Onivyde (irinotecan) is indicated in combination with 5-fluorouracil and leucovorin (two other cancer medicines
) for the treatment of patients with metastatic adenocarcinoma of the pancreas after disease progression following gemcitabine-based therapy
The EMA approved
Onivyde marketed by Baxalta Innovations GmbH contains 5 mg
irinotecan hydrochloride trihydrate per 1 mL, this corresponds to the FDA and TGA approved
Onivyde marketed by Merrimack Pharmaceuticals Inc. and containing 4.3 mg
irinotecan in 1 mL 
Complete information about Onivyde (irinotecan) dosage and administration can be found here 
. Note that the EMA approved Onivyde marketed by Baxalta Innovations GmbH contains the equivalent of 5 mg irinotecan hydrochloride trihydrate (as irinotecan sucrosofate salt in a pegylated liposomal formulation) which corresponds to 4.3 mg/1 mL irinotecan 
. The latter is the strength approved by the FDA and TGA 
The standard EMA dosage (Onivyde (irinotecan) 5 mg/mL) is:
- 80 mg/m2 administered by intravenous infusion every 2 weeks followed by 5‑fluorouracil and leucovorin.
The standard FDA and TGA dosage (Onivyde (irinotecan) 4.3 mg/mL) is:
- 70 mg/m2 administered by intravenous infusion every 2 weeks followed by 5‑fluorouracil and leucovorin .
What is irinotecan and how does it work?
Onivyde (irinotecan) is a cancer medicine used to treat adults with metastatic adenocarcinoma of the pancreas. It is used together with 5-fluorouracil and leucovorin (two other cancer medicines) in adults whose cancer has worsened despite treatment containing the cancer medicine gemcitabine 
.The active substance in Onivyde, irinotecan, is a topoisomerase inhibitor. It blocks an enzyme called topoisomerase I. This enzyme is involved in copying cell DNA, which is needed to make new cells. By blocking the enzyme, cancer cells are prevented from multiplying and they eventually die. In Onivyde, irinotecan is contained within tiny fat particles called ‘liposomes’. The liposomes are expected to accumulate within the tumour and release the medicine slowly over time, thereby allowing it to act for longer 
What is irinotecan's approval status?
Onivyde (irinotecan) was approved by:
- FDA (USA) on October 22, 2015 
- EMA (EU) on October 14, 2016 
- TGA (AUS) on December 19, 2016 
for metastatic adenocarcinoma of the pancreas for use in combination with 5-fluorouracil and leucovorin in adults whose cancer has gotten worse despite treatment containing the cancer medicine gemcitabine.
The approvals were based on a study (NAPOLI–1 
) involving a total of 417 adults with metastatic adenocarcinoma of the pancreas whose cancer worsened despite cancer treatment that contained gemcitabine. Patients were given Onivyde or 5-fluorouracil plus leucovorin, or the three medicines in combination. The main measure of effectiveness was that the addition of Onivyde to the 5-fluorouracil plus leucovorin regimen prolonged patients’ lives. Patients taking the three medicines together lived for around 6.1 months (95 % CI: 4.8, 8.5), compared with 4.2 months(95 % CI: 3.3, 5.3) for patients taking 5-fluorouracil plus leucovorin 
, and 4.9 months for patients taking Onivyde alone 
The most common side effects with Onivyde are diarrhoea, nausea, vomiting, loss of appetite, neutropenia (low levels of neutrophils, a type of white blood cell), tiredness, weakness, anaemia (low red blood cell counts) stomatitis (inflammation of the lining of the mouth) and fever 
EMA. Human Medicines: Onivyde (irinotecan hydrochloride trihydrate), 25/10/2016, cited on 18/01/2017. http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/004125/human_med_002022.jsp&mid=WC0b01ac058001d124
Summary of Product Characteristics [FDA]: Onivyde (irinotecan liposome injection), Merrimack Pharmaceuticals Inc., Oct. 2015. http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/207793lbl.pdf
Summary of Product Characteristics [EMA]: Onivyde (liposomal irinotecan), Baxalta Innovations GmbH, Oct. 2016. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/004125/WC500215029.pdf
FDA News Release: FDA approves new treatment for advanced pancreatic cancer, 22/10/2015. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm468654.htm
Summary of Product Characteristics [TGA]: Onivyde (liposomal irinotecan), Baxalta Australia Pty Ltd, Dec. 2016. https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2016-PI-02871-1&d=2017102716114622483
Wikipedia. Fluorouracil. (last update: 5/11/2017), cited on 18/01/2017. https://en.wikipedia.org/wiki/Fluorouracil
Wikipedia. Folinic acid. (last update: 11/09/2017), cited on 18/01/2017. https://www.ebs.tga.gov.au/servlet/xmlmillr6?dbid=ebs/PublicHTML/pdfStore.nsf&docid=1205B876CA4F377DCA257C99003CA376&agid=(PrintDetailsPublic)&actionid=1
Wang-Gillam A., et al. Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1): a global, randomised, open-label, phase 3 trial. The Lancet. 2016 Feb 6; 387(10018):545–557. http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2815%2900986-1/abstract