Olaparib luciolap film coated tablets

[Chinese Drug Name]: Olaparani, Olaparib

[Brand Name]: Olaparib

[Dosage Form]: Tablets

[Specification]: 150 mg × 120 tablets

[Overview]

Olaparib (also known as Olaparani) is a PARP inhibitor. PARP stands for Poly(ADP-ribose) polymerase, an enzyme involved in the repair of DNA strand breaks. Healthy cells possess multiple signaling pathways for repairing broken DNA strands; therefore, inhibiting PARP alone does not typically result in significant toxicity to healthy cells. However, certain tumor cells—due to specific genetic mutations (such as *BRCA* mutations) that compromise other DNA repair pathways—become exceptionally sensitive to PARP inhibition.

The currently approved indications for Olaparib include breast cancer, as well as recurrent epithelial ovarian cancer, fallopian tube cancer, and primary peritoneal cancer.

[Indications]

1. Indicated as monotherapy for patients with advanced ovarian cancer harboring deleterious or suspected deleterious germline *BRCA* mutations, who have previously received three or more prior lines of chemotherapy.

2. Indicated for the treatment of patients with germline *BRCA*-mutated, HER2-negative metastatic breast cancer who have previously received chemotherapy in the neoadjuvant, adjuvant, or metastatic setting.

[Dosage and Administration]: Dosage and administration instructions may vary depending on the specific dosage form and strength of this product; please refer to the specific package insert for usage instructions, or follow your physician's orders.

Olaparib Tablets:

1. This product should be administered under the supervision of a physician experienced in the use of anticancer therapies.

2. Recommended Dosage: 300 mg (two 150 mg tablets) taken twice daily, for a total daily dose of 600 mg.

3. Treatment with this product should be initiated within 8 weeks of completing platinum-based chemotherapy and should be continued until disease progression or the occurrence of unacceptable toxicity.

4. Method of Administration: Oral administration. The tablets should be swallowed whole; they must not be chewed, crushed, dissolved, or broken apart. This product may be taken with or without food.

5. Missed Dose: If a patient misses a dose, the next dose should be taken at the regularly scheduled time.

Dosage Adjustments

(1) For Adverse Events

To manage adverse events—such as nausea, vomiting, diarrhea, anemia, etc.—treatment interruption or dose reduction may be considered.

If dose reduction is required, the recommended dose should be reduced to 250 mg (one 150 mg tablet and one 100 mg tablet) taken twice daily (equivalent to a total daily dose of 500 mg).

If further dose reduction is required, the recommended dose should be reduced to 200 mg (two 100 mg tablets) taken twice daily (equivalent to a total daily dose of 400 mg).

(2) Concomitant Use with Cytochrome P450 (CYP) 3A Inhibitors

Concomitant use of strong or moderate CYP3A inhibitors with this product is not recommended; alternative medications should be considered. If concomitant use with a strong CYP3A inhibitor is unavoidable, it is recommended to reduce the dose of this product to 100 mg (one 100 mg tablet) taken twice daily (equivalent to a total daily dose of 200 mg). If concomitant use with a moderate CYP3A inhibitor is unavoidable, it is recommended to reduce the dose of this product to 150 mg (one 150 mg tablet) taken twice daily (equivalent to a total daily dose of 300 mg).

Use in Specific Populations

(1) Renal Impairment: Patients with mild renal impairment (creatinine clearance 51–80 mL/min) may use this product without the need for dose adjustment. For patients with moderate renal impairment (creatinine clearance 31–50 mL/min), the recommended dose of this product is 200 mg (two 100 mg tablets) taken twice daily (equivalent to a total daily dose of 400 mg). Safety and efficacy data for the use of this product in patients with severe renal impairment or end-stage renal disease (creatinine clearance ≤ 30 mL/min) are not available; therefore, use of this product in these patients is not recommended. (2) Hepatic Impairment: Patients with mild hepatic impairment (Child-Pugh Class A) may use this product; no dose adjustment is required. Data regarding the safety and efficacy of this product in patients with moderate or severe hepatic impairment are currently unavailable; therefore, use in such patients is not recommended.

(3) Children and Adolescents: The safety and efficacy of this product in children and adolescents have not been established; use in pediatric patients is not recommended.

(4) Elderly Patients (>65 years): No adjustment to the starting dose is required for elderly patients. Clinical data for patients aged 75 years and older are limited.

[Adverse Reactions]:

1. The most common adverse reactions (≥20%) observed in clinical trials were:

1) Anemia, nausea, fatigue (including asthenia), vomiting, diarrhea.

2) Dysgeusia, dyspepsia, headache, decreased appetite, nasopharyngitis/pharyngitis/URI.

3) Cough, arthralgia/musculoskeletal pain, myalgia, back pain, dermatitis/rash, and abdominal pain/discomfort.

2. The most common laboratory abnormalities (≥25%) were:

Increased creatinine, increased mean corpuscular volume (MCV), decreased hemoglobin, decreased lymphocytes, decreased absolute neutrophil count, and decreased platelets.

[Contraindications]: Not yet established.

[Precautions]:

(1) Myelodysplastic Syndrome (MDS)/Acute Myeloid Leukemia (AML): MDS/AML has occurred in patients exposed to LuciOlap, and some cases have been fatal. Monitor patients for hematologic toxicity at baseline and monthly thereafter. Discontinue treatment if MDS/AML is confirmed.

(2) Pneumonitis: Pneumonitis has occurred in patients exposed to Lynparza, and some cases have been fatal. Interrupt treatment if pneumonitis is suspected. Discontinue treatment if confirmed.

(3) Embryo-Fetal Toxicity: LuciOlap may cause fetal harm. Advise women of reproductive potential regarding the potential hazard to the fetus and to avoid pregnancy.

Please read the package insert carefully and use as directed by a physician.

[Pediatric Use]: The safety and efficacy of LuciOlap in pediatric patients have not been established. [Use in Elderly Patients]: Clinical studies of LuciOlap enrolled 735 patients with advanced solid tumors [the majority (69%) of whom had ovarian cancer] who received LuciOlap 400 mg twice daily as monotherapy; 148 (20%) of these patients were aged ≥65 years. Although adverse reactions of CTCAE Grade ≥3 were reported more frequently in patients aged ≥65 years (53.4%) compared to those aged <65 years (43.4%), no specific adverse event or System Organ Class accounted for the observed difference, and the overall safety profiles were similar.

[Use in Pregnant and Lactating Women]: Based on its mechanism of action and findings in animal studies, LuciOlap may cause fetal harm when administered to pregnant women. At exposures lower than those observed in patients receiving the recommended human dose of 400 mg twice daily, olaparib was teratogenic and caused embryo-fetal toxicity in rats. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be advised of the potential hazard to the fetus and the potential risk of pregnancy loss. It is not known whether olaparib is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from olaparib, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

[Drug Interactions]: (1) CYP3A Inhibitors: Avoid concomitant use of strong and moderate CYP3A inhibitors. If use of an inhibitor cannot be avoided, reduce the dosage. (2) CYP3A Inducers: Avoid concomitant use of strong and moderate CYP3A inducers. If a moderate CYP3A inducer cannot be avoided, be aware of the potential for reduced efficacy.

[Overdosage]: There is no specific treatment for LuciOlap overdose, and symptoms of overdose have not been established. In the event of an overdose, physicians should follow general supportive measures and treat symptomatically. [Storage]

Store at 20°C to 25°C (68°F to 77°F); short-term transport is permitted within the temperature range of 15°C to 30°C (59°F to 86°F).