OLANDR Olaparib

I. Basic Drug Information

Generic Name: Olaparib

English Name: Olaparib

Brand Name: Lynparza

Specification: 50 mg × 112 capsules/box

Manufacturer: INDAR Pharmaceutical Co., Ltd.

Storage: Store below 30°C.

II. Mechanism of Action

Olaparib exerts its effects by inhibiting PARP enzyme activity, thereby interfering with DNA damage repair in cancer cells (specifically single-strand break repair). In cancer cells harboring homologous recombination repair deficiencies (such as BRCA1/2 mutations), Olaparib leads to the accumulation of DNA damage, triggering a "synthetic lethality" effect that selectively kills the cancer cells.

III. Indications

Olaparib is indicated for the following adult patients:

1. Ovarian Cancer / Fallopian Tube Cancer / Primary Peritoneal Cancer:

First-line Maintenance Therapy:

Patients with advanced disease harboring BRCA mutations (germline or somatic) who have achieved a complete or partial response following first-line platinum-based chemotherapy. 

Patients with HRD-positive status (defined as having a BRCA mutation and/or genomic instability), in combination with bevacizumab. 

Recurrent Maintenance Therapy: Patients with platinum-sensitive recurrent disease who have achieved a complete or partial response following platinum-containing chemotherapy (regardless of BRCA status).

2. Breast Cancer:

Adjuvant Therapy: Patients with high-risk, early-stage, HER2-negative breast cancer harboring germline BRCA (gBRCA) mutations, following completion of neoadjuvant or adjuvant chemotherapy. 

Metastatic Therapy: Patients with metastatic, HER2-negative breast cancer harboring gBRCA mutations who have previously received chemotherapy (patients with HR-positive disease must have also previously received endocrine therapy).

3. Pancreatic Cancer: Patients with metastatic pancreatic adenocarcinoma harboring gBRCA mutations, as maintenance therapy following at least 16 weeks of first-line platinum-based chemotherapy without disease progression.

4. Prostate Cancer:

Patients with metastatic castration-resistant prostate cancer (mCRPC) harboring HRR gene mutations, whose disease has progressed following prior treatment with enzalutamide or abiraterone. 

Patients with mCRPC harboring BRCA mutations, in combination with abiraterone and prednisone. IV. Dosage and Administration

Standard Recommended Dose: 300 mg (6 x 50 mg tablets) orally, twice daily (approximately 12 hours apart), for a total daily dose of 600 mg.

Administration Method: Swallow tablets whole; do not chew, crush, or split them. May be taken with or without food, or on an empty stomach.

Duration of Treatment:

| Indication                                                  | Duration of Treatment |

| Adjuvant treatment of early breast cancer               | Total of 1 year, or until recurrence/intolerable toxicity |

| First-line maintenance for ovarian cancer (BRCA-mutated or HRD-positive) | Until disease progression/intolerable toxicity, or completion of 2 years (discontinue at 2 years if complete remission is achieved) |

| Other indications (recurrent ovarian cancer, metastatic breast cancer, pancreatic cancer, prostate cancer) | Until disease progression/intolerable toxicity |

Missed Dose: Do not take a missed dose; take the next dose at the regularly scheduled time.

V. Dosage Adjustments

1. Based on Adverse Reactions

First Dose Reduction: → 250 mg (3 x 50 mg tablets + 2 x 50 mg tablets), twice daily (total daily dose: 500 mg).

Second Dose Reduction: → 200 mg (4 x 50 mg tablets), twice daily (total daily dose: 400 mg).

2. Based on Concomitant Medications

Strong CYP3A Inhibitors (e.g., clarithromycin, itraconazole): Reduce dose to 100 mg, twice daily.

Moderate CYP3A Inhibitors (e.g., fluconazole, verapamil): Reduce dose to 150 mg, twice daily.

Note: Avoid consuming grapefruit or grapefruit juice (contains CYP3A inhibitors).

3. Based on Hepatic and Renal Function

Moderate Renal Impairment (CrCl 31–50 mL/min): Start with a dose of 200 mg, twice daily.

Severe Renal Impairment (CrCl ≤30 mL/min) or Moderate-to-Severe Hepatic Impairment (Child-Pugh B/C): Contraindicated (no safety data available). VI. Adverse Reactions

Common Adverse Reactions (Incidence ≥ 10%):

Hematologic System: Anemia (up to 20% Grade 3–4), neutropenia, thrombocytopenia, lymphopenia.

Digestive System: Nausea, vomiting, diarrhea, decreased appetite.

Systemic: Fatigue (including asthenia).

Other: Headache, dysgeusia, cough, dizziness.

Serious Adverse Reactions (Requiring Immediate Intervention):

Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML): Incidence < 1.5%; may be fatal.

Pneumonia: Incidence < 1%; may be fatal (new-onset or worsening dyspnea, cough, or fever should be monitored closely).

Venous Thromboembolism (VTE): Including pulmonary embolism (incidence of 7% in patients with prostate cancer).

VII. Contraindications

1. Hypersensitivity to olaparib or to any of the excipients.

2. Pregnancy (risk of fetal malformation).

3. Breastfeeding (discontinue breastfeeding during treatment and for 1 month after the last dose).

VIII. Important Precautions

1. Hematologic Monitoring:

Prior to treatment, confirm that baseline hematologic parameters have recovered (Hb, PLT, and ANC ≤ CTCAE Grade 1). 

Monitor complete blood counts monthly during the first year of treatment, and periodically thereafter.

2. Embryo-Fetal Toxicity:

Women of reproductive potential must have a negative pregnancy test prior to treatment and must use effective contraception during treatment and for 6 months after the last dose (non-hormonal methods are preferred). 

Male patients (with female partners of reproductive potential) must use effective contraception during treatment and for 3 months after the last dose.

3. Drug Interactions:

Avoid concomitant use of strong CYP3A inducers (e.g., rifampin, carbamazepine)—this may significantly reduce olaparib plasma concentrations.

4. Special Populations:

Elderly patients (≥ 75 years): Data are limited; use with caution, though no adjustment to the starting dose is required. 

Children/Adolescents: No safety data available; contraindicated. IX. Drug Interactions

| Concomitant Drug Type                      | Effect on Olaparib | Management Recommendations

| Strong CYP3A Inhibitors (e.g., Ketoconazole) | Plasma Concentration ↑170% | Avoid use; if co-administration is necessary, reduce dose to 100 mg BID.

| Moderate CYP3A Inhibitors (e.g., Fluconazole) | Plasma Concentration ↑121% | Avoid use; if co-administration is necessary, reduce dose to 150 mg BID.

| Strong CYP3A Inducers (e.g., Rifampin)     | Plasma Concentration ↓87% | Contraindicated (significantly reduces therapeutic efficacy).

Important Safety Information

> 1. If MDS/AML or pneumonia is confirmed during treatment, permanently discontinue the drug.

> 2. If persistent hematological toxicity occurs (failure to recover within 4 weeks), a bone marrow examination is required.

> 3. This product information does not substitute for medical advice; medication must be administered under the guidance of an oncology specialist, and the treatment regimen should be adjusted according to individual patient circumstances.

Product Specifications

Product Name: Olaparib 50 mg * 112 Capsules/Box (OLANDR Olaparib)

Common Name: Olaparib Capsules

Active Ingredient: Olaparib

Dosage Form: Capsules

Specification: 50 mg * 112 Capsules/Box

Manufacturer: INDAR Pharmaceutical Co., Ltd.

Indications: Olaparib is indicated for the following adult patients:

1. Ovarian Cancer / Fallopian Tube Cancer / Primary Peritoneal Cancer:

First-line Maintenance Therapy:

Patients with advanced disease harboring a *BRCA* mutation (germline or somatic) who have achieved a complete or partial response following first-line platinum-based chemotherapy.

Patients with HRD-positive status (*BRCA* mutation and/or genomic instability), in combination with bevacizumab.

Recurrent Maintenance Therapy: Patients with platinum-sensitive recurrent disease who have achieved a complete or partial response following platinum-based chemotherapy (regardless of *BRCA* status).

2. Breast Cancer:

Adjuvant Therapy: Patients with high-risk early-stage breast cancer harboring a *gBRCA* mutation and HER2-negative status, following completion of neoadjuvant or adjuvant chemotherapy. Metastatic Setting: gBRCA-mutated, HER2-negative metastatic breast cancer, with a history of prior chemotherapy (patients with HR+ disease must have received prior endocrine therapy).

3. Pancreatic Cancer: gBRCA-mutated metastatic pancreatic adenocarcinoma, as maintenance therapy following ≥16 weeks of first-line platinum-based chemotherapy without disease progression.

4. Prostate Cancer:

HRR gene-mutated metastatic castration-resistant prostate cancer (mCRPC), following disease progression on prior enzalutamide or abiraterone.

BRCA-mutated mCRPC, in combination with abiraterone and prednisone.

Dosage and Administration: Standard Recommended Dose: 300 mg (six 50 mg tablets) orally, twice daily (approximately 12 hours apart), for a total daily dose of 600 mg.

Administration Method: Swallow tablets whole; do not chew, crush, or split. May be taken with or without food.