Drugs List

Administration

For administration into the conjunctival sac only.

Contraindications

Third trimester of pregnancy - see 'Pregnancy' section.

Precautions and Warnings

Children under 18 years: Not licensed for use in children.
Paediatric experience is limited to a few published clinical studies in strabismus surgery.

The anti-inflammatory activity of ophthalmic NSAIDs may mask the onset and/or progression of ocular infections. In the presence of infection, or if there is a risk of infection, appropriate antibiotic therapy should be given concurrently.

In patients with risk factors for corneal disorders such as during the use of corticosteroids or with concomitant diseases such as infections or rheumatoid arthritis, diclofenac has been associated, in rare cases, with ulcerative keratitis, corneal thinning, punctuate keratitis, corneal epithelium defect and corneal oedema, which might become sight-threatening. In most cases the patients were treated for a long period of time.

Although there have been no reported adverse events, there is a theoretical possibility that patients receiving other medications which may prolong bleeding time, or with known haemostatic defects may experience exacerbation with diclofenac eye drops.

Pregnancy - first and second trimesters - see ' Pregnancy' section.

Some formulations contain benzalkonium chloride.

Soft contact lenses should be removed before instillation of the eye drops and re-inserted after 15 minutes.

Eye drops may cause transient blurred vision after instillation and patients should avoid driving or operating machinery until vision is clear.

Following instillation of the eye drops, nasolacrimal occlusion or closing the eyes for 3 minutes may reduce the systemic absorption, however this may also increase in local adverse reactions.

Pregnancy and Lactation

Pregnancy

The manufacturer of diclofenac sodium eye drops states during the 1st and 2nd trimesters animal studies have shown no risk to the foetus and that no controlled studies in pregnant women are available. The use of diclofenac sodium eye drops is contraindicated during the 3rd trimester of pregnancy due to the possible risk of premature closure of the ductus arteriosus and inhibition of contractions.

NSAIDs are often discontinued in women failing to conceive although their role in inhibition of ovulation and in miscarriage is still being debated (Schaefer 2007). Studies have shown an increase in spontaneous abortion with the use of NSAIDs in early pregnancy (Briggs 2011). Discontinue if patient is attempting to become pregnant.

Diclofenac levels in foetal tissues have been similar to those in maternal blood during the 1st trimester. Until recently 1st trimester exposure to NSAIDs was not associated with an increased risk of birth defects. There has since been conflicting evidence from registry based studies regarding the risk of cardiac septal defects, risks were not confirmed in later studies and when re-evaluating the original data (Schaefer 2007). Animal studies have shown reproductive toxicity.

Diclofenac is a prostaglandin synthetase inhibitor and may have the following effects during the 2nd and 3rd trimesters:
- Pulmonary and cardiac toxicity in the foetus (pulmonary hypertension with preterm closing of the ductus arteriosus). The risk exists from the beginning of the 6th month and increases if administration is close to full term.
- Functional renal injury in the foetus. From the 12th week: oligohydramnios (usually reversible after the end of treatment) or anamnios (particularly with prolonged exposure). Following birth, renal failure may persist (especially with late and prolonged exposure).
- Inhibition of uterine contractions with delayed onset and prolongation of labour.
- Increased possibility of bleeding in mother and child.
- Increased risk of oedema formation for the mother.

Several adverse effects have been reported when very pre-term and very low birth weight infants have been exposed to NSAIDs including necrotising enterocolitis and intraventricular haemorrhages (Schaefer 2007)

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 14-17 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 ).

Crosses placenta? - Yes

Effects on foetus - Premature closure of ductus arteriosis, pulmonary hypertension, renal injury.

Pregnancy-specific adverse effects on the mother - Delayed onset and prolongation of labour.

Lactation

The manufacturer of diclofenac sodium eye drops indicates that diclofenac is excreted in breast milk, but no adverse effects on the infant are anticipated at therapeutic doses and and that they can be used during breast feeding.

Secretion in maternal milk following oral administration is minimal (Schaefer 2007) and probably too low to affect the infant (Hale 2010). Diclofenac has a short half-life of 1.1 hours (Briggs 2011) and a number of active metabolites although the clinical significance of these is not known (Schaefer 2007).

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

Burning sensation (local)
Blurred vision (transient)
Hypersensitivity reactions
Corneal epithelial discontinuity
Punctate keratitis
Corneal thinning
Dyspnoea
Exacerbation of pre-existing asthma
Ocular irritation
Ocular pruritus
Ocular hyperaemia
Corneal disorders
Corneal ulcer
Corneal oedema
Conjunctival hyperaemia
Allergic conjunctivitis
Eyelid erythema
Eyelid oedema
Eyelid pruritus
Urticaria
Rash
Eczema
Erythema
Pruritus
Cough
Rhinitis
Eye pain

Presentation

Multidose eye drop solution containing 0.1% diclofenac sodium.
Preservative-free single dose unit eye drop solution containing 0.1% diclofenac sodium.

Drugs List

Dosage

Wash hands prior to use.

Soft contact lenses should be removed before instillation of diclofenac eye drops and may be re-inserted after 15 minutes.

Avoid contact of the container with eye or other surfaces as contamination leading to ophthalmic infection may occur.

To avoid systemic absorption compress the lacrimal sac during administration and for one minute afterwards.

Leave an interval of at least 5 minutes before instilling another ophthalmic medication.

Multi-dose eye drops:
Discard 4 weeks after first opening.

Single use:
Containers are for single use only, to be used immediately after opening and discarded immediately after use.

Adults

Elderly

Children

Administration

For administration into the conjunctival sac only.

Contraindications

Third trimester of pregnancy - see 'Pregnancy' section.

Precautions and Warnings

Children under 18 years: Not licensed for use in children.
Paediatric experience is limited to a few published clinical studies in strabismus surgery.

The anti-inflammatory activity of ophthalmic NSAIDs may mask the onset and/or progression of ocular infections. In the presence of infection, or if there is a risk of infection, appropriate antibiotic therapy should be given concurrently.

In patients with risk factors for corneal disorders such as during the use of corticosteroids or with concomitant diseases such as infections or rheumatoid arthritis, diclofenac has been associated, in rare cases, with ulcerative keratitis, corneal thinning, punctuate keratitis, corneal epithelium defect and corneal oedema, which might become sight-threatening. In most cases the patients were treated for a long period of time.

Although there have been no reported adverse events, there is a theoretical possibility that patients receiving other medications which may prolong bleeding time, or with known haemostatic defects may experience exacerbation with diclofenac eye drops.

Pregnancy - first and second trimesters - see ' Pregnancy' section.

Some formulations contain benzalkonium chloride.

Soft contact lenses should be removed before instillation of the eye drops and re-inserted after 15 minutes.

Eye drops may cause transient blurred vision after instillation and patients should avoid driving or operating machinery until vision is clear.

Following instillation of the eye drops, nasolacrimal occlusion or closing the eyes for 3 minutes may reduce the systemic absorption, however this may also increase in local adverse reactions.

Pregnancy and Lactation

Pregnancy

The manufacturer of diclofenac sodium eye drops states during the 1st and 2nd trimesters animal studies have shown no risk to the foetus and that no controlled studies in pregnant women are available. The use of diclofenac sodium eye drops is contraindicated during the 3rd trimester of pregnancy due to the possible risk of premature closure of the ductus arteriosus and inhibition of contractions.

NSAIDs are often discontinued in women failing to conceive although their role in inhibition of ovulation and in miscarriage is still being debated (Schaefer 2007). Studies have shown an increase in spontaneous abortion with the use of NSAIDs in early pregnancy (Briggs 2011). Discontinue if patient is attempting to become pregnant.

Diclofenac levels in foetal tissues have been similar to those in maternal blood during the 1st trimester. Until recently 1st trimester exposure to NSAIDs was not associated with an increased risk of birth defects. There has since been conflicting evidence from registry based studies regarding the risk of cardiac septal defects, risks were not confirmed in later studies and when re-evaluating the original data (Schaefer 2007). Animal studies have shown reproductive toxicity.

Diclofenac is a prostaglandin synthetase inhibitor and may have the following effects during the 2nd and 3rd trimesters:
- Pulmonary and cardiac toxicity in the foetus (pulmonary hypertension with preterm closing of the ductus arteriosus). The risk exists from the beginning of the 6th month and increases if administration is close to full term.
- Functional renal injury in the foetus. From the 12th week: oligohydramnios (usually reversible after the end of treatment) or anamnios (particularly with prolonged exposure). Following birth, renal failure may persist (especially with late and prolonged exposure).
- Inhibition of uterine contractions with delayed onset and prolongation of labour.
- Increased possibility of bleeding in mother and child.
- Increased risk of oedema formation for the mother.

Several adverse effects have been reported when very pre-term and very low birth weight infants have been exposed to NSAIDs including necrotising enterocolitis and intraventricular haemorrhages (Schaefer 2007)

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 14-17 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 ).

Crosses placenta? - Yes

Effects on foetus - Premature closure of ductus arteriosis, pulmonary hypertension, renal injury.

Pregnancy-specific adverse effects on the mother - Delayed onset and prolongation of labour.

Lactation

The manufacturer of diclofenac sodium eye drops indicates that diclofenac is excreted in breast milk, but no adverse effects on the infant are anticipated at therapeutic doses and and that they can be used during breast feeding.

Secretion in maternal milk following oral administration is minimal (Schaefer 2007) and probably too low to affect the infant (Hale 2010). Diclofenac has a short half-life of 1.1 hours (Briggs 2011) and a number of active metabolites although the clinical significance of these is not known (Schaefer 2007).

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

Counselling

Advise patient to wash their hands prior to use.

Advise patient to avoid contact of the container with eye or other surfaces as contamination leading to ophthalmic infection may occur.

Advise patient to compress the lacrimal sac during administration and for one minute afterwards, to reduce systemic absorption.

Advise patient to leave an interval of at least 5 minutes before instilling another ophthalmic medication.

Advise patient to remove soft contact lenses before instillation of diclofenac eye drops and re-insert them after 15 minutes.

Multi-dose eye drops:
Advise patient to discard 4 weeks after first opening.

Single use:
Advise patient containers are for single use only, to be discarded immediately after use.

Advise patient that eye drops may cause transient blurred vision after instillation and to avoid driving or operating machinery until vision is clear.

Side Effects

Burning sensation (local)
Blurred vision (transient)
Hypersensitivity reactions
Corneal epithelial discontinuity
Punctate keratitis
Corneal thinning
Dyspnoea
Exacerbation of pre-existing asthma
Ocular irritation
Ocular pruritus
Ocular hyperaemia
Corneal disorders
Corneal ulcer
Corneal oedema
Conjunctival hyperaemia
Allergic conjunctivitis
Eyelid erythema
Eyelid oedema
Eyelid pruritus
Urticaria
Rash
Eczema
Erythema
Pruritus
Cough
Rhinitis
Eye pain

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 ).

Shelf Life and Storage

Multi-dose eye drops:
No special precautions for storage
Discard 28 days after first opening.

Single use:
Do not store above 25 degrees C
Stable for 28 days after opening the blister
Single use only. Use immediately after first opening

Reference Sources

British National Formulary, 63rd Edition (2012) Pharmaceutical Press, London.

BNF for Children (2011-2012) Pharmaceutical Press, London.

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.

Medications and Mothers' Milk, 14th Edition (2010) Hale, T. Hale Publishing, Amarillo, Texas.

Summary of Product Characteristics: Voltarol Ophtha. Laboratoires Thea. Revised January 2012.

Summary of Product Characteristics: Voltarol Ophtha Multidose 0.1%. Laoratoires Thea. Revised January 2012.

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Diclofenac. March 1, 2012
Last accessed: July 25, 2012