ALIOLAPARIB Olaparib Tablets

I. Basic Drug Information

Generic Name: Olaparib Tablets

Brand Names: Lipzhuo, Lynparza, ALIOLAPARIB

English Name: Olaparib

Specification: 150 mg/tablet; 120 tablets/bottle

Manufacturer: Lao United Pharmaceutical Group Co., Ltd.

Approval Number (Lao National Drug Administration): 09 L 1389/25

Drug Category: Poly (ADP-ribose) polymerase inhibitor (PARP inhibitor)

II. Indications

Olaparib has been approved in numerous countries and regions worldwide for the treatment of the following types of cancer (please refer to the approvals issued by local drug regulatory authorities for specific indications):

1. Ovarian Cancer

First-line maintenance therapy: Maintenance treatment for adult patients with advanced epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer with a *BRCA* mutation who have responded to platinum-based chemotherapy.

Maintenance therapy: Maintenance treatment for adult patients with recurrent epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer who have responded to platinum-based chemotherapy (regardless of *BRCA* status).

Advanced-stage treatment: For the treatment of adult patients with advanced ovarian cancer harboring a germline *BRCA* mutation who have previously received three or more lines of chemotherapy.

2. Breast Cancer

For the treatment of adult patients with metastatic breast cancer harboring a germline *BRCA* mutation and HER2-negative status. Patients should have previously received chemotherapy in the neoadjuvant, adjuvant, or metastatic setting.

3. Pancreatic Cancer

As maintenance therapy for adult patients with metastatic pancreatic cancer harboring a germline *BRCA* mutation who have not experienced disease progression for at least 16 weeks following a first-line platinum-based chemotherapy regimen.

4. Prostate Cancer

For the treatment of adult patients with metastatic castration-resistant prostate cancer harboring deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene mutations, who have previously received a novel hormonal agent (e.g., enzalutamide, abiraterone).

5. (Others) As research progresses, the indications for this drug may continue to expand; please follow your physician's instructions. Note: Prior to initiating treatment with Olaparib, biomarker testing (such as BRCA1/2 mutation testing, HRD testing, etc.) is typically required to confirm whether the patient is suitable for this therapy.

III. Mechanism of Action

Olaparib is a first-in-class PARP inhibitor. Its mechanism of action is based on the principle of "synthetic lethality," as detailed below:

1. Role of PARP Enzymes: In both healthy and cancerous cells, PARP enzymes (specifically PARP1 and PARP2) play a critical role in repairing single-strand DNA damage. If single-strand damage remains unrepaired, it can progress into more dangerous double-strand breaks during cell division.

2. Inhibition by Olaparib: Olaparib inhibits the activity of PARP enzymes, thereby preventing them from repairing single-strand DNA damage.

3. Synthetic Lethality Effect: In cancer cells harboring homologous recombination repair (HRR) deficiencies (e.g., those with BRCA1/BRCA2 gene mutations), the primary pathway for repairing double-strand DNA breaks is compromised. At this juncture, the PARP repair pathway is also blocked by Olaparib; consequently, the cancer cells are unable to repair DNA damage. The accumulation of extensive DNA damage ultimately triggers cancer cell death.

4. Impact on Normal Cells: Normal cells typically possess intact homologous recombination repair capabilities. Even if the PARP pathway is inhibited, these cells can still repair double-strand DNA breaks through alternative pathways; therefore, they are relatively less affected.

IV. Dosage and Administration

Route of Administration: Oral.

Recommended Dosage:

Tablets: Typically 300 mg (consisting of two 150 mg tablets), taken twice daily (once in the morning and once in the evening), for a total daily dose of 600 mg.

Note: The tablet formulation has largely replaced the capsule formulation. Since the two formulations are not bioequivalent, direct milligram-to-milligram conversion is not permissible.

Method of Administration:

Swallow the tablets whole; do not chew, crush, or split them.

May be taken with or without food.

Treatment Duration: Continue treatment until disease progression or the occurrence of intolerable toxicity.

V. Dosage Adjustment and Management

In the event of adverse reactions, the physician may recommend temporarily withholding the medication, reducing the dosage, or permanently discontinuing treatment, depending on the severity of the reaction.

Starting Dose: 300 mg, twice daily. First dose reduction: 250 mg, twice daily (one 150 mg tablet + one 100 mg tablet).

Second dose reduction: 200 mg, twice daily (two 100 mg tablets).

*   If further dose reduction is still required, treatment should be discontinued.

Specific dose adjustments must strictly follow medical advice, based on clinical assessment and hematological test results.

VI. Contraindications

Contraindicated in patients with severe hypersensitivity to olaparib or to any of the excipients.

Contraindicated in pregnant and breastfeeding women (see [Use in Pregnant and Breastfeeding Women] for details).

VII. Warnings and Precautions

1.  Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML):

Cases of MDS/AML have been reported in patients treated with olaparib; these events may be fatal.

The incidence is approximately 1.5%, and the risk may increase with long-term treatment (>1 year).

Complete blood counts should be monitored regularly prior to and during treatment. If MDS/AML is confirmed, olaparib should be permanently discontinued.

2.  Pneumonitis:

Fatal cases of pneumonitis have been reported.

Patients presenting with new or worsening respiratory symptoms (e.g., dyspnea, cough, fever) should seek immediate medical attention and undergo diagnostic evaluation. If pneumonitis is confirmed, olaparib should be permanently discontinued.

3.  Embryo-Fetal Toxicity:

Olaparib may cause fetal harm. Women of reproductive potential must use effective contraception during treatment and for at least 6 months after the last dose. Male patients (including those who have undergone vasectomy) should use condoms for contraception during treatment and for 3 months after the last dose.

VIII. Adverse Reactions

Common adverse reactions associated with olaparib are generally Grade 1 or 2 in severity and can be managed through supportive care or dose adjustment.

Very Common (≥10%) Adverse Reactions:

Hematological Toxicity: Anemia, neutropenia, thrombocytopenia, lymphopenia.

Gastrointestinal Reactions: Nausea, vomiting, diarrhea, abdominal pain, dyspepsia, constipation. Systemic Reactions: Fatigue, asthenia, headache.

Laboratory Abnormalities: Increased creatinine, increased mean corpuscular volume (MCV).

Respiratory System: Cough, dyspnea.

Common (1%-10%) Adverse Reactions:

Appetite: Decreased appetite.

Skin: Rash.

Hematologic: Leukopenia.

Other: Dysgeusia (altered taste), arthralgia, back pain, dizziness, insomnia.

Important and Serious Adverse Reactions (See [Warnings and Precautions] for details):

Myelodysplastic Syndrome (MDS) / Acute Myeloid Leukemia (AML)

Pneumonia

IX. Drug Interactions

Olaparib is primarily metabolized by the hepatic enzymes CYP3A4/5; therefore, interactions may occur with drugs that affect these enzymes.

1.  Strong CYP3A Inhibitors:

Examples: Ketoconazole, itraconazole, voriconazole, clarithromycin, ritonavir, grapefruit juice.

Effect: Significantly increases olaparib plasma concentrations, thereby increasing the risk of adverse reactions.

Recommendation: Concomitant use should be avoided. If concomitant use is unavoidable, a dose reduction of olaparib should be considered.

2.  Strong or Moderate CYP3A Inducers:

Examples: Rifampin, carbamazepine, St. John's wort.

Effect: Significantly decreases olaparib plasma concentrations, potentially leading to reduced efficacy.

Recommendation: Concomitant use should be avoided.

3.  Drugs Affecting Gastric Acid Secretion:

Proton Pump Inhibitors (PPIs): May reduce the bioavailability of olaparib.

Recommendation: Administer such medications at least 2 hours before or at least 2 hours after taking olaparib.

Please be sure to inform your doctor before starting any new medication (including prescription drugs, over-the-counter drugs, and herbal products).

X. Use in Specific Populations

Pregnant Women: Contraindicated. Based on its mechanism of action, olaparib may cause fetal harm.

Breastfeeding Women: Contraindicated. It is not known whether Olaparib is excreted in human milk; given the potential for serious adverse reactions in nursing infants, breastfeeding is not recommended during treatment and for one month after the last dose.

Children and Adolescents: Safety and efficacy have not been established.

Elderly Patients: No dose adjustment is required, but close monitoring is recommended.

Hepatic/Renal Impairment:

Mild Hepatic Impairment: No dose adjustment is required.

Moderate or Severe Hepatic Impairment: Use is not recommended.

Mild Renal Impairment: No dose adjustment is required.

Moderate Renal Impairment: Use with caution; dose adjustment may be required.

Severe Renal Impairment or End-Stage Renal Disease: Use is not recommended.

XI. Overdosage

In clinical studies, the highest single dose administered was 600 mg.

Overdosage may exacerbate adverse reactions, particularly bone marrow suppression.

In the event of an overdose, treatment should be discontinued, and immediate supportive measures should be initiated, including close monitoring of blood counts.

XII. Storage

Store below 30°C.

Store in the original packaging to protect from moisture and light.

Keep out of the reach of children.

Final Reminder: This content serves as an informational summary and is not a substitute for professional medical advice. Your treating physician is the most reliable and up-to-date source for information regarding your treatment. Please ensure you communicate closely with your healthcare team and report any discomfort or adverse reactions you experience.