SANDIMMUNE
Clinical safety rating: caution
Comprehensive 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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for SANDIMMUNE (SANDIMMUNE).
| Breastfeeding | Cyclosporine is excreted into human breast milk. The milk-to-plasma ratio (M/P) ranges from 0.17 to 1.4, with an average of approximately 0.5. The relative infant dose is estimated to be less than 2% of the maternal weight-adjusted dose. Breastfeeding is generally considered acceptable if maternal levels are maintained within therapeutic range and infant is monitored for potential adverse effects (e.g., immunosuppression). |
| 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. |
■ 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 component of the formulation","Concurrent use with PUVA or UVB therapy in psoriasis patients (increased risk of skin cancer)","Uncontrolled hypertension or malignancy (relative for non-transplant indications)"]
| 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."] |
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| 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. |