Roclanda

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



2 

 

This medicinal product is subject to additional monitoring. This will allow quick identification of 
new safety information. Healthcare professionals are asked to report any suspected adverse reactions. 
See section 4.8 for how to report adverse reactions. 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Roclanda 50 micrograms/ml + 200 micrograms/ml eye drops, solution 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each ml of solution contains 50 micrograms latanoprost and 200 micrograms netarsudil (as mesylate) . 
 
Excipient(s) with known effect 
 
Each ml of solution contains 200 micrograms benzalkonium chloride. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Eye drops, solution.  
 
Clear, colourless solution, pH 5 (approximately). 
 
Osmolality: 280 mOsm/Kg. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Roclanda is indicated for the reduction of elevated intraocular pressure (IOP) in adult patients with 
primary open-angle glaucoma or ocular hypertension for whom monotherapy with a prostaglandin or 
netarsudil provides insufficient IOP reduction. 
 
4.2 Posology and method of administration 
 
Treatment with Roclanda should only be initiated by an ophthalmologist or a healthcare professional 
qualified in ophthalmology. 
 
Posology 
 
Use in adults, including the elderly  
The recommended dosage is one drop in the affected eye(s) once daily in the evening. Patients should 
not instill more than one drop in the affected eye(s) each day. 
 
If one dose is missed, treatment should continue with the next dose in the evening.   
 
Paediatric population 
The safety and efficacy of Roclanda in children below the age of 18 years have not been established. 
No data are available. 
 



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Method of administration  
 
For ocular use. 
 
Data on potential interactions specific to latanoprost + netarsudil are described in section 4.5. If 
latanoprost + netarsudil is to be used concomitantly with other topical ophthalmic medicinal products, 
each medicinal product should be administered at least five minutes apart. Due to netarsudil’s 
vasodilating properties, other eye drops should be administered before latanoprost + netarsudil. Eye 
ointments should be administered last. 
 
Contact lenses should be removed prior to instillation of latanoprost + netarsudil and may be 
reinserted 15 minutes following its administration (see section 4.4). 
 
As with any eye drops, to reduce possible systemic absorption, it is recommended that the lachrymal 
sac be compressed at the medial canthus (punctal occlusion) for one minute. This should be performed 
immediately following the instillation of each drop. 
 
The tip of the dispensing container should avoid contacting the eye, surrounding structures, fingers, or 
any other surface in order to avoid contamination of the solution. Serious damage to the eye and 
subsequent loss of vision may result from using contaminated solutions. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance(s) or to any of the excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
Iris pigmentation 
 
Latanoprost may gradually change eye colour by increasing the amount of brown pigment in the iris. 
Before treatment is instituted, patients should be informed of the possibility of a permanent change in 
eye colour. Unilateral treatment can result in permanent heterochromia. 
 
Increased iris pigmentation has not been shown to have any negative clinical sequelae and treatment 
with medicinal products containing latanoprost can be continued if iris pigmentation ensues. However, 
patients should be monitored regularly and if the clinical situation warrants, treatment with medicinal 
products containing latanoprost may be discontinued. 
 
Herpetic keratitis condition 
 
Medicinal product(s) containing latanoprost should be used with caution in patients with a history of 
herpetic keratitis, and should be avoided in cases of active herpes simplex keratitis and in patients with 
a history of recurrent herpetic keratitis specifically associated with prostaglandin analogues. 
 
Macular oedema risk 
 
Reports of macular oedema with medicinal products containing latanoprost have occurred mainly in 
aphakic patients, in pseudophakic patients with torn posterior lens capsule or anterior chamber lenses, 
or in patients with known risk factors for cystoid macular oedema (such as diabetic retinopathy and 
retinal vein occlusion). Medicinal products containing latanoprost should be used with caution in 
aphakic patients, in pseudophakic patients with torn posterior lens capsule or anterior chamber lenses, 
or in patients with known risk factors for cystoid macular oedema. 
 
Iritis/uveitis risk 
 
In patients with known predisposing risk factors for iritis/uveitis, medicinal products containing 
latanoprost can be used with caution. 



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Asthma exacerbation 
 
There is limited experience of latanoprost use in patients with asthma, but some cases of exacerbation 
of asthma and/or dyspnoea were reported in post marketing experience. Asthmatic patients should 
therefore be treated with caution until there is sufficient experience with the combination. 
 
Periorbital skin discolouration 
 
Periorbital skin discolouration has been observed on treatment with medicinal products containing 
latanoprost, the majority of reports being in Japanese patients. Experience to date shows that 
periorbital skin discolouration is not permanent and in some cases has reversed while continuing 
treatment with latanoprost. 
 
Eyelash changes 
 
Treatment with medicinal products containing latanoprost may gradually change eyelashes and vellus 
hair in the treated eye and surrounding areas; these changes include increased length, thickness, 
pigmentation, number of lashes or hairs and misdirected growth of eyelashes. Eyelash changes are 
reversible upon discontinuation of treatment. 
 
Benzalkonium chloride content 
 
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 Roclanda has not been studied beyond 12 months. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
In vitro interaction studies have shown that precipitation can occur when eye drops containing 
thimerosal are mixed with latanoprost + netarsudil. Administer other eye drops at least five minutes 
apart (see section 4.2). 
 
In vitro studies have indicated netarsudil has the potential to inhibit CYP450 isoenzymes in the cornea, 
however no clinical evidence of local pharmacokinetic interactions has been observed to date. 
 
There have been reports of paradoxical elevations in IOP following the concomitant ophthalmic 
administration of two prostaglandin analogues. Therefore, the use of two or more prostaglandins, 
prostaglandin analogues or prostaglandin derivatives is not recommended. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
There are no or limited amount of data from the use of latanoprost + 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 of netarsudil do not indicate direct or 
indirect harmful effects with respect to reproductive toxicity at clinically relevant exposures (see 
section 5.3).  
 
Latanoprost has potentially harmful pharmacological effects during pregnancy and/or on the 
fetus/newborn child (see section 5.3).  



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Therefore, latanoprost + netarsudil should not be used during pregnancy. 
 
Breast-feeding 
 
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). 
Latanoprost and its metabolites may pass into human milk. A decision must be made whether to 
discontinue breast-feeding or to discontinue/abstain from Roclanda therapy taking into account the 
benefit of breast feeding for the child and the benefit of therapy for the woman.  
 
Fertility 
 
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). Latanoprost has not 
been found to have any effect on male or female fertility in animal studies (see section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 
Roclanda 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.  
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
The most common ocular adverse reaction observed is conjunctival hyperemia which was reported in 
52% of patients. Other ocular adverse reactions reported are instillation site pain (18%), cornea 
verticillata (13%), eye pruritis (6%), instillation site erythema (6%), increased lacrimation (5%), 
instillation site discomfort (5%) and conjunctival haemorrhage (4%).  
 
Tabulated list of adverse reactions 
 
The following adverse reactions have been reported with latanoprost + netarsudil, dosed once daily, 
and during clinical studies and post-marketing surveillance with the individual components latanoprost 
and netarsudil. Adverse reactions are presented according to the MedDRA system organ classification. 
Within each system organ class, the adverse reactions are classified by frequency according to the 
following 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). 
 

System Organ Classification Frequency Adverse reactions 
Infections and infestations Rare herpetic keratitis2 
Immune system disorders Uncommon hypersensitivity3 
Nervous system disorders Uncommon headache, 

muscle contractions involuntary, 
dizziness2,3, 
visual field defect3 

Eye disorders Very 
common 

conjunctival hyperaemia1,  
cornea verticillata1,  
instillation site pain, 
iris hyperpigmentation2, 
eyelash and vellus hair changes of the 
eyelid (increased length, thickness, 
pigmentation and number of eyelashes)2 

Common conjunctival haemorrhage,  
vision blurred,  



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System Organ Classification Frequency Adverse reactions 
lacrimation increased,  
erythema of eyelid,  
eye pruritus,  
eye irritation,  
visual acuity reduced,  
eyelid oedema,  
punctate keratitis,  
corneal disorder, 
conjunctival oedema,   
conjunctivitis allergic,  
photophobia,  
eye pain,  
dry eye,  
foreign body sensation in eyes, 
eyelid margin crusting,  
blepharitis, 
instillation site erythema,  
instillation site discomfort,  
vital dye staining cornea present 

Uncommon eyelids pruritus,  
conjunctival disorder, 
corneal opacity, 
eye discharge, 
corneal deposits, 
conjunctivitis, 
dacryostenosis acquired, 
eye inflammation, 
eye paraesthesia, 
conjunctival follicles,  
eye swelling,  
meibomian gland dysfunction,  
corneal pigmentation,  
diplopia,  
noninfective conjunctivitis,  
abnormal sensation in eye,  
keratitis,  
refraction disorder,  
anterior chamber flare,  
conjunctival irritation, 
conjunctivitis, 
intraocular pressure increased, 
eyelid rash, 
eyelid skin dryness,  
growth of eyelashes, 
lacrimal disorder,  
iritis,  
visual impairment,  
corneal dystrophy,   
instillation site dryness, 
instillation site pruritus, 
instillation site reaction,  
eye complication associated with 
device,fatigue, 
instillation site paraesthesia,  
macular oedema including cystoid 
macular oedema2, 
uveitis2 

ocular hyperaemia3 

diabetic retinopathy3, 
eye allergy3 
ocular discomfort3, 
eyelid disorder3, 



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System Organ Classification Frequency Adverse reactions 
ectropion3, 
lenticular opacities3, 
asthenopia3, 
episcleral hyperemia3, 
halo vision3, 
anterior chamber inflammation3, 
blindness3, 
conjunctivochalasis3, 
eczema eyelids3, 
glaucoma3, 
iris adhesions3, 
iris bombe3, 
ocular hypertension3, 
instillation site irritation3, 
glassy eyes3, 
instillation site oedema3, 
conjunctival staining3, 
optic nerve cup/disc ratio increased3, 
madarosis3 

 

Rare corneal oedema2, 
corneal erosion2, 
periorbital oedema2, 
trichiasis2, 
distichiasis2, 
iris cyst2, 
localised skin reaction on the eyelids2, 
darkening of the palpebral skin of the 
eyelids2, 
pseudopemphigoid of ocular conjunctiva2 

Very rare periorbital and lid changes resulting in 
deepening of the eyelid sulcus2 

Cardiac disorders Uncommon angina2, 
palpitations2 

Very rare angina unstable2 
Respiratory, thoracic and mediastinal disorders Uncommon epistaxis, 

nasal congestion, 
nasal discomfort3, 
rhinalgia3  

asthma2, 
dyspnoea2 

Rare asthma exacerbation2 
Skin and subcutaneous tissue disorders Common dermatitis contact 

Uncommon lichenification, 
dry skin, 
erythema, 
skin disorder, 
dermatitis allergic3 

petechiae3 
Rare pruritus2 

Musculoskeletal and connective tissue disorders Uncommon pain in jaw, 
myalgia2, 
arthralgia2, 
polychondritis3 

General disorders and administration site 
conditions 

Uncommon chest pain2 

Injury, poisoning and procedural complications Uncommon excoriation3 
1 See Description of selected adverse reactions for further information 
2 Additional adverse reaction observed with latanoprost monotherapy 
3 Additional adverse reaction observed with netarsudil monotherapy 
 



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Description of selected adverse reactions 

Conjunctival hyperaemia 
Conjunctival hyperaemia was the most frequently reported adverse reaction associated with latanoprost 
+ netarsudil treatment in clinical studies and it is attributed to the vasodilation effect of the Rho kinase 
inhibitor medicinal product 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 (5.0% in Phase 3 clinical studies).

Cornea verticillata 
Cornea verticillata occurred in approximately 13% of the patients in controlled Phase 3 clinical studies. 
The cornea verticillata seen in latanoprost + 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 (18.8 vs. 
11.5%); males versus females (18.8 vs. 13.0%) and in white versus other races (21.7 vs. 2.5%).  

Iris pigmentation 
Roclanda contains latanoprost which is a prostaglandin F2α analogue. The majority of adverse reactions 
associated with latanoprost are ocular in nature. In a 5-year latanoprost safety study, 33% of patients 
developed iris pigmentation (section 4.4).  

This change in eye colour has predominantly been seen in patients with mixed coloured irides, i.e. 
blue-brown, grey-brown, yellow-brown and green-brown. In studies with latanoprost, the onset of the 
change is usually within the first 8 months of treatment, rarely during the second or third year, and has 
not been seen after the fourth year of treatment. The rate of progression of iris pigmentation decreases 
with time and is stable for five years. The effect of increased pigmentation beyond five years has not 
been evaluated. The iris colour change is slight in the majority of cases and often not observed 
clinically. The incidence in patients with mixed colour irides ranged from 7 to 85%, with yellow-
brown irides having the highest incidence. In patients with homogeneously blue eyes, no change has 
been observed and in patients with homogeneously grey, green or brown eyes, the change has only 
rarely been seen. 

The colour change is due to increased melanin content in the stromal melanocytes of the iris and not to 
an increase in number of melanocytes. Typically, the brown pigmentation around the pupil spreads 
concentrically towards the periphery in affected eyes, but the entire iris or parts of it may become 
more brownish. No further increase in brown iris pigment has been observed after discontinuation of 
treatment. It has not been associated with any symptom or pathological changes in clinical studies to 
date. 

Neither naevi nor freckles of the iris have been affected by treatment. Accumulation of pigment in the 
trabecular meshwork or elsewhere in the anterior chamber has not been observed in clinical studies. 

Other special populations 

Elderly 
With the exception of cornea verticillata (see above), no difference in the safety profile for latanoprost 
+ netarsudil has been observed between subjects aged <65 or ≥65 years.

Reporting of suspected adverse reactions 

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. 



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4.9 Overdose 

Systemic exposure to the netarsudil component of latanoprost + netarsudil following topical ocular 
administration has been shown to be negligible.  

Apart from ocular irritation and conjunctival hyperaemia, no other ocular side effects are known if 
latanoprost is overdosed. 

If latanoprost is accidentally ingested the following information may be useful: one bottle contains 
125 micrograms latanoprost. More than 90% is metabolised during the first pass through the liver. 
Intravenous infusion of 3 micrograms/kg in healthy volunteers induced no symptoms, but a dose of 
5.5-10 micrograms/kg caused nausea, abdominal pain, dizziness, fatigue, hot flushes and sweating. 
In monkeys, latanoprost has been infused intravenously in doses of up to 500 micrograms/kg without 
major effects on the cardiovascular system. 

Intravenous administration of latanoprost in monkeys has been associated with transient 
bronchoconstriction. However, in patients with moderate bronchial asthma, bronchoconstriction was 
not induced by latanoprost when applied topically on the eyes in a dose of seven times the clinical 
dose of latanoprost. 

If topical overdose of latanoprost + netarsudil should occur, the eye(s) may be flushed with tap water. 
Treatment of an overdose would include supportive and symptomatic therapy. 

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties 

Pharmacotherapeutic group: Ophthalmologicals, antiglaucoma preparations and miotics, ATC code: 
S01EE51 

Mechanism of action 

Roclanda contains two active substances: latanoprost and netarsudil. These two components lower 
IOP by increasing the outflow of aqueous humor. Although both latanoprost and netarsudil lower IOP 
by increasing aqueous humor outflow, their mechanisms of action are different. 

Studies in animal and man suggest that the main mechanism of action for netarsudil, a Rho kinase 
inhibitor, is increased trabecular outflow. These studies also suggest that netarsudil lowers IOP by 
reducing episcleral venous pressure.   

Studies in animal and man indicate that the main mechanism of action for latanoprost, a prostaglandin 
F2α analoque, is increased uveoscleral outflow, although some increase in outflow facility (decrease in 
outflow resistance) has been reported in man. 

Clinical efficacy and safety 

Roclanda was evaluated in 2 randomized, double-blind, multicentre Phase 3 clinical studies in 
1,468 patients with open-angle glaucoma and ocular hypertension. Studies 301 and 302 enrolled 
subjects with IOP <36 mmHg and compared IOP lowering effect of latanoprost + netarsudil dosed 
once daily to individually administered netarsudil 0.02% once daily and latanoprost 0.005% once 
daily. The treatment duration was 12 months for Study 301 and 3 months for Study 302. The median 
age of study participants was 66 years (range 18 to 99 years).  

The studies were designed to show superiority of latanoprost + netarsudil when dosed once daily in the 
evening over its individual components netarsudil 0.02% once daily and latanoprost 0.005% once 
daily. The primary efficacy outcome measure was least squares (LS) mean IOP at each of 9 timepoints 



10 

measured at 08:00, 10:00 and 16:00 on day 15, day 43 and day 90. The average IOP lowering effect of 
latanoprost + netarsudil was 1 to 3 mmHg greater than monotherapy with either netarsudil 0.02% or 
latanoprost 0.005% throughout 3 months (Figures 1 and 2). In Study 301 IOP reductions were 
maintained, showing statistical superiority of latanoprost + netarsudil throughout the 12-month 
treatment period. In all cases, the differences in the LS mean IOP were clinically relevant and 
statistically significant (p < 0.0001) through month 3. Approximately 30% of subjects included in the 
Phase 3 studies had a baseline IOP of ≥27 mmHg (132, 136 and 143 in the latanoprost + netarsudil, 
latanoprost and netarsudil treatment groups, respectively). In these subjects, latanoprost + netarsudil 
showed statistically significantly superior IOP-lowering efficacy to each of its components at all time 
points. Across both studies, compared to latanoprost alone, the combination product reduced IOP by a 
further 1.7 mmHg to 3.7 mmHg, and compared to netarsudil alone by a further 3.4 mmHg to 
5.9 mmHg. 

Figure 1: Study 301 mean IOP (mmHg) by treatment group and treatment difference in mean IOP 
 

latanoprost + 
netarsudil vs. 
netarsudil 
95% CI 

3.0 

(2.5, 3.6) 

3.0 

(2.4, 3.6) 

2.4 

(1.9, 3.0) 

3.2 

(2.6, 3.8) 

2.9 

(2.3, 3.5) 

2.3 

(1.7, 2.8) 

3.1 

(2.5, 3.8) 

3.2 

(2.5, 3.8) 

2.0 

(1.4, 2.6) 

latanoprost + 
netarsudil vs. 
latanoprost 
95% CI 

2.3 

(1.7, 2.8) 

2.6 

(2.0, 3.2) 

2.3 

(1.8, 2.9) 

1.7 

(1.1, 2.4) 

1.9 

(1.3, 2.5) 

1.7 

(1.1, 2.2) 

1.5 

(0.9, 2.1) 

1.7 

(1.1, 2.3) 

1.3 

(0.7, 1.9) 

The LS mean IOP at each post-baseline time point was derived using an analysis of covariance adjusted for baseline IOP and based on 
observed data for all randomized subjects (238 in latanoprost + netarsudil group, 244 in netarsudil group, 236 in latanoprost group). 

15.6
14.9

14.8

16.0
15.2 15.3

16.1

15.2
15.4

18.6

17.9

17.2

19.1

18.1
17.6

19.3

18.4

17.4
17.8

17.4
17.2

17.7
17.1

17.0
17.6

16.9
16.7

14

15

16

17

18

19

20

21

22

23

Day 15
(8AM)

Day 15
(10AM)

 Day 15
(4PM)

Day 43
(8AM)

Day 43
(10AM)

Day 43
(4PM)

Day 90
(8AM)

Day 90
(10AM)

Day 90
(4PM)

Roclanda Netarsudil Latanoprost

Baseline
8AM    10AM    

4PM
24.8      23.7      

22.6

Baseline
8AM    10AM    

4PM
24.8      23.5      

22.6

Baseline
8AM    10AM    

4PM
24.6      23.4      

22.4



11 

16.1

15.3 15.2

16.4

15.5 15.5

16.4

15.6
15.6

19.4

18.0
17.5

19.6

18.4

17.9

20.0

18.4

18.0
18.1

17.7 17.1

17.9
17.4

17.1

17.9
17.5

17.1

14

15

16

17

18

19

20

21

22

23

Day 15
(8AM)

Day 15
(10AM)

 Day 15
(4PM)

Day 43
(8AM)

Day 43
(10AM)

Day 43
(4PM)

Day 90
(8AM)

Day 90
(10AM)

Day 90
(4PM)

Roclanda Netarsudil Latanoprost

Baseline
8AM    10AM    4PM
24.7      23.3      22.4

Baseline
8AM    10AM    4PM
24.7      23.4      22.8

Baseline
8AM    10AM    4PM
24.8      23.2      22.6

Figure 2: Study 302 mean IOP (mmHg) by treatment group and treatment difference in mean IOP 

latanoprost + 
netarsudil vs. 
netarsudil 
95% CI 

3.4 

(2.8, 3.9) 

2.7 

(2.2, 3.2) 

2.2 

(1.7, 2.8) 

3.2 

(2.6, 3.8) 

2.9 

(2.3, 3.4) 

2.3 

(1.8, 2.9) 

3.6 

(3.0, 4.2) 

2.8 

(2.3, 3.4) 

2.4 

(1.9, 2.9) 

latanoprost + 
netarsudil vs. 
latanoprost 
95% CI 

2.0 

(1.5, 2.6) 

2.4 

(1.9, 2.9) 

1.9 

(1.3, 2.4) 

1.5 

(0.9, 2.1) 

1.9 

(1.3, 2.4) 

1.6 

(1.0, 2.1) 

1.5 

(0.9, 2.2) 

2.0 

(1.4, 2.5) 

1.5 

(1.0, 2.1) 

The LS mean IOP at each post-baseline time point was derived using an analysis of covariance adjusted for baseline IOP and based on 
observed data for all randomized subjects (245 in latanoprost + netarsudil group, 255 in netarsudil group, 250 in latanoprost group). 

Approximately 67% of subjects included in the latanoprost + netarsudil treatment groups of Phase 3 
studies were caucasian and 30% black or african american. Over half were aged ≥ 65 years. With the 
exception of the incidence of cornea verticillata (section 4.8); no other difference in safety profile was 
observed between races or age groups. 

Completion rates in Phase 3 studies were lower in the latanoprost + netarsudil treatment groups when 
compared with the latanoprost group. Discontinuation rates due to adverse events at month 3 were 
8.7% for the pooled latanoprost + netarsudil treatment group versus 7.6% for the pooled netarsudil 
group and 1.0% for the pooled latanoprost group. Discontinuation rates due to adverse events at month 
12 in Study 301 were 19.7% for the latanoprost + netarsudil treatment group versus 21.7% for the 
netarsudil group and 1.7% for the latanoprost group. The majority of discontinuations were associated 
with ocular events. The most frequently reported adverse event associated with discontinuation in the 
pooled latanoprost + netarsudil group was conjunctival hypaeremia (7.6% at month 12). The majority 
of ocular adverse events reported with netarsudil + latanoprost were mild in intensity.  

The efficacy and safety of latanoprost + netarsudil in subjects with compromised corneal epithelium or 
co-existing ocular pathologies e.g. pseudoexfoliation and dispersion pigment syndrome has not been 
established. 

Paediatric population 

The European Medicines Agency has waived the obligation to submit the results of studies with 
Roclanda in all subsets of the paediatric population for the reduction of elevated intraocular pressure 



12 

in patients with open-angle glaucoma or ocular hypertension (see section 4.2 for information on 
paediatric use). 

5.2 Pharmacokinetic properties 

Absorption 

The systemic exposures of netarsudil and its active metabolite, AR-13503, were evaluated in 
18 healthy subjects after topical ocular administration of netarsudil 200 micrograms/ml once daily 
(one drop bilaterally in the morning) for 8 days. There were no quantifiable plasma concentrations of 
netarsudil (lower limit of quantitation (LLOQ) 0.100 ng/ml) post dose on Day 1 and Day 8. Only one 
plasma concentration at 0.11 ng/ml for the active metabolite was observed for one subject on Day 8 at 
8 hours post-dose. 

Latanoprost (molecular weight 432.58) is an isopropyl ester prodrug which per se is inactive, but after 
hydrolysis to the acid of latanoprost becomes biologically active. The prodrug is well absorbed 
through the cornea and all active substance that enters the aqueous humour is hydrolysed during the 
passage through the cornea. Studies in man indicate that the peak concentration in the aqueous humour 
is reached about two hours after topical administration. After topical application in monkeys, 
latanoprost is distributed primarily in the anterior segment, the conjunctivae and the eyelids. Only 
minute quantities of latanoprost reach the posterior segment. 

Biotransformation 

After topical ocular dosing, netarsudil is metabolized by esterases in the eye to an active metabolite, 
AR-13503. 

There is practically no metabolism of the acid of latanoprost in the eye. The main metabolism occurs 
in the liver. The half-life in plasma is 17 minutes in man. The main metabolites, the 1,2-dinor and 
1,2,3,4-tetranor metabolites, exert no or only weak biological activity in animal studies and are 
excreted primarily in the urine. 

5.3 Preclinical safety data 

Netarsudil 

Non-clinical data with netarsudil reveal no special hazard for humans based on conventional studies of 
safety pharmacology, repeated dose toxicity, genotoxicity and toxicity to development. Effects in 
non-clinical studies were observed only at exposures considered sufficiently in excess of the 
maximum human exposure indicating little relevance to clinical use. 

Intravenous administration of netarsudil to pregnant rats and rabbits during organogenesis did not 
produce adverse embryofetal effects at clinically relevant systemic exposures. In pregnant rats, 
0.1 mg/kg/day showed no adverse maternal or embryofoetal effects, whereas increased 
post-implantation loss and reduced foetal viability was observed at 0.3 mg/kg/day and higher. 
In pregnant rabbits, 3 mg/kg/day showed no maternal or embryofoetal effects, whereas an increase in 
post-implantation loss and a decrease in foetal weight were observed at 5 mg/kg/day. 

Long-term studies in animals have not been performed to evaluate the carcinogenic potential of 
netarsudil. 

Netarsudil was not mutagenic in a bacterial mutation assay, in a mouse lymphoma assay, or in a rat 
micronucleus test. 

Netarsudil and its active metabolite AR-13503 was found to have a possible phototoxic potential in a 
modified 3T3 NRU-PT in vitro assay, where the wavelength was extended to include UVB light. 



13 

Latanoprost 

The ocular as well as systemic toxicity of latanoprost has been investigated in several animal species. 
Generally, latanoprost is well tolerated with a safety margin between clinical ocular dose and systemic 
toxicity of at least 1000 times. High doses of latanoprost, approximately 100 times the clinical dose/kg 
body weight, administered intravenously to unanaesthetised monkeys have been shown to increase the 
respiration rate probably reflecting bronchoconstriction of short duration. In animal studies, 
latanoprost has not been found to have sensitising properties. 

In the eye, no toxic effects have been detected with doses of up to 100 micrograms/eye/day in rabbits 
or monkeys (clinical dose is approximately 1.5 micrograms/eye/day). In monkeys, however,  
latanoprost has been shown to induce increased pigmentation of the iris. The mechanism of increased 
pigmentation seems to be stimulation of melanin production in melanocytes of the iris with no 
proliferative changes observed. The change in iris colour may be permanent. 

In chronic ocular toxicity studies, administration of latanoprost 6 micrograms/eye/day has also been 
shown to induce increased palpebral fissure. This effect is reversible and occurs at doses above the 
clinical dose level. The effect has not been seen in humans. 

Latanoprost was found negative in reverse mutation tests in bacteria, gene mutation in mouse 
lymphoma and mouse micronucleus test. Chromosome aberrations were observed in vitro with human 
lymphocytes. Similar effects were observed with prostaglandin F2α, a naturally occurring 
prostaglandin, and indicates that this is a class effect. 

Additional mutagenicity studies on in vitro/in vivo unscheduled DNA synthesis in rats were negative 
and indicate that latanoprost does not have mutagenic potency. Carcinogenicity studies in mice and 
rats were negative. 

Latanoprost has not been found to have any effect on male or female fertility in animal studies. In the 
embryotoxicity study in rats, no embryotoxicity was observed at intravenous doses (5, 50 and 
250 micrograms/kg/day) of latanoprost. However, latanoprost induced embryolethal effects in rabbits 
at doses of 5 micrograms/kg/day and above. 

The dose of 5 micrograms/kg/day (approximately 100 times the clinical dose) caused significant 
embryofoetal toxicity characterised by increased incidence of late resorption and abortion and by 
reduced foetal weight. 

No teratogenic potential has been detected. 

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients 

Benzalkonium chloride 
Mannitol 
Boric acid 
Sodium hydroxide (for pH adjustment) 
Water for injections 

6.2 Incompatibilities 

Not applicable.  

6.3 Shelf life 

3 years.  



14 

Opened bottle: 4 weeks after first opening the bottle. Do not store above 25 °C. 

6.4 Special precautions for storage 

Store in a refrigerator (2 °C – 8 °C). Store in the original carton in order to protect from light. 

For storage conditions after first opening of the medicinal product, see section 6.3. 

6.5 Nature and contents of container 

Roclanda is supplied in clear low density polyethylene bottles (2.5 ml fill in a 4 ml container), opaque 
white low density polyethylene tips with opaque white polypropylene screw caps and anti-tamper 
seals.  

Carton containing 1 bottle. 

6.6 Special precautions for disposal 

Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements.  

7. MARKETING AUTHORISATION HOLDER

Aerie Pharmaceuticals Ireland, Limited 
Athlone Business and Technology Park, Dublin Road, 
Garrycastle, Athlone, Co Westmeath, N37 DW40, Ireland 

8. MARKETING AUTHORISATION NUMBER(S)

EU/1/20/1502/001 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 

10. DATE OF REVISION OF THE TEXT

Detailed information on this medicinal product is available on the website of the European Medicines 

Agency http://www.ema.europa.eu. 



15 

ANNEX II 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH
RELEASE

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY
AND USE

C. OTHER CONDITIONS AND REQUIREMENTS OF THE
MARKETING AUTHORISATION

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO
THE SAFE AND EFFECTIVE USE OF THE MEDICINAL
PRODUCT



16 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE

Name and address of the manufacturer(s) responsible for batch release 

Aerie Pharmaceuticals Ireland, Limited 
Athlone Business and Technology Park, Dublin Road,  
Garrycastle, Athlone, Co Westmeath, N37 DW40, Ireland 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE

Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, section 4.2). 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING
AUTHORISATION

• Periodic safety update reports (PSURs)

The requirements for submission of PSURs for this medicinal product are set out in the list of 
Union reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC 
and any subsequent updates published on the European medicines web-portal. 

The marketing authorisation holder (MAH) shall submit the first PSUR for this medicinal product 
within 6 months following authorisation.  

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND
EFFECTIVE USE OF THE MEDICINAL PRODUCT

• Risk management plan (RMP)

The marketing authorisation holder (MAH) shall perform the required pharmacovigilance 
activities and interventions detailed in the agreed RMP presented in Module 1.8.2 of the 
marketing authorisation and any agreed subsequent updates of the RMP. 

An updated RMP should be submitted: 
• At the request of the European Medicines Agency;
• Whenever the risk management system is modified, especially as the result of new information

being received that may lead to a significant change to the benefit/risk profile or as the result of
an important (pharmacovigilance or risk minimisation) milestone being reached.



17 

ANNEX III 

LABELLING AND PACKAGE LEAFLET 



18 

A. LABELLING



19 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

OUTER CARTON 

1. NAME OF THE MEDICINAL PRODUCT

Roclanda 50 micrograms/ml + 200 micrograms/ml eye drops, solution 
latanoprost + netarsudil 

2. STATEMENT OF ACTIVE SUBSTANCE(S)

1 ml of solution contains 50 micrograms latanoprost and 200 micrograms netarsudil (as mesylate). 

3. LIST OF EXCIPIENTS

Benzalkonium chloride, boric acid, mannitol, sodium hydroxide, water for injections. 

4. PHARMACEUTICAL FORM AND CONTENTS

Eye drops, solution 
1 x 2.5 ml 

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use. 
Ocular use. 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children. 

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP 
Discard 4 weeks after first opening. Once opened, do not store above 25 °C. 
Open date: __________ 

9. SPECIAL STORAGE CONDITIONS

Store in a refrigerator.  
Store in the original carton in order to protect from light. 



20 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Aerie Pharmaceuticals Ireland, Limited 
Athlone Business and Technology Park, Dublin Road, 
Garrycastle,  
Athlone, Co Westmeath,  
N37 DW40,  
Ireland. 

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/20/1502/001 

13. BATCH NUMBER

Lot 

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Roclanda 

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included. 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC 
SN 
NN 



21 

 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
BOTTLE LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Roclanda 50 micrograms/ml + 200 micrograms/ml eye drops, solution 
latanoprost + netarsudil 
Ocular use 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
2.5 ml 
 
 
6. OTHER 
 
 
  



22 

B. PACKAGE LEAFLET



23 

Package leaflet: Information for the patient 

Roclanda50 micrograms/ml + 200 micrograms/ml eye drops, solution 
latanaprost + netarsudil 

This medicine is subject to additional monitoring. This will allow quick identification of new safety 
information. You can help by reporting any side effects you may get. See the end of section 4 for how 
to report side effects.  

Read all of this leaflet carefully before you start using this medicine because it contains 
important information for you. 

- Keep this leaflet. You may need to read it again.
- If you have any further questions, ask your doctor or pharmacist.
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them,

even if their signs of illness are the same as yours.
- If you get any side effects, talk to your doctor or pharmacist. This includes any possible side

effects not listed in this leaflet. See section 4.

What is in this leaflet 

1. What Roclanda is and what it is used for
2. What you need to know before you use Roclanda
3. How to use Roclanda
4. Possible side effects
5. How to store Roclanda
6. Contents of the pack and other information

1. What Roclanda is and what it is used for

Roclanda contains the active substances latanoprost and netarsudil. Latanoprost belongs to a group of 
medicines known as prostaglandin analogues. Netarsudil belongs to a group of medicines called Rho 
kinase inhibitors. They work in different ways to reduce the amount of fluid, and so lower the 
pressure, inside the eye.  

Roclanda is used to lower pressure in the eyes in adults who have an eye condition known as 
glaucoma or who have raised pressure in their eyes. If the pressure in the eye is too high, it can 
damage your sight. 

2. What you need to know before you use Roclanda

Do not use Roclanda 
- if you are allergic to latanoprost or netarsudil or any of the other ingredients of this medicine

(listed in section 6).

Warnings and precautions  
Talk to your doctor or pharmacist before using Roclanda if you think any of the following applies to 
you: 

• If you suffer from dry eyes;
• If you have severe asthma or asthma that is not well controlled;
• If you have suffered or are currently suffering from a viral infection of the eye caused by the

herpes simplex virus.

Do not use Roclanda more than once a day, as you may experience more side effects. 



24 

Children and adolescents 
Roclanda should not be used in children and adolescents under 18 years of age as it is not known if it 
is safe or effective in this age group.  

Other medicines and Roclanda 
Roclanda may interact with other medicines. Tell your doctor or pharmacist if you are using, have 
recently used or might use any other medicines, especially any that contain another prostaglandin 
analogue like latanoprost.   

Pregnancy and breast-feeding  
If you are pregnant or breastfeeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine. Do not use Roclanda if you are 
pregnant. 

Driving and using machines 
You may find that your vision is blurred or abnormal just after using Roclanda. Do not drive or use 
machines until your vision has cleared. 

Roclanda contains benzalkonium chloride 
This medicine contains benzalkonium chloride which may be absorbed by soft contact lenses and 
change the colour of the contact lenses. You should remove contact lenses before using this medicine 
and not put them back before 15 minutes has passed.   

Benzalkonium chloride may also cause eye irritation, especially if you have dry eyes or disorders of 
the cornea (the clear layer at the front of the eye). If you feel abnormal eye sensation, stinging or pain 
in the eye after using this medicine, talk to your doctor. 

3. How to use Roclanda

Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure.  

Only use Roclanda for your eyes (ocular use). 

The recommended dose is one drop in the affected eye once a day in the evening. Use the medicine at 
around the same time each day. Do not use it more than once a day. 

How to use 

• Wash your hands before you start.
• Do not touch the dropper tip with your fingers when opening or closing the bottle. It could

infect the eye drops.
• Twist off the bottle cap, and lie the cap on a clean surface on its side. Continue to hold the

bottle, ensuring that the tip doesn’t come into contact with anything.
• Hold the bottle, pointing down, between your thumb and fingers.
• Tilt your head back.



25 

• Pull down your lower eyelid with a clean finger to form a ‘pocket’ between the eyelid and your
eye. The drop will go in here.

• Bring the dropper tip close to the eye. Do this in front of a mirror if it helps.
• Do not touch your eye, eyelid, surrounding areas or other surfaces with the dropper tip. It could

infect the eye drops.
• Gently squeeze the bottle to release one drop of Roclanda into your eye.
• Only put one drop into your eye each time. If a drop misses your eye, try again.
• Press a finger against the corner of the eye by the nose. Hold for 1 minute whilst keeping the

eye closed.
• If you need to use the drops in both eyes, repeat the steps for your other eye while you have

the bottle open.
• Put back the bottle cap to close the bottle.
• Put the bottle back into the carton to protect the drops from light until you need to use the drops

again.

If you are using other eye drops, wait at least five minutes after using them and then use Roclanda. If 
you are using an eye ointment, it should be used last. 

If you use more Roclanda than you should  
Rinse your eye with warm water. Do not put in any more drops until it is time for your next regular dose. 

If you forget to use Roclanda 
Continue with the next dose as planned. Do not use a double dose to make up for a forgotten dose. 
Do not use more than one drop in the affected eye once a day.  

If you stop using Roclanda 
Do not stop using Roclanda without first speaking to your doctor. If you stop using Roclanda the 
pressure in your eye will not be controlled which could lead to loss of sight.  

If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. 

The following side effects have been observed with Roclanda and other medicines containing 
latanoprost and netarsudil alone: 
• Very common (may affect more than 1 in 10 people)

o Effects in the eye:
 Eye redness; fine deposits on the front of the eye and pain where the drops

have been put in; a gradual increase in the amount of brown pigment in the
coloured part of the eye (the iris) leading to altered eye colour; a gradual
increase in the colour (darkening), length, thickness and number of your eye
lashes.

• Common (may affect up to 1 in 10 people)
o Effects in the eye:

 Infection or inflammation of the eye; dryness of the eye or small breaks in the
film of liquid on the surface of the eye; eye discharge; itchy eyelids; clouding
of the eye and slight decrease in vision; eye pain; feeling of grittiness or
having something in the eye; general eye redness shortly after drops are put in;
spots or patches of eye redness; conjunctivitis (eye inflammation or prominent
blood vessels) caused by an allergic reaction; watery eyes;  increased
sensitivity to light; swelling around the eye; eyelid crusting; blurred vision;

o General side effects
 redness or itching of the skin on your face



26 

• Uncommon (may affect up to 1 in 100 people)
o Effects in the eye:

 Increased fluid pressure inside the eye; inflammation of the coloured part of
the eye (the iris); bulging of iris; increased wrinkling of the clear layer over
the eye where it meets with the lower eyelid; blindness; blurred, double or
halo vision; blocked tear duct; small colored spots on the eye surface; eyelid
dryness; eye dryness caused by inflammation of the glands of the eyelids; eye
allergy; shiny/glassy eyes; tiredness; numbness or burning in the eye;
abnormal turning outward of the lower eyelid; loss of eyelashes; eye disease
related to diabetes

o Side effects in other parts of the body
 Blocked nose; nosebleed; nasal discomfort and pain; headache; dizziness;

redness or itching of the skin; dry skin; thickening of the skin; muscle pain or
spasm; joint pain; jaw pain; picking at your skin; inflammation of the
cartilage; chest pain (angina); awareness of heart beat (palpitations); asthma;
shortness of breath (dyspnoea)

• Rare (may affect up to 1 in 1000 people)
o Effects in the eye:

 Swelling or scratching with damage to the surface of the eye; swelling around
the eye (periorbital oedema); eyelashes growing in the wrong direction or an
extra row of eyelashes; scarring of the surface of the eye; fluid filled area
within the coloured part of the eye (iris cyst); skin reactions on the eyelids;
darkening of the skin of the eyelids; viral infection of the eye caused by herpes
simplex virus (HSV).

o Side effects in other parts of the body
 Worsening of asthma; severe itching of the skin

• Very rare (may affect up to 1 in 10,000 people)
o Effects in the eye:

 Sunken eye appearance (eye sulcus deepening).
o Side effects in other parts of the body

 Worsening of angina in patients who also have heart disease

Reporting of side effects 
If you get any side effects, talk to your doctor, or pharmacist. This includes any possible side effects not 
listed in this leaflet. You can also report side effects directly via the national reporting system listed in 
Appendix V. By reporting side affects you can help provide more information on the safety of this 
medicine. 

5. How to store Roclanda

Keep this medicine out of the sight and reach of children. 

Do not use this medicine after the expiry date which is stated on the bottle and the carton after “EXP”. 
The expiry date refers to the last day of that month. 

Unopened bottle: Store in a refrigerator (2 °C – 8 °C). 
After opening the bottle: Do not store above 25 °C. 

Store in the original carton in order to protect from light.   

Throw away the bottle 4 weeks after first opening to prevent infections and use a new bottle. 

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 



27 

6. Contents of the pack and other information

What Roclanda contains 
- The active substances are latanoprost and netarsudil. Each ml of solution contains 50

micrograms latanoprost and 200 micrograms netarsudil (as mesylate).
- The other excipients are benzalkonium chloride (see section 2 under ‘Roclanda contains

benzalkonium chloride’), mannitol, boric acid, sodium hydroxide (for pH adjustment) and water
for injections.

What Roclanda looks like and contents of the pack 
Roclanda is a clear, liquid eye drop solution in a plastic bottle. Each bottle contains 2.5 ml of the 
medicine and each pack contains one bottle with a screw-cap.  

Marketing Authorisation Holder and Manufacturer 
Aerie Pharmaceuticals Ireland, Limited 
Athlone Business and Technology Park, Dublin Road, 
Garrycastle, Athlone, Co Westmeath, N37 DW40, Ireland. 

This leaflet was last revised in 

Other sources of information 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C.  OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET