Niraparib (Zejula▼): reports of severe hypertension and posterior reversible encephalopathy syndrome (PRES), particularly in early treatment

Increase the frequency of blood pressure monitoring to at least weekly for the first 2 months, and then monitor monthly for the first year and periodically thereafter during treatment, following recent reports of onset of severe hypertension (including rare cases of hypertensive crisis) and rare cases of PRES within the first month of niraparib treatment.

From:
Medicines and Healthcare products Regulatory Agency
Published
22 October 2020
Therapeutic area:
Cancer

Advice for healthcare professionals:

  • there have been reports of severe hypertension (including rare cases of hypertensive crisis) with niraparib, including some with onset in the first month of treatment

  • rare cases of posterior reversible encephalopathy syndrome (PRES) have also been reported, many associated with hypertension and within the first month of treatment

  • before treatment, control pre-existing hypertension adequately before starting a patient on niraparib

  • monitor blood pressure at least weekly for 2 months from initiation and then monthly afterwards for the first year and periodically thereafter during treatment

  • consider home blood pressure monitoring for appropriate patients; provide adequate training and instruct them to contact their doctor in case of a rise in blood pressure

  • during treatment, manage hypertension with antihypertensives and if necessary, consider treatment interruption and subsequent adjustment of the niraparib dose as advised in product information

  • discontinue niraparib in case of hypertensive crisis or if medically significant hypertension cannot be adequately controlled with antihypertensive therapy

  • in cases of PRES, discontinue niraparib and treat specific symptoms including hypertension

  • report any suspected adverse drug reactions associated with niraparib to the Yellow Card scheme

Review of cases of severe hypertensive reactions and PRES

Niraparib (Zejula▼) is indicated 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.

A recent European review of the safety data for niraparib identified worldwide reports of patients who developed severe hypertension, including rare cases of hypertensive crisis (may affect up to 1 in 1000 patients), as early as within the first month of treatment with niraparib.

The review also identified rare reports of PRES (may affect up to 1 in 1000 patients). Of 5 cases worldwide, 4 patients presented with severe hypertension and 3 reported that PRES occurred during the first month of therapy. Three reports originated from post-marketing sources and 2 from clinical trials.

Hypertension was identified as an important risk with niraparib in clinical trials. The product information for niraparib had an existing warning for hypertension, including hypertensive crisis, and recommended that blood pressure should be monitored monthly in the first year. Based on the new information identified in the European review, safety warnings have been updated and hypertensive crisis and PRES both added into the product information as rare reactions. The product information has been amended to recommend more frequent blood pressure measurement, especially at the start of treatment.

For appropriate patients, home blood pressure monitoring can be considered with instruction for patients to contact their healthcare professional in case of rise in blood pressure. Adequate instructions should be provided to patients or caregivers on how to monitor blood pressure at home – consult NHS advice or local resources.

In the UK, up to 30 July 2020, the Yellow Card scheme received 6 reports associated with hypertension for niraparib. However, limited information is available for the details of the hypertension, including time of onset. No UK Yellow Card reports have been received for PRES associated with niraparib. Caution should be exercised in interpreting these data since there may be under-reporting and use of niraparib in the UK may be relatively low. Continued vigilance is recommended, and we ask for any suspected adverse drug reactions to be reported to the MHRA on a Yellow Card.

Characteristics of reactions

Hypertension, including hypertensive crisis, has been reported with the use of niraparib including in the first month of treatment.

PRES is a rare, reversible, neurological disorder. The presenting signs and symptoms of PRES include seizures, headache, altered mental status, visual disturbance, or cortical blindness, with or without associated hypertension. A diagnosis of PRES requires confirmation by brain imaging, preferably magnetic resonance imaging (MRI).

The safety of reinitiating niraparib therapy in patients who have previously experienced PRES is not known.

Report on a Yellow Card

Niraparib (Zejula▼) is subject to additional monitoring and any suspected adverse drug reactions (ADR) should be reported to the Yellow Card scheme.

Healthcare professionals, patients, and caregivers are asked to submit reports using the Yellow Card scheme electronically using:

When reporting please provide as much information as possible, including information about medical history, any concomitant medication, onset, treatment dates, and product brand name.

When reporting please provide as much information as possible, including information about medical history, any concomitant medication, onset, treatment dates, and product brand name.

Article citation: Drug Safety Update volume 14, issue 3: October 2020: 3.

 

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Published 22 October 2020
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