Ganfort

  • Name:

    Ganfort

  • Company:
    info
  • Active Ingredients:

    Bimatoprost, Timolol Maleate

  • Legal Category:

    Product subject to medical prescription which may not be renewed (A)

Patient Information Leaflet Patient Information Leaflet last updated on medicines.ie: 27/08/19

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XPIL

Summary of Product Characteristics last updated on medicines.ie: 27/8/2019

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Allergan Ltd

Allergan Ltd

Company Products

Medicine NameActive Ingredients
Medicine Name Acular Active Ingredients Ketorolac Trometamol
Medicine Name Alphagan Active Ingredients brimonidine tartrate
Medicine Name Betagan Active Ingredients Levobunolol hydrochloride
Medicine Name Betagan Unit Dose Active Ingredients Levobunolol hydrochloride
Medicine Name BOTOX 100 Units Active Ingredients Botulinum Toxin Type A
Medicine Name BOTOX 200 Units Active Ingredients Botulinum Toxin Type A
Medicine Name BOTOX 50 Units Active Ingredients Botulinum Toxin Type A
Medicine Name Celluvisc 0.5% Active Ingredients Carmellose sodium
Medicine Name Celluvisc 1.0% w/v Eye drops, solution Active Ingredients Carmellose sodium
Medicine Name Combigan Active Ingredients brimonidine tartrate, Timolol Maleate
Medicine Name Exocin Active Ingredients Ofloxacin
Medicine Name FML Active Ingredients Fluorometholone
Medicine Name Ganfort Active Ingredients Bimatoprost, Timolol Maleate
Medicine Name Ganfort SD Active Ingredients Bimatoprost, Timolol Maleate
Medicine Name Lacri-Lube Active Ingredients No Active Ingredients
Medicine Name Liquifilm Tears Active Ingredients Polyvinyl Alcohol
Medicine Name Lumigan 0.1mg/ml Active Ingredients Bimatoprost
Medicine Name Ozurdex Active Ingredients Dexamethasone
Medicine Name Pred Forte Active Ingredients Prednisolone Acetate
Medicine Name Pred Mild Active Ingredients Prednisolone Acetate
Medicine Name Refresh Ophthalmic Active Ingredients Polyvinyl Alcohol, Povidone
Medicine Name Relestat 0.5 mg/ml, eye drops, solution Active Ingredients Epinastine Hydrochloride
Medicine Name Vistabel Active Ingredients Botulinum Toxin Type A
1 - 0 of 23 items.Total: Infinity pages

When a pharmaceutical company changes any document, 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.

Updated on 27 August 2019 PIL

Reasons for updating

  • Change to section 4 - possible side effects
  • Change to section 6 - date of revision

Updated on 27 August 2019 SmPC

Reasons for updating

  • Change to section 4.8 - Undesirable effects
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

In section 4.8 (undesirable effects), hallucination was added (not known frequency).

In section 10 (date of the revision of text), the revised date was updated to 25/07/2019

Updated on 28 March 2019 PIL

Reasons for updating

  • Change to section 6 - marketing authorisation holder
  • Change to section 6 - date of revision

Updated on 31 May 2017 SmPC

Reasons for updating

  • New SmPC for new product

Legal category: Product subject to medical prescription which may not be renewed (A)

Updated on 31 May 2017 PIL

Reasons for updating

  • New PIL for new product

Updated on 31 May 2017 PIL

Reasons for updating

  • Change to section 4 - possible side effects
  • Change to section 6 - date of revision

Updated on 31 May 2017 SmPC

Reasons for updating

  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 4.8 - Undesirable effects
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

In section 2 (Qualitative and Quantitative Composition) - "Excipients" changed to "Excipient with known effect" - update in line with QRD v10.0.

In section 4.4 (Special warnings and precautions for use) - "analogs" changed to analogues - update to correct typing error.

In section 4.6 (Fertility, pregnancy and lactation) - "Lactation" changed to "Breast-feeding" - update in line with QRD v 10.0.

In section 4.8 (Undesirable effects) - combining of Adverse Reaction Terms from both multi-dose and single-dose formulations into a single table, no change in content. Adverse reactions unique for multi-dose and single-dose formulations - indicated by footnotes. In case of overlapping terms between the tables, the higher frequency was adopted for the merged table.

In section 4.8 (Undesirable effects) - combining of Adverse Reaction Terms for Bimatoprost and Timolol monotherapy into a single table. Adverse reactions unique for timolol monotherapy and for bimatoprost monotherapy - indicated by footnotes.

In section 4.8 (Undesirable effects) - addition of asthma exacerbation and chronic obstructive pulmonary disease (COPD) exacerbation.

In section 10 (Date of revision of the text) - the date of revision of the text is 06.04.2017

Updated on 3 October 2016 SmPC

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

In section 4.4 (Special warnings and precautions for use), the heading "hypoglycaemia/diabetes" has been replaced with "Endocrine disorders".

In section 4.8 (Undesirable effects), the following adverse reactions have been added:
- Under the SOC Immune system disorders with a frequency not known: hypersensitivity reactions including signs and symptoms of allergic dermatitis, angioedema, eye allergy
- Under the SOC Psychiatric disorders with a frequency not known: insomnia, nightmare
- Under the SOC Nervous system disorders with a frequency not known: dysguesia
- Under the SOC Eye disorders with a frequency not known: eye swelling, vision blurred
- Under the SOC Cardiac disorders with a frequency not known: bradycardia
- Under the SOC Respiratory, thoracic and mediastinal disorders with a frequency not known: asthma
- Under the SOC General disorders and administration site conditions with a frequency not known: fatigue
- Under the SOC Skin and subcutaneous tissue disorders with a frequency not known: alopecia

In section 10 (Date of revision of the text), the date of revision of the text is now 09/2016

Updated on 30 September 2016 PIL

Reasons for updating

  • Change to warnings or special precautions for use
  • Change to side-effects
  • Change to date of revision

Updated on 25 February 2016 PIL

Reasons for updating

  • Change to date of revision
  • Change to improve clarity and readability

Updated on 14 October 2014 SmPC

Reasons for updating

  • Change to Section 4.8 – Undesirable effects - how to report a side effect

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Update to IMB/HPRA name

Updated on 6 October 2014 PIL

Reasons for updating

  • Change to MA holder contact details

Updated on 15 October 2013 SmPC

Reasons for updating

  • Change to section 4.8 - Undesirable effects
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

sec. 4.8 Undesirable effects

1. Inclusion of warnings regarding the use of Phosphate Buffers, as requested by the EMA "Adverse reactions reported in phosphate containing eye drops

Cases of corneal calcification have been reported very rarely in association with the use of phosphate eye containing eye drops in some patients with significantly damaged corneas".

2. The Greek contact telephone number has been updated


3.  The following adverse events are moved in section 4.8 from the tables relating to adverse events seen with the individual active ingredients, to the tables relating to adverse events seen with Ganfort.  In doing so, we have also determined frequencies:

a.       Eyelid Retraction – Uncommon

b.      Bronchospasm (predominantly in patients with pre-existing bronchospastic disease) – Unknown

c.       Dyspnoea – Uncommon

d.      Dizziness – Common







Updated on 11 October 2013 PIL

Reasons for updating

  • Change to side-effects
  • Change to how the medicine works
  • Change to date of revision
  • Change to improve clarity and readability

Updated on 27 June 2013 SmPC

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Section 4.4.

Additional clarification regarding ocular warnings and precautions for use including further detail on iris pigmentation, macular oedema and uveitis.

Addition of skin associated warnings and precautions for use.

Addition of statement regarding use of more than 1 bimatoprost dose and IOP-lowering effect.

 

Section 4.8.

Updated frequencies for previously listed adverse events and addition of new adverse event associated with bimatoprost use.

Addition of adverse event reporting statement

Updated on 26 June 2013 PIL

Reasons for updating

  • Change to side-effects

Updated on 13 November 2012 SmPC

Reasons for updating

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.8 - Undesirable effects

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Section 4.2 has been updated to include informaiton on evening dosing.
Section 4.8 has been updated to include iris hyperpigmentation, deepening of eyelid sulcus and periocular skin hyperpigmentation.

Updated on 7 November 2012 PIL

Reasons for updating

  • Change to side-effects
  • Change to dosage and administration

Updated on 6 January 2012 SmPC

Reasons for updating

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 4.8 - Undesirable effects
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

The following text has been added/ amended:

4.2     Posology and method of administration

  

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

4.3     Contraindications

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

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

§    Sinus bradycardia, sick sinus syndrome, sino-atrial block, second or third degree atrioventricular block, not controlled with pace-maker. Overt cardiac failure, cardiogenic shock.

Due to the beta-adrenergic component, timolol, the same types of cardiovascular,pulmonary and other adverse reactions as seen with systemic beta-blockers may occur. Incidence of systemic ADRs after topical ophthalmic administration is lower than for systemic administration. To reduce the systemic absorption, see section 4.2.

 

Cardiac disorders

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 its 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:

Respiratory reactions, including death due to bronchospasm in patients with asthma have been reported following administration of some ophthalmic beta-blockers.

 

GANFORT 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.

 

Hypoglycaemia/diabetes

Beta-adrenergic blocking medicinal products should be administered with caution in patients subject to spontaneous hypoglycemia or to patients with labile diabetes as beta‑blockers may mask the signs and symptoms of acute hypoglycemia.

 

Beta-blockers may also mask the signs of hyperthyroidism.

 

Corneal diseases

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

 

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 the patients already receiving a systemic beta‑ blocking agent. The response of these patients should be closely observed. The use of two topical beta‑adrenergic blocking agents is not recommended (see section 4.5).

 

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.

 

Choroidal detachment

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

 

Surgical anaesthesia

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

4.5     Interaction with other medicinal products and other forms of interaction

 

No specific interaction studies have been performed with the bimatoprost / timolol fixed combination.

 

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

 

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.

 

4.6     Fertility, pregnancy and lactation

 

Pregnancy

There are no adequate data from the use of the bimatoprost / timolol fixed combination in pregnant women. GANFORT should not be used during pregnancy unless clearly necessary. To reduce the systemic absorption, see section 4.2.

 

Lactation

Timolol

Beta-blockers are excreted in breast milk. However, at therapeutic doses of timolol in eye drops it is not likely that sufficient amounts would be present in breast milk to produce clinical symptoms of beta-blockade in the infant. To reduce the systemic absorption, see section 4.2.

 

Bimatoprost

It is not known if bimatoprost is excreted in human breast milk but it is excreted in the milk of the lactating rat. GANFORT should not be used by breast-feeding women.

Timolol

 

Like other topically applied ophthalmic drugs, GANFORT (bimatoprost/timolol) is absorbed into the systemic circulation. Absorption of timolol may cause similar undesirable effects as seen with systemic beta-blocking agents.  The incidence of systemic ADRs after topical ophthalmic administration is lower than for systemic administration. To reduce the systemic absorption, see section 4.2.

 

Additional adverse reactions that have been seen with ophthalmic beta‑blockers and may potentially occur also with GANFORT are listed below:

 

System Organ Class

Adverse reaction

Immune system disorders

Systemic allergic reactions including angioedema, urticaria, localized and generalized rash, pruritus, anaphylaxis

Metabolism and nutrition disorders

Hypoglycaemia

Psychiatric disorders

Insomnia, depression, nightmares,  memory loss

Nervous system disorders

Syncope, cerebrovascular accident,dizziness,  increase in signs and symptoms of myasthenia gravis, paresthaesia, cerebral ischaemia

Eye disorders

Decreased corneal sensitivity, diplopia, ptosis, choroidal detachment following filtration surgery (see section 4.4),  keratitis, blurred vision

Cardiac disorder

Atrioventricular block, cardiac arrest, arrhythmia, bradycardia, cardiac failure, congestive heart failure, chest pain, palpitations, oedema

Vascular disorders

Hypotension, Raynaud’s phenomenon, cold hands and feet.

Respiratory, thoracic and mediastinal disorders

Bronchospasm (predominantly in patients with pre-existing bronchospastic disease) dyspnoea, cough.

Gastrointestinal disorders

Dysgeusia, nausea, diarrhoea, dyspepsia, dry mouth, abdominal pain, vomiting

Skin and subcutaneous tissue disorders

Alopecia, psoriasiform rash or exacerbation of psoriasis, skin rash

Musculoskeletal and connective tissue disorders

Myalgia,

Reproductive system and breast disorders

Sexual dysfunction, decreased libido

General disorders and administration site conditions

Asthenia/fatigue



Updated on 22 December 2011 PIL

Reasons for updating

  • Change to warnings or special precautions for use
  • Change to side-effects
  • Change to information about pregnancy or lactation
  • Change to date of revision
  • Change to dosage and administration

Updated on 4 July 2011 SmPC

Reasons for updating

  • Change to section 1 - Name of medicinal product
  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 4.7 - Effects on ability to drive and use machines
  • Change to section 4.8 - Undesirable effects
  • Change to section 4.9 - Overdose
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 5.3 - Preclinical safety data
  • Change to section 9 - Date of renewal of authorisation
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Summary of Changes to GANFORT® Summary of Product Characteristics (SPC)

 

The current GANFORT® Units SPC is dated 23th June 2011

This supersedes SPC dated 23rd July 2010

 

 

Section Number

Subject

Change

1

Name of the medicinal product

Text Removed/Added

 

GANFORT 300 micrograms 0.3mg/ml + 5 mg/ml eye drops, solution

 

2

Qualitative and Quantitative Composition

Text Removed/Added

 

One ml of solution contains 0.3 mg of bimatoprost and 5 mg of timolol (as 6.8 mg of timolol maleate).

 

Contains Excipients

Each ml of solution contains 0.05 mg of benzalkonium chloride 0.05 mg/ml.

 

For a full list of excipients, see section 6.1.

 

4.1

Therapeutic indications

Text Added

 

Reduction of intraocular pressure (IOP) in adult patients with open-angle glaucoma or ocular hypertension who are insufficiently responsive to topical beta-blockers or prostaglandin analogues.

 

4.2

Posology and method administration

Text Added/Removed

 

Posology

Recommended dosage in adults (including the elderly)

 

The recommended dose is one drop of GANFORT in the affected eye(s) once daily, administered in the morning.

 

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

 

If more than one topical ophthalmic product is to be used, the different products should be instilled at least 5 minutes apart.

 

Use in renalRenal and hepatic impairment

GANFORT has not been studied in patients with hepatic or renal impairment. Therefore caution should be used in treating such patients. 

 

UsePaediatric population

The safety and efficacy of GANFORT in children and adolescents aged 0 to 18 years has only not been studied in adults and therefore its use is not recommended in children or adolescents established. No data are available.

Method of administration

If more than one topical ophthalmic medicinal product is to be used, each one should be instilled at least 5 minutes apart

 

4.4

Special warnings and precautions for use

Text Removed/Added

 

Like other topically applied ophthalmic agents,medicinal products, the active substances in GANFORT may be absorbed systemically. No enhancement of the systemic absorption of the individual active substances has been observed.

 

Cardiovascular and respiratory

Due to the beta-adrenergic component, timolol, the same types of cardiovascular and pulmonary adverse reactions as seen with systemic beta-blockers may occur.

 

Cardiac failure should be adequately controlled before beginning GANFORT therapy. Patients with a history of severe cardiac disease should be watched for signs of cardiac failure and have their pulse rates checked. Cardiac and respiratory reactions, including death due to bronchospasm in patients with asthma, and, rarely, death in association with cardiac failures have been reported following administration of timolol maleate.

 

Other beta-blocker related warnings

Beta-blockers may also mask the signs of hyperthyroidism and cause worsening of Prinzmetal angina, severe peripheral and central circulatory disorders and hypotension.

 

Beta-adrenergic blocking agents medicinal products should be administered with caution in patients subject to spontaneous hypoglycemia or to diabetic patients (especially those with labile diabetes) as beta‑blockers may mask the signs and symptoms of acute hypoglycemia.

 

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

 

Hepatic

In patients with a history of mild liver disease or abnormal alanine aminotransferase (ALT), aspartate aminotransferase (AST) and/or bilirubin at baseline, bimatoprost had no adverse reactions on liver function over 24 months. There are no known adverse reactions of ocular timolol on liver function.

 

Ocular

 

Before treatment is initiated, patients should be informed of the possibility of eyelash growth, darkening of the eyelid skin and increased iris pigmentation since these have been observed during treatment with bimatoprost and GANFORT. Some of these changes may be permanent, and may lead to differences in appearance between the eyes if only one eye is treated. After discontinuation of GANFORT, pigmentation of iris may be permanent. After 12 months treatment with GANFORT, the incidence of iris pigmentation was 0.2%. After 12 months treatment with bimatoprost eye drops alone, the incidence was 1.5% and did not increase following 3 years treatment.

 

Cystoid macular oedema has been reported with GANFORT. Therefore, GANFORT should be used with caution in patients with known risk factors for macular oedema (e.g. aphakic patients, pseudophakic patients with a torn posterior lens capsule).

 

Excipients

The preservative in GANFORT, benzalkonium chloride, may cause eye irritation. Contact lenses must be removed prior to application, with at least a 15-minute wait before reinsertion. Benzalkonium chloride is known to discolour soft contact lenses.  Contact with soft contact lenses must be avoided.

 

Benzalkonium chloride has been reported to cause punctate keratopathy and/or toxic ulcerative keratopathy. Therefore monitoring is required with frequent or prolonged use of GANFORT in dry eye patients or where the cornea is compromised.

 

Other conditions

GANFORT has not been studied in patients with inflammatory ocular conditions, neovascular, inflammatory, angle-closure glaucoma, congenital glaucoma or narrow-angle glaucoma.

 

4.5

Interaction with other medicinal products and other forms of interaction

Text Added/Removed

 

No interaction studies have been performed.

 

There is a potential for additive effects resulting in hypotension, and/or marked bradycardia when eye drops containing timolol are administered concomitantly with oral calcium channel blockers, guanethidine, or beta-blocking agentsblockers, anti-arrhythmics, digitalis glycosides or parasympathomimetics.

 

Beta-blockers may increase the hypoglycaemic effect of antidiabetic agents medicinal products. Beta-blockers can mask the signs and symptoms of hypoglycaemia (see section 4.4).

 

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

 

4.6

PregnancyFertility, pregnancy and lactation

Text Added/Removed

 

Pregnancy

There are no adequate data from the use of GANFORT in pregnant women.

 

Bimatoprost

No adequate clinical data in exposed pregnancies are available. Animal studies have shown reproductive toxicity at high maternotoxic doses (see section 5.3).

 

Timolol

Epidemiological studies have not revealed malformative effects but shown a risk for intra uterine 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. If GANFORT is administered until delivery, the neonate should be carefully monitored during the first days of life. Animal studies with timolol have shown reproductive toxicity at doses significantly higher than would be used in clinical practice (see section 5.3). 

 

Consequently, GANFORT should not be used during pregnancy unless clearly necessary.

 

LactationBreast-feeding

Timolol is excreted in breast milk. It is not known if bimatoprost is excreted in human breast milk but it is excreted in the milk of the lactating rat. GANFORT should not be used by breast-feeding women.

 

Fertility

There are no data on the effects of GANFORT on human fertility.

 

4.7

Effects on ability to drive and use machines

Text Added/Removed

 

GANFORT has negligible influence on the ability to drive and use machines. As with any ocular treatment, if transient blurred vision occurs at instillation, the patient should wait until the vision clears before driving or using machinerymachines.

 

4.8

Undesirable effects

Text Added/Removed

 

No Ganfort

Summary of the safety profile

The adverse drug reactions (ADRs) specific for GANFORT have been observed reported in clinical studies.  The ADRs have been using GANFORT were limited to those earlier reported for either of the single active substances bimatoprost and timolol. No new adverse reactions specific for GANFORT have been observed in clinical studies.

 

 

The majority of ADRs adverse reactions reported in clinical studies using GANFORT were ocular, mild in severity and none were serious.  Based on 12-month clinical data, the most commonly reported ADR adverse reaction was conjunctival hyperaemia (mostly trace to mild and thought to be of a non-inflammatory nature) in approximately 26% of patients and led to discontinuation in 1.5% of patients.

 

Tabulated list of adverse reactions

The following ADRs adverse reactions were reported during clinical trials with GANFORT (within each frequency grouping, undesirable effects adverse reactions are presented in order of decreasing seriousness):.

 

Nervous system disorders

Uncommon (≥1/1000 to <1/100): headache

 

Eye disorders

Very common (≥1/10): conjunctival hyperaemia, growth of eyelashes.

Common (≥1/100 to <1/10): superficial punctuate keratitis, corneal erosion, burning sensation, eye pruritus, stinging sensation in the eye, foreign body sensation, eye dryness, eyelid erythema, eye pain, photophobia, eye discharge, visual disturbance, eyelid pruritus.

Uncommon (≥1/1000 to <1/100): iritis, eye irritation, conjunctival oedema, blepharitis, epiphora, eyelid oedema, eyelid pain, visual acuity worsened, asthenopia, trichiasis.

Not known: cystoid macular oedema.

 

Respiratory, thoracic and mediastinal disorders

Uncommon (≥1/1000 to <1/100): rhinitis

 

Skin and subcutaneous tissue disorders

Common (≥1/100 to <1/10): blepharal pigmentation

Uncommon (≥1/1000 to <1/100): hirsutism

 

The frequency of possible adverse reactions listed below is defined using the following convention:

 

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

Frequency cannot be estimated available data

 

System Organ Class

Frequency

Adverse reaction

Nervous system disorders

 

Uncommon

Headache

Eye disorders

 

Very common

conjunctival hyperaemia, growth of eyelashes.

 

 

Common

superficial punctuate keratitis, corneal erosion, burning sensation, eye pruritus, stinging sensation in the eye, foreign body sensation, eye dryness, eyelid erythema, eye pain, photophobia, eye discharge, visual disturbance, eyelid pruritus.

 

Uncommon

iritis, eye irritation, conjunctival oedema, blepharitis, epiphora, eyelid oedema, eyelid pain, visual acuity worsened, asthenopia, trichiasis.

 

Not known

cystoid macular oedema.

Respiratory, thoracic and mediastinal disorders

 

Uncommon

rhinitis

Skin and subcutaneous tissuedisorders

 

Common

blepharal pigmentation

 

Uncommon

hirsutism

 

Additional adverse events reactions that have been seen with one either of the components active substances (bimatoprost or timolol) and may potentially occur also with GANFORT are listed below:

 

Bimatoprost

Infections and infestations: infection (primarily colds and upper respiratory symptoms).

Nervous system disorders: dizziness

Eye disorders: allergic conjunctivitis, cataract, eyelash darkening, increased iris pigmentation, blepharospasm, eyelid retraction, retinal haemorrhage, uveitis.

Vascular disorders: hypertension.

General disorders and administration site condition: asthenia, peripheral oedema.

Investigations: liver function tests (LFT) abnormal.

System Organ Class

Adverse reaction

Nervous system disorders

dizziness

Eye disorders

allergic conjunctivitis, eyelash darkening, increased iris pigmentation, blepharospasm, eyelid retraction, retinal haemorrhage, uveitis

Vascular disorders

hypertension

General disorders and administration site condition

asthenia

Investigations

liver function tests (LFT) abnormal

 

Timolol

Psychiatric disorders: insomnia, nightmares, decreased libido

Nervous system disorders: dizziness, memory loss, increase in signs and symptoms of myasthenia gravis, paresthaesia, cerebral ischaemia

Eye disorders: decreased corneal sensitivity, diplopia, ptosis, choroidal detachment (following filtration surgery), refractive changes (due to withdrawal of miotic therapy in some cases), keratitis.

Ear and labyrinth disorders: tinnitus.

Cardiac disorders: heart block, cardiac arrest, arrhythmia, syncope, bradycardia, cardiac failure, congestive heart failure.

Vascular disorders: hypotension, cerebrovascular accident, claudication, Raynaud’s phenomenon, cold hands and feet, palpitation.

Respiratory, thoracic and mediastinal disorders: bronchospasm (predominantly in patients with pre-existing bronchospastic disease) dyspnoea, cough.

Gastrointestinal disorders: nausea, diarrhoea, dyspepsia, dry mouth.

Skin and subcutaneous tissue disorders: alopecia, psoriasiform rash or exacerbation of psoriasis.

Musculoskeletal and connective tissue disorders: systemic lupus erythematosus.

Renal and urinary disorders: Peyronie’s disease.

General disorders and administration site conditions: oedema, chest pain, fatigue.

System Organ Class

Adverse reaction

Psychiatric disorders

insomnia, nightmares, decreased libido

Nervous system disorders

dizziness, memory loss, increase in signs and symptoms of myasthenia gravis, paresthaesia, cerebral ischaemia

Eye disorders

decreased corneal sensitivity, diplopia, ptosis, choroidal detachment (following filtration surgery), refractive changes (due to withdrawal of miotic therapy in some cases), keratitis

Ear and labyrinth disorders

tinnitus

Cardiac disorder

heart block, cardiac arrest, arrhythmia, syncope, bradycardia, cardiac failure, congestive heart failure

Vascular disorders

hypotension, cerebrovascular accident, claudication, Raynaud’s phenomenon, cold hands and feet, palpitation.

Respiratory, thoracic and mediastinal disorders

bronchospasm (predominantly in patients with pre-existing bronchospastic disease) dyspnoea, cough.

Gastrointestinal disorders

nausea, diarrhoea, dyspepsia, dry mouth

Skin and subcutaneous tissue disorders

psoriasiform rash or exacerbation of psoriasis

Musculoskeletal and connective tissue disorders

systemic lupus erythematosus

Renal and urinary disorders

Peyronie’s disease

General disorders and administration site conditions

oedema, chest pain, fatigue

4.9

Overdose

Text Added/Removed

 

No case of A topical overdose has been reported, and with GANFORT is unlikely not likely to occur after ocular administration or be associated with toxicity.

 

Bimatoprost

If GANFORT is accidentally ingested, the following information may be useful: in two-week oral rat and mouse studies, doses of bimatoprost up to 100 mg/kg/day did not produce any toxicity.  This dose expressed as mg/m2 is at least 70-times higher than the accidental dose of one bottle of GANFORT in a 10 kg child.

 

Timolol

Symptoms of systemic timolol overdose are: bradycardia, hypotension, bronchospasm, headache, dizziness, shortness of breath, and cardiac arrest.  A study of patients showed that timolol did not dialyse readily.

 

If overdose occurs treatment should be symptomatic and supportive.

 

5.1

Pharmacodynamics properties

Text Added/Removed

 

Pharmacotherapeutic group: Ophthalmological – beta-blocking agents – timolol, combinations, ATC code: S01ED 51 S01ED51

 

Mechanism of action:

GANFORT consists of two active substances: bimatoprost and timolol maleate. These two components decrease elevated intraocular pressure (IOP) by complementary mechanisms of action and the combined effect results in additional IOP reduction compared to either compound administered alone. GANFORT has a rapid onset of action.

 

Bimatoprost is a potent ocular hypotensive agent active substance.  It is a synthetic prostamide, structurally related to prostaglandin F2a (PGF2a) that does not act through any known prostaglandin receptors.  Bimatoprost selectively mimics the effects of newly discovered biosynthesised substances called prostamides.  The prostamide receptor, however, has not yet been structurally identified.  The mechanism of action by which bimatoprost reduces intraocular pressure in man is by increasing aqueous humour outflow through the trabecular meshwork and enhancing uveoscleral outflow.

 

Timolol is a beta1 and beta2 non-selective adrenergic receptor blocking agent that does not have significant intrinsic sympathomimetic, direct myocardial depressant, or local anaesthetic (membrane‑stabilising) activity.  Timolol lowers IOP by reducing aqueous humour formation.  The precise mechanism of action is not clearly established, but inhibition of the increased cyclic AMP synthesis caused by endogenous beta-adrenergic stimulation is probable.

 

Clinical effects:

The IOP-lowering effect of GANFORT is non-inferior to that achieved by adjunctive therapy of bimatoprost (once daily) and timolol (twice daily).

 

There are no studies with evening dosing of GANFORT. Morning dosing of GANFORT is therefore recommended to ensure maximal IOP‑lowering effect at the time of the physiological IOP rise. However, if necessary for patient compliance, an evening dosing may be considered. Once‑daily dosing of timolol 0.5% has a rapid onset of maximal effect, corresponding with the time of this rise, and maintains clinically meaningful IOP‑lowering over the 24‑hour period.  Bimatoprost studies show comparable IOP control regardless of morning or evening dosing.

 

Paediatric population

The safety and efficacy of GANFORT in children aged 0 to 18 years has not been established.

5.2

Pharmacokinetic properties

Text Added/Removed

 

GANFORT:medicineal product

Plasma bimatoprost and timolol concentrations were determined in a crossover study comparing the monotherapy treatments to GANFORT treatment in healthy subjects.  Systemic absorption of the individual components was minimal and not affected by co-administration in a single formulation.

 

In two 12-month studies where systemic absorption was measured, no accumulation was observed with either of the individual components.

 

Bimatoprost:

Bimatoprost penetrates the human cornea and sclera well in vitro.  After ocular administration, the systemic exposure of bimatoprost is very low with no accumulation over time.  After once daily ocular administration of one drop of 0.03% bimatoprost to both eyes for two weeks, blood concentrations peaked within 10 minutes after dosing and declined to below the lower limit of detection (0.025 ng/ml) within 1.5 hours after dosing.  Mean Cmax and AUC 0-24hrs values were similar on days 7 and 14 at approximately 0.08 ng/ml and 0.09 ng·hr/ml respectively, indicating that a steady drug concentration was reached during the first week of ocular dosing.

 

Bimatoprost is moderately distributed into body tissues and the systemic volume of distribution in humans at steady-state was 0.67 1/kg.  In human blood, bimatoprost resides mainly in the plasma.  The plasma protein binding of bimatoprost is approximately 88%.

 

Bimatoprost is the major circulating species in the blood once it reaches the systemic circulation following ocular dosing.  Bimatoprost then undergoes oxidation, N-deethylation and glucuronidation to form a diverse variety of metabolites.

 

Bimatoprost is eliminated primarily by renal excretion, up to 67% of an intravenous dose administered to healthy volunteers was excreted in the urine, 25% of the dose was excreted via the faeces.  The elimination half-life, determined after intravenous administration, was approximately 45 minutes; the total blood clearance was 1.5 1/hr/kg.

 

Characteristics in elderly patients:

After twice daily dosing, the mean AUC 0-24hrs value of 0.0634 ng·hr/ml bimatoprost in the elderly (subjects 65 years or older) were significantly higher than 0.0218 ng·hr/ml in young healthy adults.  However, this finding is not clinically relevant as systemic exposure for both elderly and young subjects remained very low from ocular dosing.  There was no accumulation of bimatoprost in the blood over time and the safety profile was similar in elderly and young patients.

 

Timolol:

After ocular administration of a 0.5% eye drops solution in humans undergoing cataract surgery, peak timolol concentration was 898 ng/ml in the aqueous humour at one hour post-dose.  Part of the dose is absorbed systemically where it is extensively metabolised in the liver. The half-life of timolol in plasma is about 4 to 6 hours.  Timolol is partially metabolised by the liver with timolol and its metabolites excreted by the kidney.  Timolol is not extensively bound to plasma.

5.3

Preclinial Safety Data

Text Added

 

GANFORT:medicinal product

Repeated dose ocular toxicity studies on GANFORT showed no special hazard for humans. The ocular and systemic safety profile of the individual components is well established.

 

Bimatoprost

Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, genotoxicity, carcinogenic potential. Studies in rodents produced species-specific abortion at systemic exposure levels 33- to 97-times that achieved in humans after ocular administration.

 

Monkeys administered ocular bimatoprost concentrations of ³0.03% daily for 1 year had an increase in iris pigmentation and reversible dose-related periocular effects characterised by a prominent upper and/or lower sulcus and widening of the palpebral fissure. The increased iris pigmentation appears to be caused by increased stimulation of melanin production in melanocytes and not by an increase in melanocyte number. No functional or microscopic changes related to the periocular effects have been observed, and the mechanism of action for the periocular changes is unknown.

 

Timolol

Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, toxicity to reproduction.

 

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Text Added

 

Date of first authorisation 19 May 2006

Date of latest renewal 19 May 2011

 

10

DATE OF REVISION OF THE TEXT

Text Added/Removed

 

07/2010 06/2011

 

 

Key:

Unchanged text appears as follows: eg Paediatric population

Added text appears as follows: eg medicinal product

Deleted (Removed) text appears as follows: eg Not applicable

 

Updated on 1 July 2011 PIL

Reasons for updating

  • Change to, or new use for medicine
  • Change of contraindications
  • Change to storage instructions
  • Change to side-effects
  • Change to information about pregnancy or lactation
  • Change to information about driving or using machinery
  • Change to how the medicine works
  • Change to further information section
  • Change to date of revision
  • Change to MA holder contact details
  • Change due to harmonisation of PIL

Updated on 20 January 2010 PIL

Reasons for updating

  • Change to MA holder contact details

Updated on 18 March 2009 SmPC

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Summary of Changes to Ganfort Ireland Summary of Product Characteristics (SPC)

 

The current Ganfort SPC is dated March 2009

This supersedes SPC dated May 2006

 

 

Section Number

Subject

Change

4.4

 

Special warnings and precautions for use

Text amended to reflect the fact that CMO has been reported.

 

Cystoid macular oedema has not been reported with GANFORT, however, it has been uncommonly reported (>0.1% to <1%) following treatment with bimatoprost.  Therefore, GANFORT should be used with caution in patients with known risk factors for macular oedema (e.g. aphakic patients, pseudophakic patients with a torn posterior lens capsule).

 

4.8

 

Undesirable effects

 

Lower end of ADR groupings changed from > to

 

Adverse effect added to Ganfort section.

Not known: cystoid macular oedema.

 

Cystoid macular oedema removed from bimatoprost section of additional adverse events that have been seen with one of the components and may potentially occur also with GANFORT.

 

5.1

 

 

Pharmacodynamic properties

Amended from SO1ED 51 to read S01ED 51 (typo)

 

10

Date of revision of the text

Amended from 19 May 2006 to 02 March 2009.

Updated on 17 March 2009 PIL

Reasons for updating

  • Change to warnings or special precautions for use
  • Change to side-effects
  • Change of distributor details

Updated on 4 September 2008 PIL

Reasons for updating

  • Change to marketing authorisation holder address

Updated on 31 August 2007 PIL

Reasons for updating

  • Addition of marketing authorisation holder

Updated on 27 July 2006 SmPC

Reasons for updating

  • New SPC for new product

Legal category: Product subject to medical prescription which may not be renewed (A)

Updated on 21 July 2006 PIL

Reasons for updating

  • New PIL for new product