cyclosporine

cyclosporine /cy·clo·spor·ine/ (-spor´ēn) a cyclic peptide from an extract of soil fungi that selectively inhibits T cell function; used as an immunosuppressant to prevent rejection in organ transplant recipients and to treat severe psoriasis and severe rheumatoid arhtritis.

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cy·clo·spor·ine (skl-spôrn, -n) or cy·clo·spor·in A (-n)

n.

A cyclic oligopeptide immunosuppressant produced by fungus and used to inhibit organ transplant rejection.

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cyclosporine (sī´klōspor´ēn),

n brand name: Sandimmune;
drug class: immunosuppressant;
action: produces immunosuppression by inhibiting lymphocytes;
uses: to prevent rejection of tissues and/or organ transplants.

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cyclosporine

a neutral cyclic peptide, the major metabolic product of the fungus Tolypocladium inflatum; a specific suppressor of the T lymphocyte response, important in tissue transplantation.

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ciclosporin (cyclosporine) 

An immunosuppressant used in the treatment of the ocular manifestation of autoimmune diseases, uveitis, scleritis, keratoconjunctivitis sicca, ligneous conjunctivitis, and to prevent rejection of corneal grafts, etc. It is believed to exert its immunosuppressive effect by inhibiting the activation of cytotoxic T-lymphocytes. See immunosuppressants.

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cyclosporine Warning - Hazardous drug!

Gengraf, Neoral, Sandimmune

Pharmacologic class: Polypeptide antibiotic

Therapeutic class: Immunosuppressant

Pregnancy risk category C

FDA Boxed Warning

• Drug should be prescribed only by physicians experienced in managing systemic immunosuppressive therapy for indicated disease. At doses used for solid-organ transplantation, it should be prescribed only by physicians experienced in immunosuppressive therapy and management of organ transplant recipients. Patient should be managed in facility with adequate laboratory and medical resources. Physician responsible for maintenance therapy should have complete information needed for patient follow-up.
• Neoral may increase susceptibility to infection and neoplasia. In kidney, liver, and heart transplant patients, drug may be given with other immunosuppressants.
• Sandimmune should be given with adrenal corticosteroids but not other immunosuppressants. In transplant patients, increased susceptibility to infection and development of lymphoma and other neoplasms may result from increased immunosuppression.
• Sandimmune and Neoral aren't bioequivalent. Don't use interchangeably without physician supervision.
• In patients receiving Sandimmune soft-gelatin capsules and oral solution, monitor at repeated intervals (due to erratic absorption).

Action

Unclear. Thought to act by specific, reversible inhibition of immunocompetent lymphocytes in G₀-G₁ phase of cell cycle. Preferentially inhibits T lymphocytes; also inhibits lymphokine production. Ophthalmic action is unknown.

Availability

Capsules: 25 mg, 100 mg

Injection: 50 mg/ml

Oral solution: 100 mg/ml

Solution (ophthalmic): 0.05% (0.4 ml in 0.9 ml single-use vial)

⊘Indications and dosages

➣ Psoriasis

Adults: Neoral only - 1.25 mg/kg P.O. b.i.d. for 4 weeks. Based on patient response, may increase by 0.5 mg/kg/day once q 2 weeks, to a maximum dosage of 4 mg/kg/day.

➣ Severe active rheumatoid arthritis

Adults: Neoral only - 1.25 mg/kg P.O. b.i.d. May adjust dosage by 0.5 to 0.75 mg/kg/day after 8 weeks and again after 12 weeks, to a maximum dosage of 4 mg/kg/day. If no response occurs after 16 weeks, discontinue therapy. Gengraf only - 2.5 mg/kg P.O. daily given in two divided doses; after 8 weeks, may increase to a maximum dosage of 4 mg/kg/day.

➣ To prevent organ rejection in kidney, liver, or heart transplantation

Adults and children: Sandimmune only - Initially, 15 mg/kg P.O. 4 to 12 hours before transplantation, then daily for 1 to 2 weeks postoperatively. Reduce dosage by 5% weekly to a maintenance level of 5 to 10 mg/kg/day. Or 5 to 6 mg/kg I.V. as a continuous infusion 4 to 12 hours before transplantation.

➣ To increase tear production in patients whose tear production is presumed to be suppressed due to ocular inflammation associated with keratoconjunctivitis sicca

Adults: 1 drop in each eye b.i.d. given 12 hours apart

Off-label uses

• Aplastic anemia
• Atopic dermatitis

Contraindications

• Hypersensitivity to drug and any ophthalmic components
• Rheumatoid arthritis, psoriasis in patients with abnormal renal function, uncontrolled hypertension, cancer (Gengraf, Neoral)
• Active ocular infections (ophthalmic use)

Precautions

Use cautiously in:
• hepatic impairment, renal dysfunction, active infection, hypertension
• herpes keratitis (ophthalmic use)
• pregnant or breastfeeding patients
• children younger than age 16 (safety and efficacy not established for ophthalmic use).

Administration

• For I.V. infusion, dilute as ordered with dextrose 5% in water or 0.9% normal saline solution. Administer over 2 to 6 hours.
• Mix Neoral solution with orange juice or apple juice to improve its taste.
• Dilute Sandimmune oral solution with milk, chocolate milk, or orange juice. Be aware that grapefruit and grapefruit juice affect drug metabolism.
• In postoperative patients, switch to P.O. dosage as tolerance allows.
• Be aware that Sandimmune and Neoral aren't bioequivalent. Don't use interchangeably.
• Before administering eyedrops, invert unit-dose vial a few times to obtain a uniform, white, opaque emulsion.
• Know that eyedrops can be used concomitantly with artificial tears, allowing a 15-minute interval between products.

Route	Onset	Peak	Duration
P.O.	Unknown	1.5-3.5 hr	Unknown
I.V.	Rapid	1-2 hr	Unknown
Ophthal. (undetectable blood levels)	-	-	-

Adverse reactions

CNS: tremor, headache, confusion, paresthesia, insomnia, anxiety, depression, lethargy, weakness

CV: hypertension, chest pain, myocardial infarction

EENT: visual disturbances, hearing loss, tinnitus, rhinitis; (with ophthalmic use) ocular burning, conjunctival hyperemia, discharge, epiphora, eye pain, foreign body sensation, itching, stinging, blurring

GI: nausea, vomiting, diarrhea, constipation, abdominal discomfort, gastritis, peptic ulcer, mouth sores, difficulty swallowing, anorexia, upper GI bleeding, pancreatitis

GU: gynecomastia, hematuria, nephrotoxicity, renal dysfunction, glomerular capillary thrombosis

Hematologic: anemia, leukopenia, thrombocytopenia

Metabolic: hyperglycemia, hypomagnesemia, hyperuricemia, hyperkalemia, metabolic acidosis

Musculoskeletal: muscle and joint pain

Respiratory: cough, dyspnea, Pneumocystis jiroveci pneumonia , bronchospasm

Skin: acne, hirsutism, brittle fingernails, hair breakage, night sweats

Other: gum hyperplasia, flulike symptoms, edema, fever, weight loss, hiccups, anaphylaxis

Interactions

The following interactions pertain to oral and I.V. routes only.

Drug-drug. Acyclovir, aminoglycosides, amphotericin B, cimetidine, diclofenac, gentamicin, ketoconazole, melphalan, naproxen, ranitidine, sulindac, sulfamethoxazole, tacrolimus, tobramycin, trimethoprim, vancomycin: increased risk of nephrotoxicity

Allopurinol, amiodarone, bromocriptine, clarithromycin, colchicine, danazol, diltiazem, erythromycin, fluconazole, imipenem and cilastatin, itraconazole, ketoconazole, methylprednisolone, nicardipine, prednisolone, quinupristin/dalfopristin, verapamil: increased cyclosporine blood level

Azathioprine, corticosteroids, cyclophosphamide: increased immunosuppression

Carbamazepine, isoniazid, nafcillin, octreotide, orlistat, phenobarbital, phenytoin, rifabutin, rifampin, ticlopidine: decreased cyclosporine blood level

Digoxin: decreased digoxin clearance

Live-virus vaccines: decreased antibody response to vaccine

Lovastatin: decreased lovastatin clearance, increased risk of myopathy and rhabdomyolysis

Potassium-sparing diuretics: increased risk of hyperkalemia

Drug-diagnostic tests. Alanine aminotransferase, aspartate aminotransferase, bilirubin, blood urea nitrogen, creatinine, glucose, low-density lipoproteins: increased levels

Hemoglobin, platelets, white blood cells: decreased values

Drug-food. Grapefruit, grapefruit juice: decreased cyclosporine metabolism, increased cyclosporine blood level

High-fat diet: decreased drug absorption (Neoral)

Drug-herbs. Alfalfa sprouts, astragalus, echinacea, licorice: interference with immunosuppressant action

St. John's wort: reduced cyclosporine blood level, possibly leading to organ rejection

Patient monitoring

• Observe patient for first 30 to 60 minutes of infusion. Monitor frequently thereafter.
• Monitor cyclosporine blood level, electrolyte levels, and liver and kidney function test results.
• Assess for signs and symptoms of hyperkalemia in patients receiving concurrent potassium-sparing diuretic.

Patient teaching

• Advise patient to dilute Neoral oral solution with orange or apple juice (preferably at room temperature) to improve its flavor.
• Instruct patient to use glass container when taking oral solution. Tell him not to let solution stand before drinking, to stir solution well and then drink all at once, and to rinse glass with same liquid and then drink again to ensure that he takes entire dose.
• Tell patient taking Neoral to avoid high-fat meals, grapefruit, and grapefruit juice.
• Advise patient to dilute Sandimmune oral solution with milk, chocolate milk, or orange juice to improve its flavor.
• Instruct patient to invert vial a few times to obtain a uniform, white, opaque emulsion before using eyedrops and to discard vial immediately after use.
• Inform patient that eyedrops can be used with artificial tears but to allow 15-minute interval between products.
• Caution patient not to wear contact lenses because of decreased tear production; however, if contact lenses are used, advise patient to remove them before administering eyedrops and to reinsert 15 minutes after administration.
• Inform patient that he's at increased risk for infection. Caution him to avoid crowds and exposure to illness.
• Tell patient he'll need to undergo repeated laboratory testing during therapy.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, foods, and herbs mentioned above.

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cyclosporine

Immunology A cyclic undecapeptide, which induces potent T-cell immunosuppression; cyclosporine mitigates GVHD, allograft rejection, ulcerative colitis, autoimmune disease, schistosomiasis; it may be of use in aplastic anemia, in combination with antilymphocyte globulin and methylprednisone for psoriasis Adverse effects Nephrotoxicity, HTN, neurotoxicity–eg, tremor, seizures, encephalopathy, headache, coma, hyperlipidemia, hyperkalemia, hypomagnesemia, HTN, anemia, anaphylaxis, nausea, paresthesias, ↑ EBV, lymphoma, pseudolymphoma, fluid retention, thromboses, hirsutism, liver toxicity Lab ↑ Creatinine, ↑ uric acid, ↑ BR, ↑ cholesterol. Cf Tacrolimus.