Alliance ALIOLAPARIB Olaparib Tablets

I. Basic Drug Information

Generic Name: Olaparib Tablets

Brand Names: Lipuzhuo, Lynparza, ALIOLAPARIB

English Name: Olaparib

Specification: 150 mg/tablet; 120 tablets/bottle

Manufacturer: Lao United Pharmaceutical Group Co., Ltd.

Lao FDA Approval No.: 09 L 1389/25

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

II. Indications

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

1.  Ovarian Cancer

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

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

Advanced-stage treatment: Treatment for adult patients with advanced ovarian cancer harboring germline BRCA mutations who have previously received three or more lines of chemotherapy.

2.  Breast Cancer

Treatment for adult patients with HER2-negative metastatic breast cancer harboring germline BRCA mutations. Patients must have previously received chemotherapy in the neoadjuvant, adjuvant, or metastatic setting.

3.  Pancreatic Cancer

Maintenance treatment for adult patients with metastatic pancreatic cancer harboring germline BRCA mutations who have not experienced disease progression for at least 16 weeks following a first-line platinum-based chemotherapy regimen.

4.  Prostate Cancer

Treatment for 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 novel hormonal therapy (e.g., enzalutamide, abiraterone).

5.  (Other) Indications may expand as research progresses; please follow medical advice. Note: Before using olaparib, biomarker testing (such as BRCA1/2 mutation testing or HRD testing) is typically required to confirm the patient's suitability for the treatment.

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 follows:

1. Role of PARP enzymes: In both healthy and cancer cells, PARP enzymes (specifically PARP1 and PARP2) play a key role in repairing DNA single-strand breaks. If single-strand breaks remain unrepaired, they can progress to more dangerous double-strand breaks during cell division.

2. Inhibition by olaparib: Olaparib inhibits PARP enzyme activity, thereby preventing the repair of DNA single-strand breaks.

3. Synthetic lethality effect: In cancer cells with homologous recombination repair (HRR) deficiencies (such as BRCA1/BRCA2 gene mutations), the primary pathway for repairing DNA double-strand breaks is dysfunctional. When the PARP repair pathway is also blocked by olaparib, the cancer cells cannot repair DNA damage; the accumulation of extensive DNA damage ultimately leads to cancer cell death.

4. Impact on normal cells: Normal cells typically possess intact homologous recombination repair functions. Even when the PARP pathway is inhibited, they can still repair DNA double-strand breaks via other pathways; therefore, they are relatively less affected.

IV. Dosage and Administration

Route of administration: Oral.

Recommended dosage:

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

Note: Tablets have largely replaced capsules; the two formulations are not bioequivalent, so dosages cannot be directly converted on a milligram-for-milligram basis.

Administration instructions:

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

May be taken with or without food.

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

V. Dose Adjustment and Management

If adverse reactions occur, the physician may recommend interrupting treatment, reducing the dose, or permanently discontinuing the drug, 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 required, treatment should be discontinued.

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

VI. Contraindications

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

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

VII. Warnings and Precautions

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

MDS/AML has 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 before 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 (such as dyspnea, cough, or 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 1–2 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: Elevated creatinine, increased mean corpuscular volume (MCV).

Respiratory system: Cough, dyspnea.

Common (1%–10%) adverse reactions:

Appetite: Decreased appetite.

Skin: Rash.

Hematology: Leukopenia.

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

Important and serious adverse reactions (see [Warnings and Precautions] for details):

Myelodysplastic syndrome (MDS)/Acute myeloid leukemia (AML)

Pneumonitis

IX. Drug Interactions

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

1.  Strong CYP3A inhibitors:

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

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

Recommendation: Avoid co-administration. If co-administration is necessary, consider dose reduction of olaparib.

2.  Strong or moderate CYP3A inducers:

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

Effect: Significantly decreases olaparib plasma concentrations, potentially reducing efficacy.

Recommendation: Avoid co-administration.

3.  Drugs affecting gastric acid secretion:

Proton pump inhibitors (PPIs): May reduce the bioavailability of olaparib.

Recommendation: Administer these drugs at least 2 hours before or at least 2 hours after taking olaparib.

Always inform your doctor before starting any new medication (including prescription drugs, over-the-counter medicines, and herbal products).

X. Use in Special Populations

Pregnant women: Contraindicated. Based on its mechanism of action, olaparib may cause harm to the fetus.

Lactating women: Contraindicated. It is unknown whether olaparib is excreted in human milk; given the potential for serious adverse reactions in infants, breastfeeding should be avoided during treatment and for one month after the last dose.

Pediatric population: Safety and efficacy have not been established.

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

Hepatic/Renal impairment:

Mild hepatic impairment: No dose adjustment required.

Moderate or severe hepatic impairment: Not recommended.

Mild renal impairment: No dose adjustment required.

Moderate renal impairment: Use with caution; dose adjustment may be necessary.

Severe renal impairment or end-stage renal disease: Not recommended.

XI. Overdose

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

Overdose may exacerbate adverse reactions, particularly myelosuppression.

In the event of an overdose, treatment should be interrupted, and supportive care—including close monitoring of blood counts—should be initiated immediately.

XII. Storage

Store below 30°C.

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

Keep out of the reach of children.

A final reminder: This content is a summary of information and is not a substitute for professional medical advice. Your attending physician is the most reliable and up-to-date source of information regarding your treatment. Please maintain close communication with your medical team and report any adverse effects you experience.