Fixopost: Uses, Dosage & Side Effects

What Is Fixopost and What Is It Used For?

Fixopost is a fixed-dose combination ophthalmic solution that contains two well-established active ingredients used in the management of elevated intraocular pressure (IOP): latanoprost at a concentration of 50 micrograms per milliliter and timolol at a concentration of 5 milligrams per milliliter (equivalent to 6.8 mg timolol maleate per mL). By combining these two agents into a single formulation, Fixopost offers the therapeutic benefit of dual IOP-lowering mechanisms in one convenient eye drop, reducing the treatment burden for patients who would otherwise need to administer two separate medications.

Glaucoma is one of the leading causes of irreversible blindness worldwide, affecting more than 80 million people globally. The most common form, primary open-angle glaucoma (POAG), is characterized by a progressive optic neuropathy that damages retinal ganglion cells and their axons, leading to characteristic visual field loss. While the exact pathophysiology of glaucoma is multifactorial, elevated intraocular pressure remains the most important modifiable risk factor. Normal IOP ranges between 10 and 21 mmHg, and reducing IOP by even 1 mmHg has been shown to reduce the risk of glaucoma progression by approximately 10%. Ocular hypertension, defined as elevated IOP without demonstrable optic nerve damage or visual field loss, is also treated to prevent the development of glaucoma, particularly when additional risk factors are present such as advanced age, thin central corneal thickness, family history, or high baseline IOP.

Latanoprost, the prostaglandin analogue component of Fixopost, is an isopropyl ester prodrug of prostaglandin F2α. After topical application to the eye, latanoprost is absorbed through the cornea, where it is hydrolyzed by corneal esterases to its biologically active acid form. The latanoprost acid selectively activates the FP prostanoid receptor in the ciliary muscle and trabecular meshwork. Its primary mechanism of IOP reduction is through increasing the outflow of aqueous humor via the uveoscleral (non-conventional) pathway. Under normal physiological conditions, approximately 10–20% of aqueous humor drainage occurs through the uveoscleral route; latanoprost enhances this pathway by remodeling the extracellular matrix of the ciliary muscle, increasing the spaces between muscle bundles and facilitating fluid passage. Additionally, latanoprost may modestly increase trabecular (conventional) outflow by affecting matrix metalloproteinase activity in the trabecular meshwork. Peak IOP-lowering effect occurs approximately 8–12 hours after administration, and a single daily dose provides sustained 24-hour pressure reduction, with IOP typically reduced by 25–35% from baseline.

Timolol, the beta-blocker component of Fixopost, is a non-selective beta-adrenergic receptor antagonist that blocks both β₁ and β₂ receptors. In the eye, timolol reduces IOP by decreasing the production of aqueous humor in the ciliary epithelium. The ciliary epithelium contains β₂-adrenergic receptors, and blockade of these receptors by timolol inhibits cyclic adenosine monophosphate (cAMP)-mediated aqueous humor secretion. The onset of IOP reduction occurs within 30 minutes of topical application, with peak effect at approximately 1–2 hours. When used as monotherapy, timolol typically reduces IOP by 20–25% from baseline. The complementary mechanism of action – latanoprost increasing outflow while timolol reduces production – provides additive IOP-lowering effects that exceed what either agent achieves alone.

Clinical studies have demonstrated that the fixed-dose combination of latanoprost and timolol produces IOP reductions of 30–40% from baseline, which is significantly greater than either monotherapy. A pivotal randomized, double-masked, parallel-group clinical trial comparing the fixed combination with its individual components showed that the combination reduced mean diurnal IOP by approximately 2–3 mmHg more than latanoprost monotherapy and 3–5 mmHg more than timolol monotherapy. The fixed combination also showed non-inferiority to the concomitant administration of both agents as separate eye drops, confirming that combining the two active substances in a single formulation does not compromise efficacy.

Fixopost is indicated for adults with open-angle glaucoma or ocular hypertension whose intraocular pressure is not sufficiently controlled with topical beta-blocker or prostaglandin analogue monotherapy. It serves as a step-up therapy when first-line monotherapy – typically a prostaglandin analogue such as latanoprost, bimatoprost, travoprost, or tafluprost – provides insufficient IOP control to reach the patient’s target pressure. According to the European Glaucoma Society (EGS) guidelines, fixed-dose combination eye drops are preferred over the concomitant use of separate eye drops because they improve adherence by reducing the number of daily instillations and the number of bottles, reduce exposure to preservatives such as benzalkonium chloride, and eliminate the need for patients to time the interval between different medications.

What Should You Know Before Taking Fixopost?

Contraindications

Fixopost must not be used in patients with any of the following conditions, primarily due to the systemic effects of the timolol (beta-blocker) component. Even though timolol is applied topically to the eye, it can be absorbed into the systemic circulation through the nasolacrimal duct and conjunctival blood vessels, producing clinically significant beta-adrenergic blockade in susceptible individuals.

• Hypersensitivity: Known allergy to latanoprost, timolol, other beta-adrenergic blocking agents, or any of the excipients (including benzalkonium chloride, sodium chloride, sodium dihydrogen phosphate monohydrate, disodium hydrogen phosphate anhydrous, and water for injections).
• Reactive airway disease: Bronchial asthma (current or history of), severe chronic obstructive pulmonary disease (COPD), or bronchial hyperreactivity. Timolol can cause bronchospasm by blocking β₂-receptors in the bronchial smooth muscle, which can be life-threatening in patients with underlying airways disease.
• Sinus bradycardia: Resting heart rate below 55–60 beats per minute.
• Second- or third-degree atrioventricular (AV) block: Heart conduction abnormalities not controlled with a pacemaker.
• Overt cardiac failure: Symptomatic heart failure or cardiogenic shock.

Warnings and Precautions

Before starting Fixopost, discuss the following conditions and considerations with your healthcare provider. While the eye drops are applied locally, the timolol component can reach systemic concentrations sufficient to produce beta-adrenergic blocking effects throughout the body:

• Cardiovascular conditions: Patients with coronary artery disease, Prinzmetal’s angina, congestive heart failure (even compensated), peripheral vascular disease, Raynaud’s phenomenon, or hypotension should use Fixopost with caution. Timolol can reduce resting heart rate, decrease cardiac output, and lower blood pressure. Patients with first-degree AV block should be monitored closely, as timolol may prolong conduction time.
• Diabetes mellitus: Beta-blockers may mask the signs and symptoms of hypoglycemia (low blood sugar), particularly tachycardia and tremor. Patients with diabetes, especially those on insulin or oral hypoglycemic agents, should be aware that hypoglycemia symptoms may be blunted.
• Thyroid disorders: Beta-blockers may mask the clinical signs of hyperthyroidism (overactive thyroid). Abrupt withdrawal of beta-blockers in patients with thyrotoxicosis can precipitate a thyroid storm.
• Myasthenia gravis: Timolol may worsen muscle weakness in patients with myasthenia gravis, an autoimmune neuromuscular disorder.
• Ocular effects of latanoprost: Latanoprost may gradually change the color of the treated eye(s) by increasing the amount of brown melanin pigment in the iris. This change occurs slowly (over months to years) and is more common in patients with mixed-color irises (blue-brown, grey-brown, green-brown, or yellow-brown). The iris color change may be permanent even after discontinuation. If only one eye is treated, the patient may develop different-colored eyes (heterochromia). Latanoprost may also cause increased length, thickness, pigmentation, and number of eyelashes, as well as misdirected growth of eyelashes. In aphakic patients (those without a natural lens), pseudophakic patients with a torn posterior lens capsule, or patients with known risk factors for macular edema (such as a history of retinal vein occlusion, uveitis, or diabetic retinopathy), latanoprost should be used with caution due to the risk of cystoid macular edema.
• Ocular inflammation: Latanoprost should be used with caution in patients with active intraocular inflammation (e.g., iritis or uveitis), as prostaglandin analogues may exacerbate inflammatory conditions.
• Corneal conditions: Benzalkonium chloride, the preservative in Fixopost, may cause irritation, dry eye, and damage to the corneal epithelium, particularly in patients with dry eye disease or compromised corneas. Contact lens wearers are at particular risk, as benzalkonium chloride can be absorbed by soft contact lenses.
• Planned surgery: If you are scheduled for any type of surgery, including dental procedures, inform the anesthesiologist that you are using ophthalmic timolol, as interactions with general anesthetic agents may occur. The decision to withdraw beta-blocker therapy before surgery should be made by the treating physician, considering the risk–benefit balance.

Pregnancy and Breastfeeding

Fixopost should not be used during pregnancy unless the potential benefit to the mother outweighs the potential risk to the fetus. There are two concerns based on the individual active substances:

Latanoprost: Adequate and well-controlled studies in pregnant women have not been conducted. Animal studies with latanoprost have shown embryotoxic and fetotoxic effects at intravenous doses significantly higher than the clinical ophthalmic dose, including increased incidence of late resorptions and abortion. Although systemic exposure after ocular administration is very low, the potential risk to the human fetus cannot be excluded.

Timolol: Epidemiological studies have not revealed malformative effects, but retrospective case reports have described neonatal effects including bradycardia, hypotension, respiratory distress, and hypoglycemia in newborns whose mothers received systemic or ophthalmic beta-blockers near the time of delivery. If Fixopost is administered until delivery, the neonate should be carefully monitored during the first days of life. Timolol crosses the placental barrier.

Regarding breastfeeding, timolol has been detected in human breast milk after both oral and ophthalmic administration. Latanoprost and its metabolites may also pass into breast milk. Given the potential for serious adverse reactions in nursing infants (bradycardia, respiratory effects), a decision should be made whether to discontinue breastfeeding or to discontinue the medication, taking into account the importance of the treatment to the mother.

Children and Adolescents

Fixopost is not recommended for use in children and adolescents under 18 years of age. The safety and efficacy of the latanoprost/timolol fixed-dose combination have not been established in the pediatric population. Pediatric glaucoma requires specialized evaluation and management, and treatment decisions should be made by a pediatric ophthalmologist.

Driving and Operating Machinery

Eye drops may cause temporary blurred vision after instillation. If blurred vision occurs, you should not drive or operate machinery until your vision has cleared. Additionally, if Fixopost causes systemic side effects such as dizziness, fatigue, or bradycardia that affect your alertness, refrain from driving or operating heavy machinery until these effects have resolved.

How Does Fixopost Interact with Other Drugs?

Drug interactions with Fixopost are primarily related to the systemic absorption of timolol following topical ocular administration. Although the amount of timolol reaching the systemic circulation is relatively small compared with oral dosing, it can be sufficient to produce clinically relevant interactions in some patients, particularly the elderly or those on multiple cardiovascular medications. Below is a summary of the most important drug interactions.

Major Interactions

Minor Interactions

What Is the Correct Dosage of Fixopost?

Adults

Proper administration technique is essential to maximize the efficacy of Fixopost and minimize systemic side effects. Follow these steps carefully each time you use the eye drops:

1. Wash your hands thoroughly before handling the eye drop bottle.
2. Remove contact lenses if worn. Benzalkonium chloride (the preservative in Fixopost) can be absorbed by soft contact lenses and may cause eye irritation. Lenses may be reinserted 15 minutes after instillation.
3. Tilt your head back and pull down the lower eyelid gently with a clean finger to create a small pocket (conjunctival sac).
4. Invert the bottle and squeeze gently to release one drop into the conjunctival sac. Do not touch the dropper tip to the eye, eyelid, or any other surface to avoid contamination.
5. Close your eye gently – do not blink or squeeze the eye shut.
6. Apply nasolacrimal occlusion by pressing a finger against the inner corner of the eye (near the nose) for 1–2 minutes. This reduces drainage of the eye drop into the nasal passages and systemic circulation, thereby minimizing side effects from the timolol component.
7. Blot away any excess solution with a clean tissue.
8. If treating both eyes, repeat the procedure for the other eye.
9. If using other topical eye medications, wait at least 5 minutes between each medication.

Children

Elderly

Renal and Hepatic Impairment

Missed Dose

If you forget to apply Fixopost at the usual time, simply apply it as soon as you remember on the same day. If it is already the next day, skip the missed dose and continue with your regular dosing schedule the following evening. Do not apply a double dose to make up for the missed one. Using Fixopost more than once daily may actually reduce its IOP-lowering effectiveness (a phenomenon known as tachyphylaxis with prostaglandin analogues) and increase the risk of systemic side effects from timolol.

Overdose

Accidental ocular overdose (applying more drops than prescribed) is unlikely to cause serious harm but may increase the likelihood of local side effects such as eye irritation, redness, and tearing. Excess solution should be rinsed out with clean water or saline. If the product is accidentally swallowed, the most likely symptoms would be related to the timolol component and could include bradycardia (slow heart rate), hypotension (low blood pressure), bronchospasm, and cardiac arrest in severe cases. Treatment of systemic overdose is supportive: atropine (0.25–2 mg IV) for symptomatic bradycardia, vasopressors for hypotension, bronchodilators (inhaled beta-agonist such as salbutamol or IV aminophylline) for bronchospasm, and cardiac pacing if necessary. In case of accidental ingestion, contact a poison control center or seek emergency medical attention immediately.

What Are the Side Effects of Fixopost?

Like all medicines, Fixopost can cause side effects, although not everybody gets them. The side effects can be broadly divided into local (ocular) effects, which are the most common, and systemic effects resulting from absorption of timolol into the bloodstream. The frequency categories below are based on combined clinical trial data and post-marketing surveillance for the latanoprost/timolol fixed-dose combination and its individual components.

The latanoprost component is specifically associated with changes in the structures around the eye, including gradual browning of the iris, increased eyelash growth (hypertrichosis), and darkening of the periorbital skin. These changes are related to the prostaglandin-mediated stimulation of melanogenesis and hair follicle activity. The iris color change is caused by an increase in the melanin content of the iris stromal melanocytes, not by an increase in the number of melanocytes, and is considered benign. However, it is typically irreversible even after stopping treatment. Patients should be informed about this effect before starting therapy, especially if only one eye is to be treated, which could lead to permanent heterochromia (different-colored eyes).

The timolol component can produce systemic effects even after ophthalmic administration. Cardiovascular effects (bradycardia, hypotension, exacerbation of heart failure), respiratory effects (bronchospasm, dyspnea), and central nervous system effects (dizziness, depression, fatigue, insomnia) are all known class effects of beta-blockers. These systemic effects can be minimized by proper application technique, particularly nasolacrimal occlusion (pressing on the inner corner of the eye for 1–2 minutes after instillation), which reduces drainage of the medication into the nasal passages and subsequent absorption into the systemic circulation.

How Should You Store Fixopost?

Proper storage of Fixopost is important to maintain the stability and sterility of the eye drops. Latanoprost, in particular, is sensitive to temperature degradation, so following storage guidelines is essential to ensure the medication remains effective throughout its use.

• Before opening: Store in a refrigerator at 2–8°C (36–46°F). Keep the bottle in the outer carton to protect from light.
• After first opening: The bottle may be stored at room temperature not exceeding 25°C (77°F) for up to 4 weeks. After 4 weeks of first opening, any remaining solution must be discarded even if the bottle is not empty, as the preservative (benzalkonium chloride) may not maintain sterility beyond this period.
• Do not freeze. If the eye drops have been accidentally frozen, discard the bottle and use a new one.
• Keep the bottle tightly closed when not in use to prevent contamination and evaporation.
• Do not use after the expiry date printed on the bottle and outer carton.
• Keep out of the reach and sight of children.
• Do not dispose of medicines in household waste or wastewater. Return unused or expired medicines to your pharmacist for proper disposal.

During travel, Fixopost can be kept at room temperature (up to 25°C) for the remaining period of the 4-week open-bottle shelf life. If traveling to hot climates, consider using an insulated pouch to keep the temperature below 25°C. An unopened bottle should ideally be transported in a cool bag or with a cold pack (without direct contact with the bottle) to maintain refrigerator temperatures during transit.

What Does Fixopost Contain?

Active Substances

Fixopost contains two active pharmaceutical ingredients that work together to lower intraocular pressure:

• Latanoprost 50 micrograms/mL: A synthetic prostaglandin F2α analogue in the form of an isopropyl ester prodrug. Its molecular formula is C₂₆H₄₀O₅, with a molecular weight of 432.58 g/mol. Latanoprost is a colorless to slightly yellow oily liquid that is converted to the biologically active free acid form after absorption through the cornea. The free acid is a selective FP prostanoid receptor agonist that increases uveoscleral outflow of aqueous humor.
• Timolol 5 mg/mL (as timolol maleate 6.8 mg/mL): A non-selective beta-adrenergic receptor antagonist. Its molecular formula (as the maleate salt) is C₁₃H₂₄N₄O₃S · C₄H₄O₄, with a molecular weight of 432.49 g/mol. Timolol blocks both β₁ and β₂ adrenergic receptors and reduces aqueous humor production by the ciliary body.

Inactive Ingredients (Excipients)

The following excipients are included in the Fixopost formulation to maintain stability, sterility, pH, and tonicity:

• Benzalkonium chloride (200 micrograms/mL): A quaternary ammonium preservative that prevents microbial growth in the multi-dose bottle. It is a known ocular surface irritant that may cause or worsen dry eye disease and can be absorbed by soft contact lenses. Patients with dry eye or those who use the medication long-term should be monitored for signs of corneal toxicity.
• Sodium chloride: Used to adjust the tonicity (osmolarity) of the solution to be compatible with the eye.
• Sodium dihydrogen phosphate monohydrate: Buffering agent to maintain pH stability.
• Disodium hydrogen phosphate anhydrous: Buffering agent to maintain pH stability.
• Water for injections: The pharmaceutical-grade solvent used as the vehicle for the solution.

The pH of Fixopost solution is adjusted to approximately 6.0–7.0 to balance the stability of both active ingredients (latanoprost is more stable at lower pH, while timolol is more stable at higher pH) and to minimize ocular irritation. The solution is supplied in a multi-dose plastic dropper bottle, typically containing 2.5 mL of solution.