What s s up with Omegaven????? Kathleen Gura PharmD Children s s Hospital Boston

Size: px

Start display at page:

Download "What s s up with Omegaven????? Kathleen Gura PharmD Children s s Hospital Boston"

Chester Powell
5 years ago
Views:

1 What s s up with Omegaven????? Kathleen Gura PharmD Children s s Hospital Boston

2 Disclosures Funding : March of Dimes FDA Orphan Drug Grants Program NIH Children s s Hospital Surgical Foundation Patent application by Children s Hospital Boston

3 PN liver Injury Histology Fatty deposits Ballooning of hepatocytes Inflammation Bile duct proliferation Laboratory Elevations of serum liver enzymes (LFTs( LFTs) Cholestasis:: Direct bilirubin >2.0 mg/dl

4 Omegaven Typically used in combination with Intralipid Max labeled dose 0.2g/kg/day Not indicated for use in children Not intended to be used as monotherapy Not FDA approved

5 OIL Intralipid Soybean 10 5 Safflower 5 Liposyn II Fish 10 % FATS Comparison of Parenteral Fat Emulsions (10 grams fat/100 ml) Omegaven Linoleic α-linolenic 9 4 <0.2 E.P.A D.H.A Glycerol Egg Phospholipid

6 Biosynthesis of Fatty Acids Δ 6 desaturase elongase n-3 α-linolenic acid (18:3) octadecatetraenoic acid (18:4) eicosatetraenoic acid (20:4) Δ 5 desaturase n-6 linoleic acid (18:2) γ-linolenic acid (18:3) dihomo-γ-linolenic acid (20:3) n-9 oleic acid (18:1) octadecadienoic acid (18:2) eicosadienoic acid (20:2) elongase eicosapentaenoic acid (20:5) arachidonic acid (20:4) eicosatrienoic acid (20:3) elongase docosapentaenoic acid (22:5) Δ 6 desaturase retroconvertase docosahexaenoic acid (22:6) Gura PSAP 5 th Edition

7 Potential Benefits of Omega-3 3 Fatty Acids Anti-inflammatory inflammatory properties - decreased production of proinflammatory cytokines Clearance Omega-3 3 Fatty acids diminish de novo lipogenesis

8 Liver Histology H&E 400x Normal chow PN alone Omegaven oral

9 Liver Histology H&E 400x Normal chow PN alone Omegaven IV

10 Normal Liver PAS

11 PN Alone PAS

12 PN + IV Intralipid PAS

13 PN + IV Omegaven PAS

14 H&E CHOW PN + IL PN + SMOF PN + OM

15 CHB Omegaven Protocol

16 Protocol Details Patients must have pre-existing existing PNALD Direct bili > 2 mg/dl or histological evidence of cholestasis Patient must be expected to be on PN/IFE at least 30 additional days Neither patient nor their insurer can be charged without FDA approval

17 Dosing/Administration Conventional fat emulsions are discontinued Dosing: Omegaven 1 g/kg/day infused over 12 hours Additional NPC given as carbohydrates May co-administer into PN line (no TNA) May be filtered through 1.2 micron filter Do not mix with other drugs

18 Exclusion Criteria Other causes of chronic liver disease - hepatitis C - cystic fibrosis - biliary atresia Allergy to eggs or fish Involvement in any other clinical trial unless approved by other investigators

19 Clinical Experience Recent Findings.

20 Accepted Annals of Surgery Direct Bilirubin (n=51) Direct Bilirubin (mg/dl) (29) (44) (47) (82) (55) (34) (23) (14) (11) (6) (3) Weeks from Enrollment (Omegaven Started)

21 Triene/Tetraene Ratio (n=51) Triene/tetraene ratio (2) (44) (81) (53) (35) (23) (14) (12) (7) (5) (NA) Weeks from Enrollment (Omegaven Started) Accepted Annals of Surgery

22 Triglycerides Triglycerides (mg/dl) (22) (35) (43) (77) (50) (35) (23) (15) (12) (8) (5) Weeks from Enrollment (Omegaven Started)

23 Platelets Platelets (23) (40) (45) (83) (55) (36) (23) (15) (12) (8) (5) Weeks from Enrollment (Omegaven Started) Accepted Annals of Surgery

24 Coagulation (INR) INR (6) (11) (43) (80) (52) (33) (24) (15) (12) (8) (5) Weeks from Enrollment (Omegaven Started) Accepted Annals of Surgery

27 Efficacy of Omegaven in Comparison to Soybean Controls in Children with PNALD Patients < 2 years of age All had PNALD (dbili( > 2mg/dL) Omegaven cohort n=57 -treated from Sept 2004 Dec 2008 Soybean control n=49 -treated from Feb 2000 Dec 2007

28 Highlights Mean time from baseline to reversal of cholestasis while on PN among survivors who did not undergo liver transplantation while on PN in the Omegaven cohort was 78 days vs. 200 days in the Soybean control cohort (P =0.0005) For patients still on PN 40/52 Omegaven patients exhibited reversal of cholestasis, only 2/26 Soybean control patients exhibited reversal of cholestasis while on PN.

29 Other published evidence..

31 Results 12 patients with PNALD treated (Canada) EFA profiles not routinely followed Complete resolution of PNALD occurred in 9 patients In 8 cases, hepatic function while on the blended regimen continue to worsen until Intralipid stopped and Omegaven was given alone Concluded that Omegaven has the ability to restore liver function without complications or mortality

34 Comments Case series describing 4 preterm infants (China) Intralipid stopped and patients switched to Omegaven Three of the four infants had complete resolution of their cholestasis while on Omegaven Two eventually weaned off PN; discharged home on full EN One infant did not improve had multiple bouts of sepsis and ongoing intra-abdominal abdominal inflammation and later expired Suggests some patients with ongoing complex multi-organ disease may be beyond the point of rescue

36 Comments Case report (Italy) Infant with PNALD treated with Omegaven Goal dose 1.5g/kg/day Cholestasis resolved after 8 months of treatment with Omegaven monotherapy despite being on 50% EN and 50% PN No clinical signs of fatty acid deficiency or evidence of bleeding

38 Comments case report (Kentucky) infant who suffered from midgut volvulus by 5 months of age, this patient developed severe PNALD listed for transplant Within two months, his serum bilirubin began to decrease, and returned to normal by 7 months. At the same time, the patient reached his enteral nutrition goal, and was weaned from PN

39 122 patients and growing.

43 If you can t t get Omegaven Avoid overfeeding Limit lipid dose Consider enteral fish oil Prevent infection (? Ethanol lock) Early, aggressive and appropriate treatment of CVC infections

44 The Center for Advanced Intestinal Rehabilitation (CAIR)

45 Questions?

Fish oil based lipid emulsion s role in transitioning pediatric patients from plant based to combination plant and fish oil based lipid emulsion

Fish oil based lipid emulsion s role in transitioning pediatric patients from plant based to combination plant and fish oil based lipid emulsion Kayley Liuzzo, PharmD PGY 1 Pharmacy Practice Resident Children