Table 4.

Non-hematologic adverse events grading and management

Non-hematologic*: Regularly monitor patients for gastrointestinal adverse events
Adverse event	Grade	Management
Fatigue	Grade 1 Fatigue relieved by rest	Supportive interventions for fatigue might include exercise and physical fitness regimes, advice on conserving energy during everyday tasks Massage, cognitive-behavioral therapy, and other mind-body approaches Pharmacologic agents such as psychostimulants (eg, methylphenidate)
	Grade 2 Fatigue not relieved by rest; limiting instrumental ADL
	Grade 3 Fatigue not relieved by rest; limiting self-care ADL
	Grade 4 NA
Nausea	Grade 1 Loss of appetite without alteration in eating habits	Night-time administration of niraparib; use of anti-emetics 30 min before administration; intake of food 30–60 min before niraparib; benzodiazepines, steroids, domperidone, olanzapine, dronabinol, haloperidol, or scopolamine transdermal patch; consider supportive care guidelines on the management of anti-emesis20
	Grade 2 Oral intake decreased without significant weight loss, dehydration, or malnutrition
	Grade 3 Inadequate oral caloric or fluid intake; tube feeding, TPN, or hospitalization indicated
	Grade 4 NA
Vomiting	Grade 1 Intervention not indicated	Night-time administration of niraparib; use of anti-emetics 30 min before administration; intake of food 30–60 min before niraparib; benzodiazepines, steroids, domperidone, olanzapine, dronabinol, haloperidol, or scopolamine transdermal patch; consider supportive care guidelines on the management of anti-emesis20
	Grade 2 Outpatient intravenous hydration; medical intervention indicated
	Grade 3 Tube feeding, TPN, or hospitalization indicated
	Grade 4 Life-threatening consequences
Dyspepsia	Dyspepsia	Dietary modification and avoiding large meals, proton pump inhibitor therapy, tricyclic antidepressants or prokinetics14
Hypertension	Grade 1 Systolic BP 120–139 mm Hg or diastolic BP 80–89 mm Hg	Ask patients if they have been diagnosed with hypertension or have had increased blood pressure in the past, and whether they are taking any antihypertensive agents Monitor blood pressure and heart rate at least weekly for the first 2 months, then monthly for the first year and periodically thereafter during niraparib treatment Closely monitor patients with cardiovascular disorders, especially coronary insufficiency and cardiac arrhythmias Medically manage hypertension with antihypertensive medications Follow niraparib label-recommended dose modifications for non-hematologic toxicities20 37 Refer to standard guidelines for the management of hypertension
	Grade 2 Systolic BP 140–159 mm Hg or diastolic BP 90–99 mm Hg if previously within normal limits; change in baseline medical intervention indicated; recurrent or persistent (≥24 hour); symptomatic increase by >20 mm Hg (diastolic) or to >140/90 mm Hg; monotherapy initiated
	Grade 3 Systolic BP ≥160 mm Hg or diastolic BP ≥100 mm Hg; medical intervention indicated; more than one drug or more intensive therapy than previously used indicated
	Grade 4 Life-threatening consequences (eg, malignant hypertension, transient or permanent neurologic deficit, hypertensive crisis); urgent intervention indicated
Insomnia	Grade 1 Mild difficulty falling asleep, staying asleep, or waking up early	Sleep hygiene education: advise patient to maintain sleep schedule, stay active throughout the day, avoid or limit naps, avoid or limit caffeine and alcohol, and refrain from using nicotine, manage painful conditions that may interfere with sleeping, avoid large meals and beverages before bed Cognitive behavioral therapy for insomnia is generally recommended as first-line treatment and is most often equal to or more effective than sleep medications Over-the-counter sleep aids are not intended for regular use, but consider whether antihistamine-containing products may cause unwanted drowsiness or additional adverse events (ie, dizziness, confusion, cognitive decline, difficulty urinating) Prescription sleeping medication can be prescribed, however only eszopiclone, ramelteon, zaleplon, and zolpidem are approved for long-term use (ie, more than a few weeks)49
	Grade 2 Moderate difficulty falling asleep, staying asleep, or waking up early
	Grade 3 Severe difficulty in falling asleep, staying asleep, or waking up early
	Grade 4 NA
Palpitations	Grade 1 Mild symptoms, intervention not indicated	Review the patient’s medical history Perform a physical examination for signs of medical conditions that can cause palpitations (ie, swollen thyroid gland); note: palpitations can also be a symptom of anemia If the palpitations are not caused by a medical condition, treatment is not usually prescribed. Instead recommend that patients avoid triggers which result in palpitations (eg, stress, stimulants (eg, caffeine), illegal drugs) If an arrhythmia or other heart condition is suspected, follow-on tests may include ECG, Holter monitoring usually for 24–72 hours, and echocardiogram Ask the patient to keep a diary of when palpitations occur
	Grade 2 Moderate
	Grade 3 NA
	Grade 4 NA

*For non-hematologic CTCAE grade ≥3 adverse reaction where prophylaxis is not considered feasible or adverse reaction persists despite treatment, withhold niraparib for a maximum of 28 days or until resolution of the adverse reaction; resume niraparib at a reduced dose. If the non-hematologic CTCAE grade ≥3 adverse reaction lasts >28 days while receiving niraparib 100 mg/day, discontinue niraparib.

ADL, activities of daily living; BP, blood pressure; NA, not applicable; TPN, total parenteral nutrition.