{ "query": "cyclosporine", "ingredient": "cyclosporine", "slug": "cyclosporine", "rxcui": "3008", "brands": [ "Restasis", "Cequa", "Vevye", "Sandimmune", "Verkazia" ], "names": [ "cyclosporine", "cyclosporine microemulsion" ], "classes": [ { "id": "L04AD", "name": "Calcineurin inhibitors" } ], "alternatives": [ "tacrolimus", "voclosporin" ], "label": { "route_mode": "ORAL", "route_counts": { "OPHTHALMIC": 15, "ORAL": 11, "TOPICAL": 3, "INTRAVENOUS": 1 }, "boxed_warning": "WARNING Only physicians experienced in management of systemic immunosuppressive therapy for the indicated disease should prescribe cyclosporine [MODIFIED]. At doses used in solid organ transplantation, only physicians experienced in immunosuppressive therapy and management of organ transplant recipients should prescribe cyclosporine [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 [MODIFIED], a systemic immunosuppressant, may increase the susceptibility to infection and the development of neoplasia. In kidney, liver, and heart transplant patients, cyclosporine [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 [MODIFIED] and cyclosporine oral solution [MODIFIED] have increased bioavailability in comparison to Sandimmune\u00ae ...", "indications_and_usage": "INDICATIONS AND USAGE Kidney, Liver, and Heart Transplantation Cyclosporine capsules, USP [MODIFIED] and cyclosporine oral solution, USP [MODIFIED] are indicated for the prophylaxis of organ rejection in kidney, liver, and heart allogeneic transplants. Cyclosporine capsules, USP [MODIFIED] and cyclosporine oral solution, USP [MODIFIED] have been used in combination with azathioprine and corticosteroids. Rheumatoid Arthritis Cyclosporine capsules, USP [MODIFIED] and cyclosporine oral solution, 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] and 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 capsules, USP [MODIFIED] and cyclosporine oral solution, 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, ret...", "contraindications": "CONTRAINDICATIONS General Cyclosporine [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 [MODIFIED]. Psoriasis Psoriasis patients who are treated with cyclosporine [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 [MODIFIED].", "warnings_and_cautions": "", "warnings": "WARNINGS (See also Boxed WARNING ) All Patients Cyclosporine, the active ingredient in cyclosporine capsules [MODIFIED] and cyclosporine oral solution [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 [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 [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 [MODIFIED] therapy and reflect a reduction in the glomerular filtration rate. Impaired renal function at any time requires close monitoring, and f...", "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 fa...", "drug_abuse_and_dependence": "", "controlled_substance": "", "recent_major_changes": "", "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 [MODIFIED] should be diluted, preferably with orange or apple juice that is at room temperature. The combination of cyclosporine oral solution [MODIFIED] with milk can be unpalatable. Patients should be advised to take cyclosporine [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...", "spl_medguide": "", "clinical_studies": "Clinical Studies In controlled studies, the nature, severity, and incidence of the adverse events that were observed in 493 transplanted patients treated with cyclosporine [MODIFIED] were comparable with those observed in 208 transplanted patients who received Sandimmune\u00ae (cyclosporine) 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\u00ae, 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\u00ae) Body System Adverse Reactions Sandimmune\u00ae (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 Sys...", "brand_name": "Cyclosporine", "manufacturer": "Dr. Reddy's Laboratories Inc", "application_number": "ANDA065044", "pharm_class_epc": [ "Calcineurin Inhibitor Immunosuppressant [EPC]" ], "route": [ "ORAL" ], "effective_time": "20240603", "set_id": "64ec430a-e930-145c-e766-13fb49b64644", "has_boxed_warning": true, "controlled": false, "mentions_rems": false }, "faers": { "total": 109336, "serious": 74396, "death": 12968, "hospitalization": 24880, "primary_suspect": 108915, "top_reactions": [ [ "Drug Ineffective", 15804 ], [ "Off Label Use", 11299 ], [ "Eye Irritation", 8309 ], [ "Product Use In Unapproved Indication", 6020 ], [ "Eye Pain", 3981 ], [ "Headache", 3722 ], [ "Condition Aggravated", 3663 ], [ "Nausea", 3628 ], [ "Fatigue", 3515 ], [ "Diarrhoea", 3458 ], [ "Pyrexia", 3321 ], [ "Pain", 3243 ], [ "Pneumonia", 3173 ], [ "Rash", 2887 ], [ "Pruritus", 2830 ] ], "by_year": { "2019": 10921, "2020": 10951, "2021": 8585, "2022": 8255, "2023": 8359, "2024": 11069, "2025": 10556, "2026": 6177 }, "by_year_primary": { "2019": 10909, "2020": 10945, "2021": 8570, "2022": 8168, "2023": 8281, "2024": 10992, "2025": 10476, "2026": 6136 } }, "faers_base": { "total": 20692304, "serious_share": 0.5742697381596559, "death_share": 0.09102355155810585 }, "recalls": [ { "class": "Class III", "date": "20230907", "reason": "Subpotent: Out of Specification result observed for low assay", "firm": "SUN PHARMACEUTICAL INDUSTRIES INC", "status": "Terminated" }, { "class": "Class II", "date": "20220916", "reason": "CGMP deviations: Out of specification results obtained during routine stability testing for ethanol content.", "firm": "Novartis Pharmaceuticals Corporation", "status": "Terminated" }, { "class": "Class III", "date": "20220401", "reason": "Subpotent Drug and Presence of Particulate Matter: low out-of-specification results obtained for assay and the presence of particulate matter.", "firm": "SUN PHARMACEUTICAL INDUSTRIES INC", "status": "Terminated" }, { "class": "Class III", "date": "20210507", "reason": "Subpotent and Presence of Particulates .", "firm": "SUN PHARMACEUTICAL INDUSTRIES INC", "status": "Terminated" }, { "class": "Class III", "date": "20210222", "reason": "Subpotent", "firm": "SUN PHARMACEUTICAL INDUSTRIES INC", "status": "Terminated" }, { "class": "Class II", "date": "20170208", "reason": "Failed Impurities/Degradations Specifications; out of specification results for Maximum Unknown Impurities and Total Impurities", "firm": "Amerisource Health Services", "status": "Terminated" }, { "class": "Class II", "date": "20170203", "reason": "Failed Impurities/Degradations Specifications; out of specification results for Maximum Unknown Impurities and Total Impurities.", "firm": "Apotex Inc.", "status": "Terminated" } ], "recall_total": 7, "drugsfda": { "applications": 38, "nda": 14, "anda": 24, "first_approval": "19831114", "rems": false, "rems_last": "", "labeling_supplements": 103, "labeling_recent": 16, "sponsors": [ "ABBVIE", "ALLERGAN", "AMNEAL", "APOTEX", "AUROBINDO PHARMA LTD", "DEVA HOLDING AS", "DR REDDYS LABS SA", "HARROW EYE" ], "unapproved": false, "first_approval_fmt": "11/14/1983" }, "trials": { "total": 1320, "completed": 808, "terminated": 177, "with_results": 342, "industry": 460, "phase3": 252, "results_share": 0.42326732673267325, "terminated_share": 0.1340909090909091 }, "pubmed": { "rct": 1120, "meta": 84, "recent_rct": 70, "cochrane": [ { "pmid": "42464966", "title": "Topical cyclosporine A therapy for dry eye disease", "year": "2026" }, { "pmid": "31517988", "title": "Topical cyclosporine A therapy for dry eye syndrome", "year": "2019" }, { "pmid": "22972132", "title": "Topical cyclosporine for atopic keratoconjunctivitis", "year": "2012" }, { "pmid": "20091657", "title": "Effect of cyclosporine on blood pressure", "year": "2010" }, { "pmid": "15846602", "title": "Cyclosporine for induction of remission in Crohn's disease", "year": "2005" }, { "pmid": "15674937", "title": "Cyclosporine A for induction of remission in severe ulcerative colitis", "year": "2005" }, { "pmid": "10796412", "title": "Cyclosporine for rheumatoid arthritis", "year": "2000" } ] }, "payments": { "year": "2024", "usd": 2371167.93, "records": 29402, "by_name": [ [ "Cequa", 1723028.87 ], [ "Vevye", 648139.06 ] ], "names_checked": [ "cyclosporine", "Restasis", "Cequa", "Vevye", "Sandimmune", "Verkazia" ], "source": "bulk-index" }, "partd": { "year": "2024", "claims": 2291687, "beneficiaries": 816975, "spend": 1749681664.8200002, "by_brand": [ { "brand": "Restasis", "claims": 1360998, "per_claim": 947.65248871, "is_generic": false }, { "brand": "Cyclosporine", "claims": 744577, "per_claim": 409.93255546, "is_generic": true }, { "brand": "Cequa", "claims": 90056, "per_claim": 850.12946389, "is_generic": false }, { "brand": "Restasis Multidose", "claims": 79985, "per_claim": 802.67186873, "is_generic": false }, { "brand": "Vevye", "claims": 15393, "per_claim": 858.69169623, "is_generic": false }, { "brand": "Sandimmune", "claims": 549, "per_claim": 843.53748634, "is_generic": false }, { "brand": "Verkazia", "claims": 129, "per_claim": 2017.5107752, "is_generic": false } ], "per_claim": 763.490679495062 }, "mdl": [], "dsc": [], "settlements": [], "prescrire": null, "eml": { "listed": false, "status": "", "name": "", "matched": null, "stewardship": [] }, "exposure": { "years": [ "2024", "2025", "2026" ], "reports_recent": 27604, "fills": 2291687, "per_million": 12045.274943742317, "ratio": 4.350124059583757, "median": 2768.949753790441 }, "scores": { "safety": { "score": 52, "letter": "D", "why": [ "Carries an FDA boxed warning, the strongest warning the FDA issues (-30)", "12,045 FDA reports naming it as the suspect drug per million Medicare fills, 4.4x the median drug on this site (-13)", "Death share in reports is near or below the FAERS average (1.3x)", "Off-label use is among the five most-reported items: widely used beyond its approved evidence (-5)" ], "weight": 0.35 }, "evidence": { "score": 78, "letter": "B", "why": [ "1120 randomized trials and 84 systematic reviews/meta-analyses indexed in PubMed", "7 independent Cochrane review(s) exist", "Only 42% of completed registered trials posted results (-8)", "'Drug ineffective' is the single most-reported item about this drug in FAERS (-5)" ], "weight": 0.25 }, "regulatory": { "score": 86, "letter": "B", "why": [ "Recalls since 2016: 0 Class I, 3 Class II, 4 Class III across 24 generic makers (-6)", "16 label changes approved since 2021: the safety story is still moving (-8)" ], "weight": 0.15 }, "conflict": { "score": 70, "letter": "C", "why": [ "Pharma paid doctors $2,371,168 tied to this drug last year (-30)", "Not named in any pending federal MDL" ], "weight": 0.15 }, "options": { "score": 90, "letter": "A", "why": [ "Generic versions approved (24 applications)", "2 same-class alternative(s) (-10)" ], "weight": 0.1 } }, "total": 70, "grade": "C", "questions": [ "This drug carries a boxed warning. Which specific risk does it cover, and does it apply to me?", "The most-reported problems in FDA's adverse event data are eye irritation, product use in unapproved indication. How would we recognize and handle those?", "Off-label use is among the most-reported items for this drug. Is my use on-label, and if not, what evidence supports it?", "Why this one over tacrolimus, voclosporin? What would make you pick one of those instead?", "The manufacturer pays physicians heavily to promote this drug. Have you received anything from them?", "What result are we expecting, by when, and what is the plan if it does not happen?", "If 100 people like me took this drug, how many would actually get better because of it, and how many would be harmed by it? (Doctors call these the number needed to treat and the number needed to harm.)" ] }