Niraparib

Key takeaways

Niraparib belongs to science; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect Niraparib to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of Niraparib from memory before moving on to harder problems.

Reference excerpt

Niraparib, sold under the brand name Zejula, is an anti-cancer medication used for the treatment of epithelial ovarian, fallopian tube, or primary peritoneal cancer. It is taken by mouth. It is a PARP inhibitor. The most common side effects include nausea (feeling sick), thrombocytopenia (low blood platelet counts), tiredness and weakness, anemia (low red blood cell counts), constipation, vomiting, abdominal (belly) pain, neutropenia (low levels of neutrophils, a type of white blood cell), insomnia (difficulty sleeping), headache, lack of appetite, diarrhea, dyspnea (difficulty breathing), hypertension (high blood pressure), back pain, dizziness, cough, joint pain, hot flushes and decrease in white blood cells. Niraparib was approved for medical use in the United States and in the European Union in 2017.

Medical uses Niraparib is indicated for the maintenance treatment of adults with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy. In October 2019, the indication for niraparib was expanded to include people with advanced ovarian, fallopian tube, or primary peritoneal cancer treated with three or more prior chemotherapy regimens and whose cancer is associated with homologous recombination deficiency (HRD)-positive status. HRD is defined by either a deleterious or suspected deleterious BRCA mutation, or genomic instability in patients with disease progression greater than six months after response to the last platinum-based chemotherapy. In April 2020, the indication for niraparib was expanded to include the maintenance treatment of adults with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to first-line platinum-based chemotherapy. In the European Union, niraparib is indicated: as monotherapy for the maintenance treatment of adults with advanced epithelial (FIGO Stages III and IV) high-grade ovarian, fallopian tube or primary peritoneal cancer who are in response (complete or partial) following completion of first-line platinum-based chemotherapy; and as monotherapy for the maintenance treatment of adults with platinum sensitive relapsed high grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) to platinum based chemotherapy.

Contraindications No contraindications are listed in the prescribing information.

Side effects The most common side effects in studies were low blood cell counts, namely thrombocytopenia (in 61% of patients, severe in 29%), anemia (in 50%, severe in 25%) and neutropenia (in 30%, severe in 20%). Other, mostly mild to moderate side effects included nausea, fatigue, and constipation. In a study running over 250 days (median), 15% of patients had to permanently discontinue niraparib due to adverse effects.

Interactions No clinical interaction studies have been performed. The potential for interactions with other drugs is low as niraparib and its main metabolite M1 do not significantly interact with any of the important cytochrome P450 liver enzymes in vitro. Niraparib, but not M1, is transported by P-glycoprotein and BCRP, but does not significantly inhibit them. Neither niraparib nor M1 significantly interact with any of the other important transporter proteins.

Pharmacology

Mechanism of action

Niraparib is an inhibitor of the enzymes PARP1 and PARP2.

Pharmacokinetics

73% of ingested niraparib is absorbed in the gut, and it reaches highest blood plasma concentrations after about three hours, independently of food intake. In the circulation, 83% of the substance are bound to plasma proteins. It is inactivated by carboxylesterases to the main metabolite M1, the carboxylic acid derivative, which is subsequently glucuronidated. The mean biological half-life is 36 hours. 47.5% of the substance are found in the urine and 38.8% in the feces. Unmetabolised niraparib accounts for 11% in the urine and 19% in the feces.

Chemistry The drug is used in form of the salt niraparib tosylate monohydrate, which is white to off-white, non-hygroscopic crystals.

Studies A 2012 study in a cell line found that PARP inhibitors exhibit cytotoxic effects not based solely on their enzymatic inhibition of PARP, but by their trapping of PARP on damaged DNA, and the strength of this trapping activity was ordered niraparib >> olaparib >> veliparib.

History Niraparib was granted fast track designation by the US Food and Drug Administration (FDA), and Tesaro submitted a new drug application in 2016. It was approved on 27 March 2017 in the US, and approved in European Union on 16 November 2017. In a study with 553 patients, progression-free survival (PFS) for patients with a deleterious or suspected deleterious BRCA mutation in the germline was 21.0 months under niraparib therapy, as compared to 5.5 months under placebo. Patients without such a mutation had a PFS of 9.3 months under niraparib versus 3.9 months under placebo. The US Food and Drug Administration (FDA) granted the application for niraparib fast track, priority review, breakthrough therapy, and orphan drug designations.

References

External links "Niraparib tosylate monohydrate". NCI Drug Dictionary. National Cancer Institute. "Niraparib tosylate monohydrate". National Cancer Institute. 14 April 2017.

Illustrations

Worked examples

Example 1 — a first encounter with Niraparib

Start with the simplest possible case. Write down what Niraparib claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In science, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Niraparib before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Niraparib ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Niraparib

In research: Niraparib appears in science research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses Niraparib in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: Niraparib is common in secondary-school and first-year university syllabi. It links to neighbouring topics Drugs developed by GSK plc, Indazolecarboxamides, Orphan drugs, so understanding it makes those chapters shorter.
In everyday life: Look for Niraparib outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

How to study Niraparib in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what Niraparib means in your own words.
Compare your version with the excerpt and mark what you missed.
Work through the three examples above with pen and paper.
Explain Niraparib out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is Niraparib in simple terms?

Niraparib, sold under the brand name Zejula, is an anti-cancer medication used for the treatment of epithelial ovarian, fallopian tube, or primary peritoneal cancer. It is taken by mouth.

Why does Niraparib matter?

Because it connects several science ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study Niraparib?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on Niraparib.