosporine (non-modified): Start with daily dose previously used and adjust to obtain preconversion cyclosporine trough concentration. Plasma concentrations should be monitored every 4-7 days and dose adjusted as necessary, until desired trough level is obtained. When transferring patients with previously poor absorption of cyclosporine (non-modified), monitor trough levels at least twice weekly (especially if initial dose exceeds 10 mg/kg/day); high plasma levels are likely to occur.

Rheumatoid arthritis: Oral: Cyclosporine (modified): Initial dose: 2.5 mg/kg/day, divided twice daily; salicylates, NSAIDs, and oral glucocorticoids may be continued (refer to Drug Interactions); dose may be increased by 0.5-0.75 mg/kg/day if insufficient response is seen after 8 weeks of treatment; additional dosage increases may be made again at 12 weeks (maximum dose: 4 mg/kg/day). Discontinue if no benefit is seen by 16 weeks of therapy.

Note: Increase the frequency of blood pressure monitoring after each alteration in dosage of cyclosporine. Cyclosporine dosage should be decreased by 25% to 50% in patients with no history of hypertension who develop sustained hypertension during therapy and, if hypertension persists, treatment with cyclosporine should be discontinued.

Psoriasis: Oral: Cyclosporine (modified): Initial dose: 2.5 mg/kg/day, divided twice daily; dose may be increased by 0.5 mg/kg/day if insufficient response is seen after 4 weeks of treatment. Additional dosage increases may be made every 2 weeks if needed (maximum dose: 4 mg/kg/day). Discontinue if no benefit is seen by 6 weeks of therapy. Once patients are adequately controlled, the dose should be decreased to the lowest effective dose. Doses lower than 2.5 mg/kg/day may be effective. Treatment longer than 1 year is not recommended.

Note: Increase the frequency of blood pressure monitoring after each alteration in dosage of cyclosporine. Cyclosporine dosage should be decreased by 25% to 50% in patients with no history of hypertension who develop sustained hypertension during therapy and, if hypertension persists, treatment with cyclosporine should be discontinued.

Focal segmental glomerulosclerosis: Initial: 3 mg/kg/day divided every 12 hours

Autoimmune diseases: 1-3 mg/kg/day

Keratoconjunctivitis sicca: Ophthalmic: Children 16 years and Adults: Instill 1 drop in each eye every 12 hours

Dosage adjustment in renal impairment: For severe psoriasis:

Serum creatinine levels 25% above pretreatment levels: Take another sample within 2 weeks; if the level remains 25% above pretreatment levels, decrease dosage of cyclosporine (modified) by 25% to 50%. If two dosage adjustments do not reverse the increase in serum creatinine levels, treatment should be discontinued.

Serum creatinine levels 50% above pretreatment levels: Decrease cyclosporine dosage by 25% to 50%. If two dosage adjustments do not reverse the increase in serum creatinine levels, treatment should be discontinued.

Hemodialysis: Supplemental dose is not necessary.

Peritoneal dialysis: Supplemental dose is not necessary.

Dosage adjustment in hepatic impairment: Probably necessary; monitor levels closely

Administration:

Oral solution: Do not administer liquid from plastic or styrofoam cup. May dilute Neoral® oral solution with orange juice or apple juice. May dilute Sandimmune® oral solution with milk, chocolate milk, or orange juice. Avoid changing diluents frequently. Mix thoroughly and drink at once. Use syringe provided to measure dose. Mix in a glass container and rinse container with more diluent to ensure total dose is taken. Do not rinse syringe before or after use (may cause dose variation).

I.V.: Following dilution, intravenous admixture should be administered over 2-6 hours. Discard solution after 24 hours. Anaphylaxis has been reported with I.V. use; reserve for patients who cannot take oral form. Patients should be under continuous observation for at least the first 30 minutes of the infusion, and should be monitored frequently thereafter. Maintain patent airway; other supportive measures and agents for treating anaphylaxis should be present when I.V. drug is given.

Ophthalmic emulsion: Prior to use, invert vial several times to obtain a uniform emulsion. Remove contact lenses prior to instillation of drops; may be reinserted 15 minutes after administration. May be used with artificial tears; allow 15 minute interval between products.

Monitoring Parameters:

Transplant patients: Cyclosporine trough levels, serum electrolytes, renal function, hepatic function, blood pressure, lipid profile

Psoriasis therapy: Baseline blood pressure, serum creatinine (2 levels each), BUN, CBC, serum magnesium, potassium, uric acid, lipid profile. Biweekly monitoring of blood pressure, complete blood count, and levels of BUN, uric acid, potassium, lipids, and magnesium during the first 3 months of treatment for psoriasis. Monthly monitoring is recommended after this initial period. Also evaluate any atypical skin lesions prior to therapy. Increase the frequency of blood pressure monitoring after each alteration in dosage of cyclosporine. Cyclosporine dosage should be decreased by 25% to 50% in patients with no history of hypertension who develop sustained hypertension during therapy and, if hypertension persists, treatment with cyclosporine should be discontinued.

Rheumatoid arthritis: Baseline blood pressure, and serum creatinine (2 levels each); serum creatinine every 2 weeks for first 3 months, then monthly if patient is stable. Increase the frequency of blood pressure monitoring after each alteration in dosage of cyclosporine. Cyclosporine dosage should be decreased by 25% to 50% in patients with no history of hypertension who develop sustained hypertension during therapy and, if hypertension persists, treatment with cyclosporine should be discontinued.

Reference Range:

Method-dependent and specimen-dependent: Trough levels should be obtained:

Oral: 12-18 hours after dose (chronic usage)

I.V.: 12 hours after dose or immediately prior to next dose

Therapeutic range: Not absolutely defined, dependent on organ transplanted, time after transplant, organ function and CsA toxicity:

General range of 100-400 ng/mL

Toxic level: Not well defined, nephrotoxicity may occur at any level

Test Interactions:

Dietary Considerations:

Patient Education:

Additional Information:

Cardiovascular Considerations:

Dental Health: Effects on Dental Treatment:

Dental Health: Vasoconstrictor/Local Anesthetic Precautions:

Mental Health: Effects on Mental Status:

Mental Health: Effects on Psychiatric Treatment:

Oncology: Emetic Potential:

Oncology: Vesicant:

Dosage Forms:

Capsule, soft gel, modified: 25 mg, 100 mg [contains castor oil, ethanol]

Gengraf®: 25 mg, 100 mg [contains ethanol, castor oil, propylene glycol]

Neoral®: 25 mg, 100 mg [contains dehydrated ethanol, corn oil, castor oil, propylene glycol]

Capsule, soft gel, non-modified (Sandimmune®): 25 mg, 100 mg [contains dehydrated ethanol, corn oil]

Emulsion, ophthalmic [preservative free, single-use vial] (Restasis™): 0.05% (0.4 mL) [contains glycerin, castor oil, polysorbate 80, carbomer 1342; 32 vials/box]

Injection, solution, non-modified (Sandimmune®): 50 mg/mL (5 mL) [contains Cremophor® EL (polyoxyethylated castor oil), ethanol]

Solution, oral, modified:

Gengraf®: 100 mg/mL (50 mL) [contains castor oil, propylene glycol]

Neoral®: 100 mg/mL (50 mL) [contains dehydrated ethanol, corn oil, castor oil, propylene glycol]

Solution, oral, non-modified (Sandimmune®): 100 mg/mL (50 mL) [contains olive oil, ethanol]

International Brand Names: