has been restored. Longer waiting periods may be required for drugs that maintain their immunosuppressive effects for more than 3 months after discontinuation (eg, ocrelizumab). . >10% Tremor (12-55%) Nephrotoxicity (32%) Hypertension (26%) Infection (3-25%) Headache (2-25%) Nausea (23%) Hirsutism (21%) Hypertrichosis (5-19%) Female reproductive disorder (5-19%) Gum hyperplasia (2-16%) Triglycerides increased (15%) Abdominal discomfort (1-15%) URI (1-14%) Diarrhea (3-13%) Dyspepsia (2-12%) Leg cramps (2-12%) Parathesia (1-11%) 1-10% Acne Convulsions Pruitus Hyperkalemia, hypomagnesemia Pancreatitis Hepatotoxicity Flu-like syndrome Frequency Not Defined Leukopenia Thrombocytopenia Anaphylaxis Glomerular capillary thrombosis Hypomagnesemia Migraine Hyponatremia Postmarketing Reports Pain in lower extremities Black Box Warnings Should be prescribed only by physicians who have experience with immunosuppression in solid organ transplant recipients and can provide necessary follow-up and appropriate monitoring Coadministration with other immunosuppressants in kidney, liver, and heart transplant recipients, but risk of infection and neoplasia may be increased Increased risk for development of lymphomas and other malignancies, particularly those of the skin; avoid excess UV light exposure Increased risk appears related to the intensity and duration of immunosuppression rather than to the use of specific agents; oversuppression of the immune system may result in infection or malignancy; caution with regimens containing multiple immunosuppressants Sandimmune and Neoral are not bioequivalent and should not be interchanged without physician approval; Neoral (capsules and oral solution) has increased bioavailability compared with Sandimmune (capsules and oral solution) For a given trough concentration, cyclosporine exposure will be greater with Neoral than with Sandimmune Sandimmune has decreased bioavailability compared with Neoral and erratic absorption; requires careful monitoring of blood levels and subsequent dosage adjustments Patients with psoriasis who have been treated with PUVA, methotrexate or immunosuppressants, UVB, coal tar, or radiation are at increased risk for skin malignancies, hypertension, and renal dysfunctionContraindications Hypersensitivity Breastfeeding (RA/Psoriasis use): Abnormal renal function, uncontrolled HTN, malignancies (Psoriasis use) Concomitant PUVA, UVB radiation, coal tar, methotrexate, other immunosuppressants Cautions Injection: monitor closely for at least 30 min Risk of hepatotoxicity and nephrotoxicity Myelosuppression may be severe and prolonged; monitor complete blood and platelet counts Potential increase risk for optic disk edema and infusion-related anaphylactic reactions Some malignancies caused by cyclosporine immunosuppression may be fatal (eg, lymphoma) Serious and fatal cerebral, gastrointestinal and pulmonary hemorrhage; monitor platelets and coagulation parameters and treat accordingly Anticipate and monitor for signs and symptoms of tumor lysis syndrome occur; treat promptly Monitor for and discontinue promptly if systemic inflammatory response or capillary leak syndrome suspected Monitor for signs and symptoms of infection; severe and fatal sepsis as a result of bone marrow suppression; discontinue therapy promptly if infection occur Monitor for and discontinue if venous occlusive disease of the liver suspected Monitor liver enzymes and discontinue therapy at first signs of severe hepatotoxicity; fatal hepatotoxicity may occur Monitor renal function and interrupt or discontinue if creatinine levels increase or acute renal failure occur Increased risk for serious infection with fatal outcome because of immunosuppression, including activation of latent viruses, eg, BK virus-induced nephropathy Patients with psoriasis who received coal tar, PUVA, methotrexate, or other immunosuppressants have higher risk of skin cancer with Neoral Discontinue therapy if exfoliative or bullous rash suspected or if Stevens-Johnson syndrome or toxic epidermal necrolysis suspected Monitor for signs and symptoms of enterocolitis and treat promptly Extensively metabolized by CYP3A isoenzymes, in particular CYP3A4, and is a substrate of the multidrug efflux transporter P-glycoprotein (P-gp); various agents are known to either increase or decrease plasma or whole blood of cyclosporine levels usually by inhibition or induction of CYP3A4 or P-gp or both Occasionally, patients develop a syndrome of thrombocytopenia and thrombotic microangiopathic hemolytic anemia may result in graft failure Significant hyperkalemia and hyperuricemia may occur Neurotoxicity may occur, particularly with high dose methylprednisolone; caution with other drugs that may cause neurotoxicity Mild or moderate hypertension and rarely severe hypertension may occur; incidence decreases over time; antihypertensive therapy may be required in recipients of kidney, liver, and heart allografts treated with cyclosporine; potassium-sparing diuretics should not be used to treat cyclosporine associated hypertension as cyclosporine may cause hyperkalemia; calcium antagonists can be effective but can interfere with cyclosporine metabolism Gingival hyperplasia may occur; avoid concomitant nifedipine administration in patients who develop gingival hyperplasia Seizures may occur when used in combination with high-dose corticosteroids Pregnancy Category: C; take into consideration alcohol content of various cyclosporine formulations Lactation: excreted in breast milk, do not nursePregnancy Categories A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk. B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available. Mechanism of Action Calcineurin inhibitor Suppresses cellular and humoral immunity (mainly T cells) Absorption Bioavailability: Neoral >Sandimmune Peak plasma time: Neoral 1.5-2 hr; Sandimmune 3.5 hr Onset: unknown Duration: unknown Distribution Protein Bound: 90% Vd: 13 L/kg Metabolism Via hepatic CYP3A4 Metabolites: AM1, AM9, AM4N Enzymes inhibited: CYP3A4 and P-gp Elimination Half-Life: 8.4-27 hr Clearance: 5-7 mL/min/kg Excretion: Mainly bile and feces; 6% urine Pharmacogenomics Substrate of CYP3A4 and CYP3A5 Genetic variant in CYP3A4 containing an A- to G- mutation (called CYP3A4-V or CYP3A4*1B) is associated with impaired enzyme activity Frequency of this mutation is 4% in the white population, but 67% in the black population This may be important in the early postsurgical phase when trying to establish adequate therapeutic serum levels IV Incompatibilities Additive: MgSO4 Y-site: amphotericin B cholesteryl sulfate IV Compatibilities Solution: NS, D5W Additive: ciprofloxacin Y-site: gatifloxacin, linezolid, propofol, sargramostim IV Preparation Dilute 1 mL (50 mg) of concentrated inj soln in 20-100 mL of D5W or NS Stability of injection of parenteral admixture at room temp (25°C) is 6 hr in PVC; 24 hr in Excel, PAB containers, or glass Polyoxyethylated castor oil surfactant in cyclosporine injection may leach phthalate from PVC containers such as bags and tubing Actual amount of DEHP plasticizer leached from PVC containers and administration sets may vary in clinical situations, depending on surfactant concentration, bag size, & contact time IV Administration Following dilution, infuse over 2-6 hr Continuously monitor for at least the first 30 min of the infusion, and then frequently thereafter Anaphylaxis possible with IV use; reserve only for patients unable to take oral form Maintain airway; other supportive measures & agents for treating anaphylaxis should be present Oral Administration Neoral and Sandimmune are NOT bioequivalent, exercise caution if switching between brands/generics Storage Store ampules at controlled room temp; do not refrigerate Protect ampules from light BRAND FORM. UNIT PRICE PILL IMAGE Sandimmune oral- 100 mg capsuleSandimmune oral- 25 mg capsuleSandimmune oral- 100 mg/mL solutionSandimmune intravenous- 250 mg/5 mL solutionRestasis MultiDose ophthalmic (eye)- 0.05 % dropsVerkazia ophthalmic (eye)- 0.1 % liquidcyclosporine oral- 100 mg capsulecyclosporine oral- 25 mg capsulecyclosporine intravenous- 250 mg/5 mL solutioncyclosporine intravenous- 250 mg/5 mL solutioncyclosporine intravenous- 250 mg/5 mL solutionRestasis ophthalmic (eye)- 0.05 % liquidRestasis ophthalmic (eye)- 0.05 % liquidCopyright © 2010 First DataBank, Inc.Select a drug:cyclosporine oralcyclosporine intravenouscyclosporine ophthalmic (eye)Print Patient Educationcyclosporine oral CYCLOSPORINE - ORAL (SYE-kloe-SPOR-in) COMMON BRAND NAME(S): Sandimmune WARNING: Cyclosporine lowers your ability to fight infections. This may make you more likely to get a serious (rarely fatal) infection or make any infection you have worse. This effect may also increase your risk of getting certain types of cancer (such as skin cancer, lymphoma). Tell your doctor right away if you have any signs of infection or cancer such as sore throat that doesn't go away, fever, chills, cough, burning/frequent urination, unusual skin changes, change in appearance or size of moles, unusual weight loss, swollen lymph glands, unusual lumps, night sweats.Cyclosporine can also cause high blood pressure and kidney problems. The risk of both problems increases with higher doses and longer treatment with this drug. Your doctor will monitor your blood pressure and kidney function while you take this medication.Psoriasis patients who have had certain previous treatments (such as coal tar, methotrexate, radiation treatment, light treatment with PUVA/UVB) are at increased risk to develop skin cancer. Talk to your doctor of the risks and benefits of this medication.Different brands of this medication may deliver different amounts of medication. Do not switch brands of cyclosporine without your doctor's permission and directions. USES: Cyclosporine is used to prevent organ rejection in people who have received a liver, kidney, or heart transplant. It is usually taken along with other medications to allow your new organ to function normally. Cyclosporine belongs to a class of drugs known as immunosuppressants. It works by weakening the immune system to help your body accept the new organ as if it were your own. HOW TO USE: Take this medication by mouth as directed by your doctor, usually once daily. You may take this medication with or without food, but it is important to choose one way and take this medication the same way with every dose.The dosage is based on your weight, medical condition, lab tests, and response to treatment.Avoid eating grapefruit or drinking grapefruit juice while using this medication unless your doctor or pharmacist says you may do so safely. Grapefruit can increase the chance of side effects with this medicine. Ask your doctor or pharmacist for more details.Use this medication regularly to get the most benefit from it. To help you remember, take it at the same time each day. SIDE EFFECTS: See also Warning section.Shaking, headache, dizziness, unusual growth of body hair, nausea/vomiting, diarrhea, stomach upset, or flushing may occur. If any of these effects last or get worse, tell your doctor or pharmacist promptly.Unusual growth and swelling of the gums may occur. Brush your teeth and floss daily to reduce this problem. See your dentist regularly.Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.This medication may raise your blood pressure. Check your blood pressure regularly and tell your doctor if the results are high. Your doctor may control your blood pressure with medication.Tell your doctor right away if you have any serious side effects, including: signs of kidney problems (such as a change in the amount of urine), signs of liver disease (such as nausea/vomiting that doesn't stop, dark urine, yellowing eyes/skin, stomach/abdominal pain), easy bruising/bleeding, unusual tiredness, muscle weakness/spasms, slow/irregular heartbeat, numb/tingling skin, severe leg pain.Get medical help right away if you have any very serious side effects, including: mental/mood changes (such as confusion, difficulty concentrating), vision changes, problems with speech, clumsiness, loss of coordination, weakness on one side of the body, chest pain, seizures.A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345. PRECAUTIONS: Before taking cyclosporine, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: kidney disease, liver disease, high blood pressure, cancer, skin lesions of unknown cause, radiation treatment (including light treatment with PUVA or UVB), mineral imbalance (such as low level of magnesium or high level of potassium), recent/current infections, high cholesterol/triglycerides levels.This drug may make you dizzy. Alcohol or marijuana (cannabis) can make you more dizzy. Do not drive, use machinery, or do anything that needs alertness until you can do it safely. Limit alcoholic beverages. Talk