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Cyclosporin
Blood
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No Fasting Required
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Immunosuppressant drug monitoring.
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Cyclosporin Test Information Guide
- Why is it done?
- Measures blood levels of cyclosporin, a potent immunosuppressant medication used to prevent organ rejection and treat autoimmune conditions
- Ensures therapeutic drug levels are maintained within the optimal range for efficacy while minimizing toxicity
- Monitors patients who have received solid organ transplants (heart, kidney, liver, lung, pancreas) or bone marrow/stem cell transplants
- Used in management of autoimmune diseases such as rheumatoid arthritis, psoriasis, atopic dermatitis, and nephrotic syndrome
- Performed initially 1-2 weeks after starting therapy, then regularly at intervals (weekly to monthly depending on clinical stability)
- Ordered when medication adjustments are made or if signs of toxicity or rejection emerge
- Normal Range
- Therapeutic Range (Whole Blood): • Post-transplant acute phase: 250-350 ng/mL • Post-transplant maintenance phase: 100-200 ng/mL • Autoimmune disease management: 50-200 ng/mL • Range varies based on clinical indication and time after transplantation
- Unit of Measurement: ng/mL (nanograms per milliliter) - typically measured in whole blood
- Interpretation Guidelines: • Within therapeutic range: Optimal immunosuppression with minimal toxicity • Below therapeutic range: Increased risk of organ rejection or autoimmune disease flare-up • Above therapeutic range: Increased risk of nephrotoxicity, neurotoxicity, infection, and malignancy
- Critical Values: • >400 ng/mL: Risk of severe toxicity; immediate physician notification recommended • <50 ng/mL: Risk of inadequate immunosuppression; requires dose adjustment
- Interpretation
- Low Levels (<50 ng/mL): • May indicate non-compliance with medication regimen • Could result from drug interactions or malabsorption • Associated with increased risk of acute or chronic rejection in transplant recipients • May lead to disease exacerbation in autoimmune conditions • Requires dose increase and patient counseling on medication adherence
- Therapeutic Range (50-350 ng/mL): • Optimal immunosuppressive effect with acceptable safety profile • Maintains balance between rejection prevention and toxicity minimization • Exact target varies by clinical context and time post-transplantation • Continue current dosing with regular monitoring intervals
- High Levels (>350 ng/mL): • Increased risk of cyclosporin-related nephrotoxicity (acute renal dysfunction or chronic kidney disease) • Risk of neurotoxicity: tremor, headache, confusion, seizures, reversible posterior leukoencephalopathy • Elevated infection risk including opportunistic infections • May increase malignancy risk with chronic exposure • Risk of hepatotoxicity and hypertension • Requires immediate dose reduction and close clinical monitoring
- Factors Affecting Results: • Drug interactions with CYP3A4 inhibitors (azole antifungals, macrolide antibiotics, diltiazem) increase levels • Drug interactions with CYP3A4 inducers (rifampin, phenytoin, St. John's Wort) decrease levels • Gastrointestinal malabsorption due to diarrhea, food intake changes, or GI disease • Hepatic function changes affecting metabolism • Renal function affecting drug clearance • Graft versus host disease (GVHD) affecting absorption • Timing of blood draw relative to medication dose (trough vs. peak levels) • Food intake (high-fat meals may increase absorption) • Individual genetic variations in CYP3A4 expression
- Clinical Significance Patterns: • Rapidly rising levels: Consider drug interaction or reduced renal function • Rapidly falling levels: Assess medication compliance and possible drug interactions • Fluctuating levels: May indicate inconsistent absorption or dietary factors • Stable levels with rejection signs: May indicate tissue-specific resistance or inadequate local drug concentration
- Associated Organs
- Primary Target Organ Systems: • Immune system: T-lymphocytes (primary site of drug action) • Kidneys: Major site of toxicity; dose-dependent nephrotoxicity • Liver: Metabolism site; hepatotoxicity can occur • Central nervous system: Neurotoxicity effects • Transplanted organs: Protected by immunosuppressive effect
- Diseases Monitored or Diagnosed: • Organ transplant rejection (acute and chronic) in heart, kidney, liver, lung, and pancreas transplants • Graft versus host disease (GVHD) in bone marrow and stem cell transplant recipients • Rheumatoid arthritis • Psoriasis and atopic dermatitis • Nephrotic syndrome • Behçet's disease • Autoimmune uveitis • Inflammatory bowel disease
- Common Abnormal Result Complications: • Low levels → Acute rejection episodes, graft loss, disease flare-ups • High levels → Acute tubular necrosis, chronic kidney disease, end-stage renal disease requiring dialysis • Toxicity → Hypertension, hyperkalemia, hyperglycemia • CNS effects → Tremor, headache, confusion, encephalopathy, seizures • Infectious complications → Opportunistic infections (CMV, fungal, bacterial, viral) • Malignancy → Increased risk of lymphoma and skin cancers with chronic immunosuppression • Hepatotoxicity → Cirrhosis with chronic use • GI complications → Nausea, vomiting, anorexia, gum hyperplasia
- Follow-up Tests
- Routine Monitoring Tests: • Serum creatinine and estimated glomerular filtration rate (eGFR): Assess renal function at every visit • Complete blood count (CBC): Monitor for infections and malignancy-related changes • Comprehensive metabolic panel: Electrolytes (especially potassium), glucose, liver function tests • Blood pressure monitoring: Essential due to cyclosporin-induced hypertension risk • Magnesium level: Hypomagnesemia is common with cyclosporin use
- Organ-Specific Monitoring: • For kidney transplant recipients: 24-hour urine protein, renal ultrasound if rejection suspected • For heart transplant recipients: Echocardiography, electrocardiography for graft function • For liver transplant recipients: Liver function panel, ultrasound with Doppler • For lung transplant recipients: Pulmonary function tests, high-resolution CT if indicated • Graft biopsy if rejection is clinically suspected despite therapeutic cyclosporin levels
- Infection and Malignancy Screening: • CMV PCR: If signs of infection or post-transplant prophylaxis monitoring • Infectious disease serology as clinically indicated • Skin cancer surveillance: Regular dermatology examination • Age-appropriate cancer screening: Colonoscopy, mammography, other standard screening
- Monitoring Frequency: • Initial phase (first 3 months post-transplant): Weekly cyclosporin levels • Early maintenance (3-12 months): Biweekly to monthly cyclosporin levels • Late maintenance (>1 year): Monthly to every 3 months depending on stability • Autoimmune disease management: Monthly to every 3 months as clinically appropriate • More frequent testing if dose adjustments made or clinical changes occur
- Additional Tests Based on Results: • If levels too low: Assess medication compliance, evaluate for drug interactions, consider absorption issues • If levels too high: Evaluate for drug interactions, assess renal and hepatic function, monitor for toxicity signs • If toxicity suspected: Brain imaging (MRI) for neurotoxicity, renal ultrasound for nephrotoxicity, liver ultrasound for hepatotoxicity • HLA antibody testing: If rejection suspected despite therapeutic levels (antibody-mediated rejection) • Donor-specific antibody (DSA): Post-transplant monitoring in selected cases
- Fasting Required?
- Fasting Requirement: No
- Key Timing Considerations: • Blood draw should be trough level (just before next dose or 12 hours after last dose) • Trough levels are most clinically relevant for therapeutic drug monitoring • Consistent timing for serial measurements is crucial for accurate interpretation • Document exact time of blood draw and last cyclosporin dose on lab request
- Patient Preparation: • No specific fasting required • No need to skip meals or restrict water intake • Continue cyclosporin dose as normally scheduled • Maintain consistent dosing time daily for reliable monitoring • Avoid dose changes on testing day to ensure accurate level interpretation
- Medications and Interactions: • Continue all cyclosporin doses as scheduled; do not skip or delay • Report all current medications to healthcare provider • Inform lab personnel of all supplements, herbal products, and over-the-counter medications • Avoid starting new medications without consulting prescribing physician prior to testing • Be aware that significant diet changes (especially high-fat meals) may affect results • Avoid grapefruit and grapefruit juice for 48 hours before testing (major CYP3A4 interaction)
- Specimen Collection: • Collected via standard venipuncture • EDTA anticoagulant tube (purple-top) typically used • Whole blood specimen (not plasma or serum) provides most accurate results • Specimens should be processed promptly • Transport to lab at room temperature or as per lab protocol • Hemolyzed specimens should be rejected as they may yield inaccurate results
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