SANDIMMUNE
Clinical safety rating
cautionComprehensive clinical and safety monograph for SANDIMMUNE (SANDIMMUNE).
Cyclosporine is a calcineurin inhibitor. It binds to cyclophilin, forming a complex that inhibits calcineurin, thereby blocking the dephosphorylation and nuclear translocation of NF-AT, reducing T-cell activation and cytokine production.
| Metabolism | Primarily hepatic via CYP3A4; undergoes extensive first-pass metabolism. Metabolites are excreted primarily in bile and feces. |
| Excretion | Primarily biliary/fecal (94% of metabolites); renal elimination is minimal (<6% as unchanged drug and metabolites). |
| Half-life | Terminal elimination half-life is approximately 8.4 hours (range 6–24 hours) in adults; prolonged in patients with hepatic impairment. |
| Protein binding | 90–98% bound, primarily to lipoproteins and albumin. |
| Volume of Distribution | 3–5 L/kg in adults; high distribution indicates extensive tissue binding, including to erythrocytes and lymphocytes. |
| Bioavailability | Oral: 30% (range 10–60%) due to extensive first-pass metabolism; IV: 100%; ophthalmic: not quantified, minimal systemic absorption. |
| Onset of Action | Oral: 2–6 hours for peak immunosuppression; IV: 30–60 minutes for initial effect; topical: variable (days to weeks for psoriasis relief). |
| Duration of Action | Immunosuppressive effects persist 12–24 hours after oral dosing; clinical duration is prolonged due to intracellular binding and inhibition of calcineurin. |
| Molecular Weight | 1202.61 |
Initial oral dose: 10-15 mg/kg/day divided q12h, then taper to 5-10 mg/kg/day. IV dose: 5-6 mg/kg/day continuous infusion or divided q12h.
| Dosage form | CAPSULE |
| Renal impairment | For CrCl < 30 mL/min: reduce dose by 25-50%. Monitor serum creatinine closely. Avoid in severe renal impairment unless benefit outweighs risk. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B or C: reduce dose by 25-50%. Monitor cyclosporine levels and hepatic function. |
| Pediatric use | Children: 10-15 mg/kg/day oral divided q12h; IV: 5-6 mg/kg/day. Adjust based on trough levels (target 100-400 ng/mL). |
| Geriatric use | Start at low end of dosing range due to reduced renal and hepatic function. Monitor renal function and cyclosporine levels, as elderly are more susceptible to nephrotoxicity. |
| 1st trimester | Cyclosporine (Sandimmune) crosses the placenta and is associated with increased risks of prematurity, low birth weight, and intrauterine growth restriction. It does not appear to be a major human teratogen, but data are limited. Use only if benefit outweighs risk. |
| 2nd trimester | Exposure during the second trimester requires monitoring for maternal hypertension and renal function, as cyclosporine can exacerbate pregnancy-induced hypertension and nephrotoxicity. Fetal growth should be assessed. |
| 3rd trimester | Third-trimester use may increase risk of maternal hypertension, preeclampsia, and renal impairment. Neonatal monitoring for immunosuppression, infections, and hypoglycemia is advised. Consider dose adjustment near delivery. |
Clinical note
Comprehensive clinical and safety monograph for SANDIMMUNE (SANDIMMUNE).
| Placental transfer | Cyclosporine crosses the placenta readily; cord blood concentrations are approximately 50-60% of maternal plasma levels. Placental transfer is passive and non-saturable. |
| Breastfeeding | Cyclosporine is excreted into breast milk in low concentrations (milk-to-plasma ratio ~0.1-0.3). Limited data show no adverse effects in breastfed infants, but theoretical risk of immunosuppression. Consider risk-benefit; if used, monitor infant for infections, diarrhea, and growth. American Academy of Pediatrics considers it compatible with breastfeeding. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | Cyclosporine is not a major human teratogen. First trimester exposure is not associated with an increased risk of major birth defects, but may increase the risk of preterm birth (28-33 weeks) and low birth weight. Second and third trimester use is associated with increased risk of gestational hypertension, preeclampsia, and fetal growth restriction. Prematurity and transient neonatal immunosuppression have been reported. |
| Fetal Monitoring | Monitor maternal blood pressure and renal function (serum creatinine, BUN) throughout pregnancy. Perform regular fetal ultrasound to assess growth (every 2-4 weeks after 24 weeks). Monitor cyclosporine trough levels closely as pregnancy may alter pharmacokinetics; adjust dose to maintain therapeutic levels. Monitor for signs of preeclampsia (proteinuria, elevated blood pressure). Assess neonatal bilirubin, renal function, and hematologic parameters after delivery. |
| Fertility Effects | Cyclosporine does not appear to impair female fertility. In males, cyclosporine has been associated with reduced sperm motility and count, but these effects are reversible upon dose reduction or discontinuation. There is no evidence of increased risk of infertility in either sex with long-term use. |
■ FDA Black Box Warning
Increased susceptibility to infection and possible development of lymphoma and other malignancies. Only physicians experienced in immunosuppressive therapy and management of organ transplant patients should prescribe Sandimmune.
| Common Effects | Headache Nausea Vomiting Increased hair growth High blood pressure Renal dysfunction Loss of appetite Diarrhea Tremors Gingival hypertrophy gum enlargement |
| Serious Effects |
Hypersensitivity to cyclosporine or any of its excipientsConcomitant use with PUVA or UVB therapy (due to increased risk of skin cancer)Concomitant use with methotrexate in rheumatoid arthritis (increased nephrotoxicity)Uncontrolled hypertensionUncontrolled infectionsMalignancy (in organ transplant patients, except for transplant-related indications); in psoriasis: previous skin cancer, concurrent hepatotoxic drugs, abnormal renal function
| Precautions | Nephrotoxicity: Monitor renal function closely; dose-dependent and may progress to chronic nephropathy., Hepatotoxicity: Elevations in liver enzymes and bilirubin., Hypertension: Common; may require antihypertensive therapy., Neurotoxicity: Tremor, convulsions, headache, and other neurological effects., Hyperkalemia: Risk increases with concurrent use of potassium-sparing diuretics or ACE inhibitors., Hypomagnesemia: Monitor magnesium levels., Vaccinations: Live vaccines may be less effective and should be avoided., Carcinogenesis: Increased risk of skin cancer and lymphoproliferative disorders. |
| Food/Dietary | Avoid grapefruit and grapefruit juice. High-fat meals may reduce absorption; administer consistently with or without food. Do not take with potassium-rich foods or salt substitutes without monitoring. |
| Clinical Pearls | Monitor trough levels 12 hours post-dose; target varies by transplant organ (e.g., 200-400 ng/mL for kidney, 250-800 ng/mL for liver early post-transplant). Adjust for hepatic dysfunction; cyclosporine is extensively metabolized by CYP3A4. Avoid live vaccines. Use with caution in renal impairment; dose reduction may be needed. Drug interactions: avoid with potassium-sparing diuretics due to hyperkalemia risk; monitor for gingival hyperplasia and hypertension. |
| Patient Advice | Take at the same time every day with a full glass of water, consistently with or without food. · Do not consume grapefruit or grapefruit juice; it can increase cyclosporine levels. · Report signs of infection (fever, sore throat), tremors, or changes in urine output. · Avoid live vaccines (e.g., MMR, nasal flu spray) and contact with recently vaccinated individuals. · Use sunscreen as cyclosporine may increase sensitivity to sunlight. · Do not change brand or dosage form without consulting prescriber. |
Loading safety data…