Latanoprost and Timolol
(la TA noe prost & TIM oh lol)
- Timolol Maleate and Latanoprost
- Beta-Blocker, Nonselective
- Ophthalmic Agent, Antiglaucoma
- Prostaglandin, Ophthalmic
Latanoprost: A prostaglandin F2-alpha analog believed to reduce intraocular pressure by increasing the outflow of the aqueous humor
Timolol: Blocks both beta1- and beta2-adrenergic receptors, reduces intraocular pressure by reducing aqueous humor production or possibly increases the outflow of aqueous humor
Use: Labeled Indications
Note: Not approved in the US
Elevated intraocular pressure: Reduction of intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension who are insufficiently responsive to topical beta-blockers, prostaglandin analogues, or other IOP-reducing agents and in whom combination therapy is appropriate
Hypersensitivity to latanoprost, timolol, benzalkonium chloride, or any component of the formulation; reactive airway disease including severe chronic obstructive pulmonary disease (COPD) and presence or history of bronchial asthma; sinus bradycardia, sick sinus syndrome, sinoatrial block, second- or third-degree atrioventricular block not controlled with pacemaker, overt cardiac failure, cardiogenic shock
Elevated intraocular pressure: Ophthalmic: Instill 1 drop into affected eye(s) once daily
Refer to adult dosing.
Dosing: Renal Impairment
There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied); use caution.
Dosing: Hepatic Impairment
There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied); use caution.
Ophthalmic: Wash hands prior to use. Remove contact lenses prior to administration; wait 15 minutes before reinserting if using products containing benzalkonium chloride. Separate administration of other ophthalmic agents by 5 minutes. Nasolacrimal occlusion or closing the eye for 2 minutes after administration may limit systemic absorption.
Prior to opening, store at 2°C to 8°C (36°F to 46°F). After opening may store up to 25°C (77°F) for 10 weeks. Protect from light.
Abiraterone Acetate: May increase the serum concentration of CYP2D6 Substrates. Management: Avoid concurrent use of abiraterone with CYP2D6 substrates that have a narrow therapeutic index whenever possible. When concurrent use is not avoidable, monitor patients closely for signs/symptoms of toxicity. Consider therapy modification
Acetylcholinesterase Inhibitors: May enhance the bradycardic effect of Beta-Blockers. Monitor therapy
Ajmaline: May increase the serum concentration of CYP2D6 Substrates. Monitor therapy
Alpha-/Beta-Agonists (Direct-Acting): Beta-Blockers may enhance the vasopressor effect of Alpha-/Beta-Agonists (Direct-Acting). Epinephrine used as a local anesthetic for dental procedures will not likely cause clinically relevant problems. Some beta-adrenoceptor mediated effects of Alpha-/Beta-Agonists (Direct-Acting), including anti-anaphylactic effects of epinephrine, may be diminished by Beta-Blockers. Management: Cardioselective beta-blockers and lower doses of epinephrine may confer a more limited risk. Patients who may require acute subcutaneous epinephrine (e.g., bee sting kits) should probably avoid beta blockers. Exceptions: Dipivefrin. Consider therapy modification
Alpha1-Blockers: Beta-Blockers may enhance the orthostatic hypotensive effect of Alpha1-Blockers. The risk associated with ophthalmic products is probably less than systemic products. Monitor therapy
Alpha2-Agonists: May enhance the AV-blocking effect of Beta-Blockers. Sinus node dysfunction may also be enhanced. Beta-Blockers may enhance the rebound hypertensive effect of Alpha2-Agonists. This effect can occur when the Alpha2-Agonist is abruptly withdrawn. Management: Closely monitor heart rate during treatment with a beta blocker and clonidine. Withdraw beta blockers several days before clonidine withdrawal when possible, and monitor blood pressure closely. Recommendations for other alpha2-agonists are unavailable. Exceptions: Apraclonidine. Consider therapy modification
Aminoquinolines (Antimalarial): May decrease the metabolism of Beta-Blockers. Monitor therapy
Amiodarone: May enhance the bradycardic effect of Beta-Blockers. Possibly to the point of cardiac arrest. Amiodarone may increase the serum concentration of Beta-Blockers. Monitor therapy
Anilidopiperidine Opioids: May enhance the bradycardic effect of Beta-Blockers. Anilidopiperidine Opioids may enhance the hypotensive effect of Beta-Blockers. Monitor therapy
Antipsychotic Agents (Phenothiazines): May enhance the hypotensive effect of Beta-Blockers. Beta-Blockers may decrease the metabolism of Antipsychotic Agents (Phenothiazines). Antipsychotic Agents (Phenothiazines) may decrease the metabolism of Beta-Blockers. Monitor therapy
Asunaprevir: May increase the serum concentration of CYP2D6 Substrates. Consider therapy modification
Barbiturates: May decrease the serum concentration of Beta-Blockers. Monitor therapy
Beta2-Agonists: Beta-Blockers (Nonselective) may diminish the bronchodilatory effect of Beta2-Agonists. Avoid combination
Bimatoprost: The concomitant use of Latanoprost and Bimatoprost may result in increased intraocular pressure. Consider therapy modification
Bradycardia-Causing Agents: May enhance the bradycardic effect of other Bradycardia-Causing Agents. Monitor therapy
Bretylium: May enhance the bradycardic effect of Bradycardia-Causing Agents. Bretylium may also enhance atrioventricular (AV) blockade in patients receiving AV blocking agents. Monitor therapy
Bupivacaine: Beta-Blockers may increase the serum concentration of Bupivacaine. Monitor therapy
Calcium Channel Blockers (Nondihydropyridine): May enhance the hypotensive effect of Beta-Blockers. Bradycardia and signs of heart failure have also been reported. Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Beta-Blockers. Exceptions: Bepridil. Monitor therapy
Cardiac Glycosides: Beta-Blockers may enhance the bradycardic effect of Cardiac Glycosides. Monitor therapy
Ceritinib: Bradycardia-Causing Agents may enhance the bradycardic effect of Ceritinib. Management: If this combination cannot be avoided, monitor patients for evidence of symptomatic bradycardia, and closely monitor blood pressure and heart rate during therapy. Avoid combination
Cholinergic Agonists: Beta-Blockers may enhance the adverse/toxic effect of Cholinergic Agonists. Of particular concern are the potential for cardiac conduction abnormalities and bronchoconstriction. Management: Administer these agents in combination with caution, and monitor for conduction disturbances. Avoid methacholine with any beta blocker due to the potential for additive bronchoconstriction. Monitor therapy
Cobicistat: May increase the serum concentration of CYP2D6 Substrates. Monitor therapy
CYP2D6 Inhibitors (Moderate): May decrease the metabolism of CYP2D6 Substrates. Monitor therapy
CYP2D6 Inhibitors (Strong): May increase the serum concentration of Timolol (Ophthalmic). Monitor therapy
Darunavir: May increase the serum concentration of CYP2D6 Substrates. Monitor therapy
Dipyridamole: May enhance the bradycardic effect of Beta-Blockers. Monitor therapy
Disopyramide: May enhance the bradycardic effect of Beta-Blockers. Beta-Blockers may enhance the negative inotropic effect of Disopyramide. Monitor therapy
Dronedarone: May enhance the bradycardic effect of Beta-Blockers. Dronedarone may increase the serum concentration of Beta-Blockers. This likely applies only to those agents that are metabolized by CYP2D6. Management: Use lower initial beta-blocker doses; adequate tolerance of the combination, based on ECG findings, should be confirmed prior to any increase in beta-blocker dose. Consider therapy modification
Ergot Derivatives: Beta-Blockers may enhance the vasoconstricting effect of Ergot Derivatives. Exceptions: Nicergoline. Consider therapy modification
Fingolimod: Beta-Blockers may enhance the bradycardic effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and beta-blockers if possible. If coadministration is necessary, patients should have overnight continuous ECG monitoring conducted after the first dose of fingolimod. Monitor patients for bradycardia. Consider therapy modification
Floctafenine: May enhance the adverse/toxic effect of Beta-Blockers. Avoid combination
Grass Pollen Allergen Extract (5 Grass Extract): Beta-Blockers may enhance the adverse/toxic effect of Grass Pollen Allergen Extract (5 Grass Extract). More specifically, Beta-Blockers may inhibit the ability to effectively treat severe allergic reactions to Grass Pollen Allergen Extract (5 Grass Extract) with epinephrine. Some other effects of epinephrine may be unaffected or even enhanced (e.g., vasoconstriction) during treatment with Beta-Blockers. Consider therapy modification
Imatinib: May increase the serum concentration of CYP2D6 Substrates. Monitor therapy
Insulin: Beta-Blockers may enhance the hypoglycemic effect of Insulin. Monitor therapy
Ivabradine: Bradycardia-Causing Agents may enhance the bradycardic effect of Ivabradine. Monitor therapy
Lacosamide: Bradycardia-Causing Agents may enhance the AV-blocking effect of Lacosamide. Monitor therapy
Lidocaine (Systemic): Beta-Blockers may increase the serum concentration of Lidocaine (Systemic). Monitor therapy
Lidocaine (Topical): Beta-Blockers may increase the serum concentration of Lidocaine (Topical). Monitor therapy
Lumefantrine: May increase the serum concentration of CYP2D6 Substrates. Monitor therapy
Mepivacaine: Beta-Blockers may increase the serum concentration of Mepivacaine. Monitor therapy
Methacholine: Beta-Blockers may enhance the adverse/toxic effect of Methacholine. Avoid combination
Midodrine: Beta-Blockers may enhance the bradycardic effect of Midodrine. Monitor therapy
NIFEdipine: May enhance the hypotensive effect of Beta-Blockers. NIFEdipine may enhance the negative inotropic effect of Beta-Blockers. Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May diminish the antihypertensive effect of Beta-Blockers. Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May diminish the therapeutic effect of Prostaglandins (Ophthalmic). Nonsteroidal Anti-Inflammatory Agents may also enhance the therapeutic effects of Prostaglandins (Ophthalmic). Monitor therapy
Panobinostat: May increase the serum concentration of CYP2D6 Substrates. Management: Avoid concurrent use of sensitive CYP2D6 substrates when possible, particularly those substrates with a narrow therapeutic index. Consider therapy modification
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Peginterferon Alfa-2b may increase the serum concentration of CYP2D6 Substrates. Monitor therapy
Perhexiline: CYP2D6 Substrates may increase the serum concentration of Perhexiline. Perhexiline may increase the serum concentration of CYP2D6 Substrates. Monitor therapy
Propafenone: May increase the serum concentration of Beta-Blockers. Propafenone possesses some independent beta blocking activity. Monitor therapy
QuiNINE: May increase the serum concentration of CYP2D6 Substrates. Monitor therapy
Regorafenib: May enhance the bradycardic effect of Beta-Blockers. Monitor therapy
Reserpine: May enhance the hypotensive effect of Beta-Blockers. Monitor therapy
Rifamycin Derivatives: May decrease the serum concentration of Beta-Blockers. Exceptions: Rifabutin. Monitor therapy
Rivastigmine: May enhance the bradycardic effect of Beta-Blockers. Avoid combination
Ruxolitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Management: Ruxolitinib Canadian product labeling recommends avoiding use with bradycardia-causing agents to the extent possible. Monitor therapy
Selective Serotonin Reuptake Inhibitors: May increase the serum concentration of Beta-Blockers. Exceptions: Citalopram; Escitalopram; FluvoxaMINE. Monitor therapy
Sulfonylureas: Beta-Blockers may enhance the hypoglycemic effect of Sulfonylureas. Cardioselective beta-blockers (eg, acebutolol, atenolol, metoprolol, and penbutolol) may be safer than nonselective beta-blockers. All beta-blockers appear to mask tachycardia as an initial symptom of hypoglycemia. Ophthalmic beta-blockers are probably associated with lower risk than systemic agents. Monitor therapy
Theophylline Derivatives: Beta-Blockers (Nonselective) may diminish the bronchodilatory effect of Theophylline Derivatives. Consider therapy modification
Tofacitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Monitor therapy
Percentages as reported with combination product. Also see individual agents.
>10%: Ophthalmic: Abnormal eyelash growth (including darkening, lengthening, thickening; 37%), iris hyperpigmentation (2% to 20%; color change due to increase melanin content and is most common in mixed color irises), eye irritation (12%)
1% to 10%:
Cardiovascular: Hypertension (4%), chest pain (1%)
Central nervous system: Depression (2%), headache (2%)
Dermatologic: Dermatological disease (2%), skin rash (1%)
Endocrine & metabolic: Hypercholesterolemia (2%), diabetes mellitus (1%)
Infection: Infection (1%)
Neuromuscular & skeletal: Arthritis (2%), back pain (1%)
Ophthalmic: Ocular hyperemia (7%), visual disturbance (7%), visual field defect (5%), blepharitis (3%), cataract (3%), conjunctivitis (3%), corneal disorder (3%), eye pain (2%), photophobia (2%), error of refraction (2%), conjunctival disease (1%), keratitis (1%)
Respiratory: Upper respiratory tract infection (6%), flu-like symptoms (3%), sinusitis (2%)
<1% (Limited to important or life-threatening): Bronchitis, cardiac failure, corneal ulcer, cystitis, cystoid macular edema, dizziness, dyspepsia, dyspnea, epiphora, exacerbation of hypertension, eyelid edema, glycosuria, hyperglycemia, increased intraocular pressure, insomnia, optic atrophy, pneumonia, retinopathy, seborrhea, skin discoloration, urinary tract infection, uveitis
Concerns related to adverse effects:
• Anaphylactic reactions: Use caution with history of atopy or severe anaphylaxis to allergens; patients taking beta-blockers may become more sensitive to repeated challenges. Treatment of anaphylaxis (eg, epinephrine) in patients taking beta-blockers may be ineffective or promote undesirable effects.
• Bacterial keratitis: Inadvertent contamination of multiple-dose ophthalmic solutions has caused bacterial keratitis.
• Ocular effects: Use of agents that reduce/suppress aqueous humor production has been associated with choroidal detachment after filtration procedures. Discontinue use in patients with chronic or recurrent choroidal detachment. Macular edema (including cystoid macular edema), mainly in aphakic or pseudophakic patients with a torn posterior lens capsule, has been associated with use of prostaglandin analogues such as latanoprost. May permanently change/increase brown pigmentation of the iris, the eyelid skin, and eyelashes. Patients should be examined regularly and, depending on the clinical situation, treatment may be stopped if increased iris pigmentation ensues. In addition, may increase the length, darken and thicken eyelashes (may vary between eyes); changes occur slowly and may not be noticeable for months or years. Long-term consequences and potential injury to eye are not known. Ophthalmic beta-blockers may cause eye dryness; use caution in corneal diseases.
• Cardiovascular disease: Consider pre-existing conduction abnormalities prior to initiation; use is contraindicated in several conditions (refer to contraindications). Use with caution in first-degree heart block. Use with caution in heart failure (HF); fatalities have been reported. Prior to initiating therapy HF should be controlled. Monitor for signs/symptoms of HF and discontinue use immediately if suspected. Use with caution in patients with orthostatic hypotension; signs and symptoms of hypotension may be enhanced.
• Closed-angle glaucoma: Should not be used alone in the treatment of acute closed angle glaucoma (immediate objective is to reopen the angle by constricting the pupil). Latanoprost and timolol maleate have little or no effect on the pupil.
• Diabetes: Use with caution in patients with diabetes mellitus (especially labile diabetes); may potentiate hypoglycemia and/or mask signs and symptoms.
• Hepatic impairment: Use with caution in hepatic impairment (has not been studied).
• Herpetic keratitis: Use with caution in patients with a history of herpes simplex keratitis; reactivation may occur. Avoid use in patients with active herpes simplex keratitis or patients with a history of recurrent herpetic keratitis specifically associated with prostaglandin analogs.
• Iritis/uveitis: Use caution in patients with active intraocular inflammation.
• Myasthenia gravis: Use with caution in patients with myasthenia gravis; may worsen disease or other myasthenic symptoms (diplopia, ptosis, generalized weakness).
• Peripheral vascular disease (PVD) and Raynaud disease: Can precipitate or aggravate symptoms of arterial insufficiency in patients with PVD and Raynaud disease. Use with caution and monitor for progression of arterial obstruction.
• Pulmonary disease: Use with caution in patients with mild or moderate COPD and closely monitor; beta blockers should generally be avoided in patients with bronchospastic disease.
• Renal impairment: Use with caution in renal impairment (has not been studied).
• Thyroid disease: May mask signs of hyperthyroidism (eg, tachycardia). If thyrotoxicosis is suspected, carefully manage and monitor; abrupt withdrawal may exacerbate symptoms of hyperthyroidism or precipitate thyroid storm.
Concurrent drug therapy issues:
• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
• Thimerosal: Precipitation may occur if mixed with benzalkonium chloride-containing products; allow at least 5 minutes between the application of latanoprost/timolol and ophthalmic preparations containing thimerosal.
• Contact lens wearers: Product contains benzalkonium chloride which may be absorbed by soft contact lenses; remove lens prior to administration and wait 15 minutes before reinserting.
• Absorption: Systemic absorption of timolol and adverse effects may occur with ophthalmic use, including bradycardia and/or hypotension. Beta-blocker therapy should not be withdrawn abruptly in order to avoid acute tachycardia, hypertension, and/or ischemia. In patients undergoing major surgery, anesthesia provider should be informed that patient is receiving timolol; gradually taper off therapy prior to procedure if possible.
• Appropriate use: Limited or no experience in the treatment of chronic angle-closure, congenital, inflammatory, neovascular, or pigmentary glaucoma or in pseudophakic patients with open angle glaucoma.
• Initial therapy: Combination product should not be used for initial therapy.
IOP, iris color changes, eyelash changes; systemic effects of beta blockade
Reproductive studies have not been conducted with this combination. See individual agents.
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience burning, stinging, foreign body sensation, dry eyes, watery eyes, eye redness, or eyelid/eyelash changes. Have patient report immediately to prescriber vision changes, eye pain, severe eye irritation, shortness of breath, excessive weight gain, swelling of arms or legs, angina, severe dizziness, passing out, severe headache, bradycardia, arrhythmia, muscle weakness, or eye discoloration (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.