Travoprost/ Timolol

Registered South African indications: 

• Elevated intraocular pressure (IOP)
  - In patients with ocular hypertension or open-angle glaucoma for whom treatment with either travoprost or timolol given alone provides insufficient IOP reduction

Registered South African contraindications

• Hypersensitivity to the active ingredient or any of the excipients in this combination product
• Bronchial asthma or history thereof
• Severe chronic obstructive pulmonary disease
• Sinus bradycardia
• Second or third degree atrioventricular block
• Overt cardiac failure
• Cardiogenic shock
• Pregnancy
• Breastfeeding

• Renal impairment
• Cardiovascular disease
• First degree heart block
• Severe peripheral circulatory disorders 
• Mild to moderate chronic obstructive pulmonary disease 
• Diabetes mellitus
• Corneal diseases
• Choroidal detachment
• Hyperthyroidism
• Contact with skin
• History of atopy
• History of severe anaphylactic reaction 
• Aphakic patients
• Pseudophakic patients with a torn posterior lens capsule or anterior chamber lenses 
• Risk factors for cystoid macular oedema
• Risk factors for iritis/uveitis
• Active intraocular inflammation
• Concomitant use of contact lenses 

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

South African registered indications and dosages

Elevated intraocular pressure (IOP)
- In patients with ocular hypertension or open-angle glaucoma for whom treatment with either travoprost or timolol given alone provides insufficient IOP reduction

Travoprost/ Timolol
40µg/5mg (per ml)

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

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Administer at the same time every day

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Method of administration

Remove the protective overwrap immediately prior to initial 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
Nasolacrimal occlusion or gently closing the eyelid after administration is recommended. This may reduce the systemic absorption administered via the ocular route and result in a decrease in systemic side effects
If more than one topical ophthalmic medicine is being used, the medicines must be administered at least 5 minutes apart
When substituting another ophthalmic anti-glaucoma medicine with travoprost/timolol, discontinue the other medicine after proper dosing on one day and start the following day with travoprost/timolol

Not established for use in children below 18 years

Pregnancy

South African recommendations

• Contraindicated
• There are no adequate data from the use of travoprost/timolol in pregnant women
• Animal studies with travoprost have shown reproductive toxicity. Travoprost/timolol should not be used during pregnancy
• Travoprost has harmful pharmacological effects on pregnancy and/or the foetus/newborn child. Epidemiological studies have not revealed malformative effects but show a risk for intrauterine growth retardation when beta blockers are administered by the oral route
• In addition, signs and symptoms of beta blockade (e.g. bradycardia, hypotension, respiratory distress and hypoglycaemia) have been observed in the neonate when beta blockers have been administered until delivery

Breastfeeding

South African recommendations

• Contraindicated
• Timolol is excreted in breast milk and has the potential to cause serious adverse reactions in the breast-fed infant. However, at therapeutic doses of timolol in eye drops it is unlikely that sufficient amounts would be present in breast milk to produce clinical symptoms of beta blockade in the infant
• Mothers breastfeeding their babies should not be treated with travoprost/timolol. It is unknown whether travoprost from eye drops is excreted in human breast milk, however, animal studies have shown excretion of travoprost and metabolites in breast milk

Fertility

South African recommendations

• No information available

• Caution; no dose adjustment recommended

• No dose adjustment recommended

• No dose adjustment recommended

Central Nervous System Disorders

• Nervousness
• Depression
• Headache
• Dizziness
• Cerebrovascular accident
• Syncope
• Paraesthesia
• Insomnia
• Nightmares
• Memory loss
• Cerebral ischaemia
• Increase in signs and symptoms of myasthenia gravis
• Ptosis
• Asthenia

Cardiovascular Disorders

• Hypertension
• Hypotension
• Peripheral oedema 
• Bradycardia
• Arrhythmia
• Irregular pulse
• Cardiac failure
• Tachycardia
• Chest pain
• Palpitations
• Atrioventricular block
• Cardiac arrest
• Raynaud's phenomenon

Respiratory Disorders

• Bronchospasm
• Cough
• Dyspnoea
• Postnasal drip
• Throat irritation
• Oropharyngeal pain
• Nasal discomfort

Gastrointestinal Disorders

• Nausea and vomiting
• Dyspepsia
• Diarrhoea
• Dry mouth
• Abdominal pain

Hepatobiliary disorders

• Increased alanine aminotransferase
• Increased aspartate aminotransferase

Genitourinary Disorders

• Chromaturia
• Sexual dysfunction

Endocrine and Metabolic Disorders

• Hypoglycaemia
• Decreased libido

Musculoskeletal Disorders

• Pain in extremities
• Myalgia

Skin and Subcutaneous Tissue Disorders

• Urticaria
• Eye swelling
• Eyelid oedema
• Skin discolouration
• Alopecia
• Periocular skin hyperpigmentation
• Rash
• Skin exfoliation
• Psoriasiform rash
• Exacerbation of psoriasis
• Eyelid margin crusting

Immune, Blood and Lymphatic System Disorders

• Hypersensitivity
• Systemic allergic reactions

Sensory Disorders

• Punctate keratitis
• Dysgeusia
• Eye pain
• Visual disturbance
• Blurred vision
• Dry eye
• Eye pruritus
• Ocular discomfort
• Eye irritation
• Keratitis
• Iritis
• Conjunctivitis
• Anterior chamber inflammation
• Blepharitis
• Photophobia
• Reduced visual acuity 
• Asthenopia
• Increased lacrimation 
• Erythema of eyelid
• Growth of eyelashes
• Eye allergy
• Conjunctival oedema
• Corneal erosion
• Meibomianitis
• Conjunctival haemorrhage
• Trichiasis
• Distichiasis
• Macular oedema
• Corneal disorder
• Uveitis
• Conjunctival disorder
• Conjunctival follicles
• Iris hyperpigmentation
• Ocular irritation 
• Choroidal detachment following filtration surgery 
• Decreased corneal sensitivity
• Diplopia

Others

• Thirst

• Calcium channel blockers
• Beta blockers
• Antiarrhythmics 
• Digitalis glycosides
• Parasympathomimetics
• Guanethidine
• Clonidine 
• CYP2D6 inhibitors 
• Adrenaline 

Ophthalmic examination

Travoprost and timolol maleate both lower intraocular pressure. Travoprost, a prostaglandin F2-alpha analogue, is a full agonist which is highly selective and has a high affinity for the prostaglandin FP receptor. It reduces the intraocular pressure by increasing the outflow of aqueous humour via the trabecular meshwork and uveoscleral pathways. Timolol is a non-selective adrenergic-blocking agent that has no intrinsic sympathomimetic, direct myocardial depressant or membrane-stabilising activity. It reduces aqueous humour formation and slightly increases aqueous humour outflow.

COMBINATION PREPARATIONS

Travaprost/ Timolol

Eye drops (per ml) 40µg/5mg

• DuoTrav (Novartis South Africa) originator
• Ocutra Co (Pharma Dynamics)