Adverse reactions : תופעות לוואי

4.8   Undesirable effects

GANFORT
Summary of the safety profile
The adverse reactions reported in clinical studies 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 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 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
Table 1 presents the adverse reactions that have been reported during clinical studies with all GANFORT formulations (multi-dose and single dose) (within each frequency grouping, adverse reactions are presented in order of decreasing seriousness) or in the post-marketing period.

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 from available data 

Table 1
System Organ Class              Frequency              Adverse reaction Immune system disorders         Not known              hypersensitivity reactions including signs or symptoms of allergic dermatitis, angioedema,
eye allergy
Psychiatric disorders           Not known              Insomnia2, nightmare2 Nervous system disorders        Common                 headache
Not known              Dysgeusia2, dizziness
Eye disorders                   Very common            conjunctival hyperaemia.
Common                 punctuate keratitis, corneal erosion2,
burning sensation2, conjunctival irritation1, eye pruritus, stinging sensation in the eye2, foreign body sensation, dry eye, erythema of eyelid,
eye pain, photophobia, eye discharge,
visual disturbance2, eyelid pruritus,
visual acuity worsened2, blepharitis2,
eyelid oedema, eye irritation, lacrimation increased, growth of eyelashes.


Uncommon               iritis2, conjunctival oedema2, eyelid pain2, abnormal sensation in the eye 1,
asthenopia, trichiasis2, iris hyperpigmentation2,
periorbital and lid changes associated with periorbital fat atrophy and skin tightness resulting in deepening of eyelid sulcus, eyelid ptosis,
enophthalmos, lagophthalmos and eyelid retraction 1&2, eyelash discolouration (darkening) 1.

Not known              cystoid macular oedema2, eye swelling,
vision blurred 2, ocular discomfort
Cardiac disorders               Not known              Bradycardia
Vascular disorders              Not known              Hypertension
Respiratory, thoracic and       Common                 Rhinitis2 mediastinal disorders
Uncommon               dyspnoea
Not known              bronchospasm (predominantly in patients with pre-existing bronchospastic disease) 2, asthma.

Skin and subcutaneous tissue    Common                 blepharal pigmentation2, hirsutism2, disorders                                              skin hyperpigmentation (periocular).

Not known              Alopecia, skin discolouration
(periocular)

General disorders and           Not known              fatigue administration site conditions
1 adverse reactions only observed with Ganfort single-dose formulation (not registered in Israel)
2 adverse reactions only observed with Ganfort multi-dose formulation


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 either of the active substances (bimatoprost or timolol), and may potentially occur also with GANFORT are listed below in Table 2:

Table 2
System Organ Class                               Adverse reaction
Immune system disorders                          systemic allergic reactions including anaphylaxis1

Metabolism and nutrition disorders               hypoglycaemia1
Psychiatric disorders                            depression1, memory loss1, hallucination1 
Nervous system disorders                         syncope1, cerebrovascular accident1, increase in signs and symptoms of myasthenia gravis1,
paraesthesia1 , cerebral ischaemia1
Eye disorders                                    decreased corneal sensitivity1, diplopia1, ptosis1, choroidal detachment following filtration surgery (see section 4.4) 1,
keratitis1, blepharospasm2, retinal haemorrhage2, uveitis2

Cardiac disorder                                 atrioventricular block1, cardiac arrest1, arrhythmia1, cardiac failure1, congestive heart failure1, chest pain1, palpitations1,
oedema1
Vascular disorders                               hypotension1, Raynaud’s phenomenon1, cold hands and feet1
Respiratory, thoracic and mediastinal             Asthma exacerbation2, COPD exacerbation2, disorders                                        cough1.
Gastrointestinal disorders                       nausea1,2, diarrhoea1, dyspepsia1, dry mouth1, abdominal pain1, vomiting1
Skin and subcutaneous tissue disorders           psoriasiform rash1 or exacerbation of psoriasis1, skin rash1
Musculoskeletal and connective tissue            myalgia1 disorders
Reproductive system and breast disorders         sexual dysfunction1, decreased libido1 General disorders and administration site        asthenia1,2 conditions
Investigations                                   liver function tests (LFT) abnormal2 

1 adverse reactions observed with Timolol
2 adverse reactions observed with Bimatoprost
Adverse reactions reported in phosphate containing eye drops

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

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form:

https://sideeffects.health.gov.il