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Methotrexate - Quantitative, Serum

Blood
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Report in 120Hrs

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At Home

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No Fasting Required

Details

Drug monitoring test.

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Methotrexate - Quantitative Serum Test Information Guide

  • Why is it done?
    • Monitors serum concentration of methotrexate (MTX), a chemotherapy and immunosuppressive medication used to treat cancer, autoimmune diseases, and inflammatory conditions
    • Ensures therapeutic drug levels are maintained for effective treatment while minimizing toxicity
    • Detects potentially toxic levels that may cause severe side effects including bone marrow suppression, hepatotoxicity, and nephrotoxicity
    • Commonly ordered in high-dose methotrexate (HD-MTX) therapy protocols, typically drawn at 24, 48, and 72 hours post-infusion
    • Guides leucovorin (folinic acid) rescue therapy decisions to prevent methotrexate toxicity
    • Used in patients with rheumatoid arthritis, psoriasis, Crohn's disease, and certain malignancies receiving low-dose chronic therapy
    • Assists in identifying drug interactions and renal dysfunction that may impair drug clearance
  • Normal Range
    • Baseline/Therapeutic levels vary depending on treatment protocol and timing: • Undetectable or <0.01 μmol/L at baseline (pre-treatment) • Therapeutic range for chronic low-dose therapy: typically <5 μmol/L at steady state • High-dose methotrexate (HD-MTX) targets depend on protocol timing
    • 24-hour post-HD-MTX: Generally <5 μmol/L (normal range) • Values >5 μmol/L may require additional monitoring or intervention
    • 48-hour post-HD-MTX: Should be <0.5 μmol/L • Values >0.5 μmol/L indicate delayed clearance and increased toxicity risk
    • 72-hour post-HD-MTX: Should be <0.1 μmol/L • Values >0.1 μmol/L indicate significant toxicity risk requiring aggressive intervention
    • Units of measurement: μmol/L (micromoles per liter) or ng/mL (nanograms per milliliter)
    • Normal interpretation: Levels within therapeutic range indicate appropriate drug exposure with acceptable toxicity risk
    • Abnormal interpretation: Elevated levels indicate delayed clearance, potential toxicity, and need for increased leucovorin rescue or other supportive measures
  • Interpretation
    • Low/Undetectable levels: • Indicates effective drug clearance or inadequate drug dosing • May reflect non-compliance or medication not reaching patient • Generally favorable but may require dose escalation if therapeutic response is inadequate • In HD-MTX therapy: Normal and expected when levels are dropping appropriately
    • Therapeutic range levels: • Optimal for therapeutic efficacy with acceptable toxicity profile • Indicates appropriate dosing and drug metabolism • Suggests good renal function and drug clearance • Patient tolerating therapy well with expected clinical response
    • Moderately elevated levels (above reference but <1 μmol/L at 48 hours): • Indicates delayed drug clearance, possibly due to mild renal impairment • May signal drug-drug interactions affecting metabolism • Requires increased monitoring and possible increase in leucovorin rescue • Close observation for toxicity symptoms recommended
    • Significantly elevated levels (>1 μmol/L at 48 hours or >0.1 μmol/L at 72 hours): • Indicates severe toxicity risk with potential for serious adverse effects • May result from renal failure, liver disease, or severe drug interactions • Requires aggressive leucovorin rescue therapy and supportive care • High risk for bone marrow suppression, mucositis, hepatotoxicity, nephrotoxicity • May necessitate hospitalization and intensive monitoring
    • Factors affecting interpretation: • Renal function: Most significant factor; impaired kidneys reduce MTX clearance • Drug interactions: NSAIDs, certain antibiotics, and other medications may impair clearance • Dehydration: Reduced urine output concentrates drug in kidneys • Third-space accumulation: Pleural effusions or ascites sequester drug • Liver function: Affects drug metabolism and elimination • Age and body composition: May influence drug distribution • Dosing errors or medication adherence issues
    • Clinical significance patterns: • Rising levels at sequential time points: Ominous sign indicating severe clearance impairment • Delayed peak clearance: Suggests renal dysfunction requiring intervention • Rapid clearance: Favorable sign in HD-MTX therapy, generally safe profile • Persistent elevated levels: May require dose adjustment or treatment discontinuation
  • Associated Organs
    • Primary organ systems involved: • Kidneys: MTX primary excretion route; renal dysfunction causes elevated levels • Liver: Metabolizes MTX; hepatic disease impairs drug clearance • Bone marrow: Target organ for toxicity; elevated MTX causes myelosuppression • Gastrointestinal tract: Toxicity manifests as mucositis and diarrhea • Central nervous system: Risk of neurotoxicity with high-dose therapy
    • Medical conditions commonly associated with abnormal results: • Acute kidney injury or chronic kidney disease: Impairs MTX clearance • Hepatic cirrhosis or liver dysfunction: Reduces drug metabolism • Dehydration or volume depletion: Increases drug concentration • Sepsis or severe infection: May alter drug clearance • Pleural effusions or ascites: Third-space sequestration prolongs half-life • Diabetes mellitus: May affect renal function and MTX clearance
    • Diseases this test helps diagnose or monitor: • Osteosarcoma and other MTX-responsive malignancies • Acute lymphoblastic leukemia (ALL) requiring HD-MTX • Non-Hodgkin's lymphoma • Rheumatoid arthritis (monitoring low-dose chronic therapy) • Systemic lupus erythematosus • Psoriasis • Crohn's disease • Ectopic pregnancy (off-label use)
    • Potential complications from elevated MTX levels: • Myelosuppression: Severe neutropenia, thrombocytopenia, anemia increasing infection and bleeding risk • Acute kidney injury: From MTX precipitation in renal tubules • Hepatotoxicity: Cirrhosis development with chronic exposure • Mucositis: Severe ulceration of GI tract • Neurotoxicity: Seizures, confusion, or leukoencephalopathy • Immunosuppression: Increased susceptibility to opportunistic infections • Teratogenicity: Severe birth defects if exposure during pregnancy • Secondary malignancies: Long-term complication of therapy
  • Follow-up Tests
    • Recommended follow-up tests based on results: • Repeat MTX level: Performed at 24, 48, and 72 hours post-HD-MTX infusion to track clearance pattern • If levels remain elevated: Obtain concurrent serum creatinine to assess renal function
    • Additional tests for elevated MTX levels: • Serum creatinine and blood urea nitrogen (BUN): Evaluate renal function and assess for acute kidney injury • Urinalysis: Detect crystalluria or signs of nephrolithiasis • 24-hour urine creatinine clearance: Quantify glomerular filtration rate • Liver function tests (ALT, AST, bilirubin, albumin): Assess hepatic function • Complete blood count (CBC): Monitor for myelosuppression and cytopenia • Electrolyte panel: Evaluate for renal dysfunction effects • Uric acid level: Monitor for tumor lysis syndrome in malignancy patients
    • Further investigations if toxicity suspected: • Chest X-ray: Evaluate for pulmonary toxicity or infections • Blood cultures: If fever or sepsis suspected • Bone marrow biopsy: If severe cytopenias develop • Genetic testing: For pharmacogenomic MTX metabolism markers if available • Drug interaction review: Consult with pharmacy regarding concurrent medications
    • Monitoring frequency for ongoing conditions: • HD-MTX chemotherapy: MTX levels at 24, 48, and 72 hours post-infusion for each cycle • Chronic low-dose MTX (rheumatoid arthritis, psoriasis): Baseline and then every 8-12 weeks initially • Once stable on chronic therapy: May monitor MTX levels annually or as clinically indicated • With renal impairment: More frequent monitoring recommended (every 4-6 weeks) • After dose adjustments: Retest in 2-4 weeks to achieve new steady state
    • Related complementary tests: • Folate and vitamin B12 levels: MTX is an antimetabolite affecting these nutrients • Homocysteine: Elevated with MTX-induced folate depletion • Drug interaction screening: Especially NSAIDs, proton pump inhibitors, trimethoprim • Pharmacogenomic testing: MTHFR gene variants may affect MTX metabolism (emerging research) • Serial MTX levels: Essential for dose optimization in individual patients
  • Fasting Required?
    • Fasting requirement: No • Fasting is not necessary for serum methotrexate level testing • Blood can be drawn at any time without regard to food intake • Food does not affect MTX serum concentration measurement
    • Timing considerations (critical for accurate results): • HD-MTX: Draw samples at specific times post-infusion (24, 48, 72 hours) as protocol mandates • Consistent timing: Essential for interpreting results and comparing to previous levels • Document exact time of MTX administration and blood draw • Delays in drawing or processing affect result interpretation
    • Medications to avoid: • No specific medications must be avoided for this test • However, many drugs interact with MTX and may affect its levels: - NSAIDs (ibuprofen, naproxen): Reduce renal clearance of MTX - Proton pump inhibitors: May increase MTX levels - Trimethoprim-sulfamethoxazole: Increases MTX toxicity - Penicillins: May reduce renal clearance - Certain antibiotics (fluoroquinolones, aminoglycosides): Affect clearance • Consult with healthcare provider before starting or stopping medications during MTX therapy • Do not discontinue essential medications without physician guidance
    • Other patient preparation requirements: • Adequate hydration: Especially before and during HD-MTX therapy (typically 2-3 liters daily) • Maintain normal urine output: Facilitates MTX renal excretion • Void frequently: Reduces renal tubular exposure to concentrated MTX • Urinary alkalinization: Some protocols use sodium bicarbonate to alkalinize urine and prevent MTX precipitation • Inform laboratory of MTX therapy and exact timing of administration • Bring MTX administration records or treatment schedule to blood draw • Report any symptoms of toxicity: Fever, rash, severe diarrhea, mouth ulcers • Continue taking prescribed leucovorin (folinic acid) rescue therapy as directed
    • Special instructions: • Ensure blood specimen is collected in appropriate tube (typically serum separator tube) • Specimen should be processed promptly to prevent MTX degradation • Laboratory should handle with biohazard precautions • Results are time-sensitive; communicate delays to healthcare provider • Results must be interpreted with clinical context and other laboratory values • Patient should maintain list of all concurrent medications for physician review • Report to healthcare provider if experiencing unusual symptoms or toxicity signs

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