Lynparza

Small Molecule Antineoplastic Poly (ADP-ribose) Polymerase (PARP) Inhibitors

Hazardous Drugs Classification
NIOSH (Draft) 2020 List: Table 2
Approved by FDA after NIOSH 2016 list published. The manufacturer recommends this drug be handled as a hazardous drug.
Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
Use gloves to handle. Cutting, crushing, or otherwise manipulating tablets/capsules will increase exposure.
Emetic Risk
Moderate/High
Administer routine antiemetic prophylaxis prior to treatment.

Information on FDA-approved tests for the detection of BRCA-mutations is available at http://www.fda.gov/companiondiagnostics.
Store in the original bottle to protect from moisture.
Swallow tablets whole; do not chew, crush, dissolve, or divide tablets.
Olaparib may be administered with or without food. The patient should avoid grapefruit, grapefruit juice, Seville oranges, and Seville orange juice during treatment since these fruits and juices will raise blood levels of the drug, increasing toxicity risk.
If a dose is missed, the patient should take the next dose at the regularly scheduled time; instruct the patient not to take 2 doses at the same time.

anemia / Delayed / 7.0-21.0
neutropenia / Delayed / 0-9.0
leukopenia / Delayed / 0-9.0
fatigue / Early / 1.8-9.0
thromboembolism / Delayed / 0.5-8.0
pulmonary embolism / Delayed / 0-6.0
thrombocytopenia / Delayed / 0-4.0
nausea / Early / 0-3.0
diarrhea / Early / 0-3.0
anorexia / Delayed / 0-3.0
infection / Delayed / 0-2.0
renal failure (unspecified) / Delayed / 0-2.0
vomiting / Early / 0-2.0
abdominal pain / Early / 0-2.0
dyspnea / Early / 0-2.0
new primary malignancy / Delayed / 1.5-1.5
constipation / Delayed / 0-1.0
stomatitis / Delayed / 0-1.0
arthralgia / Delayed / 0-1.0
headache / Early / 0-1.0
dizziness / Early / 0-0.3
GI perforation / Delayed / Incidence not known
erythema nodosum / Delayed / Incidence not known
stroke / Early / Incidence not known
angioedema / Rapid / Incidence not known

cystitis / Delayed / 0-15.0
hypomagnesemia / Delayed / 0-14.0
edema / Delayed / 0-9.0
lymphopenia / Delayed / 1.0-8.0
pneumonitis / Delayed / 0.8-2.0
colitis / Delayed / Incidence not known
oral ulceration / Delayed / Incidence not known
erythema / Early / Incidence not known

dysgeusia / Early / 7.0-27.0
dyspepsia / Early / 5.0-20.0
cough / Delayed / 9.0-18.0
rash / Early / 0-15.0
fever / Early / 0-10.0
sinusitis / Delayed / Incidence not known
influenza / Delayed / Incidence not known
rhinitis / Early / Incidence not known
pharyngitis / Delayed / Incidence not known
asthenia / Delayed / Incidence not known
lethargy / Early / Incidence not known
malaise / Early / Incidence not known
vertigo / Early / Incidence not known

Lynparza

Rx

Oral PARP inhibitor
Used for certain types of ovarian, breast, pancreatic, and prostate cancer
Most common adverse events include anemia, fatigue, nausea, vomiting, diarrhea, upper respiratory tract infection, and arthralgia/myalgia

Dosage not available.

300 mg PO twice daily until disease progression or unacceptable toxicity. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Maintenance treatment with olaparib (n = 196) significantly improved the primary endpoint of median progression-free survival (PFS) compared with placebo (n = 99) in a randomized, double-blind clinical trial of patients with gBRCAm ovarian, fallopian tube, or primary peritoneal cancer who had obtained either a complete or partial response to platinum-based chemotherapy (19.1 months vs. 5.5 months) (SOLO2 trial). Approximately 44% of olaparib patients and 37% of placebo patients in this trial had received 3 or more lines of platinum-based treatment. In long-term follow-up, 24% of patients were treated with olaparib for 2 years and 11% received treatment for over 6 years. Olaparib improved overall survival compared with placebo (51.7 months vs. 38.8 months) irrespective of BRCA 1/2 mutation status but did not meet the predefined threshold for statistical significance.[58662]

300 mg PO twice daily until disease progression, unacceptable toxicity, or completion of 2 years of treatment. Patients with a complete response (no radiological evidence of disease) at 2 years should stop treatment. Patients with evidence of disease at 2 years can continue treatment with olaparib if the treating healthcare provider feels the patient can derive further benefit. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In a multicenter, randomized, double-blind, phase 3 clinical trial, maintenance therapy with olaparib significantly improved PFS (not reached vs.13.8 months) and time to first subsequent treatment (51.8 months vs. 15.1 months) compared with placebo in patients with newly diagnosed gBRCAm advanced or high-grade serous or endometrioid ovarian, fallopian tube, or primary peritoneal cancer in patients who were in a complete or partial response to platinum-based chemotherapy (SOLO1 trial).

300 mg PO twice daily until disease progression, unacceptable toxicity, or completion of 2 years of treatment, in combination with bevacizumab (15 mg/kg IV every 3 weeks for 15 months total, including the period given with chemotherapy and given with maintenance). Patients with a complete response (no radiological evidence of disease) at 2 years should stop treatment with olaparib. Patients with evidence of disease at 2 years can continue treatment with olaparib if the treating healthcare provider feels the patient can derive further benefit. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Maintenance therapy with olaparib plus bevacizumab significantly improved the median progression-free survival compared with patients receiving bevacizumab plus placebo in HRD-positive patients with advanced high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer following first-line platinum-based chemotherapy and bevacizumab in a multicenter, randomized, double-blind clinical trial (PAOLA-1) (37.2 months vs. 17.7 months).

300 mg orally twice daily until disease progression or unacceptable toxicity. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Olaparib monotherapy significantly improved the primary endpoint of progression-free survival (PFS) compared with physician's choice of single-agent chemotherapy in patients with HER2-negative, gBRCAm metastatic breast cancer in a phase 3 clinical trial; subgroup analysis indicates patients with triple-negative breast cancer or BRCA1 mutations confer significant benefit.[62322] [58662]

300 mg orally twice daily for a total of 1 year, or until disease progression or unacceptable toxicity if occurring before 1 year. Patients with hormone receptor-positive breast cancer should continue to receive concurrent endocrine therapy according to current clinical practice guidelines. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In a multicenter, randomized, double-blind, phase 3 clinical trial (OlympiA), patients with gBRCAm HER2-negative high risk early breast cancer who had completed definitive local treatment and neoadjuvant or adjuvant chemotherapy were randomized to receive 1 year of olaparib or placebo. Treatment with olaparib significantly improved 3-year invasive disease-free survival (85.9% vs. 77.1%) and 3-year distant disease-free survival (87.5% vs. 804%) compared with placebo. Olaparib was also associated with fewer deaths than placebo, although at the interim analysis this difference was not statistically significant.

300 mg PO twice daily until disease progression or unacceptable toxicity. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In a multicenter, randomized clinical trial, maintenance therapy with olaparib after a lack of disease progression on at least 16 weeks of first-line platinum-based chemotherapy significantly improved median progression-free survival compared with placebo (7.4 months vs. 3.8 months) in patients with deleterious or suspected deleterious gBRCA-mutated metastatic pancreatic cancer. The objective response rate was 23% (complete response [CR], 2.6%) in the olaparib arm compared with 12% (CR, 0%) in patients who received placebo, for a median duration of 25 months versus 4 months, respectively. In the final analysis, median overall survival was 19 months in patients who received olaparib and 19.2 months in patients who received placebo.

300 mg PO twice daily until disease progression or unacceptable toxicity. Patients should concurrently receive treatment with a gonadotropin-releasing hormone (GnRH) analog or have had a bilateral orchiectomy. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In a multicenter, randomized, open-label clinical trial (the PROfound study), treatment of HRR-mutated mCRPC with olaparib significantly improved the median radiological progression-free survival (rPFS) compared with enzalutamide or abiraterone in patients with mutations in BRCA1, BRCA2, or ATM (7.4 months vs. 3.6 months); when patients with mutations in other genes involved in the HRR pathway (BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D, or RAD54L) were included in the analysis, rPFS was still significantly improved (5.8 months vs. 3.5 months). The confirmed objective response rate (33% vs. 2%) and median overall survival (19.1 months vs. 14.7 months) were also significantly improved in patients with BRCA1, BRCA2, or ATM mutations. Prior taxane therapy did not affect the results compared to patients who had not previously received a taxane. Olaparib is not indicated for patients with PPP2R2A mutations due to an unfavorable risk-benefit.

300 mg PO twice daily in combination with abiraterone (1,000 mg PO once daily) and either prednisone or prednisolone (5 mg PO twice daily) until disease progression or unacceptable toxicity. Patients should concurrently receive treatment with a gonadotropin-releasing hormone (GnRH) analog or have had a bilateral orchiectomy. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In a multicenter, randomized, double-blind clinical trial (PROpel), treatment with olaparib in combination with abiraterone and prednisone or prednisolone significantly improved median radiological progression-free survival (not reached vs. 8 months) and median overall survival (not reached vs. 23 months) compared with placebo plus abiraterone and prednisone/prednisolone in patients with metastatic castration-resistant prostate cancer. Prior treatment with docetaxel for localized or metastatic hormone-sensitive prostate cancer was allowed; patients with prior treatment with abiraterone were excluded.

Baseline Hepatic Impairment:
Mild to moderate hepatic impairment (Child-Pugh class A and B): No dosage adjustment necessary.
Severe hepatic impairment (Child-Pugh class C): No data are available.

Baseline Renal Impairment:
Mild renal impairment (CrCl 51 to 80 mL/min): No dosage adjustment needed.
Moderate renal impairment (CrCl 31 to 50 mL/min): Reduce the dose of olaparib to 200 mg PO twice daily.
Severe renal impairment or end-stage renal disease (CrCl 30 mL/min or less): No data are available.

Adagrasib: (Major) Avoid coadministration of olaparib with adagrasib due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 100 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after adagrasib is discontinued. Olaparib is a CYP3A substrate and adagrasib is a strong CYP3A inhibitor; concomitant use may increase olaparib exposure. Coadministration with another strong CYP3A inhibitor increased the olaparib Cmax by 42% and the AUC by 170%.
Amiodarone: (Major) Avoid coadministration of olaparib with amiodarone due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 150 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after amiodarone is discontinued. Olaparib is a CYP3A substrate and amiodarone is a moderate CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with a moderate CYP3A inhibitor is predicted to increase the olaparib Cmax by 14% and the AUC by 121%.
Amobarbital: (Major) Avoid coadministration of olaparib with amobarbital due to the risk of decreasing the efficacy of olaparib. Olaparib is a CYP3A substrate and amobarbital is a moderate CYP3A4 inducer; concomitant use may decrease olaparib exposure. Coadministration with a moderate CYP3A inducer is predicted to decrease the olaparib Cmax by 31% and the AUC by 60%.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Avoid coadministration of olaparib with clarithromycin due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 100 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after clarithromycin is discontinued. Olaparib is a CYP3A substrate and clarithromycin is a strong CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with another strong CYP3A inhibitor increased the olaparib Cmax by 42% and the AUC by 170%.
Apalutamide: (Major) Avoid coadministration of olaparib with apalutamide due to the risk of decreasing the efficacy of olaparib. Olaparib is a CYP3A substrate and apalutamide is a strong CYP3A4 inducer; concomitant use may decrease olaparib exposure. Coadministration with another strong CYP3A inducer decreased the olaparib Cmax by 71% and the AUC by 87%.
Aprepitant, Fosaprepitant: (Major) Avoid coadministration of olaparib for several days after a multi-day regimen of oral aprepitant due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 150 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after aprepitant is discontinued. Olaparib is a CYP3A substrate. Aprepitant is a moderate CYP3A4 inhibitor when administered as a 3-day oral regimen. Coadministration with a moderate CYP3A inhibitor is predicted to increase the olaparib Cmax by 14% and the AUC by 121%. When administered as a single oral or single intravenous dose (fosaprepitant), the inhibitory effect of aprepitant on CYP3A4 is weak and did not result in a clinically significant increase in the AUC of a sensitive substrate.
Aspirin, ASA; Butalbital; Caffeine: (Major) Avoid coadministration of olaparib with butalbital due to the risk of decreasing the efficacy of olaparib. Olaparib is a CYP3A substrate and butalbital is a moderate CYP3A4 inducer; concomitant use may decrease olaparib exposure. Coadministration with a moderate CYP3A inducer is predicted to decrease the olaparib Cmax by 31% and the AUC by 60%.
Atazanavir: (Major) Avoid coadministration of olaparib with atazanavir due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 100 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after atazanavir is discontinued. Olaparib is a CYP3A substrate and atazanavir is a strong CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with another strong CYP3A inhibitor increased the olaparib Cmax by 42% and the AUC by 170%.
Atazanavir; Cobicistat: (Major) Avoid coadministration of olaparib with atazanavir due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 100 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after atazanavir is discontinued. Olaparib is a CYP3A substrate and atazanavir is a strong CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with another strong CYP3A inhibitor increased the olaparib Cmax by 42% and the AUC by 170%. (Major) Avoid coadministration of olaparib with cobicistat due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 100 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after cobicistat is discontinued. Olaparib is a CYP3A substrate and cobicistat is a strong CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with another strong CYP3A inhibitor increased the olaparib Cmax by 42% and the AUC by 170%.
Berotralstat: (Major) Avoid coadministration of olaparib with berotralstat due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 150 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after berotralstat is discontinued. Olaparib is a CYP3A4 substrate and berotralstat is a moderate CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with a moderate CYP3A inhibitor is predicted to increase the olaparib Cmax by 14% and the AUC by 121%.
Bexarotene: (Major) Avoid coadministration of olaparib with bexarotene due to the risk of decreasing the efficacy of olaparib. Olaparib is a CYP3A substrate and bexarotene is a moderate CYP3A4 inducer; concomitant use may decrease olaparib exposure. Coadministration with a moderate CYP3A inducer is predicted to decrease the olaparib Cmax by 31% and the AUC by 60%.
Bosentan: (Major) Avoid coadministration of olaparib with bosentan due to the risk of decreasing the efficacy of olaparib. Olaparib is a CYP3A substrate and bosentan is a moderate CYP3A4 inducer; concomitant use may decrease olaparib exposure. Coadministration with a moderate CYP3A inducer is predicted to decrease the olaparib Cmax by 31% and the AUC by 60%.
Butabarbital: (Major) Avoid coadministration of olaparib with butabarbital due to the risk of decreasing the efficacy of olaparib. Olaparib is a CYP3A substrate and butabarbital is a moderate CYP3A4 inducer; concomitant use may decrease olaparib exposure. Coadministration with a moderate CYP3A inducer is predicted to decrease the olaparib Cmax by 31% and the AUC by 60%.
Butalbital; Acetaminophen: (Major) Avoid coadministration of olaparib with butalbital due to the risk of decreasing the efficacy of olaparib. Olaparib is a CYP3A substrate and butalbital is a moderate CYP3A4 inducer; concomitant use may decrease olaparib exposure. Coadministration with a moderate CYP3A inducer is predicted to decrease the olaparib Cmax by 31% and the AUC by 60%.
Butalbital; Acetaminophen; Caffeine: (Major) Avoid coadministration of olaparib with butalbital due to the risk of decreasing the efficacy of olaparib. Olaparib is a CYP3A substrate and butalbital is a moderate CYP3A4 inducer; concomitant use may decrease olaparib exposure. Coadministration with a moderate CYP3A inducer is predicted to decrease the olaparib Cmax by 31% and the AUC by 60%.
Butalbital; Acetaminophen; Caffeine; Codeine: (Major) Avoid coadministration of olaparib with butalbital due to the risk of decreasing the efficacy of olaparib. Olaparib is a CYP3A substrate and butalbital is a moderate CYP3A4 inducer; concomitant use may decrease olaparib exposure. Coadministration with a moderate CYP3A inducer is predicted to decrease the olaparib Cmax by 31% and the AUC by 60%.
Butalbital; Aspirin; Caffeine; Codeine: (Major) Avoid coadministration of olaparib with butalbital due to the risk of decreasing the efficacy of olaparib. Olaparib is a CYP3A substrate and butalbital is a moderate CYP3A4 inducer; concomitant use may decrease olaparib exposure. Coadministration with a moderate CYP3A inducer is predicted to decrease the olaparib Cmax by 31% and the AUC by 60%.
Carbamazepine: (Major) Avoid coadministration of olaparib with carbamazepine due to the risk of decreasing the efficacy of olaparib. Olaparib is a CYP3A substrate and carbamazepine is a strong CYP3A4 inducer; concomitant use may decrease olaparib exposure. Coadministration with another strong CYP3A inducer decreased the olaparib Cmax by 71% and the AUC by 87%.
Cenobamate: (Major) Avoid coadministration of olaparib with cenobamate due to the risk of decreasing the efficacy of olaparib. Olaparib is a CYP3A substrate and cenobamate is a moderate CYP3A4 inducer; concomitant use may decrease olaparib exposure. Coadministration with a moderate CYP3A inducer is predicted to decrease the olaparib Cmax by 31% and the AUC by 60%.
Ceritinib: (Major) Avoid coadministration of olaparib with ceritinib due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 100 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after ceritinib is discontinued. Olaparib is a CYP3A substrate and ceritinib is a strong CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with another strong CYP3A inhibitor increased the olaparib Cmax by 42% and the AUC by 170%.
Chloramphenicol: (Major) Avoid coadministration of olaparib with chloramphenicol due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 100 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after chloramphenicol is discontinued. Olaparib is a CYP3A substrate and chloramphenicol is a strong CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with another strong CYP3A inhibitor increased the olaparib Cmax by 42% and the AUC by 170%.
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Ciprofloxacin: (Major) Avoid coadministration of olaparib with ciprofloxacin due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 150 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after ciprofloxacin is discontinued. Olaparib is a CYP3A substrate and ciprofloxacin is a moderate CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with a moderate CYP3A inhibitor is predicted to increase the olaparib Cmax by 14% and the AUC by 121%.
Clarithromycin: (Major) Avoid coadministration of olaparib with clarithromycin due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 100 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after clarithromycin is discontinued. Olaparib is a CYP3A substrate and clarithromycin is a strong CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with another strong CYP3A inhibitor increased the olaparib Cmax by 42% and the AUC by 170%.
Cobicistat: (Major) Avoid coadministration of olaparib with cobicistat due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 100 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after cobicistat is discontinued. Olaparib is a CYP3A substrate and cobicistat is a strong CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with another strong CYP3A inhibitor increased the olaparib Cmax by 42% and the AUC by 170%.
Conivaptan: (Major) Avoid coadministration of olaparib with conivaptan due to the risk of increased olaparib-related adverse reactions. If concomitant use is necessary, reduce the dose of olaparib to 150 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after conivaptan is discontinued. Olaparib is a CYP3A substrate and conivaptan is a moderate CYP3A inhibitor; concomitant use may increase olaparib exposure. Coadministration with a moderate CYP3A inhibitor is predicted to increase the olaparib peak by 14% and the overall exposure by 121%.
Crizotinib: (Major) Avoid coadministration of olaparib with crizotinib due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 150 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after crizotinib is discontinued. Olaparib is a CYP3A substrate and crizotinib is a moderate CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with a moderate CYP3A inhibitor is predicted to increase the olaparib Cmax by 14% and the AUC by 121%.
Cyclosporine: (Major) Avoid coadministration of olaparib with cyclosporine due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 150 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after cyclosporine is discontinued. Olaparib is a CYP3A substrate and cyclosporine is a moderate CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with a moderate CYP3A inhibitor is predicted to increase the olaparib Cmax by 14% and the AUC by 121%.
Dabrafenib: (Major) Avoid coadministration of olaparib with dabrafenib due to the risk of decreasing the efficacy of olaparib. Olaparib is a CYP3A substrate and dabrafenib is a moderate CYP3A4 inducer; concomitant use may decrease olaparib exposure. Coadministration with a moderate CYP3A inducer is predicted to decrease the olaparib Cmax by 31% and the AUC by 60%.
Danazol: (Major) Avoid coadministration of olaparib with danazol due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 150 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after danazol is discontinued. Olaparib is a CYP3A substrate and danazol is a moderate CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with a moderate CYP3A inhibitor is predicted to increase the olaparib Cmax by 14% and the AUC by 121%.
Darunavir: (Major) Avoid coadministration of olaparib with darunavir due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 100 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after darunavir is discontinued. Olaparib is a CYP3A substrate and darunavir is a strong CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with another strong CYP3A inhibitor increased the olaparib Cmax by 42% and the AUC by 170%.
Darunavir; Cobicistat: (Major) Avoid coadministration of olaparib with cobicistat due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 100 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after cobicistat is discontinued. Olaparib is a CYP3A substrate and cobicistat is a strong CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with another strong CYP3A inhibitor increased the olaparib Cmax by 42% and the AUC by 170%. (Major) Avoid coadministration of olaparib with darunavir due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 100 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after darunavir is discontinued. Olaparib is a CYP3A substrate and darunavir is a strong CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with another strong CYP3A inhibitor increased the olaparib Cmax by 42% and the AUC by 170%.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Avoid coadministration of olaparib with cobicistat due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 100 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after cobicistat is discontinued. Olaparib is a CYP3A substrate and cobicistat is a strong CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with another strong CYP3A inhibitor increased the olaparib Cmax by 42% and the AUC by 170%. (Major) Avoid coadministration of olaparib with darunavir due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 100 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after darunavir is discontinued. Olaparib is a CYP3A substrate and darunavir is a strong CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with another strong CYP3A inhibitor increased the olaparib Cmax by 42% and the AUC by 170%.
Delavirdine: (Major) Avoid coadministration of olaparib with delavirdine due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 100 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after delavirdine is discontinued. Olaparib is a CYP3A substrate and delavirdine is a strong CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with another strong CYP3A inhibitor increased the olaparib Cmax by 42% and the AUC by 170%.
Diltiazem: (Major) Avoid coadministration of olaparib with diltiazem due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 150 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after diltiazem is discontinued. Olaparib is a CYP3A substrate and diltiazem is a moderate CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with a moderate CYP3A inhibitor is predicted to increase the olaparib Cmax by 14% and the AUC by 121%.
Dronedarone: (Major) Avoid coadministration of olaparib with dronedarone due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 150 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after dronedarone is discontinued. Olaparib is a CYP3A substrate and dronedarone is a moderate CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with a moderate CYP3A inhibitor is predicted to increase the olaparib Cmax by 14% and the AUC by 121%.
Duvelisib: (Major) Avoid coadministration of olaparib with duvelisib due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 150 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after duvelisib is discontinued. Olaparib is a CYP3A substrate and duvelisib is a moderate CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with a moderate CYP3A inhibitor is predicted to increase the olaparib Cmax by 14% and the AUC by 121%.
Efavirenz: (Major) Avoid coadministration of olaparib with efavirenz due to the risk of decreasing the efficacy of olaparib. Olaparib is a CYP3A substrate and efavirenz is a moderate CYP3A4 inducer; concomitant use may decrease olaparib exposure. Coadministration with efavirenz is predicted to decrease the olaparib Cmax by 31% and the AUC by 60%.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid coadministration of olaparib with efavirenz due to the risk of decreasing the efficacy of olaparib. Olaparib is a CYP3A substrate and efavirenz is a moderate CYP3A4 inducer; concomitant use may decrease olaparib exposure. Coadministration with efavirenz is predicted to decrease the olaparib Cmax by 31% and the AUC by 60%.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Avoid coadministration of olaparib with efavirenz due to the risk of decreasing the efficacy of olaparib. Olaparib is a CYP3A substrate and efavirenz is a moderate CYP3A4 inducer; concomitant use may decrease olaparib exposure. Coadministration with efavirenz is predicted to decrease the olaparib Cmax by 31% and the AUC by 60%.
Elagolix: (Major) Avoid coadministration of olaparib with elagolix due to the risk of decreasing the efficacy of olaparib. Olaparib is a CYP3A substrate and elagolix is a weak to moderate CYP3A4 inducer; concomitant use may decrease olaparib exposure. Coadministration with a moderate CYP3A inducer is predicted to decrease the olaparib Cmax by 31% and the AUC by 60%.
Elagolix; Estradiol; Norethindrone acetate: (Major) Avoid coadministration of olaparib with elagolix due to the risk of decreasing the efficacy of olaparib. Olaparib is a CYP3A substrate and elagolix is a weak to moderate CYP3A4 inducer; concomitant use may decrease olaparib exposure. Coadministration with a moderate CYP3A inducer is predicted to decrease the olaparib Cmax by 31% and the AUC by 60%.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Avoid coadministration of olaparib with cobicistat due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 100 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after cobicistat is discontinued. Olaparib is a CYP3A substrate and cobicistat is a strong CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with another strong CYP3A inhibitor increased the olaparib Cmax by 42% and the AUC by 170%.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid coadministration of olaparib with cobicistat due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 100 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after cobicistat is discontinued. Olaparib is a CYP3A substrate and cobicistat is a strong CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with another strong CYP3A inhibitor increased the olaparib Cmax by 42% and the AUC by 170%.
Enzalutamide: (Major) Avoid coadministration of olaparib with enzalutamide due to the risk of decreasing the efficacy of olaparib. Olaparib is a CYP3A substrate and enzalutamide is a strong CYP3A4 inducer; concomitant use may decrease olaparib exposure. Coadministration with another strong CYP3A inducer decreased the olaparib Cmax by 71% and the AUC by 87%.
Erythromycin: (Major) Avoid coadministration of olaparib with erythromycin due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 150 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after erythromycin is discontinued. Olaparib is a CYP3A substrate and erythromycin is a moderate CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with a moderate CYP3A inhibitor is predicted to increase the olaparib Cmax by 14% and the AUC by 121%.
Eslicarbazepine: (Major) Avoid coadministration of olaparib with eslicarbazepine due to the risk of decreasing the efficacy of olaparib. Olaparib is a CYP3A substrate and eslicarbazepine is a moderate CYP3A4 inducer; concomitant use may decrease olaparib exposure. Coadministration with a moderate CYP3A inducer is predicted to decrease the olaparib Cmax by 31% and the AUC by 60%.
Etravirine: (Major) Avoid coadministration of olaparib with etravirine due to the risk of decreasing the efficacy of olaparib. Olaparib is a CYP3A substrate and etravirine is a moderate CYP3A4 inducer; concomitant use may decrease olaparib exposure. Coadministration with a moderate CYP3A inducer is predicted to decrease the olaparib Cmax by 31% and the AUC by 60%.
Fedratinib: (Major) Avoid coadministration of olaparib with fedratinib due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 150 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after fedratinib is discontinued. Olaparib is a CYP3A substrate and fedratinib is a moderate CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with a moderate CYP3A inhibitor is predicted to increase the olaparib Cmax by 14% and the AUC by 121%.
Fluconazole: (Major) Avoid coadministration of olaparib with fluconazole due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 150 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after fluconazole is discontinued. Olaparib is a CYP3A substrate and fluconazole is a moderate CYP3A4 inhibitor. Coadministration with fluconazole is predicted to increase the olaparib Cmax by 14% and the AUC by 121%.
Fluvoxamine: (Major) Avoid coadministration of olaparib with fluvoxamine due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 150 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after fluvoxamine is discontinued. Olaparib is a CYP3A substrate and fluvoxamine is a moderate CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with a moderate CYP3A inhibitor is predicted to increase the olaparib Cmax by 14% and the AUC by 121%.
Fosamprenavir: (Major) Avoid coadministration of olaparib with fosamprenavir due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 150 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after fosamprenavir is discontinued. Olaparib is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor; concomitant use may increase olaparib exposure. Coadministration with a moderate CYP3A inhibitor is predicted to increase the olaparib Cmax by 14% and the AUC by 121%.
Fosphenytoin: (Major) Avoid coadministration of olaparib with fosphenytoin due to the risk of decreasing the efficacy of olaparib. Olaparib is a CYP3A substrate and fosphenytoin is a strong CYP3A4 inducer; concomitant use may decrease olaparib exposure. Coadministration with another strong CYP3A inducer decreased the olaparib Cmax by 71% and the AUC by 87%.
Grapefruit juice: (Major) Due to the potential for increased olaparib exposure and side effects, patients should be advised to avoid intake of grapefruit, grapefruit juice, Seville oranges, and Seville orange juice during olaparib therapy. Olaparib is a CYP3A substrate and both grapefruit and Seville oranges are strong CYP3A4 inhibitors. Coadministration with another strong CYP3A inhibitor increased the olaparib Cmax by 42% and the AUC by 170%.
Idelalisib: (Major) Avoid coadministration of olaparib with idelalisib due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 100 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after idelalisib is discontinued. Olaparib is a CYP3A substrate and idelalisib is a strong CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with another strong CYP3A inhibitor increased the olaparib Cmax by 42% and the AUC by 170%.
Imatinib: (Major) Avoid coadministration of olaparib with imatinib due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 150 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after imatinib is discontinued. Olaparib is a CYP3A substrate and imatinib is a moderate CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with a moderate CYP3A inhibitor is predicted to increase the olaparib Cmax by 14% and the AUC by 121%.
Indinavir: (Major) Avoid coadministration of olaparib with indinavir due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 100 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after indinavir is discontinued. Olaparib is a CYP3A substrate and indinavir is a strong CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with another strong CYP3A inhibitor increased the olaparib Cmax by 42% and the AUC by 170%.
Isavuconazonium: (Major) Avoid coadministration of olaparib with isavuconazonium due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 150 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after isavuconazonium is discontinued. Olaparib is a CYP3A substrate and isavuconazonium is a moderate CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with a moderate CYP3A inhibitor is predicted to increase the olaparib Cmax by 14% and the AUC by 121%.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Avoid coadministration of olaparib with rifampin due to the risk of decreasing the efficacy of olaparib. Olaparib is a CYP3A substrate and rifampin is a strong CYP3A4 inducer; concomitant use may decrease olaparib exposure. Coadministration with rifampin decreased the olaparib Cmax by 71% and the AUC by 87%.
Isoniazid, INH; Rifampin: (Major) Avoid coadministration of olaparib with rifampin due to the risk of decreasing the efficacy of olaparib. Olaparib is a CYP3A substrate and rifampin is a strong CYP3A4 inducer; concomitant use may decrease olaparib exposure. Coadministration with rifampin decreased the olaparib Cmax by 71% and the AUC by 87%.
Itraconazole: (Major) Avoid coadministration of olaparib with itraconazole due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 100 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after itraconazole is discontinued. Olaparib is a CYP3A substrate and itraconazole is a strong CYP3A4 inhibitor. Coadministration with itraconazole increased the olaparib Cmax by 42% and the AUC by 170%.
Ketoconazole: (Major) Avoid coadministration of olaparib with ketoconazole due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 100 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after ketoconazole is discontinued. Olaparib is a CYP3A substrate and ketoconazole is a strong CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with another strong CYP3A inhibitor increased the olaparib Cmax by 42% and the AUC by 170%.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Avoid coadministration of olaparib with clarithromycin due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 100 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after clarithromycin is discontinued. Olaparib is a CYP3A substrate and clarithromycin is a strong CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with another strong CYP3A inhibitor increased the olaparib Cmax by 42% and the AUC by 170%.
Lefamulin: (Major) Avoid coadministration of olaparib with oral lefamulin due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 150 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after lefamulin is discontinued. Olaparib is a CYP3A substrate and oral lefamulin is a moderate CYP3A4 inhibitor; an interaction is not expected with intravenous lefamulin. Concomitant use may increase olaparib exposure. Coadministration with another moderate CYP3A inhibitor is predicted to increase the olaparib Cmax by 14% and the AUC by 121%.
Lenacapavir: (Major) Avoid coadministration of olaparib with lenacapavir due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 150 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after lenacapavir is discontinued. Olaparib is a CYP3A substrate and lenacapavir is a moderate CYP3A inhibitor; concomitant use may increase olaparib exposure. Coadministration with a moderate CYP3A inhibitor is predicted to increase the olaparib AUC by 121%.
Letermovir: (Major) Avoid coadministration of olaparib with letermovir due to the risk of increased olaparib-related adverse reactions. In patients who are also receiving treatment with cyclosporine, the magnitude of this interaction may be amplified. If concomitant use is unavoidable, reduce the dose of olaparib to 150 mg twice daily if patients are taking letermovir without cyclosporine. If olaparib must be given with both letermovir and cyclosporine, reduce the dose of olaparib to 100 mg twice daily. The original dose of olaparib may be resumed 3 to 5 elimination half-lives after letermovir is discontinued. Olaparib is a CYP3A substrate. Letermovir is a moderate CYP3A4 inhibitor; however, the combined effect of letermovir and cyclosporine on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor. Coadministration with a moderate CYP3A inhibitor is predicted to increase the olaparib Cmax by 14% and the AUC by 121%. Coadministration with another strong CYP3A inhibitor increased the olaparib Cmax by 42% and the AUC by 170%.
Levoketoconazole: (Major) Avoid coadministration of olaparib with ketoconazole due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 100 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after ketoconazole is discontinued. Olaparib is a CYP3A substrate and ketoconazole is a strong CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with another strong CYP3A inhibitor increased the olaparib Cmax by 42% and the AUC by 170%.
Lonafarnib: (Major) Avoid coadministration of olaparib with lonafarnib due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 100 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after lonafarnib is discontinued. Olaparib is a CYP3A4 substrate and lonafarnib is a strong CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with another strong CYP3A4 inhibitor increased the olaparib Cmax by 42% and the AUC by 170%.
Lopinavir; Ritonavir: (Major) Avoid coadministration of olaparib with ritonavir due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 100 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after ritonavir is discontinued. Olaparib is a CYP3A substrate and ritonavir is a strong CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with another strong CYP3A inhibitor increased the olaparib Cmax by 42% and the AUC by 170%.
Lorlatinib: (Major) Avoid coadministration of olaparib with lorlatinib due to the risk of decreasing the efficacy of olaparib. Olaparib is a CYP3A substrate and lorlatinib is a moderate CYP3A4 inducer; concomitant use may decrease olaparib exposure. Coadministration with a moderate CYP3A inducer is predicted to decrease the olaparib Cmax by 31% and the AUC by 60%.
Lumacaftor; Ivacaftor: (Major) Avoid coadministration of olaparib with lumacaftor; ivacaftor due to the risk of decreasing the efficacy of olaparib. Olaparib is a CYP3A substrate and lumacaftor is a strong CYP3A4 inducer; concomitant use may decrease olaparib exposure. Coadministration with another strong CYP3A inducer decreased the olaparib Cmax by 71% and the AUC by 87%.
Mavacamten: (Major) Avoid coadministration of olaparib with mavacamten due to the risk of decreasing the efficacy of olaparib. Olaparib is a CYP3A substrate and mavacamten is a moderate CYP3A inducer; concomitant use may decrease olaparib exposure. Coadministration with a moderate CYP3A inducer is predicted to decrease the olaparib Cmax by 31% and the AUC by 60%.
Methohexital: (Major) Avoid coadministration of olaparib with methohexital due to the risk of decreasing the efficacy of olaparib. Olaparib is a CYP3A substrate and methohexital is a moderate CYP3A4 inducer; concomitant use may decrease olaparib exposure. Coadministration with a moderate CYP3A inducer is predicted to decrease the olaparib Cmax by 31% and the AUC by 60%.
Mifepristone: (Major) Avoid coadministration of olaparib with mifepristone due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 100 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after mifepristone is discontinued. Olaparib is a CYP3A substrate and mifepristone is a strong CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with another strong CYP3A inhibitor increased the olaparib Cmax by 42% and the AUC by 170%. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
Mitotane: (Major) Avoid coadministration of olaparib with mitotane due to the risk of decreasing the efficacy of olaparib. Olaparib is a CYP3A substrate and mitotane is a strong CYP3A4 inducer; concomitant use may decrease olaparib exposure. Coadministration with another strong CYP3A inducer decreased the olaparib Cmax by 71% and the AUC by 87%.
Modafinil: (Major) Avoid coadministration of olaparib with modafinil due to the risk of decreasing the efficacy of olaparib. Olaparib is a CYP3A substrate and modafinil is a moderate CYP3A4 inducer; concomitant use may decrease olaparib exposure. Coadministration with a moderate CYP3A inducer is predicted to decrease the olaparib Cmax by 31% and the AUC by 60%.
Nafcillin: (Major) Avoid coadministration of olaparib with nafcillin due to the risk of decreasing the efficacy of olaparib. Olaparib is a CYP3A substrate and nafcillin is a moderate CYP3A4 inducer; concomitant use may decrease olaparib exposure. Coadministration with a moderate CYP3A inducer is predicted to decrease the olaparib Cmax by 31% and the AUC by 60%.
Nefazodone: (Major) Avoid coadministration of olaparib with nefazodone due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 100 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after nefazodone is discontinued. Olaparib is a CYP3A substrate and nefazodone is a strong CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with another strong CYP3A inhibitor increased the olaparib Cmax by 42% and the AUC by 170%.
Nelfinavir: (Major) Avoid coadministration of olaparib with nelfinavir due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 100 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after nelfinavir is discontinued. Olaparib is a CYP3A substrate and nelfinavir is a strong CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with another strong CYP3A inhibitor increased the olaparib Cmax by 42% and the AUC by 170%.
Netupitant, Fosnetupitant; Palonosetron: (Major) Avoid coadministration of olaparib with netupitant due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 150 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after netupitant is discontinued. Olaparib is a CYP3A substrate and netupitant is a moderate CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with a moderate CYP3A inhibitor is predicted to increase the olaparib Cmax by 14% and the AUC by 121%.
Nilotinib: (Major) Avoid coadministration of olaparib with nilotinib due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 150 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after nilotinib is discontinued. Olaparib is a CYP3A substrate and nilotinib is a moderate CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with a moderate CYP3A inhibitor is predicted to increase the olaparib Cmax by 14% and the AUC by 121%.
Nirmatrelvir; Ritonavir: (Major) Avoid coadministration of olaparib with ritonavir due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 100 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after ritonavir is discontinued. Olaparib is a CYP3A substrate and ritonavir is a strong CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with another strong CYP3A inhibitor increased the olaparib Cmax by 42% and the AUC by 170%.
Omeprazole; Amoxicillin; Rifabutin: (Major) Avoid coadministration of olaparib with rifabutin due to the risk of decreasing the efficacy of olaparib. Olaparib is a CYP3A substrate and rifabutin is a moderate CYP3A4 inducer; concomitant use may decrease olaparib exposure. Coadministration with a moderate CYP3A inducer is predicted to decrease the olaparib Cmax by 31% and the AUC by 60%.
Pentobarbital: (Major) Avoid coadministration of olaparib with pentobarbital due to the risk of decreasing the efficacy of olaparib. Olaparib is a CYP3A substrate and pentobarbital is a moderate CYP3A4 inducer; concomitant use may decrease olaparib exposure. Coadministration with a moderate CYP3A inducer is predicted to decrease the olaparib Cmax by 31% and the AUC by 60%.
Pexidartinib: (Major) Avoid coadministration of olaparib with pexidartinib due to the risk of decreasing the efficacy of olaparib. Olaparib is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer; concomitant use may decrease olaparib exposure. Coadministration with a moderate CYP3A4 inducer is predicted to decrease the olaparib Cmax by 31% and the AUC by 60%.
Phenobarbital: (Major) Avoid coadministration of olaparib with phenobarbital due to the risk of decreasing the efficacy of olaparib. Olaparib is a CYP3A substrate and phenobarbital is a strong CYP3A4 inducer; concomitant use may decrease olaparib exposure. Coadministration with another strong CYP3A inducer decreased the olaparib Cmax by 71% and the AUC by 87%.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Avoid coadministration of olaparib with phenobarbital due to the risk of decreasing the efficacy of olaparib. Olaparib is a CYP3A substrate and phenobarbital is a strong CYP3A4 inducer; concomitant use may decrease olaparib exposure. Coadministration with another strong CYP3A inducer decreased the olaparib Cmax by 71% and the AUC by 87%.
Phenytoin: (Major) Avoid coadministration of olaparib with phenytoin due to the risk of decreasing the efficacy of olaparib. Olaparib is a CYP3A substrate and phenytoin is a strong CYP3A4 inducer; concomitant use may decrease olaparib exposure. Coadministration with another strong CYP3A inducer decreased the olaparib Cmax by 71% and the AUC by 87%.
Posaconazole: (Major) Avoid coadministration of olaparib with posaconazole due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 100 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after posaconazole is discontinued. Olaparib is a CYP3A substrate and posaconazole is a strong CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with another strong CYP3A inhibitor increased the olaparib Cmax by 42% and the AUC by 170%.
Primidone: (Major) Avoid coadministration of olaparib with primidone due to the risk of decreasing the efficacy of olaparib. Olaparib is a CYP3A substrate and primidone is a strong CYP3A4 inducer; concomitant use may decrease olaparib exposure. Coadministration with another strong CYP3A inducer decreased the olaparib Cmax by 71% and the AUC by 87%.
Ribociclib: (Major) Avoid coadministration of olaparib with ribociclib due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 100 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after ribociclib is discontinued. Olaparib is a CYP3A substrate and ribociclib is a strong CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with another strong CYP3A inhibitor increased the olaparib Cmax by 42% and the AUC by 170%.
Ribociclib; Letrozole: (Major) Avoid coadministration of olaparib with ribociclib due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 100 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after ribociclib is discontinued. Olaparib is a CYP3A substrate and ribociclib is a strong CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with another strong CYP3A inhibitor increased the olaparib Cmax by 42% and the AUC by 170%.
Rifabutin: (Major) Avoid coadministration of olaparib with rifabutin due to the risk of decreasing the efficacy of olaparib. Olaparib is a CYP3A substrate and rifabutin is a moderate CYP3A4 inducer; concomitant use may decrease olaparib exposure. Coadministration with a moderate CYP3A inducer is predicted to decrease the olaparib Cmax by 31% and the AUC by 60%.
Rifampin: (Major) Avoid coadministration of olaparib with rifampin due to the risk of decreasing the efficacy of olaparib. Olaparib is a CYP3A substrate and rifampin is a strong CYP3A4 inducer; concomitant use may decrease olaparib exposure. Coadministration with rifampin decreased the olaparib Cmax by 71% and the AUC by 87%.
Rifapentine: (Major) Avoid coadministration of olaparib with rifapentine due to the risk of decreasing the efficacy of olaparib. Olaparib is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer; concomitant use may decrease olaparib exposure. Coadministration with another strong CYP3A4 inducer decreased the olaparib Cmax by 71% and the AUC by 87%.
Ritlecitinib: (Major) Avoid coadministration of olaparib with ritlecitinib due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 150 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after ritlecitinib is discontinued. Olaparib is a CYP3A substrate and ritlecitinib is a moderate CYP3A inhibitor; concomitant use may increase olaparib exposure. Coadministration with a moderate CYP3A inhibitor is predicted to increase the olaparib AUC by 121%.
Ritonavir: (Major) Avoid coadministration of olaparib with ritonavir due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 100 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after ritonavir is discontinued. Olaparib is a CYP3A substrate and ritonavir is a strong CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with another strong CYP3A inhibitor increased the olaparib Cmax by 42% and the AUC by 170%.
Saquinavir: (Major) Avoid coadministration of olaparib with saquinavir due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 100 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after saquinavir is discontinued. Olaparib is a CYP3A substrate and saquinavir is a strong CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with another strong CYP3A inhibitor increased the olaparib Cmax by 42% and the AUC by 170%.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Secobarbital: (Major) Avoid coadministration of olaparib with secobarbital due to the risk of decreasing the efficacy of olaparib. Olaparib is a CYP3A substrate and secobarbital is a moderate CYP3A4 inducer; concomitant use may decrease olaparib exposure. Coadministration with a moderate CYP3A inducer is predicted to decrease the olaparib Cmax by 31% and the AUC by 60%.
Sotorasib: (Major) Avoid coadministration of olaparib with sotorasib due to the risk of decreasing the efficacy of olaparib. Olaparib is a CYP3A4 substrate and sotorasib is a moderate CYP3A4 inducer; concomitant use may decrease olaparib exposure. Coadministration with a moderate CYP3A4 inducer is predicted to decrease the olaparib Cmax by 31% and the AUC by 60%.
St. John's Wort, Hypericum perforatum: (Major) Avoid coadministration of olaparib with St. Johns Wort due to the risk of decreasing the efficacy of olaparib. Olaparib is a CYP3A substrate and St. Johns Wort is a strong CYP3A4 inducer; concomitant use may decrease olaparib exposure. Coadministration with another strong CYP3A inducer decreased the olaparib Cmax by 71% and the AUC by 87%.
Tipranavir: (Major) Avoid coadministration of olaparib with tipranavir due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 100 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after tipranavir is discontinued. Olaparib is a CYP3A substrate and tipranavir is a strong CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with another strong CYP3A inhibitor increased the olaparib Cmax by 42% and the AUC by 170%.
Trandolapril; Verapamil: (Major) Avoid coadministration of olaparib with verapamil due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 150 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after verapamil is discontinued. Olaparib is a CYP3A substrate and verapamil is a moderate CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with a moderate CYP3A inhibitor is predicted to increase the olaparib Cmax by 14% and the AUC by 121%.
Tucatinib: (Major) Avoid coadministration of olaparib with tucatinib due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 100 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after tucatinib is discontinued. Olaparib is a CYP3A4 substrate and tucatinib is a strong CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with another strong CYP3A4 inhibitor increased the olaparib Cmax by 42% and the AUC by 170%.
Verapamil: (Major) Avoid coadministration of olaparib with verapamil due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 150 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after verapamil is discontinued. Olaparib is a CYP3A substrate and verapamil is a moderate CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with a moderate CYP3A inhibitor is predicted to increase the olaparib Cmax by 14% and the AUC by 121%.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Avoid coadministration of olaparib with clarithromycin due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 100 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after clarithromycin is discontinued. Olaparib is a CYP3A substrate and clarithromycin is a strong CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with another strong CYP3A inhibitor increased the olaparib Cmax by 42% and the AUC by 170%.
Voriconazole: (Major) Avoid coadministration of olaparib with voriconazole due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 100 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after voriconazole is discontinued. Olaparib is a CYP3A substrate and voriconazole is a strong CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with another strong CYP3A inhibitor increased the olaparib Cmax by 42% and the AUC by 170%.
Voxelotor: (Major) Avoid coadministration of olaparib with voxelotor due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 150 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after voxelotor is discontinued. Olaparib is a CYP3A substrate and voxelotor is a moderate CYP3A inhibitor; concomitant use may increase olaparib exposure. Coadministration with a moderate CYP3A inhibitor is predicted to increase the olaparib Cmax by 14% and the AUC by 121%.

Lynparza Oral Cap: 50mg
Olaparib Oral Tab: 100mg, 150mg

300 mg PO twice daily.

300 mg PO twice daily.

Safety and effectiveness have not been established.

Safety and effectiveness have not been established.

Not indicated.

Not indicated.

Olaparib inhibits poly (ADP-ribose) polymerase (PARP) enzymes, including PARP1, PARP2, and PARP3. PARP enzymes are involved in normal cellular functions, such as DNA transcription and DNA repair. Olaparib has been shown to inhibit growth of select tumor cell lines in vitro and decrease tumor growth in mouse xenograft models of human cancer, both as monotherapy or following platinum-based chemotherapy. Increased cytotoxicity and anti-tumor activity following treatment with olaparib were noted in cell lines and mouse tumor models with deficiencies in BRCA and non-BRCA proteins involved in the homologous recombination repair of DNA damage and correlated with platinum response. Olaparib-induced cytotoxicity may involve inhibition of PARP enzymatic activity and increased formation of PARP-DNA complex, resulting in DNA damage and cancer cell death. In prostate cancer models, PARP1 has been shown to contribute to androgen receptor (AR) activity regulation; the combination of olaparib and AR inhibition resulted in cytotoxicity in vitro and anti-tumor activity in mouse xenograft models.

Olaparib is administered orally and shows time-dependent pharmacokinetics. It is approximately 82% protein-bound in vitro. After a single 300 mg oral dose of olaparib, the mean volume of distribution is 158 +/- 136 L in vitro. After oral dosing of radiolabeled olaparib, 86% of the radioactivity was recovered within 7 days: 44% via urine and 42% via feces. The majority (70%) of the material was excreted as metabolites. The mean terminal half-life after a single 300 mg dose of olaparib was 14.9 +/- 8.2 hours, while the apparent plasma clearance was 7.4 +/- 3.9 L/hour.
 
Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: CYP3A4
Olaparib is extensively metabolized by oxidation reactions, with many components undergoing subsequent glucuronide or sulfate conjugation; unchanged drug accounts for only 15% and 6% of the radioactivity in urine and feces, respectively. Coadministration with itraconazole, a strong CYP3A inhibitor, increased the AUC and Cmax of olaparib by 170% and 42%, respectively, in a drug interaction trial (n = 57). Simulations suggested that a moderate CYP3A inhibitor (fluconazole) may increase the AUC and Cmax of olaparib by 121% and 14%, respectively. Concomitant use of strong and moderate CYP3A inhibitors should be avoided; if unavoidable, a dose adjustment is recommended. Coadministration with rifampicin, a strong CYP3A inducer, decreased the AUC and Cmax of olaparib by 87% and 71%, respectively, in a drug interaction trial (n = 22). Simulations suggested that a moderate CYP3A inducer (efavirenz) may decrease the AUC and Cmax of olaparib by 60% and 31%, respectively. Concomitant use of strong and moderate CYP3A inducers should be avoided; if moderate inducers are unavoidable, there is a potential for decreased efficacy of olaparib.
 
Olaparib is also an inducer and (weak) inhibitor of CYP3A, and an inducer of CYP2B6 in vitro. In vitro, it is also an inhibitor of UGT1A1, BCRP, OATP1B1, OCT1, OCT2, OAT3, MATE1 and MATE2K. In vitro, olaparib is a substrate of and inhibitor of P-glycoprotein (P-gp). The potential for olaparib to induce P-gp has not been evaluated.

The mean Cmax of olaparib is 5.4 mcg/mL (CV, 32%) following a single dose and 7.6 mcg/mL (CV, 35%) at steady-state. Absorption of olaparib is rapid following oral administration, with the median time to peak plasma concentrations (Tmax) of 1.5 hours. The mean AUC of olaparib is 39.2 mcg x hour/mL (CV, 44%) following a single dose and 49.2 mcg x hour/mL (CV, 44%) at steady-state; the AUC mean accumulation ratio at steady-state is 1.8. Systemic exposure to olaparib increases approximately proportionally with doses over the dose range of 25 mg to 450 mg (0.08 to 1.5 times the recommended dose); Cmax increased slightly less than proportionally for the same dose range.
 
Coadministration of a high-fat meal (800 to 1,000 kcal with 50% fat) delayed the Tmax by 2.5 hours but did not significantly alter the extent of olaparib absorption (mean AUC increased by approximately 8%).

Pregnancy should be avoided by females of reproductive potential during olaparib treatment and for 6 months after the last dose. Although there are no adequately controlled studies in pregnant animals or humans, olaparib can cause fetal harm or death when administered during pregnancy based on its mechanism of action and animal studies. Women who are pregnant or who become pregnant while receiving olaparib should be apprised of the potential hazard to the fetus. Olaparib caused teratogenicity and embryo-fetal toxicity in rats at exposures below those in patients receiving the recommended human dose when administered during the period of organogenesis. When given orally for 14 days before mating through day 6 of pregnancy, olaparib resulted in increased postimplantation loss at maternal exposures of approximately 7% the AUC at the recommended human dose. At exposures approximately 0.18% the exposure of the recommended dose, pregnant rats experienced increased postimplantation loss and major malformations of the eyes (anophthalmia, microphthalmia), vertebrae/ribs (extra rib or ossification center; fused or absent neural arches, ribs, and sternebrae), skull (fused exoccipital), and diaphragm (hernia). Additional abnormalities included incomplete or absent ossification of the vertebrae/sternebrae, ribs, and limbs, as well as other findings in the vertebrae/sternebrae, pelvic girdle, lung, thymus, liver, ureter, and umbilical artery.

Counsel patients about the reproductive risk and contraception requirements during olaparib treatment. Olaparib can be teratogenic and embryotoxic if the mother is exposed during pregnancy. Females of reproductive potential should avoid pregnancy and use effective contraception during treatment and for 6 months after the last dose of olaparib. Due to the risk of male-mediated teratogenicity, male patients with female partners of reproductive potential should use effective contraception during treatment and for at least 3 months after the last dose of olaparib. Male patients should also not donate sperm during therapy and for 3 months after the last dose. Females of reproductive potential should undergo pregnancy testing prior to the initiation of olaparib treatment. Women who become pregnant while receiving olaparib should be apprised of the potential hazard to the fetus. Olaparib does not appear to cause infertility in males or females based on animal studies.