Source: European Medicines Agency (EU) Revision Year: 2019 Publisher: Aerie Pharmaceuticals Ireland, Limited, Athlone Business and Technology Park, Dublin Road, Garrycastle, Athlone, Co Westmeath, N37 DW40, Ireland
Hypersensitivity to the active substance(s) or to any of the excipients listed in section 6.1.
Twice a day dosing is not well tolerated and is not recommended. Netarsudil dosed twice daily provided slightly larger IOP reductions, but had a less favorable safety profile as reflected in a higher rate and increased severity of ocular adverse reactions. Twice a day dosing was also associated with a higher discontinuation rate due to adverse reactions (53.8%) during a 12-month study. It is therefore recommended to dose netarsudil once daily.
This medicinal product contains benzalkonium chloride. Benzalkonium chloride has been reported to cause eye irritation, symptoms of dry eyes and may affect the tear film and corneal surface and is known to discolour soft contact lenses. It should be used with caution in dry eye patients and in patients where the cornea may be compromised. Patients should be monitored in case of prolonged use.
The efficacy of netarsudil has not been studied beyond 12 months.
No interaction studies have been performed.
There are no or limited amount of data from the use of netarsudil in pregnant women. No effects during pregnancy are anticipated, since systemic exposure to netarsudil is negligible (see section 5.2). Animal studies with intravenous administration do not indicate direct or indirect harmful effects with respect to reproductive toxicity at clinically relevant exposures (see section 5.3). Rhokiinsa should not be used during pregnancy unless the clinical condition of the woman requires treatment with netarsudil.
It is unknown whether netarsudil/metabolites are excreted in human milk. However, while no effects on the breastfed newborn/infant are anticipated since the systemic exposure of breast-feeding women to netarsudil is expected to be negligible, no relevant clinical data are available (see section 5.2). A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Rhokiinsa therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman.
There are no data on the effects of netarsudil on male or female fertility. However, no effects are anticipated, since systemic exposure to netarsudil is negligible (see section 5.2).
Rhokiinsa has negligible influence on the ability to drive and use machines. If transient blurred vision occurs at instillation, the patient should wait until the vision clears before driving or using machines.
The most common ocular adverse reaction observed is conjunctival hyperemia which was reported in 51% of patients. Other ocular adverse reactions reported are: cornea verticillata (17%), instillation site pain (17%), and conjunctival haemorrhage (8%). Instillation site erythema (8%), corneal staining (7%), blurred vision (6%), increased lacrimation (6%) and erythema of eyelid (5%) were also reported.
The following adverse reactions have been reported with netarsudil, dosed once daily. Reactions are classified according to the convention: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000) or not known (cannot be estimated from the available data).
| System Organ Classification | Frequency | Adverse reactions |
|---|---|---|
| Immune system disorders | Uncommon | hypersensitivity |
| Nervous system disorders | Common | headache |
| Uncommon | dizziness, visual field defect | |
| Eye disorders | Very common | conjunctival hyperaemia1, cornea verticillata1, instillation site pain |
| Common | conjunctival haemorrhage, vision blurred, lacrimation increased, erythema of eyelid, eye pruritis, eye irritation, visual acuity reduced, eyelid oedema, punctate keratitis, conjunctival oedema, foreign body sensation in eyes, conjunctivitis, conjunctivitis allergic, photophobia, eyelid pruritus, eye pain, corneal opacity, dry eye, eye discharge, instillation site erythema, instillation site discomfort, instillation site pruritis, vital dye staining cornea present, intraocular pressure increased | |
| Uncommon | ocular hyperaemia, blepharitis, corneal disorder, eyelid margin crusting, eye allergy, conjunctival follicles, ocular discomfort, eye swelling, corneal deposits, eyelid disorder, meibomian gland dysfuntion, corneal pigmentation, diplopia, ectropion, lenticular opacities, noninfective conjunctivitis, abnormal sensation in the eye, asthenopia, episcleral hyperaemia, halo vision, keratitis, refraction disorder, anterior chamber flare, anterior chamber inflammation, blindness, conjunctival irritation, conjunctivochalasis, diabetic retinopathy, eczema eyelids, eyelid skin dryness, glaucoma, growth of eyelashes, iris adhesions, iris bombe, iritis, ocular hypertension, visual impairment, corneal dystrophy, instillation site foreign body sensation, instillation site irritation, glassy eyes, fatigue, instillation site dryness, instillation site oedema, instillation site paraesthesia, conjunctival staining, optic nerve cup/disc ratio increased, madarosis | |
| Respiratory, thoracic and mediastinal disorders | Uncommon | nasal discomfort, rhinalgia |
| Skin and subcutaneous tissue disorders | Uncommon | dermatitis allergic, dermatitis contact, lichenification, petechiae |
| Musculoskeletal and connective tissue disorders | Uncommon | polychondritis |
| Injury, poisoning and procedural complications | Uncommon | excoriation |
1 See Description of selected adverse reactions for further information
Conjunctival hyperaemia was the most frequently reported adverse reaction associated with netarsudil treatment in clinical trials and it is attributed to the vasodilation effect of the Rho kinase inhibitor drug class. Conjunctival hyperaemia was typically mild in severity and sporadic. However, there was a relatively small proportion of subjects with moderate or severe hyperaemia who discontinued treatment because of this adverse reaction (6.0% in Phase 3 clinical studies).
Cornea verticillata occurred in approximately 20% of the patients in controlled Phase 3 clinical studies. The cornea verticillata seen in netarsudil-treated patients were first noted at 4 weeks of daily dosing. This reaction did not result in any apparent visual functional changes in patients. The majority of cornea verticillata resolved upon discontinuation of treatment. The incidence of cornea verticillata was higher in certain subpopulations: elderly (≥65 years) versus non-elderly (24.8 vs. 15.9%); males versus females (24.4 vs. 18.4%) and in white versus other races (25.6 vs. 7.0%).
With the exception of cornea verticillata (see above), no difference in the safety profile for Rhokiinsa has been observed between subjects aged <65 or ≥65 years.
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.
Not applicable.
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