olaparib (Rx)

Brand and Other Names:Lynparza
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

tablet

  • 100mg
  • 150mg

Ovarian Cancer

Maintenance treatment of recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer

  • Indicated for patients who are in complete or partial response to platinum-based chemotherapy
  • Tablets: 300 mg (two 150-mg tablets) PO BID
  • Continue treatment until disease progression or unacceptable toxicity

Monotherapy for deleterious or suspected deleterious germline BRCA-mutated advanced ovarian cancer

  • Patients who have been treated with ≥3 prior lines of chemotherapy
  • Tablets: 300 mg (two 150-mg tablets) PO BID
  • Continue treatment until disease progression or unacceptable toxicity

First-line maintenance treatment for deleterious or suspected deleterious germlineBRCA-mutated or somatic BRCA-mutated

  • Indicated for advanced epithelial ovarian, fallopian tube or primary peritoneal cancer
  • Patients in complete or partial response to first-line platinum-based chemotherapy
  • Tablets: 300 mg (two 150-mg tablets) PO BID
  • Continue treatment until disease progression, unacceptable toxicity, or completion of 2 years of treatment
  • Completion of 2 years of treatment
    • Patients with complete response (no radiologic evidence): Stop treatment
    • Patients with evidence of disease and may benefit from continuous treatment: Treat beyond 2 years

Breast Cancer

Indicated for deleterious or suspected deleterious gBRCAm, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer

Patients 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 prior endocrine therapy or be considered inappropriate for endocrine therapy

Tablets: 300 mg (two 150-mg tablets) PO BID

Continue treatment until disease progression or unacceptable toxicity

Dosage Modifications

Management of adverse reactions

  • Consider dose interruption or dose reduction to manage adverse reactions
  • Tablets
    • Recommended dose reduction: 250 mg (one 150-mg tablet and one 100-mg tablet) PO BID
    • If a further final dose reduction is required, then reduce to 200 mg (two 100-mg tablets) PO BID

Coadministration with CYP3A inhibitors

  • Strong or moderate CYP3A inhibitors: Avoid use, consider alternatives
  • Tablets
    • If strong CYP3A inhibitors cannot be avoided: Reduce olaparib dose to 100 mg (one 100-mg tablet) PO BID
    • If moderate CYP3A inhibitors cannot be avoided: Reduce olaparib dose to 150 mg (one 150-mg tablet) PO BID

Hepatic impairment

  • Mild to moderate hepatic impairment (Child-Pugh Class A and B): No dosage adjustment necessary
  • Severe hepatic impairment (Child-Pugh Class C): Not studied

Renal impairment

  • Mild (CrCl 50-80 mL/min): No dosage adjustment necessary
  • Tablets
    • Moderate (CrCl 31-50 mL/min): Reduce dose to 200 mg (two 100-mg tablets) BID
    • Severe (CrCl <30 mL/min or dialysis): Not evaluated

Dosing Considerations

Do not substitute olaparib tablets with olaparib capsules on a mg-to-mg basis due to differences in the dosing and bioavailability of each formulation

Withdrawal of capsules

  • In 2017, FDA reported olaparib capsules were being phased out of the US market
  • Capsules were withdrawn from the market to avoid confusion and potential dosing errors with the tablets, and to reduce the pill burden

Patient selection

  • Select patients for therapy based on an FDA-approved companion diagnostic for olaparib
  • Information on FDA-approved test for the detection of BRCA mutations is available at http://www.fda.gov/companiondiagnostics
  • Indications supported by diagnostic tests
    • gBRCAm HER2-negative metastatic breast cancer
    • Advanced gBRCAm ovarian cancer
    • First-line maintenance treatment for BRCA-mutated advanced ovarian cancer

Pancreatic Cancer (Orphan)

Orphan designation for treatment of pancreatic cancer

Orphan sponsor

  • AstraZeneca Pharmaceuticals LP; 1800 Concord Pike, P.O. Box 8355; Wilmington, Delaware 19803

Safety and efficacy not established

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Interactions

Interaction Checker

and olaparib

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    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

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            Adverse Effects

            All grades of severity are listed unless otherwise indicated

            >10% (Maintenance Treatment for BRCA-mutated Advanced Ovarian)

            Decreased hemoglobin (87%)

            Increased mean corpuscular volume (87%)

            Nausea (77%)

            Decrease leukocytes (70%)

            Fatigue (67%)

            Decreased lymphocytes (67%)

            Decreased ANC (51%)

            Abdominal pain (45%)

            Vomiting (40%)

            Anemia (38%)

            Diarrhea (37%)

            Decreased platelets (35%)

            Increased serum creatinine (34%)

            Constipation (28%)

            Upper respiratory tract infection (eg, influenza, nasopharyngitis, bronchitis) (28%)

            Dysgeusia (26%)

            Anemia, Grade 3 or 4 (21%)

            Dizziness (20%)

            Decreased appetite (20%)

            Decreased hemoglobin, Grade 3 or 4 (19%)

            Neutropenia (17%)

            Dyspepsia (17%)

            Dyspnea (15%)

            Decreased lymphocytes, Grade 3 or 4 (14%)

            Urinary tract infection (13%)

            Thrombocytopenia (11%)

            Stomatitis (11%)

            >10% (Maintenance Treatment for Recurrent Advanced Ovarian)

            Increased mean corpuscular volume (89%)

            Decreased hemoglobin (83%)

            Nausea (76%)

            Decreased leukocytes (69%)

            Decreased lymphocytes (67%)

            Fatigue (66%)

            Decreased ANC (51%)

            Anemia (44%)

            Increased serum creatinine (44%)

            Decreased platelets (42%)

            Vomiting (37%)

            Upper respiratory tract infection (36%)

            Diarrhea (33%)

            Arthralgia/myalgia (30%)

            Dysgeusia (27%)

            Headache (26%)

            Decreased appetite (22%)

            Stomatitis (20%)

            Neutropenia (19%)

            Cough (18%)

            Leukopenia (16%)

            Hypomagnesemia (14%)

            Thrombocytopenia (14%)

            Dizziness (13%)

            Dyspepsia (11%)

            Increased creatinine (11%)

            1-10% (BRCA-mutated Advanced Ovarian)

            Maintenance treatment

            • Neutropenia, Grade 3 or 4 (6%)
            • Fatigue, Grade 3 or 4 (4%)
            • Leukopenia, Grade 3 or 4 (3%)
            • Diarrhea, Grade 3 or 4 (3%)
            • Abdominal pain, Grade 3 or 4 (2%)
            • Thrombocytopenia, Grade 3 or 4 (1%)
            • Nausea, Grade 3 or 4 (1%)

            1-10% (Maintenance Treatment for Recurrent Advanced Ovarian)

            Edema (8%)

            Rash (6%)

            Fatigue, Grade 3 or 4 (4%)

            Nausea, Grade 3 or 4 (3%)

            Vomiting, Grade 3 or 4 (3%)

            Diarrhea, Grade 3 or 4 (2%)

            Lymphopenia (1%)

            Headache, Grade 3 or 4 (1%)

            Stomatitis, Grade 3 or 4 (1%)

            Postmarketing Reports

            Hypersensitivity (rash, dermatitis)

            Cough

            Thrombocytopenia

            Dysgeusia

            Lymphopenia

            Dizziness

            Stomatitis

            Upper abdominal pain

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            Warnings

            Contraindications

            None

            Cautions

            Pneumonitis, including fatal cases, occurred in <1%; interrupt treatment if pneumonitis is suspected; discontinue if pneumonitis is confirmed

            Can cause fetal harm when administered to a pregnant woman based on its mechanism of action and findings in animals; (see Pregnancy)

            Myelodysplastic syndrome/ acute myeloid leukemia

            • Incidence of myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) in clinical trials, including long-term follow up, was <1.5% (21/1680)
            • Majority of MDS/AML cases had a fatal outcome; of these, 19/21 patients had a documented BRCA mutation, 1 patient had gBRCA wild-type and in 1 patient the BRCA mutation status was unknown
            • Monitor complete blood count for cytopenia at baseline and monthly thereafter for clinically significant changes during treatment
            • Do not initiate treatment until hematological toxicity caused by previous chemotherapy (CTCAE Grade ≤1) resolves
            • For prolonged hematological toxicities, interrupt treatment and promptly assess source of symptoms; monitor blood counts weekly until recovery
            • If levels have not recovered to CTCAE Grade ≤1 after 4 weeks, refer to a hematologist for further investigations, including bone marrow analysis and blood sample for cytogenetics
            • All patients with myelodysplastic syndrome reported to have received previous chemotherapy with platinum agents and/or other DNA damaging agents including radiotherapy; some of these patients also had a history of more than one primary malignancy or of bone marrow dysplasia
            • If MDS/AML is confirmed, discontinue olaparib

            Drug interactions overview

            • Clinical studies of olaparib in combination with other myelosuppressive anticancer agents (eg, DNA damaging agents) indicate a potentiation and prolongation of myelosuppressive toxicity
            • CYP3A4 inhibitors
              • Olaparib is a CYP3A4 substrate; coadministration of strong or moderate CYP3A4 inhibitors may increase olaparib plasma concentrations
              • Avoid concomitant use of strong or moderate CYP3A inhibitors (see Dosage Modifications)
              • If strong or moderate CYP3A inhibitors must be coadministered, reduce dose of olaparib (see Dosage Modifications)
              • Avoid grapefruit, grapefruit juice, Seville oranges and Seville orange juice during olarparib treatment since they are CYP3A inhibitors
            • CYP3A4 inducers
              • Coadministration of strong or moderate CYP3A4 inducers may decrease olaparib plasma concentrations
              • Avoid concomitant use of strong or moderate CYP3A inducers
              • If a strong or moderate CYP3A inducer cannot be avoided, be aware of a potential for decreased efficacy of olaparib (see Dosage Modifications)
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            Pregnancy & Lactation

            Pregnancy

            Based on findings in animals and mechanism of action, fetal harm may occur when administered to a pregnant woman; there are no available data on use in pregnant women to inform of drug associated risk

            Olaparib was teratogenic and caused embryo-fetal toxicity in rats at exposures below those in patients receiving the recommended human dose of 400 mg BID

            Contraception

            • In women of childbearing potential, avoid pregnancy by using effective contraception during treatment and for at least 6 month after receiving the last dose; pregnancy testing is recommended for females of reproductive potential prior to initiating treatment
            • 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 olaparib
            • Advise male patients not to donate sperm during therapy and for 3 months following the last dose of olaparib

            Lactation

            No data are available regarding presence of olaparib in human milk, or on effects on breastfed infant or on milk production; because of potential for serious adverse reactions in breastfed infants from therapy, advise lactating women not to breastfeed during treatment and for 1 month after receiving last dose

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Inhibitor of poly (ADP-ribose) polymerase (PARP) enzymes, including PARP1, PARP2, and PARP3

            PARP enzymes are involved in normal cellular homeostasis, such as DNA transcription, cell cycle regulation, and DNA repair

            Absorption

            Bioavailability of tablet formulation is higher than the capsule formulation (AUC at steady-state 77% higher with tablet)

            Peak plasma time: 1.5 hr (tablet); 1-3 hr (capsule)

            Peak plasma concentration: 7.7 mcg/mL (tablet at steady-state)

            AUC: 49 mcg·hr/mL (tablet at steady-state)

            Steady-state achieved: 3-4 days

            Coadministration with a high-fat meal slowed the rate (Peak plasma time delayed by 2.5 hr [tablet] or 2 hr [capsule]) of absorption, but did not significantly alter the extent of absorption (mean AUC increased by ~8% [tablet] or ~20% [capsule])

            Distribution

            Protein bound: 82%

            Vd: 158 L (tablet); 167 L (capsule)

            Metabolism

            Metabolized primarily by CYP3A4/5

            Elimination

            Half-life: 14.9 hr (tablet); 11.9 hr (capsule)

            Plasma clearance: 7.4 L/hr (tablet); 8.6 L/hr (capsule)

            Excretion: 44% urine; 42% feces

            Excreted mostly as metabolites

            Pharmacogenomics

            Indicated as monotherapy in patients with deleterious or suspected deleterious germline BRCA-mutated (as detected by an FDA-approved test) advanced ovarian cancer or breast cancer

            Information on FDA-approved test for the detection of BRCA mutations is available at http://www.fda.gov/companiondiagnostics

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            Administration

            Oral Administration

            To avoid substitution errors and overdose, do not substitute olaparib tablets with olaparib capsules on a mg-to-mg basis due to differences in the dosing and bioavailability of each formulation

            Tablets or capsules: May take with or without food

            Swallow tablets whole; do not chew, crush, dissolve or divide

            Missed dose: Instruct patient to take their next dose at its scheduled time

            Storage

            Tablets: Store at 20-25ºC (68-77°F), excursions permitted to 15-30ºC (59-86°F)

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            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

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            • View the formulary and any restrictions for each plan.
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            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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