Cyclosporine

Table of contents

  • Brand Names
  • Chemistry
  • Pharmacologic Category
  • Mechanism of Action
  • Therapeutic Use
  • Unlabeled Use
  • Pregnancy and Lactation Implications
  • Contraindications
  • Warnings and Precautions
  • Adverse Reactions
  • Caution and personalized dose adjustment in patients with the following genotypes
  • Other genes that may be involved
  • Substrate of
  • Inhibits
  • Induces
  • Drug Interactions
  • Nutrition/Nutraceutical Interactions
  • Dosage
  • Pharmacokinetics and Pharmacodynamics
  • Special Considerations

Brand Names

Europe

Austria: CicloralHexal, Neoimmun, Sandimmun; Belgium: Sandimmun; Bulgaria: Equoral, Sandimmun; Cyprus: Sandimmun; Czech Republic: Ciclosporin, Cyclaid, Equoral, Sandimmun, Sigmasporin; Denmark: Sandimmun; Estonia: Ciclosporin, Equoral, Sandimmun; Finland: Sandimmun; France: Neoral, Sandimmun; Germany: Cicloral, Ciclosporin, Deximune, Immunosporin, Neoral, Sandimmun; Greece: Neoral, Sandimmun; Ireland: Ciclosporin, Deximune, Neoral, Sandimmun; Italy: Sandimmun; Latvia: Ciclosporin, Equoral, Sandimmun; Lithuania: CicloralHexal, Ciclosporin, Equoral, Sandimmun; Malta: Sandimmun; Netherlands: Ciclosporine, Neoral, Sandimmune; Poland: Equoral, Gengraf, Sandimmun; Portugal: Ciclosporina, Ciclostar, Sandimmun; Romania: Cicloral, Ciclosporina, Equoral, Imusporin, Sandimmun; Slovakia: Ciclosporin, Equoral, Sandimmun; Slovenia: Ciklosporin, Sandimmun; Spain: Sandimmun; Sweden: Cyclosporin, Sandimmun; UK: Deximune, Neoral, Sandimmun.

North America

Canada: Cyclosporine, Neoral, Sandimmune; USA: Cyclosporine, Gengraf, Neoral, Restasis, Sandimmune.

Latin America

Argentina: Cermox, Lacrinmune, Restasis, Sandimmun, Sigmasporin; Brazil: Gengraf, Restasis, Sandimmun, Sigmasporin; Mexico: Immulen, Modisik-A, Restasis, Sandimmun, Supremunn.

Asia

Japan: Amadra, Cicporal, Neomerck, Neoral, Papilock Mini, Sandimmun.

Drug combinations

Chemistry

Cyclosporine: C~62~H~111~N~11~O~12~. Mw: 1202.61. (1) Cyclosporine A; (2) Cyclo[[(E)-(2S,3R,4R)-3-hydroxy-4-methyl-2-(methylamino)-6-octenoyl]-L-2-aminobutyryl-N-methylglycyl-N-methyl-L-leucyl-L-valyl-N-methyl-L-leucyl-L-alanyl-D-alanyl-N-methyl-L-leucyl-N-methyl-L-leucyl-N-methyl-L-valyl]; (3) [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-a-aminobutyryl-N-methylglycyl-N-methyl-L-leucyl-L-valyl-N-methyl-L-leucyl). CAS-59865-13-3 (1981).

Pharmacologic Category

Biologic Response Modifiers. Disease-modifying Antirheumatic Drugs. Immunosuppressive Agents. EENT Anti-inflammatory Agents, Miscellaneous. (ATC-Code: L04AD01; S01XA18).

Mechanism of action

Inhibition of production and release of interleukin II and inhibition of interleukin II-induced activation of resting T-lymphocytes. Exact mechanism of action not fully elucidated, but thought to act as a partial immunomodulator with anti-inflammatory effects when administered topically to the eye. Exhibits immunosuppressive activity when administered systemically. Appears mainly to involve inhibition of lymphocytic proliferation and function. Produces nephrotoxic effects (generally dose-dependent and reversible).

Therapeutic use

Prophylaxis of organ rejection in kidney, liver, and heart transplants. Severe, active rheumatoid arthritis not responsive to methotrexate alone. Severe, recalcitrant plaque psoriasis in nonimmunocompromised adults. As ophthalmic emulsion increases tear production in keratoconjunctivitis sicca-associated ocular inflammation.

Pregnancy and lactiation implications

Reproductive toxicity in animal studies. Mutagenic and teratogenic effects not observed following oral administration. In humans, cyclosporine crosses the placenta. Use only if the benefit to the mother outweighs the possible risks to the fetus. Not recommended during lactation.

Unlabeled use

Short-term, high-dose cyclosporine as a modulator of multidrug resistance in cancer treatment. Allogenic bone marrow transplants. Severe autoimmune diseases (e.g. SLE, myasthenia gravis, inflammatory bowel disease) which are resistant to corticosteroids and other therapy. Focal segmental glomerulosclerosis.

Contraindications

Hypersensitivity to cyclosporine or any component of the formulation. Abnormal renal function, uncontrolled hypertension, and malignancies are contraindications if rheumatoid arthritis and psoriasis. Concomitant treatment with PUVA or UVB therapy, methotrexate, other immunosuppressive agents, coal tar, or radiation therapy are contraindications if psoriasis. Ophthalmic emulsion is contraindicated in active ocular infections.

Warnings and precautions

Risk of increased hepatic enzymes and bilirubin (when used at high doses). May cause hypertension. Increased risk of infection. Increased risk of lymphomas and other malignancies (mainly in skin). Renal impairment has occurred. In transplant patients to be used initially with corticosteroids. May cause significant hyperkalemia and hyperuricemia. May cause seizures (higher risk if adjuvant high-dose corticosteroids). Encephalopathy reported (higher risk if hypertension, hypomagnesemia, hypocholesterolemia, high-dose corticosteroids, high cyclosporine serum concentration, graft vs host disease, or liver transplant). Anaphylaxis reported with I.V. use. Products may contain corn oil, ethanol, or propylene glycol. Live, attenuated vaccines may be less effective (use should be avoided). Cyclosporine metabolites cross-react with radioimmunoassay and fluorescence polarization immunoassay.

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