Cyclosporine

Neoral prevents rejection of kidney, liver and heart allogeneic transplants; it also treats severe active rheumatoid arthritis insufficiently responsive to methotrexate, including appropriate combination with methotrexate, and selected adult nonimmunocompromised severe recalcitrant plaque psoriasis after systemic-therapy failure or contraindication / intolerance. Sandimmune capsules / injection, with adrenal corticosteroids, prevent kidney / liver / heart graft rejection and treat chronic rejection after prior immunosuppressive treatment. Its IV form is reserved for inability to take capsules because anaphylaxis can occur.

Restasis increases tears when production is presumed suppressed by ocular inflammation associated with keratoconjunctivitis sicca; increased production was not demonstrated with concurrent topical anti-inflammatory drugs or punctal plugs. Cequa increases tear production in keratoconjunctivitis sicca. Vevye treats signs and symptoms of dry-eye disease. These are separate indications, not systemic-immunosuppression regimens.

This profile reviews Neoral modified capsules / solution, current Sandimmune nonmodified capsules / IV concentrate, Restasis single-use emulsion, Cequa single-use solution and Vevye multidose solution. Restasis Multidose, other generic products, veterinary preparations, historical Sandimmune oral solution, other-country indications and specialist off-label protocols require separate verification. No universal transplant blood-level target or automatic conversion is supplied here.

Neoral dosing is individualized by organ, other immunosuppressants, rejection / tolerance and predefined assay-specific blood concentrations; total daily oral dose is divided twice daily. Its label’s initial-dose examples are a 1994 center survey, not a universal current starting protocol. Current Sandimmune retains a label initial single oral 15 mg / kg dose 4–12 hours before transplant, continued daily initially 1–2 weeks then tapered 5% weekly toward 5–10 mg / kg / day, with lower starting / maintenance approaches also described. These label examples do not replace the transplant center’s protocol or justify applying one regimen to every organ / population.

Current Sandimmune warns against mg-for-mg switching to / from Neoral and requires more frequent level monitoring and individualized adjustment. Neoral retains older supervised 1: 1 Sandimmune-to-Neoral initiation text; because these sources differ, obtain a specialist plan rather than use an automatic conversion. In transplant patients renal impairment requires nephrotoxicity monitoring and reduction if indicated, not a simple renal-clearance table. Neoral for rheumatoid arthritis / psoriasis should not be given with abnormal renal function. Severe hepatic impairment may require reduced systemic doses based on blood levels.

Give Neoral on a consistent schedule relative to time and meals. Avoid grapefruit / grapefruit juice. Measure the 100 mg / mL oral solution with its supplied syringe; mix in room-temperature orange or apple juice in glass, stir / drink immediately and rinse glass with more diluent. Do not repeatedly change diluents. Dry the syringe exterior and replace cover; do not rinse with water / cleaning agents, and any cleaned syringe must be completely dry before reuse.

For patients unable to take capsules, the selected IV label uses one-third of the Sandimmune oral dose, with initial 5–6 mg / kg / day 4–12 hours before transplant; this is not one-third of any arbitrary Neoral dose. Dilute 1 mL of 50 mg / mL concentrate in 20–100 mL saline 0.9% or dextrose 5% aseptically; infuse slowly over 2–6 hours, never undiluted or IV push. Complete at room temperature within 6 hours; if refrigerated 2–8°C before use, total storage plus infusion must be less than 24 hours. Discard unused dilution. Switch to capsules as soon as feasible under specialist monitoring.

Separate Restasis from lubricant drops, Cequa from artificial tears and Vevye from other eye drops by 15 minutes. Remove contact lenses before these products and wait 15 minutes before reinsertion. Keep tips off eyes / surfaces. Do not reuse single-use vials or apply systemic dose conversions to eye drops; follow the actual ophthalmic prescription.

Neoral: cyclosporine / excipient hypersensitivity; for rheumatoid arthritis or psoriasis, abnormal renal function, uncontrolled hypertension or malignancy; psoriasis also the prohibited concurrent therapies listed above. Sandimmune: cyclosporine hypersensitivity; IV additionally prior Cremophor EL hypersensitivity. Restasis: known / suspected ingredient hypersensitivity. Current Cequa and Vevye list no formal contraindications; this does not negate contamination, contact-lens or adverse-reaction precautions.

Neoral’s box requires experienced systemic-immunosuppression supervision, warns of infection / neoplasia, nonbioequivalence with Sandimmune and blood-level monitoring; its psoriasis box highlights nephrotoxicity / hypertension and malignancy / UV-treatment risk. Current Sandimmune’s box covers specialist use, corticosteroid co-treatment, infection / lymphoma, inappropriate switching and erratic absorption requiring monitoring. The three selected ophthalmic labels have no boxed warning.

Systemic principal reactions include renal dysfunction, hypertension, tremor, increased hair growth, gingival enlargement, headache and GI symptoms, with serious organ / infectious / malignant / neurologic complications described above. Eye-product trials differ: Restasis commonly caused burning; Cequa instillation pain / redness; Vevye instillation reactions and transient visual-acuity decrease. Trial rates across routes / formulations should not be treated as one common incidence.

Systemic concentrations can rise with agents such as azole antifungals, macrolides, diltiazem / verapamil and CYP3A / P-glycoprotein inhibitors, and fall with rifampin, enzyme-inducing anticonvulsants or St John’s wort. Avoid grapefruit and orlistat; changes can lead to toxicity or graft loss. Obtain specialist level / dose monitoring rather than one blanket adjustment percentage.

Cyclosporine may increase digoxin, colchicine, statin, repaglinide and other substrate exposure; serious toxicity, muscle injury or hypoglycemia can result. Individual companion labels may prohibit combinations or impose specific limits, so the cyclosporine label’s general dose-reduction wording is not permission to combine every statin or colchicine regimen. Avoid bosentan or dabigatran under the selected systemic labels; aliskiren coadministration is not recommended. The label advises sirolimus 4 hours after cyclosporine and notes reduced mycophenolic-acid exposure requiring efficacy review.

NSAIDs and other nephrotoxic medicines can worsen kidney function; review new / increased NSAID therapy. Avoid potassium-sparing diuretics and monitor potassium with ACE inhibitors / ARBs, supplements or other potassium-raising exposures. Live vaccines should be avoided and other vaccines may work less well during systemic treatment. Methotrexate combination is an appropriate Neoral RA option but prohibited for Neoral psoriasis. Eye-product 15 minute spacing does not imply systemic interaction-dose rules for local drops.

Systemic observational data have not identified a major-birth-defect or miscarriage association, but increased maternal hypertension / preeclampsia, prematurity and low birth weight occur in populations with confounding underlying disease. Use specialist benefit / risk assessment and consider the transplant pregnancy registry and formulation ethanol. Cyclosporine / metabolites occur in milk after oral / IV use; weigh maternal need and breastfeeding benefits. Ophthalmic pregnancy / lactation data are limited: Restasis / Vevye studied blood levels were unquantifiable, Cequa very low; this does not establish zero milk exposure or universal reproductive safety.

Systemic transplant pediatric experience exists without adequate controlled pediatric studies: Neoral reports use from age 1 and Sandimmune from 6 months; these observations are not universal age / weight protocols. Neoral juvenile RA or psoriasis below 18 is unestablished. Ophthalmic effectiveness is unestablished below 16 for Restasis and below 18 for Cequa / Vevye. Older systemic patients need cautious selection and renal / BP monitoring; older RA patients had greater hypertension / creatinine vulnerability.

Minimal renal elimination does not protect against nephrotoxicity. Transplant doses are adjusted from renal function, blood levels and rejection / tolerance; Neoral RA / psoriasis contraindicates abnormal renal function. Severe liver disease reduces systemic clearance and may require dose reduction. Selected eye labels provide no numerical renal / hepatic adjustment tables; do not scale drops from systemic milligrams.

Cyclosporine inhibits calcineurin-related immune signaling and T-cell activation / lymphokine production, including interleukin-2. Systemic immunosuppression helps prevent rejection but increases infection risk. Ophthalmic anti-inflammatory / immunomodulatory action supports the selected dry-eye indications; exact tear-production mechanisms are not fully understood.

Systemic oral absorption is incomplete and formulation-dependent; Neoral microemulsion has greater exposure than Sandimmune and is not bioequivalent. CYP3A metabolism, P-glycoprotein transport and predominantly biliary elimination explain many interactions; dialysis removes little drug. Current labels report differing studied terminal half-life estimates, so none is imposed universally. Eye studies show Restasis and Vevye below 0.1 ng / mL quantification limits, while Cequa was undetectable or near that limit in studied samples; low exposure does not authorize swallowing / injecting drops.

Systemic baseline / follow-up includes renal / liver function, BP, electrolytes including potassium / magnesium, lipids, blood counts and infection / malignancy assessment as appropriate. Transplant blood concentrations require organ / protocol / assay-specific targets and do not replace renal monitoring or biopsy. Neoral RA / psoriasis: BP / creatinine every 2 weeks for initial 3 months, thenmonthly if stable; psoriasis also other listed laboratory tests on that schedule. RA plus methotrexate warrants monthly CBC / liver tests. Changes in interacting medicines / formulation require extra monitoring; do not treat one study’s trough target as universal.

For Neoral RA, 25–50% dose reductions are used for significant toxicity including creatinine 30% above baseline; stop if reductions fail or toxicity is severe. For psoriasis, repeat a ≥25% creatinine rise within 2 weeks and reduce 25–50% if persistent; a ≥50% rise requires reduction, and stop if not reversible within 25% of baseline after two adjustments. Report infection, neurologic / visual changes, jaundice or reduced urine promptly. Maintain dose / meal consistency, avoid grapefruit / live vaccines / excess sun, maintain oral hygiene and never change formulation independently. Eye users follow exact tip / lens / spacing / discard directions and seek assessment for significant allergy, pain or visual change.

Contact the treating specialist / Poison Control for overdose, an uncertain dose or wrong-route use; do not double or automatically replace missed / partially delivered doses. Systemic overdose needs supportive clinical treatment and organ monitoring; dialysis is not effective clearance. Do not use historic forced-emesis / lavage wording as a home instruction. Never inject oral solution or ophthalmic products, and never give IV concentrate undiluted.

Product

Neoral modified cyclosporine 25 mg capsule

Route

Oral; specialist prescription

Appearance

Oval blue-gray; Neoral /25 mg in red

Example package

30 unit-dose blisters · NDC 0078-0246-15

Neoral modified capsules 25 / 100 mg and oral solution 100 mg / mL; Sandimmune current nonmodified capsules 25 / 100 mg and IV concentrate 50 mg / mL in 5 mL ampuls. Current Sandimmune does not list the historical oral solution. Restasis single-use emulsion 0.05% (0.5 mg / mL), 0.4 mL vials; Cequa solution 0.09% (0.9 mg / mL), 0.25 mL vials; Vevye solution 0.1% (1 mg / mL), 2 mL multidose bottle NDC 82667-900-02. Restasis Multidose and other products require separate instructions; strengths do not imply dose equivalence.

Neoral capsules / solution: 20–25°C original containers; no solution refrigeration; opened solution use within 2 months. Low-temperature gelling / light sediment can reverse on warming to 25°C per label. Sandimmune capsules: 20–25°C, excursions 15–30°C; IV ampuls below 30°C protected from light, with dilution time limits above. Restasis single-use: 15–25°C; discard immediately after use. Cequa: 20–25°C in original foil pouch; discard used vial immediately. Vevye: 15–25°C, do not freeze / refrigerate, keep capped and use after opening until bottle expiration per current label. Do not invent a uniform 28 day discard rule.