Latanoprostene Bunod

Registered South African indications:

• Reduction of intraocular pressure (IOP) in patients with open angle glaucoma or ocular hypertension

Registered South African contraindications

• Hypersensitivity to the active ingredient or any of its excipients

South African recommendations

Caution in the following patient groups

• Pregnancy
• Breastfeeding
• Renal impairment
• Hepatic impairment

When to seek medical advice

• Patients should consult a healthcare provider if they:
  • Experience a new eye condition, such as trauma or infection
  • Notice a sudden decrease in vision
  • Undergo eye surgery
  • Develop any eye reactions, especially conjunctivitis or eyelid reactions

Pigmentation

• Latanoprostene bunod may cause changes to pigmented tissues, especially increased pigmentation of the iris
  and periorbital tissue (eyelids)

After discontinuation of treatment

• The increased pigmentation of the iris is likely permanent after stopping latanoprostene bunod
• Pigmentation changes in the periorbital tissue (eyelids) are usually reversible
• The long-term consequences of increased pigmentation are unknown
• Patients with increased iris pigmentation can continue latanoprostene bunod but need regular eye exams

Eyelash changes

• Treatment with latanoprostene bunod may affect eyelashes and and vellus hair, leading to differences in appearance between the two eyes
• These changes, including differences in length, thickness, pigmentation, number, and growth direction of eyelashes, are typically reversible after stopping the medication

Intraocular inflammation

• Use latanoprostene bunod cautiously in patients with a history of eye inflammation (iritis/uveitis)
• It is generally recommended not to use latanoprostene bunod in patients with active intraocular inflammation as it may worsen the condition

Macular oedema

• Macular oedema, including cystoid macular oedema, has been reported during treatment with prostaglandin analogues. These reports have mainly occurred in aphakic patients, in psuedophakic patients with torn posterior lens capsule
• Latanoprostene bunod should be used with caution in aphakic patients, in pseudophakic patients with a 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)

Bacterial keratitis

• Use of multi-dose ophthalmic products has been linked to bacterial keratitis, often due to container contamination by patients, particularly those with corneal disease or a compromised ocular surface
• Prevent container tip from contacting the eye, skin, or any surface to avoid contaminating the solution with bacteria that can cause eye infections, potentially leading to serious eye damage or vision loss

Benzalkonium chloride

• Regular eye exams are necessary due to potential adverse effects on corneal permeability and risks of corneal epithelium damage from prolonged or repeated use of eye drops preserved with benzalkonium chloride
• Exercise caution when using benzalkonium chloride preserved eye drops for an extended time in patients with significant ocular surface disease

Use with contact lenses

• Benzalkonium chloride can be absorbed by contact lenses, possibly altering their color.
• Remove lenses before applying latanoprostene bunod and wait 15 minutes before reinsertion

Effects on ability to drive and use machines

• Temporary blurred vision, irritation, pain, or itching in the treated eye(s) may occur with eye drops
• Patients experiencing blurred vision after application should wait until their vision clears before driving or operating machinery

Forms avail. in SA and covered in this monograph: opd

South African registered indications and dosages

Reduction of intraocular pressure (IOP) in patients with open angle glaucoma or ocular hypertension

• Ophthalmic (opd): 1 drop, in the conjunctival sac of the affected eye(s) once dly in the evening

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Do not administer latanoprostene bunod more than once daily since it has been shown that more frequent administration of prostaglandin analogues may lessen the intraocular pressure lowering effect

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If latanoprostene bunod is to be used concomitantly with other topical ophthalmic medicinal products to lower intraocular pressure, administer each medicine at least 5 minutes apart

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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

Paed. forms avail. in SA and covered in this monograph: opd

South African registered indications and dosages

Reduction of intraocular pressure (IOP) in patients with open angle glaucoma or ocular hypertension

16 years and younger

• Not recommended for use

Older than 16 years

• Ophthalmic (opd): See adult dosage

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There were no notable differences in incidence of specific adverse reactions across treatment groups and age groups

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The use of latanoprostene bunod in paediatric patients aged 16 years and younger is not recommended because of potential safety concerns relating to the increased pigmentation following long-term chronic use

Pregnancy

South African recommendations

• Caution; positive evidence of risk in animal studies
• There are no available human data for the use of latanoprostene bunod during pregnancy to inform any medicine-associated risks
• Latanoprostene bunod has caused miscarriages, abortion, and foetal harm in rabbits
• Latanoprostene bunod was shown to be abortifacient and teratogenic when administered intravenously (IV) to pregnant rabbits at exposures ≥0.28 times the clinical dose
• Doses ≥20mcg/kg/day (23 times the clinical dose) produced 100% embryo-foetal lethality
• Structural abnormalities observed in rabbit foetuses included anomalies of the great vessels and aortic arch vessels, domed head, sternebral and vertebral skeletal anomalies, limb hyperextension and malrotation, abdominal distension, and oedema
• Latanoprostene bunod was not teratogenic in the rat when administered IV at 150mcg/kg/day (87 times the clinical dose)
• The background risk of major birth defects and miscarriage for the indicated population is unknown. However, the background risk in the U.S. general population of major birth defects is 2 to 4%, and of miscarriage is 15 to 20%, of clinically recognized pregnancies

Breastfeeding

South African recommendations

• Caution
• There are no data on the presence of latanoprostene bunod in human milk, the effects on the breastfed infant, or the effects on milk production
• The developmental and health benefits of breastfeeding should be considered, along with the mother’s clinical need for latanoprostene bunod, and any potential adverse effects on the breastfed infant from latanoprostene bunod

Fertility

South African recommendations

• Fertility studies have not been conducted with latanoprostene bunod
• The potential to impact fertility can be partially characterized by exposure to latanoprost acid, a common metabolite of both latanoprostene bunod and latanoprost
• Latanoprost acid has not been found to have any effect on male or female fertility in animal studies

South African recommendations

• Caution; no information available

South African recommendations

• Caution; no information available

South African recommendations

• No dose adjustment recommended

Eye Disorders

Common

• Conjunctival hyperaemia
• Ocular hyperaemia
• Eye irritation
• Eye pain
• Eye pruritus
• Foreign body sensation in the eye

Uncommon

• Abnormal sensation in the eye
• Asthenopia
• Blepharitis
• Blurred vision
• Chemical eye injury
• Conjunctival disorder
• Conjunctival haemorrhage
• Conjunctival irritation
• Conjunctival oedema
• Cornea presents vital dye staining
• Dry eye
• Eye colour change
• Eye discharge
• Eyelid erythema
• Eyelid hypopigmentation
• Eyelid margin crusting
• Eyelid oedema
• Eyelid pain
• Eyelid pigmentation (increased pigmentation of the periorbital tissue (eyelid))
• Eyelids pruritus
• Growth of eyelashes (increased length, thickness, and the number of lashes or hairs)
• Increased lacrimation
• Iris hyperpigmentation
• Increased intraocular pressure
• Keratitis (bacterial keratitis)
• Meibomianitis
• Ocular discomfort
• Photophobia
• Punctate keratitis
• Reduced visual acuity
• Transiently reduced visual acuity
• Trichiasis
• Uveitis

General Disorders and Administration Site Conditions

Common (ocular)

• Instillation site pain

Uncommon (ocular)

• Instillation site discomfort
• Instillation site erythema
• Instillation site hypersensitivity
• Instillation site irritation
• Instillation site reaction
• Pain

Uncommon (non-ocular)

• Chest discomfort
• Fatigue

Skin and Subcutaneous Tissue Disorders

Uncommon (ocular)

• Abnormal hair growth
• Hair colour changes
• Madarosis
• Rash
• Skin hyperpigmentation

Uncommon (non-ocular)

• Hyperhidrosis
• Urticaria

Infections and Infestations

Uncommon

• Ear infection
• Tooth infection
• Urinary tract infection
• Vaginal infection

Psychiatric Disorders

Uncommon

• Insomnia

Nervous System Disorders

Uncommon

• Dysgeusia
• Headache

Respiratory, Thoracic and Mediastinal Disorders

Uncommon

• Cough
• Dyspnoea
• Sinus congestion

Gastrointestinal Disorders

Uncommon

• Dry mouth
• Nausea

Reproductive System and Breast Disorders

Uncommon

• Breast mass

• Prostaglandins
• Prostaglandin analogues
• Prostaglandin derivatives

• Intraocular pressure

Additional Observations

• Regularly examine patients who develop increased iris pigmentation

Latanoprostene bunod is a selective FP receptor agonist. It is thought to lower intraocular pressure by increasing the outflow of aqueous humour through both the trabecular meshwork and uveoscleral routes. Intraocular pressure is a major modifiable risk factor for glaucoma progression. Reduction of intraocular pressure reduces risk of glaucomatous visual field loss.