Niraparib

Action and Spectrum

Niraparib is a highly selective inhibitor of PARP-1 and PARP-2, enzymes essential for repairing DNA damage. It disrupts key DNA repair pathways, particularly in cancer cells with BRCA mutations or homologous recombination (HR) deficiencies. This leads to synthetic lethality, where accumulated DNA damage causes cell death. Niraparib’s anti-cancer effects result from both blocking PARP activity and promoting harmful PARP-DNA complexes, leading to apoptosis. 

Drug Interaction

Adverse Reaction

Adverse drug reactions:  

Frequency reported  

>10%  

Anemia  

Abdominal pain/distention  

Anemia   

Nasopharyngitis   

Rash   

Hypertension  

Neutropenia  

Mucositis  

Neutropenia  

Constipation  

Vomiting   

Nausea  

Fatigue  

Thrombocytopenia   

Insomnia   

Headache   

Diarrhea   

Dyspepsia   

Myalgia   

Back pain   

Dyspepsia   

Dizziness   

Leukopenia   

Cough   

UTI   

Arthralgia   

Anxiety   

1-10%  

AST/ALT elevation  

Palpitations   

Dry mouth   

Dysgeusia   

Hypertension   

Leukopenia   

Black Box Warning

Myelodysplastic Syndrome (MDS) / Acute Myeloid Leukemia (AML): Rare but potentially fatal cases have occurred. 

Bone Marrow Suppression: Severe thrombocytopenia, neutropenia, and anemia are risks. Monitor CBCs closely. 

Contraindication / Caution

Contraindication 

None 

Cautions 

Niraparib treatment has been linked to serious conditions like myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), some of which have been fatal. If prolonged blood-related side effects occur or MDS/AML is suspected, patients should be referred to a hematologist and the drug should be discontinued if the diagnosis is confirmed. 

High blood pressure, including hypertensive crises, has also been reported. Blood pressure and heart rate should be monitored monthly during the first year and checked regularly thereafter. Hypertension should be managed medically, and dose adjustments may be necessary. 

The capsules contain tartrazine (FD&C Yellow No. 5), which can trigger allergic reactions in sensitive individuals, especially those with aspirin sensitivity. 

Due to its action on DNA, niraparib may harm a developing fetus and should not be used during pregnancy. 

Posterior reversible encephalopathy syndrome (PRES), a neurological condition, has been observed. Symptoms include seizures, headaches, visual disturbances, and changes in mental state. Diagnosis requires brain imaging. If PRES is suspected, niraparib should be stopped and the condition treated appropriately. It’s unclear if the drug can be safely resumed after PRES. 

Pregnancy / Lactation

Pregnancy warnings:    

• US FDA pregnancy category: Not assigned 

Breastfeeding warnings: 

• The release of the drug into the human breastmilk is unknown  
• The release of the drug into the animal milk is unknown 
• Therefore, the use of the drug may contraindicate 

Pregnancy Categories:      

• Category A: Satisfactory and well-controlled studies show no risk to the fetus in the first trimester or the later trimester      
• Category B: No evidence shown of risk to the fetus found in animal reproduction studies, and there are not enough studies on pregnant women      
• Category C: Adverse effects on the fetus found with evidence in animal reproduction studies and no adequate evidence for a result in humans must take care of potential risks in pregnant women      
• Category D: There is adequate data available with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits      
• Category X: Drugs listed in this category outweigh risks over benefits Hence these categories of drugs need to be avoided by pregnant women      
• Category N: There is no data available for the drug under this category   

Pharmacology

Niraparib is an oral PARP-1/2 inhibitor that targets cancer cells with BRCA or PTEN mutations by disrupting DNA repair and inducing synthetic lethality. In early clinical trials, the maximum tolerated dose was 300 mg/day, with main toxicities including thrombocytopenia, fatigue, and pneumonitis. It showed a 40% response rate in BRCA-mutated ovarian and peritoneal cancers, with better outcomes in platinum-sensitive tumors (50%) than platinum-resistant ones (33%). In sporadic high-grade serous ovarian cancer, response rates were 67% for platinum-sensitive and 16% for platinum-resistant cases, with some achieving extended disease control. 

Pharmacokinetics 

Absorption 

Oral bioavailability is approximately 73%. 

Peak plasma concentration (C_max) of 804 ng/mL is reached around 3 hours after administration. 

Distribution 

Approximately 83% of niraparib binds to plasma proteins. 

Volume of distribution (V_d) is large, estimated at 1200 liters, indicating extensive tissue distribution. 

Metabolism 

Niraparib is primarily metabolized by carboxylesterases (CEs) into an inactive metabolite. This metabolite undergoes further biotransformation via glucuronidation. 

Elimination/Excretion 

The terminal half-life is around 36 hours. 

Excretion occurs through both renal (47.5% in urine) and fecal (38.8%) routes. 

Pharmacodynamics 

Niraparib exerts cytotoxic effects by inhibiting tumor growth in cancer cells regardless of BRCA1/2 status, including those with homologous recombination deficiency (HRD). It has demonstrated effectiveness in both mouse xenograft models and patient-derived tumor models with either mutated or wild-type BRCA genes. Additionally, in vitro studies indicate that niraparib may inhibit dopamine, norepinephrine, and serotonin transporters, which could contribute to off-target cardiovascular effects such as increased heart rate and blood pressure. 

Adminstartion

Niraparib capsules can be taken with or without food and should be taken at the same time each day. Swallow the capsules whole without breaking or chewing. Taking the dose at bedtime might help reduce nausea. If a dose is missed or vomited, simply take the next dose at the regular scheduled time—do not double up. Store the medication at room temperature between 20–25°C (68–77°F), allowing occasional variations from 15–30°C (59–86°F). 

Patient Information Leaflet

Generic Name: niraparib 

Pronounced: ni-RA-pa-rib 

Why do we use niraparib?  

Niraparib is a chemotherapy medication that works by inhibiting specific enzymes in cancer cells to prevent their growth. It is primarily used to treat ovarian cancer, fallopian tube cancer, and peritoneal cancer.