HOW I USE METHOTREXATE IN CHILDREN?
T. P. Yadav *
Department of Pediatrics.*
METHOTREXATE
  • FOLIC ACID ANALOGUE
  • ANTI-INFLAMMATORY
  • ANTI-METABOLITE
  • IMMUNO-MODULATOR
  • - a ADENOSINELEVELS
    - INHIBITS NEUTRO-ADHERENCE
  • INHIBITS PROLIFERATION OF
    SYNOVIAL CELLS
  • INHIBITS CMI

INHIBITS ENZYMES
  • DIHYDROFOLATE REDUCTASE
  • 5. AMINOIMIDAZOLE - 4 - CARBOXANIDE RIBO NUCLEOTIDE TRANSFORMYLASE
  • THYMIDYLATE SYNTHETASE
  • ADENOSINE DEAMINASE

KINETICS
  • 50-70% Abs - ORAL Admn
  • PLASMA HALF LIFE - 2 Hrs
  • TRIPHASIC PHARMACOKINETICS
    - BLOOD LEVELS ASSAY
    - LATENT PERIOD OF WEEKS
    - PROBABLY TRUE ANTI-INFLAM
  • 80% eliminated by kidneys within 8-48 hrs
  • 11-57% Protein bound at low doses
  • Oral MTX abs - saturable process, SC is not.

METHOTREXATE IN CHILDREN
  • WHERE & WHEN TO USE
  • HOW TO USE
  • SAFETY ISSUES
  • MONITORING
  • HOW LONG TO USE
  • WHEN TO DISCONTINUE

WHERE & WHEN
  • JIA - POLYARTICULAR
    - EXTENDED PAUCI
    - SOJIA>
    - ERA
    - JPsA
  • JDMS " Steroid non-responsive"
  • SLE
  • SARCOIDOSIS
  • SCLERODERMA

HOW TO USE
  • DOSE - 10-15 mg/kg/wk
    or 0.3 - 0.6 mg/kg/wk
    (20-25 mg/m2/wk, 1.1 mg/kg/wk)
  • ROUTE Oral - empty stomach
    - With clear liquids
    - Or 1 Hr before BF Parenteral - SC, IM, IV
  • Availability - Tablets 2.5, 5, 7.3, 10 mg
    Inj 15 mg/ml

PARENTERAL MTX
  • Patients with poor clinical response to oral MTX
  • Need a dose in excess of 15 mg/m2/wk
  • Develop significant GI Toxicity with oral MTX
  • Is SC better than Oral ?
  • Folic acid-to give or not ?
  • Avoid in renal insufficiency.

SIDE-EFFECTS
  • GIT - Nausea, vomiting, ulceration, diarrhea
  • Haematological - Bone marrow suppression cytopenia
  • Hepatic - Raised enzymes (9%), Fibrosis?
  • Alopecia, Dermatitis
  • Renal
  • Risk of infection
  • Oncogenicity, Gonadal dysfunction, Nodulosis
  • Teratogenicity

MONITORING
BASELINE -

Wt, Ht Surface Area
- CBC, UA, LFT, KFT, S. protein
- ESR, CRP
Clinical - Global assessment
- No of Active joints / joints with limited ROM
- Duration of morning stiffness
After Starting MTX - Initially Lab - every 2 wks x 3 mths
then every 1-3 mths
Clinical 1-3 mth

MONITORING
  • DISCONTINUE / REDUCE > 3 TIMES UPPER NORMAL LIMIT
  • FULL BLOOD COUNT Platelets < 150 x 109/L
    WBC < 3.5 x 109xL
    Neutrophils < 1.5x109L

* Rash/Severe oral ulcers/new or increasing dyspnoea or cough

DURATION / DISCONTINUATION

MTX-GIVE FOR 3-6 MONTHS
RESPONSE-CONTINUE
IF NO RESPONSE-I DOSE/

CHANGE ROUTE 3-6 MONTHS
IF STILL NO RESPONSE-CHANGE
No VALIDATED GUIDELINES FOR DURATION
- Clinical remission for 1 year
- Disease Flare in more than 50%

R. M. L. H Experience

MTX TOTAL NO. OF PATIENTS
ANALYSED 24+2

POLY JIA = 10

SOJIA = 12

EXTENDED PAUCI = 2

-

POLY (n = 10)

SOJIA (n = 12)

AGE (yr)

5-12

3.5-10

DIS. DURATION (yr)

1-6 (3.25 ± 1.75

2-4.5 (3.3 ± 1.3)

DUR. MTX (WK)

60-208 (104 ± 64)

16-162 (86 ± 70)

ROUTE

ORAL / SC-2

ORAL

RESPONSE

- -

COMPLETE

5 2

PARTIAL

3 6

NONE

2 3

SIDE-EFFECTS

Nausea 2, Vomiting 2

Pneumonia, boils

OTHER DRUGS

NSAID, SSZ

NSAID, STRD



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