Data from FDA - Curated by EPG Health - Last updated 01 August 2019

Indication(s)

1 INDICATIONS AND USAGE Lynparza is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated: Ovarian cancer •for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer, who are in a complete or partial response to platinum-based chemotherapy. (1.1) •for the treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for Lynparza. (1.2, 2.3) Breast cancer •in patients with deleterious or suspected deleterious gBRCAm, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer who have been treated with chemotherapy in the neoadjuvant, adjuvant or metastatic setting. Patients with hormone receptor (HR)-positive breast cancer should have been treated with a prior endocrine therapy or be considered inappropriate for endocrine therapy. Select patients for therapy based on an FDA-approved companion diagnostic for Lynparza. (1.3, 2.4) 1.1 Maintenance Treatment of Recurrent Ovarian Cancer Lynparza is indicated for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer, who are in a complete or partial response to platinum-based chemotherapy. 1.2 Advanced gBRCA-mutated Ovarian Cancer After 3 or More Lines of Chemotherapy Lynparza is indicated for the treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for Lynparza [see Dosage and Administration (2.3)]. 1.3 Germline BRCA-mutated HER2-negative Metastatic Breast Cancer Lynparza is indicated in patients with deleterious or suspected deleterious gBRCAm, HER2-negative metastatic breast cancer, who have been treated with chemotherapy in the neoadjuvant, adjuvant, or metastatic setting. Patients with hormone receptor (HR)-positive breast cancer should have been treated with a prior endocrine therapy or be considered inappropriate for endocrine therapy. Select patients for therapy based on an FDA-approved companion diagnostic for Lynparza [see Dosage and Administration (2.4) ] .

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contraindications
4 CONTRAINDICATIONS None. None. (4)
Adverse reactions
6 ADVERSE REACTIONS The following adverse reactions are discussed elsewhere in the labeling: •Myelodysplastic Syndrome/Acute Myeloid Leukemia [see Warnings and Precautions (5.1)] •Pneumonitis [see Warnings and Precautions (5.2)] •Most common adverse reactions (≥20%) in clinical trials were anemia, nausea, fatigue (including asthenia), vomiting, neutropenia leukopenia, nasopharyngitis/upper respiratory tract infection/influenza, respiratory tract infection, diarrhea, arthralgia/myalgia, dysgeusia, headache, dyspepsia, decreased appetite, constipation and stomatitis. (6.1) •Most common laboratory abnormalities (≥25%) were decrease in hemoglobin, increase in mean corpuscular volume, decrease in lymphocytes, decrease in leukocytes, decrease in absolute neutrophil count, increase in serum creatinine and decrease in platelets. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact AstraZeneca at 1-800-236-9933 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adverse reactions presented below were reported from clinical trials in 782 patients with ovarian cancer (555 received Lynparza, 227 received placebo). Maintenance Treatment of Recurrent Ovarian Cancer SOLO-2 The safety of Lynparza for the maintenance treatment of patients with platinum sensitive gBRCAm ovarian cancer was investigated in SOLO-2. This study was a placebo-controlled, double-blind study in which 294 patients received either Lynparza 300 mg (2 x 150 mg tablets) twice daily (n=195) or placebo tablets twice daily (n=99) until disease progression or unacceptable toxicity. The median duration of study treatment was 19.4 months for patients who received Lynparza and 5.6 months for patients who received placebo. Dose interruptions due to an adverse reaction of any grade occurred in 45% of patients receiving Lynparza and 18% of those receiving placebo; dose reductions due to an adverse reaction occurred in 27% of Lynparza patients and 3% of placebo patients. The most frequent adverse reactions leading to dose interruption or reduction of Lynparza were anemia (22%), neutropenia (9%), and fatigue/asthenia (8%). Discontinuation occurred in 11% of Lynparza patients and 2% in placebo patients. Table 1 summarizes the adverse reactions that occurred in at least 20% of patients who received Lynparza in SOLO-2. Table 2 presents the laboratory abnormalities that occurred in at least 25% of patients who received Lynparza in SOLO-2. Table 1 Adverse ReactionsGraded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.0. in SOLO-2 (≥20% of Patients who Received Lynparza) Adverse Reactions Lynparza tablets n=195 Placebo n=99 Grades 1-4 % Grades 3-4 % Grades 1-4 % Grades 3-4 % Blood and lymphatic disorders AnemiaRepresents grouped term consisting of anemia, hematocrit decreased, hemoglobin decreased, iron deficiency, mean cell volume increased and red blood cell count decreased. 44 20 9 2 Gastrointestinal disorders Nausea 76 3 33 0 Vomiting 37 3 19 1 Diarrhea 33 2 22 0 StomatitisRepresents grouped term consisting of abscess oral, aphthous ulcer, gingival abscess, gingival disorder, gingival pain, gingivitis, mouth ulceration, mucosal infection, mucosal inflammation, oral candidiasis, oral discomfort, oral herpes, oral infection, oral mucosal erythema, oral pain, oropharyngeal discomfort, and oropharyngeal pain. 20 1 16 0 Infections and Infestations Nasopharyngitis/ URI/ sinusitis/ rhinitis/ influenza 36 0 29 0 General disorders and administration site conditions Fatigue including asthenia 66 4 39 2 Metabolism and nutrition disorders Decreased appetite 22 0 11 0 Musculoskeletal and connective tissue disorder Arthralgia/myalgia 30 0 28 0 Nervous system disorders Dysgeusia 27 0 7 0 Headache 26 1 14 0 In addition, the adverse reactions observed in SOLO-2 that occurred in <20% of patients receiving Lynparza were neutropenia, rash, cough, dyspepsia, leukopenia, hypomagnesemia, dizziness, thrombocytopenia, increase in creatinine, lymphopenia and edema. Table 2 Laboratory Abnormalities Reported in ≥25% of Patients in SOLO-2 Laboratory Parameter Patients were allowed to enter clinical studies with laboratory values of CTCAE Grade 1. Lynparza tablets n This number represents the safety population. The derived values in the table are based on the total number of evaluable patients for each laboratory parameter. =195 Placebo n =99 Grades 1-4 % Grades 3-4 % Grades 1-4 % Grades 3-4 % Increase in mean corpuscular volumeRepresents the proportion of subjects whose mean corpuscular volume was > upper limit of normal (ULN). 89 - 52 - Decrease in hemoglobin 83 17 69 0 Decrease in leukocytes 69 5 48 1 Decrease in lymphocytes 67 11 37 1 Decrease in absolute neutrophil count 51 7 34 3 Increase in serum creatinine 44 0 29 0 Decrease in platelets 42 2 22 1 Study 19 The safety of Lynparza capsules as maintenance monotherapy was also evaluated in patients with platinum sensitive ovarian cancer who had received 2 or more previous platinum containing regimens in Study 19, a randomized, placebo-controlled, double-blind, multi-center study in which 264 patients received Lynparza 400 mg twice daily (n=136) or placebo (n=128). At the time of final analysis, the median duration of exposure was 8.7 months in patients who received Lynparza and 4.6 months in patients who received placebo. Adverse reactions led to dose interruptions in 35% of those receiving Lynparza and 10% of those receiving placebo; dose reductions in 26% of Lynparza and 4% of placebo; and discontinuation in 6% of Lynparza and 2% in placebo. Table 3 summarizes the adverse reactions that occurred in at least 20% of patients who received Lynparza in Study 19. Table 4 presents the laboratory abnormalities that occurred in at least 25% of patients from Study 19. Table 3 Adverse ReactionsGraded according to NCI CTCAE 4.0. in Study 19 (≥20% of Patients who Received Lynparza) Adverse Reactions Lynparza capsules n=136 Placebo n=128 Grades 1-4 % Grades 3-4 % Grades 1-4 % Grades 3-4 % Blood and lymphatic disorders AnemiaRepresents grouped terms of related terms that reflect the medical concept of the adverse reaction. 23 7 7 1 Gastrointestinal disorders Nausea 71 2 36 0 Vomiting 35 2 14 1 Diarrhea 28 2 25 2 Constipation 22 1 12 0 General disorders and administration site conditions Fatigue (including asthenia) 63 9 46 3 Infections and infestations Respiratory tract infection 22 2 11 0 Metabolism and nutrition disorders Decreased appetite 21 0 13 0 Nervous system disorders Headache 21 0 13 1 In addition, the adverse reactions in Study 19 that occurred in <20% of patients receiving Lynparza were dyspepsia, stomatitis, dysgeusia, dizziness, increase in creatinine, neutropenia, thrombocytopenia, leukopenia, lymphopenia, dyspnea, pyrexia and edema. Table 4 Laboratory Abnormalities Reported in ≥25% of Patients in Study 19 Laboratory Parameter Patients were allowed to enter clinical studies with laboratory values of CTCAE Grade 1. Lynparza capsules n This number represents the safety population. The derived values in the table are based on the total number of evaluable patients for each laboratory parameter =136 Placebo n =129 Grades 1-4 % Grades 3-4 % Grades 1-4 % Grades 3-4 % Decrease in hemoglobin 82 8 58 1 Increase in mean corpuscular volumeRepresents the proportion of subjects whose mean corpuscular volume was > ULN. 82 - 51 - Decrease in leukocytes 58 4 37 2 Decrease in lymphocytes 52 10 32 3 Decrease in absolute neutrophil count 47 7 40 2 Increase in serum creatinine 45 0 14 0 Decrease in platelets 36 4 18 0 Treatment of Advanced gBRCAm Ovarian Cancer After 3 or More Lines of Chemotherapy Pooled data Treatment with Lynparza (capsule formulation) as monotherapy was studied in 223 patients (pooled from 6 studies) with gBRCAm advanced ovarian cancer who had received 3 or more prior lines of chemotherapy. Adverse reactions led to dose interruption in 40% of patients, dose reduction in 4% of patients, and discontinuation in 7% of patients. There were 8 (4%) patients with adverse reactions leading to death, two were attributed to acute leukemia, and one each was attributed to COPD, cerebrovascular accident, intestinal perforation, pulmonary embolism, sepsis, and suture rupture. The median exposure to Lynparza capsules in these patients was 5.2 months. Table 5 presents adverse reactions reported in ≥20% of patients and Table 6 presents laboratory abnormalities that occurred in at least 25% of patients from the pooled studies. Table 5 Adverse Reactions Reported in Pooled Data (≥20% of Patients who Received Lynparza) Adverse Reactions 3 or more lines of prior Chemotherapy Grades 1-4 n=223 (%) Grades 3-4 n=223 (%) Blood and Lymphatic disorders Anemia 34 18 Gastrointestinal disorders Decreased appetite 22 1 Nausea 64 3 Vomiting 43 4 Diarrhea 31 1 Dyspepsia 25 0 General disorders Fatigue/asthenia 66 8 Infections and infestations Nasopharyngitis/URI 26 0 Musculoskeletal and Connective Tissue disorders Arthralgia/musculoskeletal pain 21 0 Myalgia 22 0 Table 6 Laboratory Abnormalities Reported ≥25% of Patients in Pooled Data Laboratory Parameter Patients were allowed to enter clinical studies with laboratory values of CTCAE Grade 1. 3 or more lines of prior Chemotherapy Grades 1-4 n This number represents the safety population. The derived values in the table are based on the total number of evaluable patients for each laboratory parameter. =223 (%) Grades 3-4 n =223 (%) Decrease in hemoglobin 90 15 Decrease in absolute neutrophil count 25 7 Decrease in platelets 30 3 Decrease in lymphocytes 56 17 Mean corpuscular volume elevation 57 - Increase in creatinine 30 2 The following adverse reactions and laboratory abnormalities have been identified in ≥10 to <20% of the 223 patients receiving Lynparza and not included in the table: cough, constipation, dysgeusia, peripheral edema, back pain, dizziness, headache, urinary tract infection, dyspnea, and rash. The following adverse reactions and laboratory abnormalities have been identified in ≥1 to <10% of the 223 patients receiving Lynparza and not included in the table: leukopenia, stomatitis, peripheral neuropathy, pyrexia, hypomagnesemia, and venous thrombosis (including pulmonary embolism). Treatment of gBRCAm HER2-negative Metastatic Breast Cancer OlympiAD The safety of Lynparza tablets as monotherapy was also evaluated in gBRCAm patients with HER2-negative metastatic breast cancer who had previously received up to two lines of chemotherapy for the treatment of metastatic disease in OlympiAD. This study was a randomized, open-label, multi-center study in which 296 patients received either Lynparza 300 mg twice daily (n=205) or a chemotherapy (capecitabine, eribulin, or vinorelbine) of the healthcare provider’s choice (n=91) until disease progression or unacceptable toxicity. The median duration of study treatment was 8.2 months in patients who received Lynparza and 3.4 months in patients who received chemotherapy. Dose interruptions due to an adverse reaction of any grade occurred in 35% of patients receiving Lynparza and 28% of those receiving chemotherapy; dose reductions due to an adverse reaction occurred in 25% of Lynparza patients and 31% of chemotherapy patients. Discontinuation occurred in 5% of Lynparza patients and 8% in chemotherapy patients. Table 7 summarizes the adverse reactions that occurred in at least 20% of patients who received Lynparza in OlympiAD. Table 8 presents the laboratory abnormalities that occurred in at least 25% of patients who received Lynparza in OlympiAD. Table 7 Adverse ReactionsGraded according to NCI CTCAE 4.0. in OlympiAD (≥20% of Patients who received Lynparza) Adverse Reactions Lynparza tablets n=205 Chemotherapy n=91 Grades 1-4 % Grades 3-4 % Grades 1-4 % Grades 3-4 % Blood and lymphatic disorders AnemiaRepresents grouped terms consisting of anemia (anemia erythropenia, hematocrit decreased, hemoglobin decreased and red blood cell count decreased). 40 16 26 4 LeukopeniaRepresents grouped terms consisting of leukopenia (leukopenia and white blood cell count decreased). 25 5 31 13 NeutropeniaRepresents grouped terms consisting of neutropenia (febrile neutropenia, granulocyte count decreased, granulocytopenia, neutropenia, neutropenic infection, neutropenic sepsis, neutrophil count decreased). 27 9 50 26 Gastrointestinal disorders Nausea 58 0 35 1 Vomiting 30 0 15 1 Diarrhea 21 1 22 0 Infections and infestations Respiratory tract infectionRepresents grouped terms consisting of bronchitis, influenza, lower respiratory tract infection, nasopharyngitis, pharyngitis, respiratory tract infection, rhinitis, sinusitis, upper respiratory tract infection, upper respiratory tract infection bacterial. 27 1 22 0 General disorders and administration site conditions Fatigue (including asthenia) 37 4 36 1 Nervous system disorders Headache 20 1 15 2 In addition, adverse reactions in OlympiAD that occurred in <20% of patients receiving Lynparza were cough, decreased appetite, thrombocytopenia, dysgeusia, lymphopenia, dizziness, dyspepsia, stomatitis, upper abdominal pain, rash, increase in serum creatinine and dermatitis. Table 8 Laboratory Abnormalities Reported ≥25% of Patients in OlympiAD Laboratory Parameter Patients were allowed to enter clinical studies with laboratory values of CTCAE Grade 1. Lynparza tablets n This number represents the safety population. The derived values in the table are based on the total number of evaluable patients for each laboratory parameter. =205 Chemotherapy n =91 Grades 1-4 % Grades 3-4 % Grades 1-4 % Grades 3-4 % Increase in mean corpuscular volumeRepresents the proportion of subjects whose mean corpuscular volume was > ULN. 71 - 33 - Decrease in hemoglobin 82 17 66 3 Decrease in leukocytes 71 8 70 23 Decrease in lymphocytes 73 21 63 3 Decrease in absolute neutrophil count 46 11 65 38 Decrease in platelets 33 3 28 0 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of Lynparza capsules. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Immune System Disorders: Hypersensitivity (rash/dermatitis).

Usage information

Dosing and administration
2 DOSAGE AND ADMINISTRATION •To avoid substitution errors and overdose, do not substitute Lynparza tablets with Lynparza capsules on a milligram-to-milligram basis due to differences in the dosing and bioavailability of each formulation. (2.1) •Recommended tablet dose is 300 mg taken orally twice daily with or without food. (2.2) •Continue treatment until disease progression or unacceptable toxicity. (2.2) •For adverse reactions, consider dose interruption or dose reduction. (2.5) •For moderate renal impairment (CLcr 31-50 mL/min), reduce dose to 200 mg twice daily. (2.7) 2.1 Important Administration Instructions Lynparza is also available as a 50 mg capsule. DO NOT substitute Lynparza tablets (100 mg and 150 mg) with Lynparza capsules (50 mg) on a milligram-to-milligram basis due to differences in the dosing and bioavailability of each formulation [see Clinical Pharmacology (12.3)]. Refer to the full prescribing information for Lynparza capsules for specific capsule dosing. 2.2 Recommended Dosing The recommended dose of Lynparza is 300 mg (two 150 mg tablets) taken orally twice daily, with or without food, for a total daily dose of 600 mg. The 100 mg tablet is available for dose reduction. Continue treatment until disease progression or unacceptable toxicity. If a patient misses a dose of Lynparza, instruct patient to take their next dose at its scheduled time. Swallow tablets whole. Do not chew, crush, dissolve, or divide tablet [see How Supplied/Storage and Handling (16.2) ]. 2.3 Patient Selection for gBRCAm Advanced Ovarian Cancer Select patients for the treatment of advanced ovarian cancer with Lynparza based on the presence of deleterious or suspected deleterious BRCA-mutations [see Indications and Usage (1.2) and Clinical Studies (14.2)]. Information on FDA-approved tests for the detection of BRCA-mutations is available at http://www.fda.gov/companiondiagnostics. 2.4 Patient Selection for gBRCAm HER2-negative Metastatic Breast Cancer Select patients for the treatment of HER2-negative metastatic breast cancer with Lynparza based on the presence of deleterious or suspected deleterious gBRCA-mutation [see Indications and Usage (1.3) and Clinical Studies (14.3) ]. Information on FDA-approved tests for the detection of BRCA-mutations is available at http://www.fda.gov/companiondiagnostics. 2.5 Dose Adjustments for Adverse Reactions To manage adverse reactions, consider interruption of treatment or dose reduction. The recommended dose reduction is 250 mg (one 150 mg tablet and one 100 mg tablet) taken twice daily, for a total daily dose of 500 mg. If a further dose reduction is required, then reduce to 200 mg (two 100 mg tablets) taken twice daily, for a total daily dose of 400 mg. 2.6 Dose Modifications for Use with CYP3A Inhibitors Avoid concomitant use of strong or moderate CYP3A inhibitors and consider alternative agents with less CYP3A inhibition. If a strong CYP3A inhibitor must be co-administered, reduce the Lynparza dose to 100 mg (one 100 mg tablet) taken twice daily (equivalent to a total daily dose of 200 mg). If a moderate CYP3A inhibitor must be co-administered, reduce the Lynparza dose to 150 mg (one 150 mg tablet) taken twice daily (equivalent to a total daily dose of 300 mg) [see Drug Interactions (7.2) and Clinical Pharmacology (12.3)]. 2.7 Dose Modifications for Patients with Renal Impairment Patients with mild renal impairment (CLcr 51-80 mL/min as estimated by Cockcroft-Gault equation) do not require an adjustment in Lynparza dosing. In patients with moderate renal impairment (CLcr 31-50 ml/min) the recommended dose reduction is to 200 mg (two 100 mg tablets) twice daily, for a total daily dose of 400 mg. The pharmacokinetics of Lynparza have not been evaluated in patients with severe renal impairment or end-stage renal disease (CLcr ≤30 mL/min) [see Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)].
Use in special populations
8 USE IN SPECIFIC POPULATIONS Lactation: Advise women not to breastfeed. (8.2) 8.1 Pregnancy Risk Summary Based on findings in animals and its mechanism of action [see Clinical Pharmacology (12.1)], Lynparza can cause fetal harm when administered to a pregnant woman. There are no available data on Lynparza use in pregnant women to inform the drug-associated risk. In an animal reproduction study, the administration of olaparib to pregnant rats during the period of organogenesis caused teratogenicity and embryo-fetal toxicity at exposures below those in patients receiving the recommended human dose of 300 mg twice daily [see Data]. Apprise pregnant women of the potential hazard to the fetus and the potential risk for loss of the pregnancy. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. The estimated background risk in the U.S. general population of major birth defects is 2-4%; and the risk for spontaneous abortion is approximately 15-20% in clinically recognized pregnancies. Data Animal Data In a fertility and early embryonic development study in female rats, olaparib was administered orally for 14 days before mating through to day 6 of pregnancy, which resulted in increased post-implantation loss at a dose level of 15 mg/kg/day (with maternal systemic exposures approximately 7% of the human exposure (AUC0-24h) at the recommended dose). In an embryo-fetal development study, pregnant rats received oral doses of 0.05 and 0.5 mg/kg/day olaparib during the period of organogenesis. A dose of 0.5 mg/kg/day (with maternal systemic exposures approximately 0.18% of human exposure (AUC0-24h) at the recommended dose) caused embryo-fetal toxicities including increased post-implantation 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 or variants included incomplete or absent ossification (vertebrae/sternebrae, ribs, limbs) and other findings in the vertebrae/sternebrae, pelvic girdle, lung, thymus, liver, ureter and umbilical artery. Some findings noted above in the eyes, ribs and ureter were observed at a dose of 0.05 mg/kg/day olaparib at lower incidence. 8.2 Lactation Risk Summary No data are available regarding the presence of olaparib in human milk, or on its effects on the breastfed infant or on milk production. Because of the potential for serious adverse reactions in the breastfed infants from Lynparza, advise a lactating woman not to breastfeed during treatment with Lynparza and for one month after receiving the last dose. 8.3 Females and Males of Reproductive Potential Pregnancy Testing Pregnancy testing is recommended for females of reproductive potential prior to initiating treatment with Lynparza. Contraception Females Lynparza can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)]. Advise females of reproductive potential to use effective contraception during treatment with Lynparza and for at least 6 months following the last dose. Males Based on findings in genetic toxicity and animal reproduction studies, advise male patients with female partners of reproductive potential or who are pregnant to use effective contraception during treatment and for 3 months following the last dose of Lynparza. Advise male patients not to donate sperm during therapy and for 3 months following the last dose of Lynparza [see Use in Specific Populations (8.1) and Nonclinical Toxicology (13.1)]. 8.4 Pediatric Use The safety and efficacy of Lynparza have not been established in pediatric patients. 8.5 Geriatric Use In clinical studies of Lynparza enrolling 687 patients with advanced solid tumors who received Lynparza tablets 300 mg twice daily as monotherapy, 146 (21%) patients were aged ≥65 years, and this included 29 (4%) patients who were aged ≥75 years. No patients were aged ≥85 years. No overall differences in the safety or effectiveness of Lynparza were observed between younger and older patients. 8.6 Hepatic Impairment No adjustment to the starting dose is required in patients with mild hepatic impairment. A 15% increase in mean exposure (AUC) was observed in patients with mild hepatic impairment (based on Child-Pugh classification A) compared to patients with normal hepatic function. There are no data in patients with moderate or severe hepatic impairment [see Clinical Pharmacology (12.3)]. 8.7 Renal Impairment No adjustment to the starting dose is required in patients with mild renal impairment, but patients should be monitored closely for toxicity. A 24% increase in mean exposure (AUC) was observed in patients with mild renal impairment (CLcr = 51-80 mL/min) compared to patients with normal renal function (CLcr >80 mL/min). A 44% increase in AUC was observed in patients with moderate renal impairment (CLcr = 31-50 mL/min) compared to patients with normal renal function (CLcr >80 mL/min). For patients with moderate renal impairment, reduce the dose of Lynparza to 200 mg twice daily [see Dosage and Administration (2.6)]. There are no data in patients with severe renal impairment or end-stage disease (CLcr ≤30 mL/min) [see Clinical Pharmacology (12.3)].

Interactions

7 DRUG INTERACTIONS •CYP3A Inhibitors: Avoid concomitant use of strong or moderate CYP3A inhibitors. If the inhibitor cannot be avoided, reduce the olaparib dose. (2.6, 7.2, 12.3) •CYP3A Inducers: Avoid concomitant use of strong or moderate CYP3A inducers as decreased efficacy can occur. (7.3, 12.3) 7.1 Anticancer Agents Clinical studies of Lynparza in combination with other myelosuppressive anticancer agents, including DNA damaging agents, indicate a potentiation and prolongation of myelosuppressive toxicity. 7.2 Drugs That May Increase Olaparib Plasma Concentrations Olaparib is primarily metabolized by CYP3A. In patients (n=57), co-administration of itraconazole, a strong CYP3A inhibitor, increased AUC of olaparib by 170%. A moderate CYP3A inhibitor, fluconazole, is predicted to increase the AUC of olaparib by 121%. Avoid concomitant use of strong CYP3A inhibitors such as itraconazole, telithromycin, clarithromycin, ketoconazole, voriconazole, nefazodone, posaconazole, ritonavir, lopinavir/ritonavir, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir or moderate CYPA inhibitors such as amprenavir, aprepitant, atazanavir, ciprofloxacin, crizotinib, darunavir/ritonavir, diltiazem, erythromycin, fluconazole, fosamprenavir, imatinib, verapamil. If the strong or moderate CYP3A inhibitors must be co-administered, reduce the dose of Lynparza [see Dosage and Administration (2.5)]. Avoid grapefruit, grapefruit juice, Seville oranges, and Seville orange juice during Lynparza treatment since they are CYP3A inhibitors [see Dosage and Administration (2.5) and Clinical Pharmacology (12.3)]. 7.3 Drugs That May Decrease Olaparib Plasma Concentrations In patients (n=22), co-administration of rifampicin, a strong CYP3A inducer, decreased AUC of olaparib by 87%. A moderate CYP3A inducer, efavirenz, is predicted to decrease the AUC of olaparib by approximately 60%. Avoid concomitant use of strong CYP3A inducers such as phenytoin, rifampicin, carbamazepine, and St. John’s Wort or moderate CYP3A4 inducers such as bosentan, efavirenz, etravirine, modafinil, and nafcillin. If a moderate CYP3A inducer cannot be avoided, there is a potential for decreased efficacy of Lynparza [see Clinical Pharmacology (12.3)].

More information

Category Value
Authorisation number NDA208558
Agency product number WOH1JD9AR8
Orphan designation No
Product NDC 0310-0679,0310-0668
Date Last Revised 06-02-2018
Type HUMAN PRESCRIPTION DRUG
Marketing authorisation holder AstraZeneca Pharmaceuticals LP