Xalanol0.005%+0.5%

Xalanol ophthalmic solution is a fixed-dose combination of a prostaglandin F2-alpha analogue and a non-selective beta-adrenergic blocker used to lower elevated intraocular pressure (IOP).

Established use

• Open-angle glaucoma and ocular hypertension: Xalanol is indicated for reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension who are insufficiently responsive to topical beta-blockers or topical prostaglandin analogues used alone (i.e., patients requiring more than one topical IOP-lowering agent).

Important note on use

Xalanol is a combination product intended for patients who need dual-mechanism therapy; it is not typically used as a first-line, single agent when monotherapy has not yet been tried, unless a physician determines combination therapy is appropriate from the outset.

Each mL of Latanoprost + Timolol ophthalmic solution typically contains:

• Latanoprost 50 micrograms (0.005% w/v)
• Timolol (as timolol maleate) 5 mg (0.5% w/v)

Contains benzalkonium chloride as a preservative in most marketed formulations (preservative-free options may exist for select formulations).

Xalanol is a sterile, isotonic, buffered ophthalmic solution combining two complementary classes of glaucoma medication in a single eye drop: a prostaglandin analogue (latanoprost) and a non-selective beta-blocker (timolol). Combining both mechanisms in one formulation allows two-drug therapy with a single daily instillation, which can improve convenience and adherence compared with using the two agents separately.

Xalanol is supplied as eye drops in multidose bottles for topical ocular administration only; it is not for injection or oral use.

Xalanol belongs to the therapeutic class of anti-glaucoma agents, specifically a fixed-dose combination of a prostaglandin analogue and a non-selective beta-adrenergic blocking agent used for ophthalmic (topical ocular) use.

Latanoprost + Timolol lowers intraocular pressure (IOP) through two complementary mechanisms:

• Latanoprost is a prostaglandin F2-alpha analogue prodrug that, once hydrolyzed to its biologically active acid form in the cornea, increases outflow of aqueous humor mainly through the uveoscleral (and to a lesser extent trabecular) pathway.
• Timolol is a non-selective beta-1/beta-2 adrenergic receptor blocker that reduces the production (formation) of aqueous humor by the ciliary epithelium, without significantly affecting pupil size or accommodation.

Because the two components act by different mechanisms (reduced aqueous production plus increased aqueous outflow), the additive effect of Latanoprost + Timolol typically produces a greater IOP reduction than either agent used alone.

Onset of IOP-lowering effect is generally seen within a few hours, with peak effect typically around 8-12 hours after dosing; timolol is absorbed systemically through the nasolacrimal duct and conjunctival vessels and can produce systemic beta-blocking effects even though it is applied topically.

Xalanol is for topical ophthalmic (eye) use only. Instil into the conjunctival sac of the affected eye(s); apply nasolacrimal occlusion or gentle eyelid closure for 1-2 minutes after each dose to reduce systemic absorption. See Dosage and Administration for full technique.

Only well-established, clinically significant interactions with Xalanol are listed below.

• Oral beta-blockers or other systemic beta-adrenergic blocking agents: concurrent use may produce additive effects on intraocular pressure lowering but also additive systemic effects (bradycardia, hypotension); monitor closely.
• Calcium channel blockers (oral, especially non-dihydropyridines such as verapamil/diltiazem): co-administration with the timolol component may increase the risk of atrioventricular conduction disturbances, left ventricular failure, and hypotension.
• Other topical ophthalmic beta-blockers: should not be used concurrently with Xalanol, as this offers no added benefit and increases risk of systemic beta-blockade.
• Catecholamine-depleting drugs (e.g., reserpine): concurrent use with the timolol component may produce additive effects and result in hypotension and/or marked bradycardia (potentially leading to syncope).
• Digoxin and other drugs affecting cardiac conduction: additive effect on atrioventricular conduction time possible with the timolol component.
• Insulin or oral hypoglycemic agents: the timolol component may mask signs and symptoms of acute hypoglycemia (e.g., tachycardia); use with caution in diabetic patients.
• Epinephrine (adrenaline): rare reports of mydriasis with concomitant use of prostaglandin analogues and epinephrine-containing products.

The following adverse effects have been reported with Xalanol; most are ocular and localized to the eye.

Common

• Ocular hyperemia (eye redness), stinging/burning on instillation, eye irritation, foreign body sensation
• Blurred vision, itching, punctate keratitis
• Gradual, permanent increase in brown pigmentation of the iris and periocular skin (more likely with mixed-color irises, e.g., blue-brown, green-brown)
• Growth changes to eyelashes (increased length, thickness, number, and pigmentation)

Less common / systemic (mainly from the timolol component)

• Bradycardia, hypotension, palpitations
• Headache, dizziness, fatigue
• Bronchospasm/dyspnea in susceptible individuals (see Contraindications)

Rare

• Iritis/uveitis (mainly in patients with predisposing risk factors), cystoid macular edema (mainly in aphakic/pseudophakic eyes with disrupted posterior lens capsule), corneal disorders

Pregnancy: Data on the use of Xalanol in pregnant women are limited. Prostaglandin analogues such as latanoprost can theoretically affect uterine tone, and timolol crosses the placenta with potential for systemic beta-blocking effects in the neonate (e.g., bradycardia, hypotension) if used near term. Xalanol should be used during pregnancy only if clearly needed and the potential benefit justifies the potential risk to the fetus. Consult a physician before use.

Lactation: It is not known with certainty whether topically applied latanoprost is excreted in human milk; timolol is excreted in breast milk in small amounts. Caution is advised, and a physician should be consulted to weigh the benefits of treatment against potential risk to the nursing infant.

Before using Xalanol, patients and physicians should consider the following precautions:

• Pigmentation changes: Xalanol can cause a gradual, permanent increase in brown pigmentation of the iris, periorbital skin, and eyelashes. Patients should be counseled about this possibility, especially when only one eye is being treated, which can result in permanent asymmetric eye color (heterochromia).
• Cardiac and respiratory effects: although administered topically, timolol is absorbed systemically and can cause the same adverse reactions as systemic beta-blockers (bradycardia, arrhythmia, heart block, bronchospasm, heart failure exacerbation). See Contraindications for absolute contraindications; use with caution in patients with other cardiac conduction abnormalities or compensated heart failure.
• Masking of hypoglycemia and hyperthyroidism: the timolol component may mask signs of acute hypoglycemia in diabetic patients and may mask signs/symptoms of hyperthyroidism (e.g., tachycardia); use cautiously and do not discontinue abruptly in these patients.
• Corneal and intraocular inflammation: use with caution in patients with a history of intraocular inflammation (iritis/uveitis), aphakia, pseudophakia with a torn posterior lens capsule, or known risk factors for macular edema. Reactivation of herpetic keratitis has been reported with prostaglandin analogues.
• Bacterial keratitis: has been reported with use of contaminated multidose ophthalmic solutions; avoid contaminating the dropper tip.
• Anesthesia and surgery: because timolol can blunt the response to beta-agonist stimulation, physicians and anesthesiologists should be informed the patient is using Xalanol prior to elective surgery.
• Contact lenses: remove before instillation due to the benzalkonium chloride preservative; reinsert at least 15 minutes after dosing.

Topical ocular overdose is uncommon, but excessive or accidental ingestion of Xalanol may cause systemic beta-blockade symptoms (bradycardia, hypotension, bronchospasm, dizziness, fainting) related to the timolol component, and ocular irritation/hyperemia from the latanoprost component. If overdose is suspected — whether from ocular instillation of excess drops or accidental oral ingestion — seek immediate medical attention or contact a poison control center/emergency services rather than attempting home treatment. There is no specific antidote; management is supportive and symptomatic under medical supervision.

Before opening: store in a refrigerator (2°C to 8°C), protected from light. After first opening, the bottle may be stored at room temperature (below 25°C), away from direct light, and should be discarded after 4 weeks of use (or per the specific product's labeling). Keep out of reach of children.

Renal impairment

No dose adjustment of Xalanol is generally required in patients with renal impairment; specific studies are limited, and caution is advised.

Hepatic impairment

No dose adjustment of Xalanol is generally required in patients with mild to moderate hepatic impairment; it has not been specifically studied in severe hepatic impairment, so caution is advised.

Elderly

No overall differences in effectiveness or safety of Xalanol have been observed between elderly and younger adult patients; no dose adjustment is needed based on age alone.

Pediatric use

See Pediatric Uses.

Xalanol is typically used long-term (chronic therapy) for ongoing control of intraocular pressure in open-angle glaucoma or ocular hypertension, for as long as the treating ophthalmologist determines it is effective and well tolerated. Regular follow-up to monitor intraocular pressure and ocular surface health is required; do not stop or alter the dosing schedule without consulting a physician.

Anti-glaucoma agent; fixed-dose combination of a prostaglandin F2-alpha analogue (latanoprost) and a non-selective beta-adrenergic receptor blocker (timolol), for topical ophthalmic use.

Latanoprost + Timolol lowers intraocular pressure through two complementary actions: latanoprost (a prostaglandin F2-alpha analogue) increases uveoscleral outflow of aqueous humor, while timolol (a non-selective beta-blocker) decreases the rate of aqueous humor production by the ciliary body. The combined effect produces a greater reduction in intraocular pressure than either mechanism alone.

The safety and efficacy of Xalanol in pediatric patients (infants, children, and adolescents) have not been established. Use in this population is generally not recommended unless specifically directed by a pediatric ophthalmologist, who will weigh the potential benefits and risks on a case-by-case basis.