LYNPARZA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LYNPARZA (LYNPARZA).
Poly (ADP-ribose) polymerase (PARP) enzyme inhibitor, including PARP1, PARP2, and PARP3. Inhibits PARP catalytic activity and traps PARP-DNA complexes, leading to replication fork stalling, double-strand breaks, and cell death in tumors with homologous recombination repair deficiencies such as BRCA mutations.
| Metabolism | Primarily metabolized by CYP3A4; minor contributions from CYP3A5. |
| Excretion | Following oral administration of olaparib, approximately 70% of the dose is recovered in feces (44% as unchanged parent drug) and 16% in urine (1% as unchanged drug). Biliary excretion is the primary route of elimination, with renal excretion playing a minor role. |
| Half-life | The terminal elimination half-life is approximately 14.9 hours in patients with advanced solid tumors. This supports twice-daily dosing to maintain therapeutic concentrations. |
| Protein binding | Approximately 82% bound to human plasma proteins, primarily to albumin. |
| Volume of Distribution | The apparent volume of distribution (Vd/F) is approximately 158 L (about 2.2 L/kg for a 70 kg patient), indicating extensive distribution into tissues. |
| Bioavailability | Oral bioavailability is not precisely defined in humans due to lack of IV formulation; however, based on animal data and clinical pharmacokinetics, oral absorption is rapid and extensive, with peak plasma concentrations achieved 1-3 hours post-dose. Food does not significantly affect absorption. |
| Onset of Action | Clinical effect (PARP inhibition) occurs within hours after oral administration; maximal inhibition of PARP activity is observed at 2-4 hours post-dose. |
| Duration of Action | PARP inhibition persists for at least 24 hours after a single dose, allowing for sustained anti-tumor activity with twice-daily dosing. The duration of clinical response depends on tumor type and patient factors. |
300 mg orally twice daily, with or without food.
| Dosage form | TABLET |
| Renal impairment | For creatinine clearance 31-60 mL/min: 300 mg twice daily; for creatinine clearance 16-30 mL/min: 200 mg twice daily; for creatinine clearance ≤15 mL/min: not recommended. |
| Liver impairment | Child-Pugh Class A: no adjustment; Child-Pugh Class B: 300 mg twice daily (caution); Child-Pugh Class C: not recommended. |
| Pediatric use | Not established; safety and efficacy not determined in patients <18 years. |
| Geriatric use | No specific dose adjustment based on age alone; monitor renal function and adjust per renal guidelines. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for LYNPARZA (LYNPARZA).
| Breastfeeding | No data on presence in human milk. Due to potential serious adverse reactions in breastfed infants (genotoxicity, developmental toxicity), breastfeeding is not recommended during treatment and for 1 month after the last dose. M/P ratio unknown. |
| Teratogenic Risk | Based on its mechanism of action (PARP inhibition) and animal studies, olaparib is embryotoxic and teratogenic. It is contraindicated in pregnancy. There is a potential for fetal harm in all trimesters due to genotoxicity and effects on rapidly dividing cells. |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to olaparib or any excipients"]
| Precautions | ["Myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) have been reported, including fatal cases","Pneumonitis including interstitial lung disease has occurred","Embryo-fetal toxicity: can cause fetal harm; advise females of reproductive potential of potential risk","Potential for myelosuppression; monitor complete blood counts","Increased risk of venous thromboembolic events (including pulmonary embolism) in patients with pancreatic cancer"] |
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| Fetal Monitoring |
| Pregnancy testing should be performed prior to initiation in females of reproductive potential. Effective contraception during treatment and for at least 6 months after the last dose is required. If exposure occurs during pregnancy, monitor for fetal growth and development. |
| Fertility Effects | Olaparib may impair fertility in females and males based on animal studies showing effects on reproductive organs. In humans, amenorrhea and reduced ovarian reserve have been reported. It is recommended to discuss fertility preservation prior to treatment. |