olaparib

High Alert

Maintenance treatment of recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer in patients who are in a complete or partial response to platinum-based chemotherapy.
First-line maintenance treatment of deleterious/suspected deleterious germline or somatic BRCA-mutated recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer in patients who are in a complete or partial response to first-line platinum-based chemotherapy.
First-line maintenance treatment of advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer in patients who are in a complete or partial response to first-line platinum-based chemotherapy and whose cancer is associated with homologous recombination deficiency positive status defined by either a deleterious/suspected deleterious BRCA mutation and/or genomic instability (in combination with bevacizumab).
Adjuvant treatment of deleterious or suspected deleterious germline BRCA-mutated human epidermal growth factor receptor 2 (HER2)-negative high-risk early breast cancer in patients who have been treated with neoadjuvant or adjuvant chemotherapy.
Deleterious/suspected deleterious germline BRCA-mutated HER2-negative metastatic breast cancer in patients who have been treated with chemotherapy in the neoadjuvant, adjuvant, or metastatic setting (should have been previously treated with or considered intolerant to an endocrine therapy).
First-line maintenance treatment of deleterious/suspected deleterious germline BRCA-mutated metastatic pancreatic adenocarcinoma in patients whose disease has not progressed on ≥16 wk of a first-line platinum-based chemotherapy regimen.
Deleterious/suspected deleterious germline or somatic homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer in patients who have progressed following previous treatment with enzalutamide or abiraterone.
Deleterious/suspected deleterious BRCA-mutated metastatic castration-resistant prostate cancer (in combination with abiraterone and prednisolone [or prednisone]).

Action ⬆ ⬇

Acts as a poly (ADP-ribose) polymerase (PARP) inhibitor; disrupts DNA transcription, cell cycle regulation, and DNA repair.

Therapeutic effects:

Improved progression-free survival in ovarian, fallopian tube, primary peritoneal, breast, pancreatic, and prostate cancer.

Pharmacokinetics ⬆ ⬇

Absorption: Well absorbed following oral administration.

Distribution: Unknown.

Metabolism/Excretion: Extensively metabolized (mostly by the CYP3A isoenzyme); 15% excreted unchanged in urine, 6% in feces.

Half-Life: 14.9 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	1–3 hr	12 hr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Moderate or severe hepatic impairment;
Moderate or severe renal impairment (CCr <50 mL/min) (dose ↓ may be needed);
Rep: Women of reproductive potential and men with female partners of reproductive potential;
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

CV: DEEP VEIN THROMBOSIS

Derm: dermatitis/rash

GI: abdominal pain, diarrhea, dyspepsia, nausea, vomiting

Hemat: anemia, lymphopenia, neutropenia, thrombocytopenia, MYELODYSPLASTIC SYNDROME (MDS)/ACUTE MYELOID LEUKEMIA (AML)

Metab: ↓appetite

MS: arthralgia, back pain, myalgia

Neuro: fatigue, headache, dysgeusia, weakness

Resp: cough, PNEUMONITIS, PULMONARY EMBOLISM

Interactions ⬆ ⬇

Drug-drug:

↑risk of prolonged myelosuppression with other antineoplastics.
Concurrent use with strong CYP3A4 inhibitors, including clarithromycin, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, posaconazole, ritonavir, or voriconazole, ↑ levels and risk of toxicity; avoid concurrent use if possible but if necessary, ↓ olaparib dose.
Concurrent use with moderate CYP3A4 inhibitors, including aprepitant, atazanavir, ciprofloxacin, crizotinib, darunavir/ritonavir, diltiazem, erythromycin, fluconazole, fosamprenavir, imatinib, or verapamil, ↑ levels and risk of toxicity; avoid concurrent use if possible but if necessary, ↓ olaparib dose.
Concurrent use with strong CYP3A inducers, including carbamazepine, phenytoin, and rifampin, ↓ blood levels and effectiveness and should be avoided.
Concurrent use with moderate CYP3A inducers, including bosentan, efavirenz, etravirine, modafinil, and nafcillin, ↓ blood levels and effectiveness; avoid if possible.

Drug-Natural Products:

St. John's wort may ↓ blood levels and effectiveness and should be avoided.

Concurrent ingestion of grapefruit and Seville oranges may ↑ blood levels and the risk of toxicity and should be avoided.

Route/Dosage ⬆ ⬇

First-Line Maintenance Treatment of BRCA-Mutated Advanced Ovarian Cancer or Advanced Ovarian Cancer (in Combination with Bevacizumab)

PO (Adults ): 300 mg twice daily until disease progression, unacceptable toxicity, or completion of 2 yr of treatment. If complete response achieved after 2 yr of treatment (i.e., no radiological evidence of disease), can stop therapy. If evidence of disease at 2 yr, may continue therapy. Concurrent use of strong CYP3A4 inhibitor: 100 mg twice daily until disease progression, unacceptable toxicity, or completion of 2 yr of treatment. If complete response achieved after 2 yr of treatment (i.e., no radiological evidence of disease), can stop therapy. If evidence of disease at 2 yr, may continue therapy. Concurrent use of moderate CYP3A4 inhibitor: 150 mg twice daily until disease progression, unacceptable toxicity, or completion of 2 yr of treatment. If complete response achieved after 2 yr of treatment (i.e., no radiological evidence of disease), can stop therapy. If evidence of disease at 2 yr, may continue therapy.

Renal Impairment

PO (Adults ): CCr 31–50 mL/min: 200 mg twice daily until disease progression, unacceptable toxicity, or completion of 2 yr of treatment. If complete response achieved after 2 yr of treatment (i.e., no radiological evidence of disease), can stop therapy. If evidence of disease at 2 yr, may continue therapy.

Adjuvant Treatment of Germline BRCA-Mutated HER2-Negative High-Risk Early Breast Cancer

PO (Adults ): 300 mg twice daily for 1 yr or until disease recurrence or unacceptable toxicity, whichever occurs first. Concurrent use of strong CYP3A4 inhibitor: 100 mg twice daily for 1 yr or until disease recurrence or unacceptable toxicity, whichever occurs first. Concurrent use of moderate CYP3A4 inhibitor: 150 mg twice daily for 1 yr or until disease recurrence or unacceptable toxicity, whichever occurs first.

Renal Impairment

PO (Adults ): CCr 31–50 mL/min: 200 mg twice daily for 1 yr or until disease recurrence or unacceptable toxicity, whichever occurs first.

Recurrent Ovarian Cancer, Germline BRCA-Mutated HER2-Negative Metastatic Breast Cancer, Germline BRCA-Mutated Metastatic Pancreatic Adenocarcinoma, HRR Gene-Mutated Metastatic Castration-Resistant Prostate Cancer, BRCA-Mutated Metastatic Castration-Resistant Prostate Cancer

PO (Adults ): 300 mg twice daily until disease progression or unacceptable toxicity. Concurrent use of strong CYP3A4 inhibitor: 100 mg twice daily until disease progression or unacceptable toxicity. Concurrent use of moderate CYP3A4 inhibitor: 150 mg twice daily until disease progression or unacceptable toxicity.

Renal Impairment

PO (Adults ): CCr 31–50 mL/min: 200 mg twice daily until disease progression or unacceptable toxicity.

Availability ⬆ ⬇

Tablets: 100 mg; 150 mg

Assessment ⬆ ⬇

Monitor for signs and symptoms of pneumonitis (new or worsening respiratory symptoms, dyspnea, fever, cough, wheezing, radiological abnormality) during therapy. Interrupt therapy; if pneumonitis confirmed, discontinue therapy.
Monitor for signs and symptoms of deep vein thrombosis and pulmonary embolism and treat as medically appropriate. May require long-term anticoagulation.

Lab Test Considerations:

Patient selection is based on the presence of deleterious or suspected deleterious HRR gene mutations, including BRCA mutations, or genomic instability based on the indication, biomarker, and sample type. Information on FDA-approved tests for the detection of genetic mutations is available at http://www.fda.gov/companiondiagnostics.
- Verify negative pregnancy test prior to starting therapy.
- Monitor CBC at baseline and monthly during therapy. Do not start olaparib until patient has recovered from hematological toxicities from previous chemotherapy (≤CTCAE Grade 1). For prolonged hematological toxicities, interrupt olaparib and monitor CBC weekly until recovery. If levels have not recovered to Grade ≤1 after 4 wk, refer to hematologist. Discontinue olaparib if MDS or AML is confirmed.
- May cause ↓ hemoglobin, neutrophils, platelets, and lymphocytes. May cause ↑ mean corpuscular volume and serum creatinine.

Implementation ⬆ ⬇

PO: Administer twice daily, about 12 hr apart, without regard to food. DNC: Swallow tablets whole; do not break, chew, or dissolve tablets.

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication. Advise patient to read Patient Information before starting therapy. Instruct patient to take as directed. If a dose is missed, do not take another to make up; omit dose and take next scheduled dose. Emphasize importance of routine lab tests.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications, especially St. John's wort.
Inform patient that mild to moderate nausea and/or vomiting is common. Notify a health care professional for antiemetic options if this is problematic.
Advise patient to avoid grapefruit, grapefruit juice, Seville oranges, and Seville orange juice during therapy.
Advise patient to notify health care professional if signs and symptoms of pneumonitis or hematological toxicity (weakness, feeling tired, fever, weight loss, frequent infections, bruising, bleeding easily, shortness of breath, blood in urine or stool, low blood cell counts on laboratory findings, need for blood transfusions) occur. May also be MDS or AML.
Rep: May cause fetal harm and risk for loss of pregnancy. Advise females of reproductive potential to use effective contraception during therapy and for 6 mo after last dose and to avoid breastfeeding for 1 mo after last dose. Advise patient to notify health care professional if pregnancy is planned or suspected. Advise males with female partners of reproductive potential to use effective contraception during and for 3 mo after last dose. Advise male patients not to donate sperm during therapy and for 3 mo following the last dose.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Contraind./Precautions ⬆ ⬇

Adv. Reactions/Side Effects ⬆ ⬇

Interactions ⬆ ⬇

Route/Dosage ⬆ ⬇

Availability ⬆ ⬇

Assessment ⬆ ⬇

Implementation ⬆ ⬇

Patient/Family Teaching ⬆ ⬇

Evaluation/Desired Outcomes ⬆ ⬇

US Brand Names ⬆