Mifamurtide
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Trade names | Mepact |
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liposomal infusion over one hour | |
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Pharmacokinetic data | |
Bioavailability | N/A |
Elimination half-life | minutes (in plasma) 18 hrs (terminal) |
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Mifamurtide (trade name Mepact, marketed by Takeda) is a drug against osteosarcoma, a kind of bone cancer mainly affecting children and young adults, which is lethal in over half of cases. The drug was approved in Europe in March 2009.
Medical uses
Mifamurtide is indicated for the treatment of high-grade, nonmetastasizing, resectable osteosarcoma following complete surgical removal in children, adolescents, and young adults, aged two to 30 years.[1][2][3] Osteosarcoma is diagnosed in about 1,000 individuals in Europe and the USA per year, most under the age of 30.[4] The drug is used in combination with postoperative, multiagent chemotherapy to kill remaining cancer cells and improve a patient's chance of overall survival.[2]
In a phase-III clinical trial in about 800 newly diagnosed osteosarcoma patients, mifamurtide was combined with the chemotherapeutic agents doxorubicin and methotrexate, with or without cisplatin and ifosfamide. The mortality could be lowered by 30% versus chemotherapy plus placebo. Six years after the treatment, 78% of patients were still alive. This equals an absolute risk reduction of 8% .[1]
Adverse effects
In a clinical study, mifamurtide was given to 332 subjects (half of whom were under age of 16) and most side effects were found to be mild to moderate in nature. Most patients experience fewer adverse events with subsequent administration.
Interactions
- Theoretical considerations suggest calcineurin inhibitors like ciclosporin and tacrolimusmight interact with mifamurtide because of their effect on macrophages.
- High-dose NSAIDsblock the mechanism of mifamurtide in vitro.
Consequently, the combination of mifamurtide with these types of drugs is contraindicated. However, mifamurtide can be coadministered with low doses of NSAIDs. No evidence suggests mifamurtide interacts with the studied chemotherapeutics, or with the cytochrome P450 system.[8]
Pharmacology
Mechanism of action
Mifamurtide is a fully synthetic derivative of muramyl dipeptide (MDP), the smallest naturally occurring immune stimulatory component of cell walls from Mycobacterium species. It has similar immunostimulatory effects as natural MDP with the advantage of a longer half-life in plasma.
Pharmacokinetics
After application of the
Chemistry
Mifamurtide is muramyl tripeptide phosphatidylethanolamine (MTP-PE), a synthetic analogue of muramyl dipeptide. The side chains of the molecule give it a longer
Synthesis
One method of synthesis (shown first) is based on
History
The drug was invented by
Mifamurtide had already been granted
References
- ^ PMID 18298131.
- ^ a b EMA (2009-03-06). "Mepact: Product Information. Annex I: Summary of Product Characteristics" (PDF). p. 2. Retrieved 2009-11-12.[dead link]
- ^ EMA (2009-05-06). "Mepact: European Public Assessment Report. Summary for the public" (PDF). p. 1. Retrieved 2016-10-06.
- S2CID 29512704.
- PMID 18235123.
- PMID 15774791.
- ^ (EMA & 2009-03-06, pp. 5–7)
- ^ (EMA & 2009-03-06, p. 4)
- ^ (EMA & 2009-03-06, pp. 7–8)
- ^ (EMA & 2009-03-06, p. 8)
- ^ Fidler IJ, Sone S, Fogler WE, Smith D, Braun DG, Tarcsay L, Gisler RH, Schroit AJ (1982). "Efficacy of liposomes containing a lipophilic muramyl dipeptide derivative for activating the tumoricidal properties of alveolar macrophages in vivo". Journal of Immunotherapy. 1 (1): 43–55.
- .
- .
- ^ "First Treatment to Improve Survival in 20 Years Now Available for Patients With Osteosarcoma (Bone Cancer)". Takeda. November 2009. Retrieved 23 March 2010.
- ^ "IDM Pharma's MEPACT (Mifamurtide, L-MTP-PE) Receives Approval in Europe for Treatment of Patients with Non-Metastatic, Resectable Osteosarcoma". PR Newswire. 2009-03-09. Retrieved 2009-11-12.
- ^ "IDM Pharma receives not approvable letter for Mifamurtide for treatment of osteosarcoma". The Medical News. 2007-08-28. Retrieved 2009-11-12.
- ^ Mepact for Healthcare Professionals, retrieved 2009-11-12