Adverse reactions : תופעות לוואי

 4.8 Undesirable effects

Summary of the safety profile
In clinical studies, 438 patients have been treated with Levodesa. No serious adverse reactions occurred.
The most commonly reported non-serious adverse reactions are eye irritation, ocular hypertension and headache.

Tabulated list of adverse reactions
The following adverse reactions have been reported with Levodesa during clinical trials that enrolled patients after cataract surgery (within each frequency grouping, adverse reactions are presented in order of decreasing frequency).

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 the available data 
Levodesa (levofloxacin/dexamethasone combination)

System Organ Class                    Frequency Adverse reactions
Nervous system disorders              Uncommon Headache, dysgeusia
Eye disorders                         Uncommon Eye irritation, abnormal sensation in eye, ocular hypertension
Skin and subcutaneous tissue          Uncommon Pruritus disorders
Investigations                        Uncommon Intraocular pressure increased (*) (*) > 6 mmHg that means significant intraocular pressure increase


Adverse reactions that have been seen with either of the ophthalmic active substances (levofloxacin or dexamethasone), and may potentially occur also with Levodesa are listed below: 
Levofloxacin

System Organ Class                        Frequency     Adverse reactions Immune system disorders                   Rare          Extra-ocular allergic reactions, including skin rash.
Very rare     Anaphylaxis.
Nervous system disorders                  Uncommon      Headache.


Eye disorders                             Common        Ocular burning, decreased vision and mucous strand.


Uncommon Lid matting, chemosis, conjunctival papillary reaction, lid oedema, ocular discomfort, ocular itching, ocular pain, conjunctival hyperaemia,
conjunctival follicles, ocular dryness,

lid erythema, and photophobia.



Respiratory, thoracic and mediastinal       Uncommon Rhinitis.
disorders                                   Very rare Laryngeal oedema.

Dexamethasone

System Organ Class                   Frequency      Adverse reactions Eye disorders                        Very           Increase of the intraocular pressure.* common
Common         Discomfort*, irritation*, burning*, stinging*, itching* and blurredvision.*
Uncommon       Allergic and hypersensitivity reactions, delayed wound healing, posterior capsular cataract*, opportunistic infections, glaucoma.*
Very rare      Conjunctivitis, mydriasis, ptosis, corticosteroid-induced uveitis, corneal calcifications, crystalline keratopathy,
changes in cornealthickness*, corneal oedema, corneal ulceration and corneal perforation.
Skin and subcutaneous tissue         Very rare      Face oedema.
disorders
Endocrine disorders                  Not known      Cushing’s syndrome, adrenal suppression.

* see section Description of selected adverse reactions

Description of selected adverse reactions
Increase of intraocular pressure
Increase of the intra-ocular pressure (IOP) and glaucoma may occur. Prolonged use of corticosteroid treatment may result in ocular hypertension/glaucoma (especially for patients with previous IOP induced by steroids or with pre-existing high IOP or glaucoma). Children and elderly patients may be particularly susceptible to steroid-induced IOP rise (see section 4.4). Diabetics are also more prone to develop subcapsular cataracts following prolonged topical steroid administration.

Post procedural adverse reactions
Ocular disorders (e.g. corneal oedema, eye irritation, abnormal sensation in the eye, lacrimation increased, asthenopia, corneal disorder, dry eye, eye pain, ocular discomfort, uveitis, blurred vision, visual brightness, conjunctivitis) and nausea have been reported during clinical trials. These reactions are usually mild and transient and are assessed to be related to the cataract surgery itself.

Possible adverse reactions related to cornea
In diseases causing thinning of the cornea, topical use of steroids could lead to cornea perforation in some cases (see section 4.4).

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.

Additional adverse reactions that have been observed with prolonged use of the active substance levofloxacin and may potentiallyoccur also with Levodesa

Ruptures of the shoulder, hand, Achilles, or other tendons that required surgical repair or resulted in prolonged disability have been reported in patients receiving systemic fluoroquinolones. Studies and post marketing experience with systemic quinolones indicate that a risk of these ruptures may be increased in patients receiving corticosteroids, especially geriatric patients and in tendons under high stress, including Achilles tendon (see section 4.4).

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.