Olaparib (Lynparza)

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General information

Class/mechanism: PARP (poly-ADP (adenosine diphosphate)–ribose polymerase) inhibitor. PARP participates in the alternative base-excision repair pathway that helps to repair single-strand DNA breaks. PARP is involved in normal cellular homeostasis processes during DNA transcription and cell cycle regulation. By inhibiting PARP1, PARP2, and PARP3, olaparib leads to the accumulation of single-strand breaks. In patients with a concurrent BRCA1/BRCA2 mutation, in which there are also defects in homologous recombination double strand DNA repair, this inhibition of PARP enzymatic activity and formation of the PARP-DNA complex can lead to irrecoverable DNA damage and cell death.[1][2][3] [4]
Route: PO
Extravasation: n/a

For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as Micromedex, Lexicomp, UpToDate (courtesy of Lexicomp), or the package insert.[1]

Diseases for which it is used

Patient drug information

History of changes in FDA indication

gBRCAm Breast cancer

Ovarian cancer

gBRCAm Pancreatic cancer

  • 12/27/2019: Approved for the maintenance treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) metastatic pancreatic adenocarcinoma, as detected by an FDA-approved test, whose disease has not progressed on at least 16 weeks of a first-line platinum-based chemotherapy regimen. (New disease entity)

Also known as

  • Code names: AZD2281, AZD-2281, KU-0059436
  • Brand name: Lynparza

References

  1. 1.0 1.1 1.2 Olaparib (Lynparza) package insert
  2. Olaparib (Lynparza) package insert (locally hosted backup)
  3. Lynparza manufacturer's website
  4. Fong PC, Boss DS, Yap TA, Tutt A, Wu P, Mergui-Roelvink M, Mortimer P, Swaisland H, Lau A, O'Connor MJ, Ashworth A, Carmichael J, Kaye SB, Schellens JH, de Bono JS. Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med. 2009 Jul 9;361(2):123-34. Epub 2009 Jun 24. link to original article PubMed
  5. Olaparib (Lynparza) patient drug information (Chemocare)
  6. Olaparib (Lynparza)patient drug information (UpToDate)