Current and Potential Applications of Pharmacogenetics and Pharmacogenomics
John Y. M. Koo, Ethan C. Levin, Argentina Leon, Jashin J. Wu, Alice B. Gottlieb in Moderate to Severe Psoriasis, 2014
Cyclosporine Cyclosporine is a commonly prescribed immunosuppressive, which has long been used in the prevention and treatment of organ transplant rejection and of graft versus host disease. It has been employed in a number of dermatologic conditions, including psoriasis and eczema. Cyclosporine is likely successful in psoriasis as a result of its ability to suppress T cells. Similar to methotrexate, the pharmacogenetics of cyclosporine have not been investigated in psoriasis but instead in transplant patients. Although cyclosporine is highly effective, it also has a narrow therapeutic index with significant risk of nephrotoxicity [61]. Consequently, polymorphisms involved in the absorption, distribution, and metabolism of cyclosporine are particularly noteworthy and clinically relevant.
Hand Dermatitis
Donald Rudikoff, Steven R. Cohen, Noah Scheinfeld in Atopic Dermatitis and Eczematous Disorders, 2014
Cyclosporine works primarily by suppressing T-lymphocyte activation, making it useful for the treatment of many inflammatory skin conditions, such as atopic dermatitis and severe chronic hand dermatitis (Granlund et al. 1996, 1998, Schmitt et al. 2007). In a double-blind study of 41 hand dermatitis patients (21 of 41 participants diagnosed with irritant or allergic contact dermatitis and the remaining individuals unclassified), participants were randomized to receive either oral cyclosporine (3 mg/kg per day) or a potent topical corticosteroid for 6 weeks (Granlund et al. 1996). There was a 50% decrease in disease activity in the cyclosporine group, compared with a 32% reduction in the corticosteroid group. However, 8 of the 20 patients receiving cyclosporine (40%) failed treatment, and both groups were noted to have a 50% relapse rate at the 2-week follow-up.
Immune system modulators
Gabriel Virella in Medical Immunology, 2019
Cyclosporine's role in medicine has expanded over the years. It has a prominent place in transplant medicine as a means to prolong the life of organ transplants and grafts. Studies have demonstrated that the use of cyclosporine decreases the incidence and severity of graft-versus-host disease in bone marrow transplant recipients. Cyclosporine works well with other immunosuppressive medications, enabling clinicians to use smaller doses of these medications to achieve their goal of immunosuppression. In terms of autoimmune diseases, cyclosporine is occasionally used in the treatment of lupus nephritis as well as psoriasis, rheumatoid arthritis, ulcerative colitis, and as part of the acute treatment of the macrophage activation syndrome. Cyclosporine does have its fair share of side effects, including hypertension, hypercholesterolemia, hepatotoxicity, hirsutism, and gingival hyperplasia. Although used in renal transplant recipients, cyclosporine can cause nephrotoxicity, especially if the daily dose exceeds 5 mg/kg. Use of cyclosporine can also increase rates of cytomegalovirus infection in transplant recipients. It has been associated with an increased incidence of lymphoproliferative syndromes as well.
Stevens-Johnson syndrome and toxic epidermal necrolysis: risk factors, causality assessment and potential prevention strategies
Published in Expert Review of Clinical Immunology, 2020
Chu-Chi Lin, Chun-Bing Chen, Chuang-Wei Wang, Shuen-Iu Hung, Wen-Hung Chung
Currently, there is still no standardized guideline for the treatment of SJS/TEN. Early identification and withdrawal of the suspected offending culprit drugs is the firstly critical step. Systemic corticosteroids is usually the first choice for the treatment of SJS/TEN in most countries [128]. However, studies had shown failure of benefit for patients treated with corticosteroids compared to those with only general supported care [129,130]. Several previous studies had shown that IVIG as another therapeutic agent for the treatment of SJS/TEN and is commonly used for pediatric patients [131]. Cyclosporine is an immunosuppressant medication for the treatment of many immune disorders, such as rheumatoid arthritis, psoriasis, Crohn’s disease, and in organ transplants to prevent rejection. Cyclosporine reduces the activity of effector T-cell by inhibition of the transcription of genes for IL-2 and related cytokines [132]. Cyclosporine has been considered for the treatment of patients with SJS/TEN. Cyclosporine had been evaluated for the treatment of SJS/TEN and found to decrease the mortality compared to supportive care. However, the beneficial effect of cyclosporine for the treatment of SJS/TEN is still controversial [133–138]. Table 4 summarizes studies related to cyclosporine for the treatment of SJS/TEN. Further robust randomized, controlled trials should be executed to confirm the efficacy and safety of cyclosporine applied in the treatment of patients with SJS/TEN.
Nanomedicine for immunosuppressive therapy: achievements in pre-clinical and clinical research
Published in Expert Opinion on Drug Delivery, 2018
Hanan Al-Lawati, Hamidreza Montazeri Aliabadi, Behzad Sharif Makhmalzadeh, Afsaneh Lavasanifar
Uncovering of the immunosuppressive activity of cyclosporine A (cyclosporine) isolated from Tolypocladium inflatum gams in 1971 have been among the greatest discoveries in the treatment of organ transplant rejection [40]. This highly lipophilic cyclic undecapeptide selectively targets the proliferation of helper T-cells, but not the suppressor T-cells [41]. Cyclosporine is indicated for the prevention of rejection following transplantation of heart, lung, and kidney; treatment of graft versus host disease with bone marrow transplant; and treatment of various autoimmune conditions such as RA, nephrotic syndrome, and psoriasis [42]. It is available for intravenous (IV) infusion at a dose of 2–4 mg/kg/day. Its oral administration as soft gelatin capsules or solution is more commonly used, however. The original cyclosporine product, Sandimmune, is an oil-in-water emulsion. A newer microemulsion formulation of cyclosporine, Neoral, with improved bioavailability is also approved for use [43]. An ophthalmic emulsion of cyclosporine, Restasis, is also approved for the treatment of inflammation in the dry eye syndrome.
Safety of the current drug treatments for vitiligo
Published in Expert Opinion on Drug Safety, 2020
Torello Lotti, Komal Agarwal, Indrashis Podder, Francesca Satolli, Martin Kassir, Robert A Schwartz, Uwe Wollina, Stephan Grabbe, Alexander A Navarini, Simon M Mueller, Mohamad Goldust
Cyclosporine is an oral calcineurin inhibitory with a predominant immunomodulatory action. It was discovered and isolated from the fungus Tolypocladiuminflatum gams [17]. Common adverse effects of cyclosporine include renal dysfunction, hypertension, gingival hyperplasia, hyperkalemia, hyperuricemia, nausea, abdominal discomfort, tremor, headache, arthralgia, etc. The blood pressure, kidney function, and electrolytes especially potassium should be monitored at regular intervals while on cyclosporine therapy. Cyclosporine is absolutely contraindicated in uncontrolled hypertension, renal dysfunction, cutaneous T-cell lymphoma, present or past history of malignancies [17]. It is a pregnancy category C drug. It is excreted in breast milk and may interfere in cellular metabolism of nursing infant. Cyclosporine is relatively contraindicated in children less than 18 years of age but it has been used in 2–16 year age group for atopic dermatitis without any major adverse effects.
Related Knowledge Centers
- Immunosuppressive Drug
- Oral Administration
- Intravenous Therapy
- Rheumatoid Arthritis
- Psoriasis
- Crohn's Disease
- Nephrotic Syndrome
- Dermatitis
- Organ Transplantation
- Transplant Rejection