When a pharmaceutical company changes an SPC or PIL, a new version is published on medicines.ie. For each version, we show the dates it was published on medicines.ie and the reasons for change.
Summary of Changes to Exocin® IE Summary of Product Characteristics (SPC)
The current FML®TM Liquifilm® SPC is dated 7th June 2011
This supersedes SPC dated 26th August 2009
Section Number
Subject
Change
4.4
Special Warnings and Precautions for Use
Text Added:
EXOCIN is not for injection. Serious and occasionally fatal hypersensitivity (anaphylactic/anaphylactoid) reactions, some following the first dose, have been reported in patients receiving systemic quinolones, including ofloxacin. Some reactions were accompanied by cardiovascular collapse, loss of consciousness, angioedema (including laryngeal, pharyngeal or facial edema), airway obstruction, dyspnea, urticaria, and itching. If an allergic reaction to ofloxacin occurs, discontinue the drug. Use EXOCIN with caution in patients who have exhibited sensitivities to other quinolones antibacterial agents. When using EXOCIN eye drops the risk of rhinopharyngeal passage which can contribute to the occurrence and the diffusion of bacterial resistance should be considered. As with other anti-infectives, prolonged use may result in overgrowth of non-susceptible organisms. If infection worsens, or if clinical improvement is not noted within a reasonable period, discontinue use and institute alternative therapy. Stevens-Johnson syndrome has been reported in patients receiving topical ophthalmic ofloxacin, however, a causal relationship has not been established. Data are very limited to establish efficacy and safety of ofloxacin eye drops 0.3% in the treatment of conjunctivitis in neonates. The use of ofloxacin eye drops in neonates with ophthalmia neonatorum caused by Neisseria gonorrhoeae or Chlamydia trachomatis is not recommended as it has not been evaluated in such patients. Neonates with ophthalmia neonatorum should receive appropriate treatment for their condition, e.g. systemic treatment in cases caused by Chlamydia trachomatis or Neisseria gonorrhoeae. Use in the elderly: No comparative data are available with topical dosing in elderly versus other groups. The following precautions are relevant for the systemic absorption of oxoquinolone antibacterial agents. However, the plasma levels of ofloxacin following absorption from topically applied EXOCIN eye drops are minimal. Persons with latent or actual defects in glucose-6-phosphate dehydrogenase activity may be prone to haemolytic reactions with systemically absorbed oxoquinolone antibacterial agents. Patients with pre-existent significant renal or hepatic disorders should be carefully monitored to detect any deterioration in function. Dosage reduction may be required. EXOCIN should be administered with caution to persons with existent central nervous system disorders, epilepsy, hepatic or renal insufficiency, or severe dehydration. Photosensitivity reactions may be induced. Evidence of CNS irritability has been reported particularly in the elderly, leading occasionally to psychosis. Clinical and non-clinical publications have reported the occurrence of corneal perforation in patients with pre-existing corneal epithelial defect or corneal ulcer, when treated with topical fluoroquinolone antibiotics. However, significant confounding factors were involved in many of these reports, including advanced age, presence of large ulcers, concomitant ocular conditions (e.g. severe dry eye), systemic inflammatory diseases (e.g. rheumatoid arthritis), and concomitant use of ocular steroids or non-steroidal anti-inflammatory drugs. Nevertheless, it is necessary to advise caution regarding the risk of corneal perforation when using product to treat patients with corneal epithelial defects or corneal ulcers. Corneal precipitates have been reported during treatment with topical ophthalmic ofloxacin. However, a causal relationship has not been established. Long-term, high-dose use of other fluoroquinolones in experimental animals has caused lenticular opacities. However, this effect has not been reported in human patients, nor has it been noted following topical ophthalmic treatment with ofloxacin for up to six months in animal studies including studies in monkeys. Caution should be taken when using fluoroquinolones, including EXOCIN, in patients with known risk factors for prolongation of the QT interval such as, for example: - Congenital long QT syndrome - Concomitant use of drugs that are known to prolong the QT interval (e.g. Class IA and III anti-arrhythmics, tricyclic antidepressants, macrolides, antipsychotics) - Uncorrected electrolyte imbalance (e.g. hypokalaemia, hypomagnesaemia) - Elderly - Cardiac disease (e.g. heart failure, myocardial infarction, bradycardia) (see section 4.2 elderly, section 4.5, section 4.8, section 4.9) EXOCIN contains the preservative benzalkonium chloride which may cause ocular irritation and discolour soft contact lenses. Use of contact lenses is not recommended in patients receiving treatment for an eye infection.
EXOCIN is not for injection.
Serious and occasionally fatal hypersensitivity (anaphylactic/anaphylactoid) reactions, some following the first dose, have been reported in patients receiving systemic quinolones, including ofloxacin. Some reactions were accompanied by cardiovascular collapse, loss of consciousness, angioedema (including laryngeal, pharyngeal or facial edema), airway obstruction, dyspnea, urticaria, and itching.
If an allergic reaction to ofloxacin occurs, discontinue the drug. Use EXOCIN with caution in patients who have exhibited sensitivities to other quinolones antibacterial agents.
When using EXOCIN eye drops the risk of rhinopharyngeal passage which can contribute to the occurrence and the diffusion of bacterial resistance should be considered. As with other anti-infectives, prolonged use may result in overgrowth of non-susceptible organisms. If infection worsens, or if clinical improvement is not noted within a reasonable period, discontinue use and institute alternative therapy.
Stevens-Johnson syndrome has been reported in patients receiving topical ophthalmic ofloxacin, however, a causal relationship has not been established.
Data are very limited to establish efficacy and safety of ofloxacin eye drops 0.3% in the treatment of conjunctivitis in neonates.
The use of ofloxacin eye drops in neonates with ophthalmia neonatorum caused by Neisseria gonorrhoeae or Chlamydia trachomatis is not recommended as it has not been evaluated in such patients. Neonates with ophthalmia neonatorum should receive appropriate treatment for their condition, e.g. systemic treatment in cases caused by Chlamydia trachomatis or Neisseria gonorrhoeae.
Use in the elderly: No comparative data are available with topical dosing in elderly versus other groups.
The following precautions are relevant for the systemic absorption of oxoquinolone antibacterial agents. However, the plasma levels of ofloxacin following absorption from topically applied EXOCIN eye drops are minimal.
Persons with latent or actual defects in glucose-6-phosphate dehydrogenase activity may be prone to haemolytic reactions with systemically absorbed oxoquinolone antibacterial agents.
Patients with pre-existent significant renal or hepatic disorders should be carefully monitored to detect any deterioration in function. Dosage reduction may be required.
EXOCIN should be administered with caution to persons with existent central nervous system disorders, epilepsy, hepatic or renal insufficiency, or severe dehydration. Photosensitivity reactions may be induced. Evidence of CNS irritability has been reported particularly in the elderly, leading occasionally to psychosis.
Clinical and non-clinical publications have reported the occurrence of corneal perforation in patients with pre-existing corneal epithelial defect or corneal ulcer, when treated with topical fluoroquinolone antibiotics. However, significant confounding factors were involved in many of these reports, including advanced age, presence of large ulcers, concomitant ocular conditions (e.g. severe dry eye), systemic inflammatory diseases (e.g. rheumatoid arthritis), and concomitant use of ocular steroids or non-steroidal anti-inflammatory drugs. Nevertheless, it is necessary to advise caution regarding the risk of corneal perforation when using product to treat patients with corneal epithelial defects or corneal ulcers.
Corneal precipitates have been reported during treatment with topical ophthalmic ofloxacin. However, a causal relationship has not been established.
Long-term, high-dose use of other fluoroquinolones in experimental animals has caused lenticular opacities. However, this effect has not been reported in human patients, nor has it been noted following topical ophthalmic treatment with ofloxacin for up to six months in animal studies including studies in monkeys.
Caution should be taken when using fluoroquinolones, including EXOCIN, in patients with known risk factors for prolongation of the QT interval such as, for example:
- Congenital long QT syndrome
- Concomitant use of drugs that are known to prolong the QT interval (e.g. Class IA and III anti-arrhythmics, tricyclic antidepressants, macrolides, antipsychotics)
- Uncorrected electrolyte imbalance (e.g. hypokalaemia, hypomagnesaemia)
- Elderly
- Cardiac disease (e.g. heart failure, myocardial infarction, bradycardia)
(see section 4.2 elderly, section 4.5, section 4.8, section 4.9)
EXOCIN contains the preservative benzalkonium chloride which may cause ocular irritation and discolour soft contact lenses.
Use of contact lenses is not recommended in patients receiving treatment for an eye infection.
4.5
Interaction with other medicinal products and other forms of interactions
Text Added
It has been shown that the systemic administration of some quinolones inhibits the metabolic clearance of caffeine and theophylline. Drug interaction studies conducted with systemic ofloxacin have demonstrated that metabolic clearance of caffeine and theophylline are not significantly affected by ofloxacin.
Although there have been reports of an increased prevalence of CNS toxicity with systemic dosing of fluoroquinolones when used concomitantly with systemic nonsteroidal anti-inflammatory drugs (NSAIDs), this has not been reported with the concomitant systemic use of NSAIDs and ofloxacin.
Mineral antacids used simultaneously may effect systemic absorption. Concomitant use of systemic quinolones with some phenylproprionic acid derived non-steroidal anti-inflammatory drugs may lead to toxicity possibly because of renal effects.
A study of concurrent administration with a coumarin anticoagulant showed no interaction.
EXOCIN, like other fluoroquinolones, should be used with caution in patients receiving drugs known to prolong the QT interval (e.g. Class IA and III anti-arrhythmics, tricyclic antidepressants, macrolides, antipsychotics) (see section 4.4)
4.8
Undesirable effects
General Serious reactions after use of systemic ofloxacin are rare and most symptoms are reversible. Since a small amount of ofloxacin is systemically absorbed after topical administration, adverse events reported with systemic use could possibly occur. Frequency categories: Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to ≤1/100); rare (≥1/10,000 to ≤1/1,000); very rare (≤1/10,000), not known (cannot be estimated from the available data). Immune System Disorders: Not known: Hypersensitivity (including Eye allergy) Nervous System Disorders: Not known: Dizziness Headache Hypoaesthesia Eye Disorders: Common: Eye irritation Ocular discomfort Not known: Keratitis, Conjunctivitis, Vision blurred, Photophobia, Eyelid oedema, Foreign body sensation in eyes, Lacrimation increased, Dry eye, Eye pain, Eye/Eyelids pruritus, Ocular hyperaemia Cardiac disorders: Not known: ventricular arrhythmia and torsades de pointes (reported predominantly in patients with risk factors for QT prolongation), ECG QT prolonged (see section 4.4 and 4.9) Gastrointestinal Disorders Not known: Nausea Skin and Subcutaneous Tissue Disorders Not known: Periorbital oedema General Disorders and Administrative Site Conditions Not known: Facial oedema
General
Serious reactions after use of systemic ofloxacin are rare and most symptoms are reversible. Since a small amount of ofloxacin is systemically absorbed after topical administration, adverse events reported with systemic use could possibly occur.
Frequency categories: Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to ≤1/100); rare (≥1/10,000 to ≤1/1,000); very rare (≤1/10,000), not known (cannot be estimated from the available data).
Immune System Disorders:
Not known: Hypersensitivity (including Eye allergy)
Nervous System Disorders:
Not known: Dizziness
Headache
Hypoaesthesia
Eye Disorders:
Common: Eye irritation
Ocular discomfort
Not known: Keratitis,
Conjunctivitis,
Vision blurred,
Photophobia,
Eyelid oedema,
Foreign body sensation in eyes,
Lacrimation increased,
Dry eye,
Eye pain,
Eye/Eyelids pruritus,
Ocular hyperaemia
Cardiac disorders:
Not known: ventricular arrhythmia and torsades de pointes (reported predominantly in patients with risk factors for QT prolongation), ECG QT prolonged (see section 4.4 and 4.9)
Gastrointestinal Disorders
Not known: Nausea
Skin and Subcutaneous Tissue Disorders
Not known: Periorbital oedema
General Disorders and Administrative Site Conditions
Not known: Facial oedema
4.9
Overdose
No case of overdose has been reported. In the event of a topical overdose, flush the eye with water. In the event of an overdose, symptomatic treatment should be implemented. ECG monitoring should be undertaken, because of the possibility of QT interval prolongation.
No case of overdose has been reported.
In the event of a topical overdose, flush the eye with water.
In the event of an overdose, symptomatic treatment should be implemented. ECG monitoring should be undertaken, because of the possibility of QT interval prolongation.
10
DATE OF REVISION OF TEXT
Text Removed/Added
26th August 2009 07 June 2011
Key:
Unchanged text appears as follows: eg Benzalkonium Chloride Added text appears as follows: eg EXOCIN
Deleted (Removed) text appears as follows: eg Not applicable
The following text was added:
If an allergic reaction to ofloxacin occurs, discontinue the drug. Use EXOCIN with caution in patients who have exhibited sensitivities to other quinolones antibacterial agents
Text has been amended as follows:
Exocin The multidose eye drop presentation contains the preservative benzalkonium chloride which may cause eye ocular irritation and discolour soft contact lenses.
Exocin contains the preservative benzalkonium chloride, which may be absorbed by soft contact lenses and discolour them. Contact lenses should be removed prior to instillation and may be reinserted 15 minutes following administration.
4.7
Effects on the ability to Drive and Use Machines
No studies on the effects on the ability to drive and use machines have been performed.
Undesirable Effects
a) The most frequently reported ADR is eye irritation which was reported with an incidence of 1.6% in clinical trials.
General Serious reactions after use of systemic ofloxacin are rare and most symptoms are reversible. Since a small amount of ofloxacin is systemically absorbed after topical administration, adverse events reported with systemic use could possibly occur. Frequency categories: Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to ≤1/100); rare (≥1/10,000 to ≤1/1,000); very rare (≤1/10,000), not known (cannot be estimated from the available data). b) Immune System Disorders: Rare Not known:Hypersensitivity (including Eye allergy) Nervous System Disorders: UncommonNot known:Dizziness Rare Headache Hypoaesthesia Eye Disorders: Common: Eye irritation (includes ocular burning) Ocular discomfort Uncommon: Eye pain (includes eye stinging) Rare Not known Ocular / Conjunctival hyperaemia Keratitis, Conjunctivitis, Vision blurred, Photophobia, Eyelid oedema, Foreign body sensation in eyes, Lacrimation increased, Dry eye, Eye pain (includes eye stinging) Eye/Eyelids pruritus, Ocular hyperaemia Gastrointestinal Disorders Rare Not known Nausea Skin and Subcutaneous Tissue Disorders Not known: Periorbital oedema General Disorders and Administrative Site Conditions Not known: Facial oedema c) Not applicable d) Since ofloxacin is systemically absorbed after topical administration, side effects reported with systemic use could possibly occur. These include vasculitis, gastrointestinal disturbances, abnormal liver function tests.
b) Immune System Disorders:
Rare Not known:Hypersensitivity (including Eye allergy)
UncommonNot known:Dizziness
Rare Headache
Common: Eye irritation (includes ocular burning)
Ocular discomfort Uncommon: Eye pain (includes eye stinging) Rare Not known Ocular / Conjunctival hyperaemia Keratitis, Conjunctivitis, Vision blurred, Photophobia, Eyelid oedema, Foreign body sensation in eyes, Lacrimation increased, Dry eye, Eye pain (includes eye stinging) Eye/Eyelids pruritus, Ocular hyperaemia Gastrointestinal Disorders Rare Not known Nausea Skin and Subcutaneous Tissue Disorders Not known: Periorbital oedema General Disorders and Administrative Site Conditions Not known: Facial oedema c) Not applicable d) Since ofloxacin is systemically absorbed after topical administration, side effects reported with systemic use could possibly occur. These include vasculitis, gastrointestinal disturbances, abnormal liver function tests.
Uncommon: Eye pain (includes eye stinging)
Rare Not known Ocular / Conjunctival hyperaemia
Keratitis,
Eye pain (includes eye stinging)
Rare Not known Nausea
c) Not applicable
d) Since ofloxacin is systemically absorbed after topical administration, side effects reported with systemic use could possibly occur. These include vasculitis, gastrointestinal disturbances, abnormal liver function tests.
5.1
Pharmacodynamic properties
Pharmacotherapeutic group: Ophthalmologicals, anti-infectives, quinolones
ATC code: S 01 AX 11
6.6
Special precautions for disposal of a used medicinal product or waste materials derived from such medicinal product and other handling of the product
No special requirements.
Any unused product or waste material should be disposed of in accordance with local requirements.
Due to the nature of Benzalkonium chloride, EXOCIN should not be used by soft (hydrophilic) contact lens wearers. Contact lenses should not be worn during instillation of the drug. After instillation there should be an interval of at least 15 minutes before reinsertion
Due to the nature of Benzalkonium chloride, EXOCIN should not be used by soft (hydrophilic) contact lens wearers.
Contact lenses should not be worn during instillation of the drug. After instillation there should be an interval of at least 15 minutes before reinsertion
Date of revision of text
26th August 2009 replaces 28th October 2006
4.2
Posology and Method of Administration
Text Added: Adults only
4.3
Contraindications
Text Added: Exocin is not recommended for use in children or adolescents before epiphyseal closure
Summary of Changes to Exocin Irish Summary of Product Characteristics (SPC)
The current Exocin SPC is dated 28th October 2008
This supersedes SPC dated 19th December 2006
Posology and method of administration
Text deleted:
Adults only
EXOCIN is not recommended for use in children or adolescents before epiphyseal closures.
Special warnings and precautions for use
Text added:
When using Exocin eye drops the risk of rhinopharyngeal passage which can contribute to the occurrence and the diffusion of bacterial resistance should be considered
Toxicological studies have shown the administration of oxoquinolone antibacterial agents at doses higher than the therapeutic range can produce erosions of the cartilage in weight bearing joints in the immature animals of some species. No such lesions have been shown to occur in man to date. This product should not be prescribed for children. Safety and efficacy in the treatment of ophthalma neonatorum has not been established.
EXOCIN contains benzalkonium chloride and should not be used while patients are wearing hydrophilic (soft) contact lenses.
The multidose eye drop presentation contains the preservative benzalkonium chloride, which may cause eye irritation.
28th October 2008
Replaces:
19th December 2006
1
Name of the medicinal Product
added - w/v Eye Drops Solution
2
QUALITATIVE AND QUANTITATIVE COMPOSITION
Added text in red
Ofloxacin 0.3% w/v (3 mg/ml)
Benzalkonium chloride (preservative) 0.005% w/v (0.05 mg/ml)
For full list of excipients, see section 6.1
3
PHARMACEUTICAL FORM
Clear, pale to light yellow-green solution, practically free from visible particles.
Removed “Special” before precautions in heading
ADDED
Clinical and non-clinical publications have reported
the occurrence of corneal perforation in patients with
pre-existing corneal epithelial defect or corneal ulcer,
when treated with topical fluoroquinolone antibiotics.
However, significant confounding factors were
involved in many of these reports, including advanced
age, presence of large ulcers, concomitant ocular
conditions (e.g. severe dry eye), systemic inflammatory
diseases (e.g. rheumatoid arthritis), and concomitant
use of ocular steroids or non-steroidal anti-inflammatory
drugs. Nevertheless, it is necessary to advise caution
regarding the risk of corneal perforation when using
product to treat patients with corneal epithelial defects
or corneal ulcers.
Interaction with other
medicinal products and
other forms of interactions
Replaced “medicaments” with “medicinal products”
Effects on ability to drive and Use Machines
Transient blurring of vision may occur on instillation of
eye drops. Do not drive or operate hazardous machinery
unless vision is clear.
COMPLETELY REWRITTEN
a)The most frequently reported ADR is eye irritation
which was reported with an incidence of 1.6% in clinical
trials.
b)Immune System Disorders:
Rare: Hypersensitivity (including Eye allergy)
Uncommon: Dizziness
Rare: Headache, Hypoaesthesia
Rare: Ocular / Conjunctival hyperaemia
Photophobia
Eye / Eyelid pruritus
Eyelid oedema
Rare: Nausea
c)Not applicable
d)Since ofloxacin is systemically absorbed after topical administration, side effects reported with systemic
use could possibly occur. These include vasculitis,
gastrointestinal disturbances, abnormal liver
function tests.
6.1
List of excipients
Sodium hydroxide (for pH adjustment)
Hydrochloric acid (for pH adjustment)
Special precautions for
disposal of a used
medicinal product or
waste materials derived
from such medicinal
product and other
handling of the product
Changed from Instructions for Use/Handling