Risk of Intraocular Floppy Iris Syndrome (IFIS) with risperidone or paliperidone in patients undergoing cataract surgery

HSA would like to alert healthcare professionals to the risk of intraoperative floppy iris syndrome (IFIS) observed during cataract surgery in patients treated with risperidone or paliperidone.

Risperidone and paliperidone are antipsychotic drugs used for the treatment and management of schizophrenic conditions. The innovator drugs, Risperdal® (risperidone) and Invega® (paliperidone), have been registered in Singapore since 1995 and 2007, respectively, and are marketed by Johnson & Johnson Pte Ltd. There are also 17 generic risperidone products registered locally.

Background

IFIS has been observed during cataract surgery in patients on α-adrenergic antagonists.¹ It is characterised by a triad of intraoperative signs (billowing of a flaccid iris stroma, progressive intraoperative pupil constriction, propensity for iris prolapse towards the phaco and side port incisions) that may vary in severity. IFIS is also associated with an increased rate of complications during cataract surgery (e.g., iris trauma, posterior capsule rupture, and vitreous loss), as well as postoperative complications of increased intraocular pressure and cystoid macular oedema.

During routine pharmacovigilance surveillance by Johnson & Johnson, six cases of IFIS associated with the use of risperidone were identified from a review of postmarketing safety data, of which two reported a plausible relationship between risperidone treatment and IFIS. In both cases, the patients had received long-term treatment with risperidone and developed typical features of IFIS during cataract surgery. A positive re-challenge was demonstrated in one of the cases where IFIS recurred in the second eye during cataract surgery four months later with continued risperidone treatment.

As risperidone is a selective monoaminergic antagonist with a high affinity for α1-adrenergic receptors, there exists a possible biological plausibility of its association with IFIS. This adverse event is very rare, being estimated at approximately 1 per 7 million person-years of treatment. The association is also extended to paliperidone since it is the active metabolite of risperidone and therefore shares similar pharmacological and safety profiles. However, to date, the company has not received any reports of IFIS associated with paliperidone.

Local Situation & HSA’s advisory

A Dear Healthcare Professional Letter, issued by Johnson & Johnson on 7 January 2014, was disseminated to psychiatrists and ophthalmologists to provide information on this emerging risk. The letter included the following advisories:

• It is recommended that cataract surgeons ask patients about current or prior use of risperidone or paliperidone when taking a medication history preoperatively.

• If IFIS is suspected, modifications to surgical technique may be required and the cataract surgery should be approached with caution.

• The potential benefit of stopping α1-adrenergic receptor blocking therapy prior to cataract surgery has not been established and must be weighed against the risk of stopping the antipsychotic therapy.

This safety information has been updated in the package inserts (PIs) of all Risperdal® and Invega® products. The PIs of generic risperidone-containing products will be strengthened to include this new safety alert.

Although no local reports of IFIS associated with risperidone or paliperidone have been received by HSA, healthcare professionals are advised to document the use of α1-adrenergic antagonists, including risperidone and paliperidone, when making a referral for cataract surgery.

Healthcare professionals are also encouraged to report any cases of IFIS suspected to be associated with risperidone or paliperidone to the Vigilance Branch of HSA.

Reference

1. Ophthalmology 2009; 116: 658-63