ICT Role in 21st Century Education & its Challenges.pptx
Choice and Monitoring of drug therapy - Dr Ashish Bavdekar
1. Chairpersons: Aabha Nagral, Prashanth LK,SK Yachha
Talk: Ashish Bavdekar
Choice and Monitoring of Drug therapy
2. Wilson’s Disease – choice and
monitoring of drug therapy
Dr. Ashish Bavdekar
Associate Professor
Consultant Ped. Gastroenterologist
K.E.M. Hospital, Pune
bavdekar@vsnl.com
3. 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
4. Zn + penicillamine
Zn + trientine
Zn sulfate
Zn acetate
trientine
penicillamine
transplanted
EuroWilson: initial treatment
Why?
“Available in our country
Cheap
Tried and tested
What we’ve always used
“Not available in our country
Kept as second line
Not as effective?
“expensive”
5. 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
Tx
DP/Trientine + zinc
‘bridge’
Modified Kings score
Tx if >11
DP/Trientine + zinc
6. Score Bilirubin
mol/Lɥ
INR AST
IU/L
WCC
x 109
/L
Albumin
g/L
0 0-100 0-1.29 0-100 0-6.7 >45
1 101-150 1.3-1.6 101-150 6.8-8.3 34-44
2 151-200 1.7-1.9 151-300 8.4-10.3 25-33
3 201-300 2.0-2.4 301-400 10.4-15.3 21-24
4 >301 >2.5 >401 >15.4 <20
Modified King’s score
A score > 11 = urgent need for transplantation
Validated in other centres; better than PELD
Dhawan et al, 2005
7. acute liver failure with encephalopathy
acute liver failure without encephalopathy
intermediate severity
Asymptomatic transaminitis
Asymptomatic and normal LFTs
Neonate detected by screening
Tx
DP/Trientine + zinc
‘bridge’
Modified Kings score
Tx if >11
DP/Trientine + zinc
Zinc
Zinc – when to start?
Treatment depending on severity
8. acute liver failure with encephalopathy
acute liver failure without encephalopathy
intermediate severity
Asymptomatic transaminitis
Asymptomatic and normal LFTs
Neonate detected by screening
List for Tx
DP/Trientine + zinc
‘bridge’
Modified Kings score
Tx if >11
DP/Trientine + zinc
Zinc
Zinc – when to start?
Treatment depending on severity
9. DP Trientine Zinc
Chelator Chelator Induces MT
Easy availability Patient named basis Easy availability
Reasonable cost
Rs. 1500/month
V. Expensive
Rs. 30,000/month
Cheap
Rs. 400/month
Side effects +++ Minimal SE Gastric discomfort
All except V. severe t-penia
DP intolerance
Neurological (?)
Initial co-Rx
Presympt. Cases
Maintenance Rx
10. DP Trientine Zinc
Chelator Chelator Induces MT
Easy availability Patient named basis Easy availability
Reasonable cost
Rs. 1500/month
V. Expensive
Rs. 30,000/month
Cheap
Rs. 400/month
Side effects +++ Minimal SE Gastric discomfort
All except V. severe t-penia
Significant renal D
DP intolerance
Neurological
Initial co-Rx
Presympt. Cases
Maintenance Rx
11. 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
12. 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
13. 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
14. DP Trientine Zinc
Early (1-3wks)
Fever, Rash
Neutropenia, Thrombo,
Proteinuria,
Lnpathy
Neurolog deterioration
Avoid iron + T
Rashes
Haem. Gastritis
Sideroblastic A
Loss of taste
Gastritis
Leucopenia
Increased
lipase and
amylase
Late
Nephrotoxicity
Lupus like S
Skin – EPS, pemphigus,
lichen planus,
V Late
Myasthenia, Polymyositis
Retinitis
15. 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
16. 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
17. 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
18. Zinc DP / Trientine
Initial Rx U Cu 100-500 ug/d
S free Cu > 25 ug/dL
U Cu > 500ug/d
S free Cu > 25 ug/dL
Good control U Cu < 75ug/d
S free Cu 10-15 ug/dL
U Cu 200-500 ug/d
U Cu < 100 ug/d 48hrs
after stopping DP
S free Cu 10-15ug/dL
Non-compliance/
Inadequate dose
U Zn < 2mg/d U Cu < 200 ug/d
U Cu > 500 ug/d
S free Cu > 15ug/dL
Over-treatment U Cu < 25 ug/d
S. free Cu < 5 ug/dL
Anemia, leucopenia
Increased ferritin
U Cu < 200 ug/d
S. free Cu < 5 ug/dL
Anemia, leucopenia
Increased ferritin
Urinary copper in Wilson’s disease
19. Zinc DP / Trientine
Initial Rx U Cu 100-500 ug/d
S free Cu > 25 ug/dL
U Cu > 500ug/d
S free Cu > 25 ug/dL
Good control U Cu < 75ug/d
S free Cu 10-15 ug/dL
U Cu 200-500 ug/d
U Cu < 100 ug/d 48hrs
after stopping DP
S free Cu 10-15ug/dL
Non-compliance/
Inadequate dose
U Zn < 2mg/d
S free Cu > 15ug/dL
U Cu < 200 ug/d
U Cu > 500 ug/d
S free Cu > 15ug/dL
Over-treatment U Cu < 25 ug/d
S. free Cu < 5 ug/dL
Anemia, leucopenia
Increased ferritin
U Cu < 200 ug/d
S. free Cu < 5 ug/dL
Anemia, leucopenia
Increased ferritin
Urinary copper / serum ‘free’ copper
20. 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
Notes de l'éditeur
Outcomes diffciult to compare – no head tp head study, results vary accoding to system involved, severity, compliance, age
ALF with E – may not help in RF
ALF without E – Kings score – 93% sen 98% spe, some have found it to be less accurate
CLD – imperfect evidence, local protocols rather that EBM, in a recent series, 40% patients had 1 change and 11% 2 changes in treatment. In a review of 288 patients with a median follow-up time of 17.1 years, Weiss et al (2011) concluded that hepatic treatment failure, defined as an increase in activity of liver enzymes occurred more frequently from zinc therapy (14/88 treatments) than from chelator therapy (4/313 treatments; P &lt; .001). Actuarial survival, without transplantation, showed an advantage for chelating agents (P &lt; .001 vs zinc). Patients who did not respond to zinc therapy showed hepatic improvement after reintroduction of a chelating agent.
Neonate Because of the risk of copper deficiency, it should not be in the first year. Because clinical presentation is rare below 3 years, commencement at the age of 2 years is a defensible, if not wholly evidence-based, decision.
Single dose trientine – 15mg/kg, 8 adult pts
Single dose trientine – 15mg/kg, 8 adult pts
DP may need to stopped in approx 30% cases
Give with food to ensure compliance.
Improvent is important
Ucu &lt; 100 after 2 days of stopping DP – good terapeutic effect, &gt;100 non compliance
To document therapeutic efficiency, urinary copper excretion after 2 days of D-penicillamine cessation should be &lt; 100. If more , suggest poor compliance
Accurate measurement important
Ucu &lt; 100 after 2 days of stopping DP – good terapeutic effect, &gt;100 non compliance
To document therapeutic efficiency, urinary copper excretion after 2 days of D-penicillamine cessation should be &lt; 100. If more , suggest poor compliance
