Sandimmune


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Related to Sandimmune: Altoprev

cycloSPORINE†

(sye-kloe-spor-een) ,

Gengraf

(trade name),

Neoral

(trade name),

SandIMMUNE

(trade name)

Classification

Therapeutic: immunosuppressants
Pharmacologic: polypeptides
Pregnancy Category: C
†See for ophthalmic use

Indications

Oral: Intravenous: Prevention and treatment of rejection in renal, cardiac, and hepatic transplantation (with corticosteroids). Oral: Treatment of severe active rheumatoid arthritis (Neoral only).Treatment of severe recalcitrant psoriasis in adult nonimmunocompromised patients (Neoral only).Management of recalcitrant ulcerative colitis.Treatment of steroid-resistant nephrotic syndrome.Treatment of severe steroid-resistant autoimmune disease.Prevention and treatment of graft vs. host disease in bone marrow transplant patients.

Action

Inhibits normal immune responses (cellular and humoral) by inhibiting interleukin-2, a factor necessary for initiation of T-cell activity.

Therapeutic effects

Prevention of rejection reactions.
Slowed progression of rheumatoid arthritis or psoriasis.

Pharmacokinetics

Absorption: Erratically absorbed (range 10–60%) after oral administration, with significant first-pass metabolism by the liver. Microemulsion (Neoral) has better bioavailability.
Distribution: Widely distributed, mainly into extracellular fluid and blood cells. Crosses the placenta; enters breast milk.
Protein Binding: 90–98%.
Metabolism and Excretion: Extensively metabolized by the liver by CYP3A4 (first pass); excreted in bile, small amounts excreted unchanged in urine.
Half-life: Children—7 hr; adults—19 hr.

Time/action profile (blood levels)

ROUTEONSETPEAKDURATION
POunknown†2–6 hrunknown
IVunknownend of infusionunknown
†Onset of action in rheumatoid arthritis is 4–8 wk and may last 4 wk after discontinuation; for psoriasis, onset is 2–6 wk and lasts 6 wk following discontinuation

Contraindications/Precautions

Contraindicated in: Hypersensitivity to cyclosporine or polyoxyethylated castor oil (vehicle for IV form); Obstetric / Lactation: Should not be given unless benefits outweigh risks;Disulfiram therapy or known alcohol intolerance (IV and oral liquid dose forms contain alcohol);Psoriasis patients receiving immunosuppressants or radiation;Renal impairment (in patients with rheumatoid arthritis or psoriasis)Uncontrolled hypertension.
Use Cautiously in: Severe hepatic impairment (dose ↓ recommended);Renal impairment (frequent dose changes may be necessary);Active infection; Pediatric: Larger or more frequent doses may be required.

Adverse Reactions/Side Effects

Central nervous system

  • posterior reversible encephalopathy syndrome (life-threatening)
  • progressive multifocal leukoencephalopathy (life-threatening)
  • seizures (life-threatening)
  • tremor (most frequent)
  • confusion
  • flushing
  • headache
  • psychiatric problems

Cardiovascular

  • hypertension (most frequent)

Gastrointestinal

  • hepatotoxicity (life-threatening)
  • diarrhea (most frequent)
  • nausea (most frequent)
  • vomiting (most frequent)
  • abdominal discomfort
  • anorexia
  • pancreatitis

Genitourinary

  • nephrotoxicity (most frequent)

Dermatologic

  • hirsutism (most frequent)
  • acne
  • psoriasis

Fluid and Electrolyte

  • hyperkalemia
  • hypomagnesemia

Hematologic

  • anemia
  • leukopenia
  • thrombocytopenia

Metabolic

  • hyperlipidemia
  • hyperuricemia

Neurologic

  • hyperesthesia
  • paresthesia

Miscellaneous

  • gingival hyperplasia (most frequent)
  • hypersensitivity reactions (most frequent)
  • infections (including activation of latent viral infections such as BK virus-associated nephropathy) (most frequent)
  • malignancy

Interactions

Drug-Drug interaction

Azithromycin,clarithomycin, allopurinol, amiodarone, bromocriptine, colchicine, danazol, digoxin, diltiazem, erythromycin, fluconazole, fluoroquinolones, imatinib, itraconazole, ketoconazole, voriconazole, metoclopramide, methylprednisolone, nefazodone, nicardipine, protease inhibitors, quinupristin/dalfopristin, verapamil, boceprevir, telaprevir, or hormonal contraceptives may ↑ serum levels and risk of toxicity.↑ immunosuppression with other immunosuppressants (cyclophosphamide, azathioprine, corticosteroids).Bosentan, carbamazepine, nafcillin, octreotide, orlistat, oxcarbazepine, phenobarbital, phenytoin, rifampin, rifabutin, or terbinafine, or ticlopidine may ↓ levels and effect.↑ risk of hyperkalemia with potassium-sparing diuretics, potassium supplements, or ACE inhibitors.May ↑ serum levels and risk of toxicity of aliskiren, ambrisentan, bosentan, colchicine, digoxin, etoposide, HMG-CoA reductase inhibitors, methotrexate, nifedipine, repaglinide, sirolimus May ↓ antibody response to live-virus vaccines and ↑ risk of adverse reactions; avoid concurrent use.Concurrent use with tacrolimus should be avoided.↑ risk of renal dysfunction with ciprofloxacin, aminoglycosides, vancomycin, trimethoprim/sulfamethoxazole, melphalan, amphotericin B, ketoconazole, colchicine, NSAIDS, cimetidine, ranitidine, or fibric acid derivatives Concomitant use with echinacea and melatonin may interfere with immunosuppression.Use with St. John’s wort may cause ↓ serum levels and organ rejection for transplant patients.Concurrent ingestion of grapefruit or grapefruit juice may ↑serum levels and should be avoided.Food ↓ absorption of microemulsion products (Neoral).

Route/Dosage

Doses are adjusted on the basis of serum level monitoringPrevention of Transplant Rejection (Sandimmune)
Oral (Adults and Children) 14–18 mg/kg/dose 4–12 hr before transplant then 5–15 mg/kg/day divided q 12–24 hr postoperatively, taper by 5% weekly to maintenance dose of 3–10 mg/kg/day.
Intravenous (Adults and Children) 5–6 mg/kg/dose 4–12 hr before transplant, then 2–10 mg/kg/day in divided doses q 8–24 hr; change to PO as soon as possible.
Prevention of Transplant Rejection (Neoral)
Oral (Adults and Children) 4–12 mg/kg/day divided q 12 hr (dose varies depending on organ transplanted).
Rheumatoid Arthritis (Neoral only)
Oral (Adults and Children) 2.5 mg/kg/day given in 2 divided doses; may ↑ by 0.5–0.75 mg/kg/day after 8 and 12 wk, up to 4 mg/kg/day. ↓ dose by 25–50% if adverse reactions occur.
Severe Psoriasis (Neoral only)
Oral (Adults) 2.5 mg/kg/day given in 2 divided doses, for at least 4 wk; then may ↑ by 0.5 mg/kg/day q 2 wk, up to 4 mg/kg/day. ↓ dose by 25–50% if adverse reactions occur.
Autoimmune Diseases (Neoral only)
Oral (Adults and Children) 1–3 mg/kg/day.

Availability (generic available)

Microemulsion soft gelatin capsules (Gengraf, Neoral): 25 mg, 50 mg, 100 mg
Microemulsion oral solution (Gengraf, Neoral): 100 mg/mL
Soft gelatin capsules (Sandimmune): 25 mg, 100 mg
Oral solution (Sandimmune): 100 mg/mL
Injection (Sandimmune): 50 mg/mL

Nursing implications

Nursing assessment

  • Monitor serum creatinine level, intake and output ratios, daily weight, and BP during therapy. Report significant changes.
  • Assess for any new signs or symptoms that may be suggestive of progressive multifocal leukoencephalopathy (PML), an opportunistic infection of the brain caused by the Jakob Cruzfeldt (JC) virus, that may be fatal; withhold dose and notify health care professional promptly. PML symptoms may begin gradually (hemiparesis, apathy, confusion, cognitive deficiencies, and ataxia) and may include deteriorating renal function and renal graft loss.
  • Monitor for signs and symptoms of posterior reversible encephalopathy syndrome (PRES) (impaired consciousness, convulsions, visual disturbances including blindness, loss of motor function, movement disorders and psychiatric disturbances, papilloedema, visual impairment). Usually reversible with discontinuation of cyclosporine. Occurs more often in patients with liver transplant than kidney transplant.
  • Prevention of Transplant Rejection: Assess for symptoms of organ rejection throughout therapy.
  • Intravenous: Monitor patient for signs and symptoms of hypersensitivity (wheezing, dyspnea, flushing of face or neck) continuously during at least the first 30 min of each treatment and frequently thereafter. Oxygen, epinephrine, and equipment for treatment of anaphylaxis should be available with each IV dose.
  • Arthritis: Assess pain and limitation of movement prior to and during administration.
    • Prior to initiating therapy, perform a physical exam including BP on 2 occasions to determine baseline. Monitor BP every 2 wk during initial 3 mo, then monthly if stable. If hypertension occurs, dose should be reduced.
  • Psoriasis: Assess skin lesions prior to and during therapy.
  • Lab Test Considerations: Measure serum creatinine, BUN, CBC, magnesium, potassium, uric acid, and lipids at baseline, every 2 wk during initial therapy, and then monthly if stable. Nephrotoxicity may occur; report significant increases.
    • May cause hepatotoxicity; monitor for ↑ AST, ALT, alkaline phosphatase, amylase, and bilirubin.
    • May cause ↑ serum potassium and uric acid levels and ↓ serum magnesium levels.
    • Serum lipid levels may be ↑.
  • Evaluate serum cyclosporine levels periodically during therapy. Dose may be adjusted daily, in response to levels, during initiation of therapy. Guidelines for desired serum levels will vary among institutions.

Potential Nursing Diagnoses

Chronic pain (Indications)
Risk for infection (Side Effects)

Implementation

  • Do not confuse cycloSPORINE with cyclophosphamide or cycloSERINE. Do not confuse Sandimmune with Sandostatin.
    • Given with other immunosuppressive agents. Protect transplant patients from staff and visitors who may carry infection. Maintain protective isolation as indicated.
    • Microemulsion products (Neoral) and other products (Sandimmune) are not interchangeable.
  • Oral: Draw up oral solution in the pipette provided with the medication. Mix oral solution with milk, chocolate milk, apple juice, or orange juice, preferably at room temperature. Stir well and drink at once. Use a glass container and rinse with more diluent to ensure that total dose is taken. Administer oral doses with meals. Wipe pipette dry; do not wash after use.
  • Intravenous Administration
  • pH: No Data.
  • Intermittent Infusion: Diluent: Dilute each 1 mL (50 mg) of IV concentrate immediately before use with 20–100 mL of D5W or 0.9% NaCl for injection. Solution is stable for 24 hr in D5W. In 0.9% NaCl, it is stable for 6 hr in a polyvinylchloride container and 12 hr in a glass container at room temperature.Concentration: 2.5 mg/mL.
  • Rate: Infuse slowly over 2–6 hr via infusion pump.
  • Continuous Infusion: May be administered over 24 hr.
  • Y-Site Compatibility: alemtuzumab, alfentanil, amikacin, aminocaproic acid, aminophylline, amphotericin B lipid complex, anidulafungin, argatroban, ascorbic acid, atracurium, atropine, azathioprine, aztreonam, benztropine, bivalirudin, bleomycin, bumetanide, buprenorphine, butorpohanol, calcium chloride, calcium gluconate, carboplatin, carmustine, caspofungin, cefazolin, cefoperazone, cefotaxime, cefotetan, cefoxitin, ceftaroline, ceftazidime, ceftriaxone, cefuroxime, chloramphenicol, chlorpromazine, cisplatin, clindamycin, cyclophosphamide, cytarabine, dactinomycin, daptomycin, dexamethasone, dexmedetomidine, dexrazoxane, digoxin, diltiazem, diphenhydramine, dobutamine, docetaxel, dopamine, doripenem, doxacurium, doxarubicin hydrochloride, doxorubicin liposomal, doxycycline, enalaprilat, ephedrine, epinephrine, epirubicin, epoetin alfa, ertapenem, erythromycin, esmolol, etoposide, etoposide phosphate, famotidine, fenoldopam, fentanyl, fluconazole, fludarabine, fluorouracil, folic acid, foscarnet, furosemide, ganciclovir, gemcitabine, gentamicin, glycopyrrolate, granisetron, heparin, hetastarch, hydrocortisone, hydromorphone, ifosfamide, imipenem/cilastatin, indomethacin, irinotecan, isoproterenol, ketorolac, labetalol, leucovorin calcium, levofloxacin, lidocaine, linezolid, lorazepam, mannitol, mechlorethamine, meperidine, meropenem, metaraminol, methotrexate, methyldopate, methylprednisolone, metoclopramide, metoprolol, metronidazole, micafungin, midazolam, milrinone, mitoxantrone, morphine, moxifloxacin, multivitamins, nafcillin, naloxone, nesiritide, nicardipine, nitroglycerin, nitroprusside, norepinephrine, octreotide, ondansetron, oxacillin, oxaliplatin, oxytocin, paclitaxel, palonosetron, pamidronate, pancuronium, papaverine, pemetrexed, penicillin G,, pentamidine, pentazocine, phentolamine, phenylephrine, phytonadione, piperacillin/tazobactam, potassium acetate, potassium chloride, prochlorperazine, promethazine, propofol, propranolol, protamine, pyridoxime, quinupristin/dalfopristin, ranitidine, sargramostim, sodium acetate, sodium bicarbonate, streptokinase, succinylcholine, sufentanil, tacrolimus, teniposide, theophylline, thiamine, thiotepa, ticarcillin/clavulanate, tigecycline, tirofiban, tobramycin, tolazoline, vancomycin, vasopressin, vecuronium, verapamil, vinblastine, vincristine, vinorelbine, zoledronic acid
  • Y-Site Incompatibility: amphotericin B cholesteryl, amphotericin B liposome, cyanocobalamin, dantrolene, diazepam, diazoxide, idarubicin, pentobarbital, phenobarbital, phenytoin, rituximab, trastuzumab, trimethoprim/sulfamethoxazole, voriconazole

Patient/Family Teaching

  • Instruct patient to take medication at the same time each day with meals, as directed. Do not skip doses or double up on missed doses. Take missed doses as soon as remembered within 12 hr. Do not discontinue medication without advice of health care professional.
  • Reinforce the need for lifelong therapy to prevent transplant rejection. Review symptoms of rejection for transplanted organ, and stress need to notify health care professional immediately if they occur.
  • Instruct patients and/or parents to notify health care professional if diarrhea develops; decreases absorption of cyclosporine and can result in rejection.
  • Instruct patient to avoid grapefruit and grapefruit juice to prevent interaction with cyclosporine.
  • Advise patient of common side effects (nephrotoxicity, increased BP, hand tremors, increased facial and body hair, gingival hyperplasia). Advise patients that if hair growth is excessive, depilatories or waxing can be used.
  • Teach patient the correct method for monitoring BP. Instruct patient to notify health care professional of significant changes in BP or if hematuria, increased frequency, cloudy urine, decreased urine output, fever, sore throat, tiredness, or unusual bruising occurs.
  • Instruct patient on proper oral hygiene. Meticulous oral hygiene and dental examinations for teeth cleaning and plaque control every 3 mo will help decrease gingival inflammation and hyperplasia.
  • Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking other Rx, OTC, or herbal products or receiving any vaccinations while taking this medication.
  • Advise patient to notify health care professional if pregnancy is planned or suspected, or if breast feeding.
  • Emphasize the importance of follow-up exams and lab tests.

Evaluation/Desired Outcomes

  • Prevention of rejection of transplanted tissues.
  • Decrease in severity of pain.
    • Increased ease of joint movement.
  • Decrease in progression of psoriasis.

Sandimmune

(săn′dĭ-myo͞on′)
A trademark for the drug cyclosporine.

Sandimmune®

Cyclosporin, see there.
References in periodicals archive ?
Novartis Pharmaceuticals Corporation, the maker of the most widely used immunosuppressive drugs in the world - Neoral and Sandimmune - has sued the US Food and Drug Administration's (FDA) process in approving a generic form of cyclosporine.
The Sandimmune formulation of CSA was used because it produces lower blood CSA concentrations than the Neoral preparation and would thus, by combining the data from studies 1 and 2, allow examination of the effects of CSA over a broader range of CSA concentrations.
Effect of assay methodology on pharmacokinetic differences between cyclosporine Neoral and Sandimmune formulations.
The paper highlights that the intravenous cyclosporine formulation CicloMulsion demonstrates bioequivalence and improved tolerability when compared with Sandimmune Injection.
Effect of Sandimmune cyclosporine on renal blood flow and function in heart transplant recipients.
Approximately 90% of the patients on Sandimmune, the older formulation of cyclosporine first introduced in 1983, have switched to Neoral, the newer, less expensive and more bioavailable formulation introduced in Europe (1994).
The results of several human trials in healthy volunteers and transplant recipients demonstrated that SangCya was more bioavailable and less variable than Sandimmune, and bioequivalent to Novartis' Neoral, an immunosuppressant used by the majority of transplant recipients worldwide and required daily for their lifetime.
The majority of all newly transplanted patients are started on the more bioavailable cyclosporine formulations, and more than 90% of European and approximately 70% of US transplant recipients previously on Sandimmune have been converted to Neoral.
3) Nonstandard abbreviations: TDM, therapeutic drug monitoring; CsA-S, -N, cyclosporine Sandimmune, Neoral; PK, pharmacokinetics; AUC, area under the curve; FPIA, fluorescence polarization immunoassay; and SDI, standard deviation intervals.
Cyclosporine, the leading immunosuppressive drug used to prevent graft rejection in transplantation, is marketed by SangStat as SangCya and by Novartis in two different formulations, Sandimmune and Neoral, and two different dosage forms, oral solution and capsules.