Drugs List

Therapeutic Indications

Uses

Treatment of elevated intraocular pressure in ocular hypertension
Treatment of elevated intraocular pressure in open-angle glaucoma

Contraindications

Children under 18 years
Asthma
Cardiogenic shock
History of asthma
Second degree atrioventricular block
Severe chronic obstructive pulmonary disease
Sinoatrial exit block
Sinus bradycardia
Third degree atrioventricular block
Uncontrolled cardiac failure

Precautions and Warnings

Atopy
History of allergies including anaphylaxis
Predisposition to iritis
Predisposition to uveitis
Risk factors for cystoid macular oedema
Soft contact lenses
Anterior chamber lens
Aphakia
Breastfeeding
Cardiac failure
Cardiovascular disorder
Chronic obstructive pulmonary disease
Congenital glaucoma
Corneal disorder
Diabetes mellitus
First degree atrioventricular block
Hepatic impairment
Hypertension
Hyperthyroidism
Hypoglycaemia
Hypotension
Ischaemic heart disease
Myasthenia gravis
Narrow angle glaucoma
Pigmentary glaucoma
Pregnancy
Prinzmetal's angina
Pseudoexfoliative glaucoma
Pseudophakia with torn posterior lens capsule
Renal impairment
Severe peripheral circulatory disorder

Advise diabetic patients that hypoglycaemic symptoms may be reduced/altered
Anaesthetist should be made aware patient is taking this medication
May mask symptoms of hyperthyroidism
May unmask the symptoms of myasthenia gravis
Advise ability to drive/operate machinery may be affected by side effects
In combined therapy, administer eye products at least five minutes apart
To reduce systemic absorption compress lacrimal sac during administration
Monitor intra-ocular pressure
Monitor patient with history of severe cardiac disease for signs of failure
Advise patient that some eye changes may be permanent
Beta blockers may reduce the response to adrenaline in anaphylaxis
May cause periorbital/eyelid skin darkening
Seek doctor's advice if intercurrent ocular condition develops
Systemic absorption & adverse effects of systemic beta blockers may occur
Do not withdraw this drug suddenly
Female: Ensure adequate contraception during treatment
Advise patient not to exceed stated dose
Advise patient to avoid touching the eye/other surfaces with container tip
Before initiating treatment inform patient of possibility of eyelash growth
Before initiating treatment inform patient of risk of eyelid skin darkening
Before starting treatment inform patient of risk of increased iris pigment
Remove contact lenses before use and re-insert 15 minutes after use

Pregnancy and Lactation

Pregnancy

Use tafluprost with timolol with caution in pregnancy.

The manufacturer notes that this medication should not be used in pregnancy unless clearly necessary (in cases where no other treatment option is available) and that it should not be used in women of childbearing potential unless adequate contraceptive measures are used.

Tafluprost
At the time of writing there is no published data concerning the use of tafluprost during human pregnancy. Studies in animals have shown reproductive toxicity. In embryo-foetal developmental studies tafluprost caused reductions in foetal body weights and increases in post-implantation losses as well as skeletal abnormalities in rats and rabbits even at very low doses. At increased doses in rats in a pre- and post-natal study the following were observed: increased mortality of newborns, decreased body weights, delayed pinna unfolding. At high doses in rats, reproduction toxicity studies with systemic administration, no effects on fertility or early embryonic development were noted.

Prostaglandins increase uterine tone and can cause reduced perfusion to the foetus so although Schaefer normally concludes that eye drops may generally be used during pregnancy for the appropriate indications, caution with prostaglandin use is advised. If there are compelling treatment indications, as is the case with severe glaucoma, prostaglandin eye drops should not be withheld, but the dosage should be kept as low as possible (Schaefer 2007).

Timolol
Studies involving the systemic use of beta blockers did not indicate malformative effects, but some pharmacological effects such as bradycardia have been observed in foetuses and neonates. Systemic use of some beta-blockers can cause intra-uterine growth retardation (IUGR) and reduced placental weight. The use of timolol eye drops during pregnancy has been reported to cause foetal bradycardia.

If, after careful consideration of the risks involved, timolol eye drops are used during pregnancy, it is advisable to consider lacrimal sac compression and removal of any excess on the skin with a tissue.

Any infant, exposed in utero to timolol eye drops should be monitored closely after birth for bradycardia and other symptoms.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Use tafluprost with timolol with caution in breastfeeding.

Tafluprost
At the time of writing there is limited published information concerning the use of tafluprost during breastfeeding and it is unknown if it is excreted into human milk. As the half life of the active metabolite (tafluprost acid) is very short the oral bioavailability is expected to be very low. Studies in rats have shown excretion of tafluprost into breast milk after topical administration.

Schaefer advises that Prostaglandins should only be used for compelling indications during breastfeeding, and if breastfeeding continues there should be careful observation of the baby.

Timolol
Timolol is excreted into breast milk. Both oral and ophthalmic drops produce modest levels in milk. In one case report, a woman with elevated intraocular pressure applied ophthalmic 0.5% timolol drops to one eye twice daily, resulting in excretion of the drug in her breast milk. Most authorities consider that the levels seen were below the daily dose that would be below that expected to produce cardiac effects in the infant.

If, after careful consideration of the risks involved, timolol eye drops are used during breastfeeding, it is advisable to consider lacrimal sac compression and removal of any excess on the skin with a tissue.

Infants exposed to timolol via breast milk should be closely observed for hypotension, weakness, hypoglycaemia, sedation, depression, bradycardia and other signs or symptoms of beta blockade.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Abnormal sensation in eye
Alopecia
Anaphylaxis
Angioedema
Anterior chamber flare
Anterior chamber inflammation
Arrhythmias
Arthropathy
Asthenia
Asthenopia
Atrioventricular block
Blepharal pigmentation
Blepharitis
Blurred vision
Bradycardia
Bronchospasm
Cardiac arrest
Cardiac failure
Cells in anterior chamber of eye
Cerebral ischaemia
Cerebrovascular accident
Chest pain
Choroidal detachment (following filtration surgery)
Claudication
Cold extremities
Congestive cardiac failure
Conjunctival follicles
Conjunctival hyperaemia
Conjunctival oedema
Conjunctival pigmentation
Conjunctivitis
Corneal erosion
Cough
Decreased corneal sensitivity
Depression
Diarrhoea
Diplopia
Dizziness
Dry eyes
Dry mouth
Dysgeusia
Dyspepsia
Dyspnoea
Exacerbation of pre-existing asthma
Exacerbation of psoriasis
Eyelash changes
Eyelid erythema
Eyelid oedema
Eyelid sulcus
Fatigue
Headache
Heart block
Hypersensitivity reactions
Hypertrichosis of eyelid
Hypoglycaemia
Hypotension
Increased iris pigmentation
Increased lacrimation
Insomnia
Iritis
Keratitis
Loss of libido
Memory loss
Myalgia
Myasthenia gravis-like syndrome
Nausea
Nervousness
Nightmares
Ocular allergy
Ocular discharge
Ocular discomfort
Ocular hyperaemia
Ocular pruritus
Oedema
Palpitations
Paraesthesia
Peyronie's disease
Photophobia
Pruritus
Psoriasiform rash
Ptosis
Rash
Raynaud's phenomenon
Reduced visual acuity
Refractive changes
Respiratory failure
Sensation of foreign body in eye
Sexual dysfunction
Superficial punctate keratitis
Syncope
Systemic lupus erythematosus
Thirst
Tinnitus
Urticaria
Uveitis
Visual disturbances
Vomiting

Presentation

Eye drops containing tafluprost with timolol (preservative-free)

Drugs List

Therapeutic Indications

Uses

Treatment of elevated intraocular pressure in ocular hypertension
Treatment of elevated intraocular pressure in open-angle glaucoma

Dosage

Adults

Elderly

Contraindications

Children under 18 years
Asthma
Cardiogenic shock
History of asthma
Second degree atrioventricular block
Severe chronic obstructive pulmonary disease
Sinoatrial exit block
Sinus bradycardia
Third degree atrioventricular block
Uncontrolled cardiac failure

Precautions and Warnings

Atopy
History of allergies including anaphylaxis
Predisposition to iritis
Predisposition to uveitis
Risk factors for cystoid macular oedema
Soft contact lenses
Anterior chamber lens
Aphakia
Breastfeeding
Cardiac failure
Cardiovascular disorder
Chronic obstructive pulmonary disease
Congenital glaucoma
Corneal disorder
Diabetes mellitus
First degree atrioventricular block
Hepatic impairment
Hypertension
Hyperthyroidism
Hypoglycaemia
Hypotension
Ischaemic heart disease
Myasthenia gravis
Narrow angle glaucoma
Pigmentary glaucoma
Pregnancy
Prinzmetal's angina
Pseudoexfoliative glaucoma
Pseudophakia with torn posterior lens capsule
Renal impairment
Severe peripheral circulatory disorder

Advise diabetic patients that hypoglycaemic symptoms may be reduced/altered
Anaesthetist should be made aware patient is taking this medication
May mask symptoms of hyperthyroidism
May unmask the symptoms of myasthenia gravis
Advise ability to drive/operate machinery may be affected by side effects
In combined therapy, administer eye products at least five minutes apart
To reduce systemic absorption compress lacrimal sac during administration
Monitor intra-ocular pressure
Monitor patient with history of severe cardiac disease for signs of failure
Advise patient that some eye changes may be permanent
Beta blockers may reduce the response to adrenaline in anaphylaxis
May cause periorbital/eyelid skin darkening
Seek doctor's advice if intercurrent ocular condition develops
Systemic absorption & adverse effects of systemic beta blockers may occur
Do not withdraw this drug suddenly
Female: Ensure adequate contraception during treatment
Advise patient not to exceed stated dose
Advise patient to avoid touching the eye/other surfaces with container tip
Before initiating treatment inform patient of possibility of eyelash growth
Before initiating treatment inform patient of risk of eyelid skin darkening
Before starting treatment inform patient of risk of increased iris pigment
Remove contact lenses before use and re-insert 15 minutes after use

Pregnancy and Lactation

Pregnancy

Use tafluprost with timolol with caution in pregnancy.

The manufacturer notes that this medication should not be used in pregnancy unless clearly necessary (in cases where no other treatment option is available) and that it should not be used in women of childbearing potential unless adequate contraceptive measures are used.

Tafluprost
At the time of writing there is no published data concerning the use of tafluprost during human pregnancy. Studies in animals have shown reproductive toxicity. In embryo-foetal developmental studies tafluprost caused reductions in foetal body weights and increases in post-implantation losses as well as skeletal abnormalities in rats and rabbits even at very low doses. At increased doses in rats in a pre- and post-natal study the following were observed: increased mortality of newborns, decreased body weights, delayed pinna unfolding. At high doses in rats, reproduction toxicity studies with systemic administration, no effects on fertility or early embryonic development were noted.

Prostaglandins increase uterine tone and can cause reduced perfusion to the foetus so although Schaefer normally concludes that eye drops may generally be used during pregnancy for the appropriate indications, caution with prostaglandin use is advised. If there are compelling treatment indications, as is the case with severe glaucoma, prostaglandin eye drops should not be withheld, but the dosage should be kept as low as possible (Schaefer 2007).

Timolol
Studies involving the systemic use of beta blockers did not indicate malformative effects, but some pharmacological effects such as bradycardia have been observed in foetuses and neonates. Systemic use of some beta-blockers can cause intra-uterine growth retardation (IUGR) and reduced placental weight. The use of timolol eye drops during pregnancy has been reported to cause foetal bradycardia.

If, after careful consideration of the risks involved, timolol eye drops are used during pregnancy, it is advisable to consider lacrimal sac compression and removal of any excess on the skin with a tissue.

Any infant, exposed in utero to timolol eye drops should be monitored closely after birth for bradycardia and other symptoms.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Use tafluprost with timolol with caution in breastfeeding.

Tafluprost
At the time of writing there is limited published information concerning the use of tafluprost during breastfeeding and it is unknown if it is excreted into human milk. As the half life of the active metabolite (tafluprost acid) is very short the oral bioavailability is expected to be very low. Studies in rats have shown excretion of tafluprost into breast milk after topical administration.

Schaefer advises that Prostaglandins should only be used for compelling indications during breastfeeding, and if breastfeeding continues there should be careful observation of the baby.

Timolol
Timolol is excreted into breast milk. Both oral and ophthalmic drops produce modest levels in milk. In one case report, a woman with elevated intraocular pressure applied ophthalmic 0.5% timolol drops to one eye twice daily, resulting in excretion of the drug in her breast milk. Most authorities consider that the levels seen were below the daily dose that would be below that expected to produce cardiac effects in the infant.

If, after careful consideration of the risks involved, timolol eye drops are used during breastfeeding, it is advisable to consider lacrimal sac compression and removal of any excess on the skin with a tissue.

Infants exposed to timolol via breast milk should be closely observed for hypotension, weakness, hypoglycaemia, sedation, depression, bradycardia and other signs or symptoms of beta blockade.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Abnormal sensation in eye
Alopecia
Anaphylaxis
Angioedema
Anterior chamber flare
Anterior chamber inflammation
Arrhythmias
Arthropathy
Asthenia
Asthenopia
Atrioventricular block
Blepharal pigmentation
Blepharitis
Blurred vision
Bradycardia
Bronchospasm
Cardiac arrest
Cardiac failure
Cells in anterior chamber of eye
Cerebral ischaemia
Cerebrovascular accident
Chest pain
Choroidal detachment (following filtration surgery)
Claudication
Cold extremities
Congestive cardiac failure
Conjunctival follicles
Conjunctival hyperaemia
Conjunctival oedema
Conjunctival pigmentation
Conjunctivitis
Corneal erosion
Cough
Decreased corneal sensitivity
Depression
Diarrhoea
Diplopia
Dizziness
Dry eyes
Dry mouth
Dysgeusia
Dyspepsia
Dyspnoea
Exacerbation of pre-existing asthma
Exacerbation of psoriasis
Eyelash changes
Eyelid erythema
Eyelid oedema
Eyelid sulcus
Fatigue
Headache
Heart block
Hypersensitivity reactions
Hypertrichosis of eyelid
Hypoglycaemia
Hypotension
Increased iris pigmentation
Increased lacrimation
Insomnia
Iritis
Keratitis
Loss of libido
Memory loss
Myalgia
Myasthenia gravis-like syndrome
Nausea
Nervousness
Nightmares
Ocular allergy
Ocular discharge
Ocular discomfort
Ocular hyperaemia
Ocular pruritus
Oedema
Palpitations
Paraesthesia
Peyronie's disease
Photophobia
Pruritus
Psoriasiform rash
Ptosis
Rash
Raynaud's phenomenon
Reduced visual acuity
Refractive changes
Respiratory failure
Sensation of foreign body in eye
Sexual dysfunction
Superficial punctate keratitis
Syncope
Systemic lupus erythematosus
Thirst
Tinnitus
Urticaria
Uveitis
Visual disturbances
Vomiting

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: July 2015.

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Joint Formulary Committee. British National Formulary(online) London: BMJ Group and Pharmaceutical Press. Accessed on 15 July 2015.

Medications and Mothers' Milk, Sixteenth Edition (2014) Hale, T and Rowe, H, Hale Publishing, Plano, Texas.

Summary of Product Characteristics: Taptiqom 15 micrograms/ml + 5 mg/ml eye drops. Santen UK Limited. Revised December 2014.