Names and pronunciation
(sye′kloe-spor-een) Gengraf, Neoral, SandIMMUNE
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Drug reference
(sye′kloe-spor-een) Gengraf, Neoral, SandIMMUNE
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Func. class.: Immunosuppressant, antirheumatic (DMARD)
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Chem. class.: Fungus-derived peptide
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Do not confuse: cycloSPORINE/cycloSERINE/ cyclophosphamide
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ACTION: Produces immunosuppres- sion by inhibiting T lymphocytes
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USES: Organ transplants (liver, kid- ney, heart) to prevent rejection (GVHD), rheumatoid arthritis, psoriasis
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CONTRAINDICATIONS: Breast- feeding, hypersensitivity to polyoxyethyl- ated castor oil (injection only); psoriasis or RA in renal disease (Neoral/Gengraf); Gengraf/Neoral used with PUVA/UVB, meth- otrexate, coal tar; ocular infections
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Black Box Warning: Uncontrolled malig- nant hypertension Precautions: Pregnancy, geriatric patients, severe hepatic disease Black Box Warning: Immunosuppres- sion, nephrotoxicity, skin cancer; requires a specialized care setting and experi- enced clinician; infections; new primary malignancy (lymphoma, skin cancer) DOSAGE AND ROUTES—NTI Prevention of transplant rejection (nonmodified) (Sandimmune) • Adult/child: PO 15 mg/kg 4-12 hr prior to surgery, daily for 2 wk, reduce C dosage by 2.5 mg/kg/wk to 5-10 mg/kg/ day; IV 5-6 mg/kg 4-12 hr prior to sur- gery, daily, switch to PO form as soon as possible Prevention of transplant rejection (modified) (Neoral) • Adult/child: PO 4-12 mg/kg/day divided q12hr, depends on organ transplanted Rheumatoid arthritis (Neoral/ Gengraf) • Adult: PO 2.5 mg/kg/day divided bid, may increase 0.5-0.75 mg/kg/day after 8-12 wk, max 4 mg/kg/day; decrease dose by 25% in HTN Psoriasis (Neoral/Gengraf) • Adult: PO 2.5 mg/kg/day divided bid, × 4 wk, then increase by 0.5 mg/kg/day q2wk, max 4 mg/kg/day; decrease dose by 25% in HTN Autoimmune diseases (Sandimmune) • Adult/child: PO 1-3 mg/kg/day Black Box Warning: Nephrotoxicity: BUN, creatinine at least monthly during treatment, 3 mo after treatment; nephro- toxicity increases with increasing doses and duration of treatment • Product blood level during treatment 12 hr after dose, toxic >400 ng/mL • Hepatic studies: alkaline phosphatase, AST, ALT, bilirubin; hepatotoxicity: dark urine, jaundice, itching, light-colored stools; product should be discontinued • Serum lipids, magnesium, potassium, C cycloSPORINE blood concentrations, therapeutic cycloSPORINE range: 100- 400 mg/mL • Posterior reversible encephalopa- thy: impaired cognition, seizures, visual changes including blindness, loss of mo- tor function, movement disorders, and psychiatric changes; dosage reduction or discontinuation may be needed • Progressive multifocal leukoen- cephalopathy (PML): apathy, confusion, cognitive changes; may be fatal, withhold dose, notify prescriber immediately • Immunosuppression/infection: bacte- rial, viral, protozoal, and fungal infec- tions are common; assess for signs of infection often • Nephrotoxicity: Increased with in- creased doses and duration • Psoriasis: Lesions baseline and during treatment • RA: Pain, ROM, ADLs baseline and dur- ing treatment Black Box Warning: Requires a spe- cialized care setting and experienced clinician: product must be given in a fa- cility equipped with adequate laboratory and supportive medical services Black Box Warning: New primary ma- lignancy: lymphoma, skin cancer; in- creased risk in psoriasis with use of PUVA or UVB therapy, methotrexate, other im- munosuppressives, coal tar or radiation; these patients may be at increased risk of skin cancer also Black Box Warning: To limit UV exposure • That treatment is lifelong to prevent rejection; to identify signs of rejection • To report severe diarrhea because drug loss and rejection may result • About the signs of nephrotoxicity: in- creased B/P, tremors of the hands, changes in gums, increased hair on body, face • To continue with all lab work and follow-up appointments • That types of products are not inter- changeable • Not to wash syringe/container with water; variation in dose may result • To notify prescriber of all medica- tions, herbal products, supplements that are taken • Pregnancy/breastfeeding: to use contraceptive measures during treatment, for 12 wk after ending therapy; to notify prescriber if pregnancy is planned or sus- pected; no well-controlled studies; use only if benefits outweigh risks; discon- tinue breastfeeding or product HIGH ALERT
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SIDE EFFECTS CNS: Tremors, headache, seizures, pro- gressive multifocal leukoencephalopathy, confusion, migraine, paresthesia GI: Nausea, vomiting, diarrhea, oral can- dida, gum hyperplasia, hepatotoxicity, pancreatitis GU: Nephrotoxicity INTEG: Rash, acne, hirsutism META: Hyperkalemia, hypomagnesemia, hyperlipidemia, hyperuricemia MISC: Infection, gingival hyperplasia, hypersensitivity, malignancy
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INTERACTIONS Increase: action, toxicity of cycloSPO- RINE—allopurinol, amiodarone, ampho- tericin B, androgens, azole antifungals, beta-blockers, bromocriptine, calcium channel blockers, carvedilol, cimetidine, colchicine, corticosteroids, fluoroquino- lones, foscarnet, imipenem-cilastatin, macrolides, metoclopramide, oral con- traceptives, NSAIDs, melphalan, SSRIs Increase: effects of aliskiren, digoxin, etoposide, HMG-CoA reductase inhibitors, methotrexate, potassium-sparing diuret- ics, sirolimus, tacrolimus Increase: action, toxicity of—digoxin, colchicine Increase: hyperkalemia—potassium- sparing diuretics, potassium supplements, ACE inhibitors Increase: renal dysfunction—aminogly- cosides, ciprofloxacin, NSAIDs, fibric acid derivatives, vancomycin, melphalan, ketoconazole Decrease: cycloSPORINE action—anticon- vulsants, nafcillin, orlistat, PHENobarbital, phenytoin, rifamycins, sulfamethoxazole- trimethoprim, terbinafine, ticlopidine Decrease: antibody reaction—live virus vaccines Drug/Herb Decrease: immunosuppression—echi- nacea, melatonin; do not use together Decrease: cycloSPORINE levels—St. John’s wort; do not use together Drug/Food • Slowed metabolism of product— grapefruit juice, food
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Available forms: Oral solution 100 mg/ mL; soft gel capsule 25, 50, 100 mg; injection 50 mg/mL
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Administer: PO route • Some brands are not interchangeable • Do not break, crush, or chew cap- sules • Use pipette provided to draw up oral solution; may mix with milk or juice; wipe pipette, do not wash (Neoral) • For several days prior to transplant surgery; give at same time of day • With corticosteroids • With meals for GI upset or in choco- late milk, milk, or orange juice (SandIM- MUNE) Rheumatoid arthritis • Give Neoral or Gengraf 2.5 mg/kg/day divided bid; may use with salicylates, NSAIDs, PO corticosteroids • Always give the daily dose of Neoral/ Gengraf in 2 divided doses on consistent schedule Rejection prevention • Give initial SandIMMUNE PO dose 4-12 hr prior to transplantation as a sin- gle dose of 15 mg/kg, continue the single daily dose for 1-2 wk, then taper 5%/wk to a maintenance dose of 5-10 mg/kg/day Intermittent IV INFUSION route • After diluting each 50 mg/20-100 mL of 0.9% NaCl or D5W (2.5 mg/mL), run over 2-6 hr, use an infusion pump Continuous IV INFUSION route • May run over 24 hr • For SandIMMUNE parenteral, give 1 3 of PO dose, initial dose 4-12 hr before transplantation as a single IV dose 5-6 mg/kg/day, continue the single daily dose until PO can be used Y-site compatibilities: Abciximab, ala trofloxacin, alfentanil, amikacin, ami- nocaproic acid, aminophylline, ampho- tericin B lipid complex, anidulafungin, argatroban, ascorbic acid injection, atenolol, atracurium, atropine, azaTHIO- prine, aztreonam, benztropine, bivaliru- din, bleomycin, bretylium, bumetanide, buprenorphine, butorphanol, calcium chloride/gluconate, CARBOplatin, car- mustine, caspofungin, ceFAZolin, cefmetazole, cefonicid, cefotaxime, cefoTEtan, cefOXitin, cefTAZidime, ceftizox ime, cefTRIAXone, cefuroxime, chloram- phenicol, chlorproMAZINE, cimetidine, ciprofloxacin, CISplatin, clindamycin, codeine, cyanocobalamin, cyclophos- phamide, cytarabine, DACTINomycin, DAPTOmycin, DAUNOrubicin, dexameth- asone, dexmedetomidine, digoxin, diltia- ZEM, diphenhydrAMINE, DOBUTamine, DOCEtaxel, DOPamine, doripenem, dox- acurium, DOXOrubicin, doxycycline, enalaprilat, ePHEDrine, EPINEPHrine, epiRUBicin, epoetin alfa, eptifibatide, ertapenem, erythromycin, esmolol, eto- poside, famotidine, fenoldopam, fen- taNYL, fluconazole, fludarabine, fluoro- uracil, folic acid, furosemide, gallium, ganciclovir, gatifloxacin, gemcitabine, gentamicin, glycopyrrolate, granisetron, heparin, hydrocortisone, HYDROmor- phone, hydrOXYzine, ifosfamide, imipenem-cilastatin, indomethacin, iri- notecan, isoproterenol, ketorolac, labetalol, lansoprazole, levoFLOXacin, lidocaine, linezolid, LORazepam, manni- tol, mechlorethamine, meperidine, meropenem, methotrexate, methyldo- pate, methylPREDNISolone, metoclo- pramide, metoprolol, metroNIDAZOLE, micafungin, miconazole, midazolam, milrinone, minocycline, mitoXANTRONE, morphine, multiple vitamins injection, nafcillin, naloxone, nesiritide, netilmicin, nitroglycerin, nitroprusside, norepineph- rine, octreotide, ondansetron, oxacillin, oxaliplatin, oxytocin, PACLitaxel, palono- setron, pamidronate, pancuronium, pan- toprazole, papaverine, PEMEtrexed, pen- icillin G potassium/sodium, pentamidine, pentazocine, phentolamine, phe nylephrine, phytonadione, piperacillin, piperacillin-tazobactam, polymyxin B, potassium acetate/chloride, procain- amide, prochlorperazine, promethazine, propofol, propranolol, protamine, pyri- doxine, quiNIDine, quinupristin- dalfopristin, raNITIdine, ritodrine, sar- gramostim, sodium acetate/bicarbonate, succinylcholine, SUFentanil, tacrolimus, teniposide, theophylline, thiamine, thio- tepa, ticarcillin, ticarcillin-clavulanate, tigecycline, tirofiban, tobramycin, trimetaphan, urokinase, vancomycin, vaso- pressin, vecuronium, verapamil, vinCRIS- tine, vinorelbine, zoledronic acid
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Assess:
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Evaluate: • Therapeutic response: absence of re- jection; decreased pain in rheumatoid arthritis, decreased lesions in psoriasis
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CLINICAL CONSIDERATIONS
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Patient and caregiver information: • To report fever, chills, sore throat, fa- tigue since serious infections may occur; tremors, bleeding gums, increased B/P • To take at same time of day, every day; not to skip doses or double dose; not to use with grapefruit juice or receive vac- cines; that there are many drug interac- tions; not to add new products without approval of prescriber
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PHARMACOKINETICS Peak 4 hr; highly protein bound; half-life (biphasic) 1.2 hr, 25 hr; metabolized in liver; excreted in feces, 6% in urine; crosses placenta; excreted in breast milk
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