(oh LAP a rib)
- PARP inhibitor AZD2281
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Lynparza: 50 mg
Brand Names: U.S.
- Antineoplastic Agent, PARP Inhibitor
Olaparib is a poly (ADP-ribose) polymerase (PARP) enzyme inhibitor, including PARP1, PARP2, and PARP3. PARP enzymes are involved in DNA transcription, cell cycle regulation, and DNA repair. Olaparib is a potent oral PARP inhibitor which induces synthetic lethality in BRCA1/2 deficient tumor cells through the formation of double-stranded DNA breaks which cannot be accurately repaired, which leads to disruption of cellular homeostasis and cell death (Ledermann 2012).
Rapid; delayed with a high-fat meal (extent of absorption not significantly altered)
167 ± 196 L
Primarily hepatic via CYP3A4; the majority of metabolism is through oxidation with some metabolites undergoing subsequent glucuronide or sulfate conjugation
Urine (44%, mostly metabolites); feces (42%, mostly metabolites)
Time to Peak
1 to 3 hours
Terminal: 11.9 ± 4.8 hours
Special Populations: Renal Function Impairment
The mean AUC and Cmax each increased by 1.2-fold when administered to patients with mild renal impairment (CrCl 51 to 80 mL/minute), and by 1.4- and 1.3-fold, respectively, in patients with moderate renal impairment (CrCl 31 to 50 mL/minute) compared to patients with normal renal function.
Special Populations: Hepatic Function Impairment
The mean AUC was increased 1.2-fold in patients with mild impairment (Child-Pugh class A), compared to patients with normal hepatic function.
Use: Labeled Indications
Ovarian cancer, advanced: Treatment (monotherapy) of deleterious or suspected deleterious germline BRCA-mutated (as detected by an approved test) advanced ovarian cancer in patients who have been treated with 3 or more prior lines of chemotherapy
Off Label Uses
Breast cancer, metastatic, HER2-negative, BRCA-mutated
Data from a phase III randomized, controlled, international, multicenter study supports the use of olaparib in the treatment of HER2-negative (hormone-receptor positive or triple negative) metastatic breast cancer in patients with a confirmed or suspected deleterious germline BRCA mutation; patients had received no more than 2 prior lines of chemotherapy for the treatment of metastatic disease [(Robson 2017)].
There are no contraindications listed in the manufacturer's US labeling.
Canadian labeling: Hypersensitivity to olaparib or any component of the formulation.
Note: Administer only to patients with deleterious or suspected deleterious germline BRCA mutations, as detected by an approved test.
Ovarian cancer, advanced: Oral: 400 mg twice daily (12 hours apart) until disease progression or unacceptable toxicity (Domchek 2016)
Breast cancer, metastatic, HER2-negative, BRCA-mutated (off-label use): Oral: 300 mg twice daily until disease progression or unacceptable toxicity (Robson 2017)
Missed doses: If a dose is missed, administer the next dose at its scheduled time.
Dosage adjustment for concomitant therapy with CYP3A inhibitors: Avoid concomitant use with moderate or strong CYP3A inhibitors. If coadministration with a moderate CYP3A inhibitor cannot be avoided, reduce dose to 200 mg twice daily. If coadministration with a strong CYP3A inhibitor cannot be avoided, reduce dose to 150 mg twice daily.
Refer to adult dosing.
Dosing: Renal Impairment
CrCl 51 to 80 mL/minute: No dosage adjustment necessary; monitor closely for toxicity, as an increase in mean AUC has been observed in patients with mild impairment.
CrCl 31 to 50 mL/minute: Reduce dose to 300 mg twice daily.
CrCl ≤30 mL/minute: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
ESRD: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
Dosing: Hepatic Impairment
Mild impairment (Child-Pugh class A): No dosage adjustment necessary.
Moderate-to-severe impairment (Child-Pugh classes B and C): There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
Dosing: Adjustment for Toxicity
Consider therapy interruption or dose reduction if adverse reactions occur. The recommended dose reduction is to 200 mg twice daily; if further reduction is required, reduce dose to 100 mg twice daily.
Secondary AML/MDS: Discontinue
Administer with or without food. Swallow capsule whole; do not chew, dissolve, or open capsule. Do not administer if capsules appear deformed or show evidence of leakage.
Based on a pharmacokinetic study, the rate of absorption was slower and the peak exposure was decreased when administered with a high-fat meal, however the extent of absorption was not affected; nausea and vomiting were reported more frequently when olaparib was administered in a fasted state (Plummer 2015).
Avoid grapefruit or Seville oranges.
Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Do not expose capsules to temperatures >40°C (104°F).
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Avoid combination
Bitter Orange: May increase the serum concentration of Olaparib. Avoid combination
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Monitor therapy
Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Avoid combination
CYP3A4 Inducers (Moderate): May decrease the serum concentration of Olaparib. Avoid combination
CYP3A4 Inducers (Strong): May decrease the serum concentration of Olaparib. Avoid combination
CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Olaparib. Management: Avoid use of moderate CYP3A4 inhibitors in patients being treated with olaparib. If such concurrent use cannot be avoided, the dose of olaparib should be reduced to 200 mg twice daily. Avoid combination
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Olaparib. Management: Avoid use of strong CYP3A4 inhibitors in patients being treated with olaparib. If such concurrent use cannot be avoided, the dose of olaparib should be reduced to 150 mg twice daily. Avoid combination
Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Avoid combination
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Avoid combination
Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates. Avoid combination
Idelalisib: May increase the serum concentration of CYP3A4 Substrates. Avoid combination
Palbociclib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy
Sarilumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Siltuximab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Simeprevir: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Stiripentol: May increase the serum concentration of CYP3A4 Substrates. Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Cardiovascular: Peripheral edema (10% to <20%)
Central nervous system: Fatigue (including weakness; 66% to 68%), headache (10% to 25%), dizziness (10% to <20%)
Dermatologic: Skin rash (10% to 25%)
Gastrointestinal: Nausea (64% to 75%), abdominal pain (43%), vomiting (32% to 43%), diarrhea (28% to 31%), dyspepsia (25%), decreased appetite (22% to 25%), dysgeusia (10% to 21%), constipation (10% to <20%)
Genitourinary: Urinary tract infection (10% to <20%)
Hematologic & oncologic: Decreased hemoglobin (85% to 90%; grades 3/4: 8% to 15%), increased MCV (57% to 85%), decreased absolute lymphocyte count (56%; grades 3/4: 17%), anemia (25% to 34%; grades 3/4: 4% to 18%), decreased neutrophils (25% to 32%; grades 3/4: 7% to 8%), decreased platelet count (26% to 30%; grades 3/4: 3% to 6%)
Neuromuscular & skeletal: Musculoskeletal pain (21% to 32%), myalgia (22% to 25%), back pain (10% to 25%)
Renal: Increased serum creatinine (26% to 30%)
Respiratory: Upper respiratory tract infection (26% to 43%), cough (10% to 21%), dyspnea (10% to <20%)
1% to ≤10%:
Cardiovascular: Hypertension, venous thrombosis (including pulmonary embolism)
Central nervous system: Anxiety, depression, insomnia, peripheral neuropathy
Dermatologic: Pruritus, xeroderma (including eczema)
Endocrine & metabolic: Hot flash, hyperglycemia, hypomagnesemia
Genitourinary: Dysuria, urinary incontinence, vulvovaginal disease
Hematologic & oncologic: Myelodysplastic syndrome (acute myeloid leukemia; 2%), leukopenia
<1% (Limited to important or life-threatening): Pneumonitis
Concerns related to adverse effects:
• Bone marrow suppression: Anemia, neutropenia, thrombocytopenia and lymphopenia have been reported. Monitor complete blood counts at baseline and monthly thereafter; do not initiate olaparib until any hematologic toxicity caused by previous chemotherapy has resolved to ≤ grade 1. If prolonged hematologic toxicity occurs during therapy, interrupt treatment and monitor blood counts weekly until recovered; if counts do not recover to ≤ grade 1 after 4 weeks, further evaluation (including bone marrow and cytogenetic analyses) is necessary.
• Gastrointestinal toxicity: Nausea and vomiting (usually mild to moderate) may commonly occur.
• Pulmonary toxicity: Pneumonitis (including some fatalities) has occurred rarely. Interrupt treatment for new or worsening respiratory symptoms such as cough, dyspnea, fever, wheezing, or radiologic abnormalities; evaluate promptly. Discontinue treatment if pneumonitis is confirmed.
• Secondary malignancy: Myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) have been reported (rarely) in a clinical trial of patients with deleterious or suspected deleterious germline BRCA-mutated advanced cancers receiving olaparib monotherapy. Most MDS/AML cases were fatal. The duration of therapy prior to development of the secondary cancers ranged from less than 6 months to greater than 2 years; all patients had received prior chemotherapy with platinum agents and/or other DNA-damaging medications, including radiation. If prolonged hematologic toxicity occurs and blood counts do not recover to ≤ grade 1 after 4 weeks, further evaluation (including bone marrow and cytogenetic analyses) is necessary. If MDS/AML is confirmed, discontinue therapy.
• Renal impairment: Monitor closely for toxicity in patients with mild or moderate renal impairment. Dosage adjustment is recommended for moderate impairment.
Concurrent drug therapy issues:
• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Complete blood count at baseline and monthly thereafter, or as clinically indicated (weekly until recovery for prolonged hematologic toxicity), renal function, pregnancy test (prior to treatment initiation in women of reproductive potential); monitor for signs/symptoms of AML/MDS and pneumonitis. Monitor adherence.
Adverse events were observed in animal reproduction studies at doses less than human exposure. Based on animal reproduction studies and the mechanism of action, olaparib may be expected to cause adverse events to the fetus. Women of reproductive potential should use highly effective contraception during therapy and for at least 6 months after the last olaparib dose. In women of reproductive potential, pregnancy testing is recommended prior to treatment initiation.
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience back pain, constipation, lack of appetite, diarrhea, dizziness, headache, abdominal pain, heartburn, muscle pain, joint pain, nausea, vomiting, rhinitis, pharyngitis, or change in taste. Have patient report immediately to prescriber signs of a urinary tract infection (hematuria, burning or painful urination, polyuria, fever, lower abdominal pain, or pelvic pain), signs of infection, signs of a severe pulmonary disorder (lung or breathing problems like difficulty breathing, shortness of breath, or a cough that is new or worse), swelling of arms or legs; hematuria; black, tarry, or bloody stools; shortness of breath; bruising; bleeding; severe loss of strength and energy; or weight loss (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
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- Drug class: PARP inhibitors
Other brands: Lynparza