Chemical formula: C₁₉H₂₀N₄O Molecular mass: 320.396 g/mol PubChem compound: 24958200
Niraparib interacts in the following cases:
In vitro, niraparib weakly inhibits the organic cation transporter 1 (OCT1) with an IC50 = 34.4 μM. Caution is recommended when niraparib is combined with active substances that undergo an uptake transport by OCT1 such as metformin.
Niraparib is an inhibitor of MATE1 and -2 with IC50 of 0.18 µM and ≤0.14 µM, respectively. Increased plasma concentrations of co-administered medicinal products that are substrates of these transporters (e.g. metformin) cannot be excluded.
In vitro, niraparib weakly induces CYP1A2 at high concentrations and the clinical relevance of this effect could not be completely ruled out. M1 is not a CYP1A2 inducer. Therefore, caution is recommended when niraparib is combined with active substances the metabolism of which is CYP1A2-dependent and, notably, those having a narrow therapeutic range (e.g. clozapine, theophylline, and ropinirole).
Even though inhibition of CYP3A4 in the liver is not expected, the potential to inhibit CYP3A4 at the intestinal level has not been established at relevant niraparib concentrations. Therefore, caution is recommended when niraparib is combined with active substances the metabolism of which is CYP3A4-dependent and, notably, those having a narrow therapeutic range (e.g. ciclosporin, tacrolimus, alfentanil, ergotamine, pimozide, quetiapine, and halofantrine).
In vitro, niraparib inhibits P-gp very weakly and BCRP with an IC50 = 161 µM and 5.8 µM, respectively. Therefore, a clinically meaningful interaction related to an inhibition of these efflux transporters, although unlikely, cannot be excluded. Caution is then recommended when niraparib is combined with substrates of BCRP (irinotecan, rosuvastatin, simvastatin, atorvastatin, and methotrexate).
There are no data in patients with severe renal impairment or end stage renal disease undergoing haemodialysis; use with caution in these patients.
For patients with moderate hepatic impairment (any AST and TB > 1.5 x – 3 x ULN) the recommended starting dose of niraparib is 200 mg once daily.
There are no data in patients with severe hepatic impairment (any AST and TB > 3 x ULN); use with caution in these patients.
Patients with severe hepatic impairment could have increased exposure of niraparib based on data from patients with moderate hepatic impairment and should be carefully monitored.
There are no clinical data on fertility. A reversible reduction of spermatogenesis was observed in rats and dogs.
There are no or limited amount of data from the use of niraparib in pregnant women. Animal reproductive and developmental toxicity studies have not been conducted. However, based on its mechanism of action, niraparib could cause embryonic or foetal harm, including embryo-lethal and teratogenic effects, when administered to a pregnant woman. Niraparib should not be used during pregnancy.
It is unknown whether niraparib or its metabolites are excreted in human milk. Breast-feeding is contraindicated during administration of niraparib and for 1 month after receiving the last dose.
Women of childbearing potential should not become pregnant while on treatment and should not be pregnant at the beginning of treatment. A pregnancy test should be performed on all women of childbearing potential prior to treatment. Women of childbearing potential must use effective contraception during therapy and for 1 month after receiving the last dose of niraparib.
There are no clinical data on fertility. A reversible reduction of spermatogenesis was observed in rats and dogs.
Niraparib has moderate influence on the ability to drive or use machines. Patients who take niraparib may experience asthenia, fatigue and dizziness. Patients who experience these symptoms should observe caution when driving or using machines.
In the pivotal ENGOT-OV16 study, adverse reactions (ADRs) occurring ≥10% of patients receiving niraparib monotherapy were nausea, thrombocytopenia, fatigue/asthenia, anaemia, constipation, vomiting, abdominal pain, neutropenia, insomnia, headache, decreased appetite, nasopharyngitis, diarrhoea, dyspnea, hypertension, dyspepsia, back pain, dizziness, cough, urinary tract infection, arthralgia, palpitations, and dysgeusia.
The most common serious adverse reactions >1% (treatment-emergent frequencies) were thrombocytopenia and anaemia.
The following adverse reactions have been identified in the ENGOT-OV16 study in patients receiving niraparib monotherapy (see below).
Frequencies of occurrence of undesirable effects are defined as: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
Adverse drug reactions: frequencies based on all-causality adverse events*:
Frequency of all CTCAE grades:
Very common: Urinary tract infection
Common: Bronchitis, conjunctivitis
Very common: Thrombocytopenia, anaemia, neutropenia
Common: Leukopenia
Uncommon: Pancytopenia, febrile neutropenia
Very common: Decreased appetite
Common: Hypokalemia
Very common: Insomnia
Common: Anxiety, depression
Very common: Headache, dizziness, dysgeusia
Very common: Palpitations
Common: Tachycardia
Very common: Hypertension
Very common: Dyspnea, cough, nasopharyngitis
Common: Epistaxis
Very common: Nausea, constipation, vomiting, abdominal pain, diarrhoea, dyspepsia
Common: Dry mouth, abdominal distension, mucosal inflammation (including mucositis), stomatitis
Common: Photosensitivity, rash
Very common: Back pain, arthralgia
Common: Myalgia
Very common: Fatigue, asthenia
Common: Oedema peripheral
Common: Gamma-glutamyl transferase increased, AST increased, blood creatinine increased, ALT increased, blood alkaline phosphatase increased, weight decreased
Frequency of CTCAE grade 3 or 4:
Uncommon: Urinary tract infection, bronchitis
Very common: Thrombocytopenia, anaemia, neutropenia
Common: Leukopenia
Uncommon: Pancytopenia, febrile neutropenia
Common: Hypokalemia
Uncommon: Decreased appetite
Uncommon: Insomnia, anxiety, depression
Uncommon: Headache
Common: Hypertension
Common: Dyspnea
Common: Nausea, vomiting, abdominal pain
Uncommon: Diarrhoea, constipation, mucosal inflammation (including mucositis), stomatitis, dry mouth
Uncommon: Photosensitivity, rash
Uncommon: Back pain, arthralgia, myalgia
Common: Fatigue, asthenia
Common: Gamma-glutamyl transferase increased
Uncommon: AST increased, ALT increased, blood alkaline phosphatase increased
* Frequencies are based on percent of patients using all-causality adverse events.
Haematologic adverse reactions (thrombocytopenia, anaemia, neutropenia) including clinical diagnoses and/or laboratory findings generally occurred early during niraparib treatment with the incidence decreasing over time.
Approximately 60% of patients receiving niraparib experienced thrombocytopenia of any grade, and 34% of patients experienced Grade ¾ thrombocytopenia. In patients with baseline platelet count less than 180 × 109/L, thrombocytopenia of any grade and Grade ¾ occurred in 76% and 45% of the patients, respectively. The median time to onset of thrombocytopenia regardless of grade and Grade ¾ thrombocytopenia was 22 and 23 days, respectively. The rate of new incidences of thrombocytopenia after intensive dose modifications were performed during the first two months of treatment from Cycle 4 was 1.2%. The median duration of thrombocytopenia events of any grade was 23 days, and the median duration of Grade ¾ thrombocytopenia was 10 days. Patients treated with niraparib who develop thrombocytopenia might have an increased risk of haemorrhage. In the clinical programme, thrombocytopenia was managed with laboratory monitoring, dose modification and platelet transfusion where appropriate. Discontinuation due to thrombocytopenia events (thrombocytopenia and platelet count decreased) occurred in approximately 3% of the patients.
Approximately 50% of patients experienced anaemia of any grade, and 25% experienced Grade ¾ anaemia. The median time to onset of anaemia of any grade was 42 days, and 85 days for Grade ¾ events. The median duration of anaemia of any grade was 63 days, and 8 days for Grade ¾ events. Anaemia of any grade might persist during niraparib treatment. In the clinical programme, anaemia was managed with laboratory monitoring, dose modification, and where appropriate with red blood cell transfusions. Discontinuation due to anaemia occurred in 1% of patients.
Approximately 30% of patients receiving niraparib experienced neutropenia of any grade, and 20% of patients experienced Grade ¾ neutropenia. The median time to onset of neutropenia of any grade was 27 days, and 29 days for Grade ¾ events. The median duration of neutropenia of any grade was 26 days, and 13 days for Grade ¾ events. In the clinical programme, neutropenia was managed with laboratory monitoring and dose modifications. In addition, Granulocyte-Colony Stimulating Factor (G-CSF) was administered to approximately 6% of patients treated with niraparib as concomitant therapy for neutropenia. Discontinuation due to neutropenia events occurred in 2% of patients.
Hypertension, including hypertensive crisis, has been reported with niraparib therapy. Hypertension of any grade occurred in 19.3% of patients treated with niraparib. Grade ¾ hypertension occurred in 8.2% of patients. In the clinical programme, hypertension was readily managed with anti-hypertensive medicinal products. Discontinuation due to hypertension occurred in <1% of patients.
No studies have been conducted in paediatric patients.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
