Choice and Monitoring of drug therapy - Dr Ashish Bavdekar

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
[email protected]

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 + penicillam
ine
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/L
ɥ
INR AST
IU/L
WCC
x 10
9
/L
Albumin
g/L
0 0-1000-1.29 0-100 0-6.7 >45
1 101-1501.3-1.6101-1506.8-8.334-44
2 151-2001.7-1.9151-3008.4-10.325-33
3 201-3002.0-2.4301-40010.4-15.321-24
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 availabilityPatient named basisEasy availability
Reasonable cost
Rs. 1500/month
V. Expensive
Rs. 30,000/month
Cheap
Rs. 400/month
Side effects +++Minimal SE Gastric discomfort
All exceptV. severe t-penia
DP intolerance
Neurological (?)
Initial co-Rx
Presympt. Cases
Maintenance Rx

10. DP Trientine Zinc
Chelator Chelator Induces MT
Easy availabilityPatient named basisEasy availability
Reasonable cost
Rs. 1500/month
V. Expensive
Rs. 30,000/month
Cheap
Rs. 400/month
Side effects +++Minimal SE Gastric discomfort
All exceptV. 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