Gengraf, Neoral, Sandimmune, Restasis
Classifications: immunosuppressant; Therapeutic: immunosuppressant; antirheumatic; antipsoriatic
Pregnancy Category: C
Sandimmune: 25 mg, 50 mg, 100 mg capsules; 100 mg/mL oral solution;
Gengraf, Neoral: (microemulsion) 25 mg, 100 mg capsules; 100 mg/mL oral solution; 50 mg/mL injection;
Restasis: 0.05% ophthalmic emulsion
Has immunosuppressant action by reducing transplant rejection due to selective and reversible inhibition of the first phase
of T-cell activation with T-lymphocytes (which normally stimulate antibody production).
It is used to prevent allograft rejection in transplant patients. Additionally, it is a disease-modifying antirheumatic
In conjunction with adrenal corticosteroids to prevent organ rejection after kidney, liver, and heart transplants (allografts).
Has had limited use in pancreas, bone marrow, and heart/lung transplantations. Also used for treatment of chronic transplant
rejection in patients previously treated with other immunosuppressants; rheumatoid arthritis, severe psoriasis. Ophthalmic
emulsion for the treatment of keratoconjunctivitis sicca.
Sjögren's syndrome, to prevent rejection of heart-lung and pancreatic transplants, ulcerative colitis.
Hypersensitivity to cyclosporine or to ingredients in commercially available formulations [e.g., Cremophor (polyoxyl 35
castor oil)]; recent contact with or bout of chickenpox, herpes zoster; administration of live virus vaccines to patient
or family members; RA patients with abnormal renal function, uncontrolled hypertension, or malignancies; ocular infection,
pregnancy (category C), lactation.
Renal, hepatic, pancreatic, or bowel dysfunction; biliary tract disease, jaundice, hyperkalemia; electrolyte imbalance,
hyperuricemia, hypertension; infection; radiation therapy, older adults, encephalopathy, females of childbearing age, fungal
or viral infection, gout, herpes infection, lymphoma, neoplastic disease, malabsorption problems (e.g., liver transplant
Route & Dosage
|Prevention of Organ Rejection
Adult/Child: PO 1418 mg/kg beginning 412 h before transplantation and continued for 12 wk after surgery, then gradual
reduction by 5%/wk, max dose of microemulsion, 10 mg/kg/d; Maintenance 510 mg/kg/d. IV 56 mg/kg beginning 412 h before transplantation and continued after surgery until patient can take oral
Rheumatoid Arthritis (Neoral)
Adult: PO 2.5 mg/kg/d divided into 2 doses. May increase by 0.50.75 mg/kg/d q4wk to a max of 4 mg/kg/d
Severe Psoriasis (Neoral)
Adult: PO 1.25 mg/kg b.i.d. If significant improvement has not occurred after 4 wk, may increase dose by 0.5 mg/kg/d every 2 wk to
max of 4 mg/kg/d
Adult: Ophthalmic 1 drop in affected eye(s) twice daily approximately 12 h apart
- Do not dilute oral solution with grapefruit juice. Dilute with orange or apple juice, stir well, then administer immediately.
- Neoral (microemulsion) and Sandimmune are not bioequivalent and cannot be used interchangeably without physician supervision.
PREPARE: IV Infusion: Dilute each 1 mL immediately before administration in 20100 mL of D5W or NS.
ADMINISTER: IV Infusion: Give by slow infusion over approximately 26 h. Rapid IV can result in nephrotoxicity.
INCOMPATIBILITIES Solution/additive: Magnesium sulfate. Y-site: Amphotericin B cholesteryl complex, TPN.
- Store preferably at 15°30° C (59°86° F) in well-closed containers. Do not refrigerate. Protect
ampules from light.
Adverse Effects (≥1%)Body as a Whole: Lymphoma
, gynecomastia, chest pain, leg cramps, edema, fever, chills, weight loss, increased risk of skin malignancies in
patients previously treated with methotrexate, psoralens, or UV light therapy. CV: Hypertension, MI
, nausea, vomiting,
abdominal discomfort, anorexia, gastritis
. Hematologic: Leukopenia
, hypermagnesemia, hyperkalemia,
hyperuricemia, decreased serum bicarbonate,
hyperglycemia. CNS: Tremor,
convulsions, headache, paresthesias, hyperesthesia, flushing, night sweats, insomnia
, visual hallucinations, confusion,
anxiety, flat affect, depression
, lethargy, weakness, paraparesis, ataxia, amnesia. Skin: Hirsutism, acne
, oily skin, flushing. Special Senses: Sinusitis
, tinnitus, hearing loss, sore throat
Urinary retention, frequency, nephrotoxicity (oliguria).
Diagnostic Test Interference
Hyperlipidemia and abnormalities in electrophoresis reported; believed to be due to polyoxyl 35 castor oil (Cremophor) in IV cyclosporine.
, danazol, diltiazem, doxycycline, erythromycin, ketoconazole, methylprednisolone, metoclopramide, nicardipine, nsaids
, prednisolone, verapamil
may increase cyclosporine levels; carbamazepine, isoniazid, octreotide, phenobarbital, phenytoin, rifampin
may decrease cyclosporine levels; acyclovir, aminoglycosides
, amphotericin B, cimetidine, erythromycin, ketoconazole, melphalan, ranitidine, cotrimoxazole, trimethoprim
may increase risk of nephrotoxicity; potassium-sparing diuretics
, ace inhibitors (captopril, enalapril)
may potentiate hyperkalemia. Food: Grapefruit juice
may increase concentration. Herbal: St. John's wort
may decrease cyclosporine levels.
Variably and incompletely absorbed (30%). Microemulsion formulation (Neoral) has less variability in absorption and
may produce significantly higher serum
levels compared with the standard formulation. Peak:
34 h. Distribution:
Widely distributed; 3347% distributed to plasma
; 4150% to RBCs; crosses placenta; distributed into breast
In liver by CYP3A4, including significant first pass metabolism
; considerable enterohepatic circulation. Elimination:
Primarily in bile and feces; 6% in urine. Half-Life:
Assessment & Drug Effects
- Observe patients receiving the drug parenterally for at least 30 min continuously after start of IV infusion, and at frequent
intervals thereafter to detect allergic or other adverse reactions.
- Hypersensitivity reactions have been associated with Cremophor emulsifying agent in the parenteral formulation but not with
the PO solution, which does not contain this ingredient.
- Monitor I&O ratio and pattern: Nephrotoxicity has been reported in about one third of transplant patients. It has occurred
in mild forms as late as 23 mo after transplantation. In severe form, it can be irreversible, and therefore early recognition
- Monitor vital signs. Be alert to indicators of local or systemic infection that can be fungal, viral, or bacterial. Also
report significant rise in BP.
- Lab tests: Baseline and periodic tests are advised for (1) renal function (BUN, serum creatinine), (2) liver function (AST,
ALT, serum amylase, bilirubin, and alkaline phosphatase), and (3) serum potassium.
- Lab tests: In psoriasis patients, CBC, BUN, uric acid, potassium, lipids, and magnesium should be monitored biweekly during
first 3 mo.
- Periodic tests should be made of neurologic function. Neurotoxic effects generally occur over 13195 d after initiation
of cyclosporine therapy. Signs and symptoms are reportedly fully reversible with dosage reduction or discontinuation of
- Monitor blood or plasma drug concentrations at regular intervals, particularly in patients receiving the drug orally for
prolonged periods, as drug absorption is erratic.
Patient & Family Education
- Use the specially calibrated pipette provided to measure dose.
- Take medication with meals to reduce nausea or GI irritation.
- Enhance palatability of oral solution by mixing it with milk, chocolate milk, or orange juice, preferably at room temperature.
Mix in a glass rather than a plastic container. Stir well, drink immediately, and rinse glass with small quantity of diluent
to assure getting entire dose.
- Take medication at same time each day to maintain therapeutic blood levels.
- Keep scheduled follow-up appointments.
- If possible, see a dentist before start of cyclosporine treatment, and practice good oral hygiene. Inspect mouth daily for
white patches, sores, swollen gums.
- Hirsutism is reversible with discontinuation of drug.