TRAVA PLUS

  • Therapeutic Category
    • OPHTHALMOLOGICAL DRUGS
    • Anti-glaucoma drugs
  • Pharmaceutical Form : Sterile Ophthalmic Suspension
  • Composition : Each mL of solution contains: Travoprost 40 micrograms +Timolol 5 mg (as timolol maleate).
  • Active Substance : Travoprost + timolol

INDICATIONS:

TRAVA PLUS is indicated in adults for the decrease of intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension who are insufficiently responsive to topical beta blockers or prostaglandin analogues.

CONTRAINDICATIONS:

Hypersensitivity to the active substances, or to any of the excipients.

Hypersensitivity to other beta blockers.

Reactive airway disease including bronchial asthma, or a history of bronchial asthma, severe chronic obstructive pulmonary disease.

Sinus bradycardia, sick sinus syndrome, including sino-atrial block, second- or third-degree atrioventricular block not controlled with pacemaker. Overt cardiac failure, cardiogenic shock. Severe allergic rhinitis and corneal dystrophies.

WARNINGS AND PRECAUTIONS:

Like other topically applied ophthalmic agents, travoprost and timolol are absorbed systemically. Due to the beta-adrenergic component, timolol, the same types of cardiovascular, pulmonary and other adverse reactions seen with systemic beta adrenergic

blocking medicinal products may occur. The incidence of systemic ADRs after topical ophthalmic administration is lower than for systemic administration

Cardiac disorders:

In patients with cardiovascular diseases (e.g., coronary heart disease, Prinzmetal’s angina and cardiac failure) and hypotension, therapy with beta blockers should be critically assessed and therapy with other active substances should be considered.

Patients with cardiovascular diseases should be watched for signs of deterioration of these diseases and of adverse reactions.

Due to their negative effect on conduction time, beta blockers should only be given with caution to patients with first-degree heart block.

Vascular disorders:

Patients with severe peripheral circulatory disturbance/disorders (i.e., severe forms of Raynaud’s disease or Raynaud’s syndrome) should be treated with caution.

Respiratory disorders:

TRAVA PLUS should be used with caution in patients with mild/moderate chronic obstructive pulmonary disease (COPD) and only if the potential benefit outweighs the potential risk.

Hypoglycemia/diabetes

Beta blockers should be administered with caution in patients subject to spontaneous hypoglycemia or in patients with labile diabetes, as beta blockers may mask the signs and symptoms of acute hypoglycemia.

Muscle weakness:

Beta-adrenergic blocking medicinal products have been reported to potentiate muscle weakness consistent with certain myasthenic symptoms (e.g., diplopia, ptosis and generalised weakness).

Corneal diseases:

Ophthalmic beta blockers may induce dryness of eyes. Patients with corneal diseases should be treated with caution.

Choroidal detachment:

Choroidal detachment has been reported with administration of aqueous suppressant therapy (e.g., timolol, acetazolamide) after filtration procedures.

Other beta-blocking agents:

The effect on intra-ocular pressure or the known effects of systemic beta blockade may be potentiated when timolol is given to patients already receiving a systemic beta-blocking medicinal product. The response of these patients should be closely observed. The use of two topical beta-adrenergic blocking agents is not recommended

Surgical anesthesia:

Beta-blocking ophthalmological preparations may block systemic beta-agonist effects, e.g., of adrenaline. The anaesthetist should be informed when the patient is receiving timolol.

Hyperthyroidism:

Beta blockers may mask the signs of hyperthyroidism.

Skin contact:

Prostaglandins and prostaglandin analogues are biologically active substances that may be absorbed through the skin. Women who are pregnant or attempting to become pregnant should exercise appropriate precautions to avoid direct exposure to the contents of the bottle.

Anaphylactic reactions:

While taking beta blockers, patients with a history of atopy or a history of severe anaphylactic reaction to a variety of allergens may be more reactive to repeated challenge with such allergens and unresponsive to the usual dose of adrenaline used to treat anaphylactic reactions.

Concomitant therapy:

Timolol may interact with other medicinal products

The use of two local prostaglandins is not recommended.

Ocular effects

Travoprost may gradually change the eye color by increasing the number of melanosomes (pigment granules) in melanocytes.

Before treatment is instituted, patients must be informed of the possibility of a permanent change in eye color. Unilateral treatment can result in permanent heterochromia. The long-term effects on the melanocytes and any consequences thereof are

currently unknown. The change in iris color occurs slowly and may not be noticeable for months to years.

The change in eye color has predominantly been seen in patients with mixed colored irides, i.e., blue-brown, grey-brown, yellow-brown and green-brown; however, it has also been observed in patients with brown eyes. 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.

After discontinuation of therapy, no further increase in brown iris pigment has been observed.

In controlled clinical trials, periorbital and/or eyelid skin darkening in association with the use of travoprost has been reported.

Travoprost may gradually change eyelashes in the treated eye(s); these changes were observed in about half of the patients in clinical trials and include: increased length, thickness, pigmentation, and/or number of lashes. The mechanism of eyelash

changes and their long-term consequences are currently unknown.

Macular oedema has been reported during treatment with prostaglandin F analogues. Caution is recommended when using TRAVA PLUS in aphakic patients, pseudophakic patients with a torn posterior lens capsule or anterior chamber lenses, or in patients

with known risk factors for cystoid macular oedema.

In patients with known predisposing risk factors for iritis/uveitis, and in patients with active intraocular inflammation, TRAVA PLUS can be used with caution.

Excipients:

TRAVA PLUS contains propylene glycol which may cause skin irritation.

TRAVA PLUS contains polyoxyethylene hydrogenated castor oil 40 which may cause skin reactions.

Patients must be instructed to remove contact lenses prior to application of TRAVA PLUS and wait 15 minutes after instillation of the dose before reinsertion.

DRUG INTERACTIONS:

No specific drug interaction studies have been performed with travoprost or timolol.

There is a potential for additive effects resulting in hypotension and/or marked bradycardia when ophthalmic beta-blocker solution is administered concomitantly with oral calcium channel blockers, beta-adrenergic blocking agents, antiarrhythmics (including amiodarone), digitalis glycosides, parasympathomimetics or guanethidine.

The hypertensive reaction to sudden withdrawal of clonidine can be potentiated when taking beta blockers.

Potentiated systemic beta blockade (e.g., decreased heart rate, depression) has been reported during combined treatment with CYP2D6 inhibitors (e.g., quinidine, fluoxetine, paroxetine) and timolol.

Mydriasis resulting from concomitant use of ophthalmic beta blockers and adrenaline (epinephrine) has been reported occasionally.

Beta blockers may increase the hypoglycemic effect of antidiabetic medicinal products. Beta blockers can mask the signs and symptoms of hypoglycemia.

Pregnancy and Breast-feeding:

TRAVA PLUS should not be used during pregnancy unless clearly necessary

The use of TRAVA PLUS by breast-feeding women is not recommended

Effects on ability to drive and use machines:

TRAVA PLUS has minor influence on the ability to drive and use machines.

As with any eye drops, temporary blurred vision or other visual disturbances may occur.

TRAVA PLUS may also cause hallucinations, dizziness, nervousness and/or fatigue which may affect the ability to drive and use machines. Patients should be advised not to drive and use machines if these symptoms occur.

UNDESIRABLE EFFECTS:

Immune system disorders: Uncommon: Hypersensitivity

Psychiatric disorders: Not known: Hallucinations*, Depression

Nervous system disorders: Uncommon: Dizziness, headache

Not known: Cerebrovascular accident, syncope, paraesthesia

Eye disorders: Very common: Ocular hyperemia

Common: Punctate keratitis, eye pain, visual disturbance, vision blurred, dry eye, eye pruritus, ocular discomfort, eye irritation

Uncommon: Keratitis, iritis, conjunctivitis, anterior chamber inflammation, blepharitis, photophobia, visual acuity reduced, asthenopia, eye swelling, lacrimation increased, erythema of eyelid, growth of eyelashes, eye allergy, conjunctival oedema, eyelid oedema

Not known: Macular oedema, eyelid ptosis, lid sulcus deepened, iris hyperpigmentation, corneal disorder

Cardiac disorders: Uncommon: Bradycardia

Not known: Cardiac failure, tachycardia, chest pain, palpitations

Vascular disorders: Uncommon: Hypertension, hypotension

Not known: Oedema peripheral

Respiratory, thoracic and mediastinal disorders:

Uncommon: Dyspnoea, postnasal drip

Not known: Asthma

Gastrointestinal disorders: Not known: Dysgeusia

Skin and subcutaneous tissue disorders:

Uncommon: Dermatitis contact, hypertrichosis, skin hyperpigmentation (periocular)

Not known: Rash

 

POSOLOGY AND METHOD OF ADMINISTRATION

Posology:

Use in adults, including the elderly

The dose is one drop of TRAVA PLUS in the conjunctival sac of the affected eye(s) once daily, in the morning or evening. It should be administered at the same time each day.

If a dose is missed, treatment should be continued with the next dose as planned. The dose should not exceed one drop in the affected eye(s) daily.

Special populations:

Hepatic and renal impairment

No studies have been conducted with TRAVA PLUS or with timolol 5 mg/mL eye drops in patients with hepatic or renal impairment.

Travoprost has been studied in patients with mild to severe hepatic impairment and in patients with mild to severe renal impairment (creatinine clearance as low as 14 mL/min). No dose adjustment was necessary in these patients.

Patients with hepatic or renal impairment are unlikely to require dose adjustment with TRAVA PLUS

Pediatric population

The safety and efficacy of TRAVA PLUS in children and adolescents below the age of 18 years have not been established. No data are available.

Method of administration:

For ocular use.

To prevent contamination of the dropper tip and solution, care must be taken not to touch the eyelids, surrounding areas or other surfaces with the dropper tip of the bottle.

When nasolacrimal occlusion is used or the eyelids are closed for 2 minutes, systemic absorption is reduced. This may result in a decrease in systemic side effects and an increase in local activity.

If more than one topical ophthalmic medicinal product is being used, the medicinal products must be administered at least 5 minutes apart

When substituting another ophthalmic antiglaucoma medicinal product with TRAVA PLUS, the other medicinal product should be discontinued and TRAVA PLUS should be started the following day.

Patients must be instructed to remove soft contact lenses prior to application of TRAVA PLUS and wait 15 minutes after instillation of the dose before reinsertion

STORAGE CONDITIONS: Do not store above 30°C.

PACKING: 2.5-5 mL