Choice and Monitoring of drug therapy - Dr Ashish Bavdekar
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Transcript of Choice and Monitoring of drug therapy - Dr Ashish Bavdekar
Chairpersons: Aabha Nagral, Prashanth LK,SK YachhaTalk: Ashish Bavdekar
Choice and Monitoring of Drug therapy
Wilson’s Disease – choice and monitoring of drug therapy
Dr. Ashish BavdekarAssociate Professor
Consultant Ped. GastroenterologistK.E.M. Hospital, [email protected]
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
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”
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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