Choice and Monitoring of drug therapy - Dr Ashish Bavdekar
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Transcript of Choice and Monitoring of drug therapy - Dr Ashish Bavdekar
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Chairpersons: Aabha Nagral, Prashanth LK,SK YachhaTalk: Ashish Bavdekar
Choice and Monitoring of Drug therapy
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Wilson’s Disease – choice and monitoring of drug therapy
Dr. Ashish BavdekarAssociate Professor
Consultant Ped. GastroenterologistK.E.M. Hospital, [email protected]
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Wilson’s Disease - therapy
1) Reduce Cu to sub-toxic threshold - takes 6-12 months - DP, Trientine, TAM
2) Maintain slightly negative Cu balance - life long therapy - DP, Trientine, Zn
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Zn + penicillamine
Zn + trientine
Zn sulfate
Zn acetate
trientine
penicillamine
transplanted
EuroWilson: initial treatment
Why?
“Available in our countryCheapTried and testedWhat we’ve always used
“Not available in our countryKept as second lineNot as effective?
“expensive”
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Treatment depending on severity
acute liver failure with encephalopathy
acute liver failure without encephalopathy
intermediate severity
Asymptomatic transaminitis
Asymptomatic and normal LFTs
Neonate detected by screening
TxDP/Trientine + zinc‘bridge’
Modified Kings scoreTx if >11DP/Trientine + zinc
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Score Bilirubinmol/Lɥ
INR ASTIU/L
WCCx 109/L
Albuming/L
0 0-100 0-1.29 0-100 0-6.7 >451 101-150 1.3-1.6 101-150 6.8-8.3 34-442 151-200 1.7-1.9 151-300 8.4-10.3 25-333 201-300 2.0-2.4 301-400 10.4-15.3 21-244 >301 >2.5 >401 >15.4 <20
Modified King’s score
A score > 11 = urgent need for transplantationValidated in other centres; better than PELD
Dhawan et al, 2005
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acute liver failure with encephalopathy
acute liver failure without encephalopathy
intermediate severity
Asymptomatic transaminitis
Asymptomatic and normal LFTs
Neonate detected by screening
TxDP/Trientine + zinc‘bridge’
Modified Kings scoreTx if >11DP/Trientine + zinc
Zinc
Zinc – when to start?
Treatment depending on severity
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acute liver failure with encephalopathy
acute liver failure without encephalopathy
intermediate severity
Asymptomatic transaminitis
Asymptomatic and normal LFTs
Neonate detected by screening
List for TxDP/Trientine + zinc‘bridge’
Modified Kings scoreTx if >11DP/Trientine + zinc
Zinc
Zinc – when to start?
Treatment depending on severity
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DP Trientine ZincChelator Chelator Induces MT
Easy availability Patient named basis Easy availability
Reasonable costRs. 1500/month
V. ExpensiveRs. 30,000/month
CheapRs. 400/month
Side effects +++ Minimal SE Gastric discomfort
All except V. severe t-peniaDP intoleranceNeurological (?)
Initial co-RxPresympt. CasesMaintenance Rx
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DP Trientine ZincChelator Chelator Induces MT
Easy availability Patient named basis Easy availability
Reasonable costRs. 1500/month
V. ExpensiveRs. 30,000/month
CheapRs. 400/month
Side effects +++ Minimal SE Gastric discomfort
All except V. severe t-peniaSignificant renal DDP intoleranceNeurological
Initial co-RxPresympt. CasesMaintenance Rx
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Monitoring in WD ?
• To determine clinical and biochemical
improvement/deterioration
• Determine effective decoppering
• Ensure compliance
• To identify adverse effects of medications
• To review diagnosis if necessary
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Monitoring plan (chelators)
• Clinical– Liver status, neuro-psychiatric worsening– KF ring annually
• Biochemical (USG)– CBC, Urine, LFTs– Initially 5, 10, 15, 30 days initially– Later 3 mo, 6mo,
• Urinary Cu, Serum free copper (Serum Cu & Cp)– Initially after a month, 4 times per year– Later 1-2 times per year
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Monitoring plan (chelators)
• Clinical– Liver status, look for side effects– KF ring annually
• Biochemical (USG)– CBC, Urine, LFTs– Initially 5, 10, 15, 30 days initially– Later 3 mo, 6mo,
• Urinary Cu, Serum free copper (Serum Cu & Cp)– Initially after a month, 4 times per year– Later 1-2 times per year
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DP Trientine ZincEarly (1-3wks)Fever, RashNeutropenia, Thrombo, Proteinuria, LnpathyNeurolog deterioration
Avoid iron + TRashesHaem. GastritisSideroblastic ALoss of taste
GastritisLeucopeniaIncreased lipase and amylase
LateNephrotoxicityLupus like SSkin – EPS, pemphigus, lichen planus, V LateMyasthenia, PolymyositisRetinitis
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Monitoring plan (chelators)
• Clinical– Liver status, neuro-psychiatric worsening– KF ring annually
• Biochemical (USG)– CBC, Urine, LFTs– Initially 5, 10, 15, 30 days initially– Later 3 mo, 6mo,
• Urinary Cu, Serum free copper (Serum Cu & Cp)– Initially after a month, 4 times per year– Later 1-2 times per year
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Biochemical improvement
• Children on long-term chelation
– 20/32 children normalised at variable times
– INR - median of 1.8 yrs (0-12.2)
– AST – median of 0.97 yrs (0-9)
– Bilirubin – median of 0. yrs (0-2.3)
• Asymptomatic sibs
– 15/17 normalised LFTs
– Median 283 days (35days-6.7yrs)Dhawan et al, 2005
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Monitoring plan (chelators)• Clinical
– Liver status, neuro-psychiatric worsening– KF ring annually
• Biochemical (USG)– CBC, Urine, LFTs– Initially 5, 10, 15, 30 days initially– Later 3 mo, 6mo,
• Urinary Cu, S. free copper (Serum Cu & Cp)– Initially after a month, 4 times per year– Later 1-2 times per year
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Zinc DP / Trientine
Initial Rx U Cu 100-500 ug/dS free Cu > 25 ug/dL
U Cu > 500ug/dS free Cu > 25 ug/dL
Good control U Cu < 75ug/dS free Cu 10-15 ug/dL
U Cu 200-500 ug/dU Cu < 100 ug/d 48hrs after stopping DPS free Cu 10-15ug/dL
Non-compliance/Inadequate dose
U Zn < 2mg/d U Cu < 200 ug/dU Cu > 500 ug/dS free Cu > 15ug/dL
Over-treatment U Cu < 25 ug/d S. free Cu < 5 ug/dLAnemia, leucopeniaIncreased ferritin
U Cu < 200 ug/dS. free Cu < 5 ug/dLAnemia, leucopeniaIncreased ferritin
Urinary copper in Wilson’s disease
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Zinc DP / Trientine
Initial Rx U Cu 100-500 ug/dS free Cu > 25 ug/dL
U Cu > 500ug/dS free Cu > 25 ug/dL
Good control U Cu < 75ug/d
S free Cu 10-15 ug/dL
U Cu 200-500 ug/dU Cu < 100 ug/d 48hrs after stopping DPS free Cu 10-15ug/dL
Non-compliance/Inadequate dose
U Zn < 2mg/d
S free Cu > 15ug/dL
U Cu < 200 ug/dU Cu > 500 ug/dS free Cu > 15ug/dL
Over-treatment U Cu < 25 ug/d S. free Cu < 5 ug/dLAnemia, leucopeniaIncreased ferritin
U Cu < 200 ug/dS. free Cu < 5 ug/dLAnemia, leucopeniaIncreased ferritin
Urinary copper / serum ‘free’ copper
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Summary
• Chelators - mainstay of treatment (hepatic)
• Zinc has role in long-term Rx, neurological, co-Rx
• Monitoring is crucial
– Clinical and improvement in LFTs slow
• Monitoring for Cu balance important
– Interpretation important
– Compliance