Adverse reactions : תופעות לוואי

4.8 Undesirable effects

In clinical studies for COSOPT the observed adverse reactions have been consistent with those that were reported previously with dorzolamide hydrochloride and/or timolol maleate.

During clinical studies, 1035 patients were treated with COSOPT. Approximately 2.4% of all patients discontinued therapy with this medicinal product because of local ocular adverse reactions, approximately 1.2% of all patients discontinued because of local adverse reactions suggestive of allergy or hypersensitivity (such as lid inflammation and conjunctivitis).

Like other topically applied ophthalmic medicines, timolol is absorbed into the systemic circulation. This may cause similar undesirable effects as seen with systemic beta-blocking agents. Incidence of systemic ADRs after topical ophthalmic administration is lower than for systemic administration.

The following adverse reactions have been reported with COSOPT or one of its components either during clinical trials or during post-marketing experience:

[Very Common: (≥1/10), Common: (≥1/100 to <1/10), Uncommon: (≥1/1,000 to <1/100), and Rare: (≥1/10,000 to <1/1,000), Not known (cannot be estimated from the available data)] System Organ      Formulation           Very          Common           Uncommon               Rare      Not Known** Class                           Common
(MedDRA)
Immune system    COSOPT                                                                 signs and disorders                                                                               symptoms of systemic allergic reactions,
including angioedema,
urticaria,
pruritus, rash,
anaphylaxis
Timolol                                                            signs and         pruritus maleate eye                                                        symptoms of drops, solution                                                    allergic reactions including angioedema,
urticaria,
localized and generalized rash,
anaphylaxis
Metabolism and   Timolol                                                                              hypoglycaemia nutrition        maleate eye disorders        drops, solution
Psychiatric      Timolol                                           depression*      insomnia*,        hallucination disorders        maleate eye                                                        nightmares*, drops, solution                                                    memory loss Nervous system   Dorzolamide                     headache*                          dizziness*, disorders        hydrochloride                                                      paraesthesia* eye drops,
solution
Timolol                         headache*         dizziness*,      paraesthesia*, maleate eye                                       syncope*         increase in drops, solution                                                    signs and symptoms of myasthenia gravis,
decreased libido*,
cerebrovascular accident*,
cerebral ischaemia
Eye disorders    COSOPT            burning and   conjunctival stinging      injection,
blurred vision,
corneal erosion,
ocular itching,
tearing
Dorzolamide                     eyelid            iridocyclitis*   irritation        Foreign body hydrochloride                   inflammation                       including         sensation in eye eye drops,                      *, eyelid                          redness*, solution                        irritation*                        pain*, eyelid crusting*,
transient myopia (which resolved upon
discontinuation of therapy),
corneal oedema*,
ocular hypotony*,
choroidal detachment
(following filtration surgery)*
Timolol           signs and       visual          ptosis,                itching, tearing, maleate eye       symptoms of     disturbances    diplopia,              redness, blurred drops, solution   ocular          including       choroidal              vision, corneal irritation      refractive      detachment             erosion including       changes (due    following blepharitis*,   to withdrawal   filtration keratitis*,     of miotic       surgery* (see decreased       therapy in      Special corneal         some cases)*    warning and sensitivity,                    precautions for and dry eyes*                   use 4.4)
Ear and         Timolol                                           tinnitus* labyrinth       maleate eye disorders       drops, solution
Cardiac         Timolol                           bradycardia*    chest pain*,           atrioventricular disorders       maleate eye                                       palpitation*,          block, cardiac drops, solution                                   oedema*,               failure arrhythmia*,
congestive heart failure*,
cardiac arrest*,
heart block
Dorzolamine                                                              Palpitations hydrochloride eye drops,
solution
Vascular        Timolol                                           hypotension*, disorders       maleate eye                                       claudication, drops, solution                                   Raynaud’s phenomenon*,
cold hands and feet*
Respiratory,    COSOPT            sinusitis                       shortness of thoracic, and                                                     breath, mediastinal                                                       respiratory failure, disorders                                                         rhinitis, rarely bronchospasm
Dorzolamide                                       epistaxis*             dyspnoea hydrochloride eye drops,
solution
Timolol                           dyspnoea*       bronchospasm
maleate eye                                                          (predominantly drops, solution                                                      in patients with pre-existing bronchospastic disease)*,
respiratory failure, cough*
Gastrointestinal    COSOPT            dysgeusia disorders
Dorzolamide                       nausea*                            throat hydrochloride                                                        irritation, dry eye drops,                                                           mouth* solution
Timolol                                             nausea*,         diarrhoea,         dysgeusia, maleate eye                                         dyspepsia*       dry mouth*         abdominal pain, drops, solution                                                                         vomiting Skin and            COSOPT                                                               contact subcutaneous                                                                             dermatitis, tissue disorders                                                                         Stevens- Johnson syndrome,
toxic epidermal necrolysis
Dorzolamide                                                          rash* hydrochloride eye drops,
solution
Timolol                                                              alopecia*,         skin rash maleate eye                                                          psoriasiform drops, solution                                                      rash or exacerbation of psoriasis*
Musculoskeletal     Timolol                                                              systemic lupus     myalgia and connective      maleate eye                                                          erythematosus tissue disorders    drops, solution
Renal and           COSOPT                                              urolithiasis urinary disorders

Reproductive        Timolol                                                              Peyronie’s         sexual system and          maleate eye                                                          disease*,          dysfunction breast disorders    drops, solution                                                      decreased libido
General             Dorzolamide                       asthenia/ disorders and       Hydrochloride                     fatigue* administration      eye drops,
site conditions     solution
Timolol                                             asthenia/ maleate eye                                         fatigue* drops, solution

*These adverse reactions were also observed with COSOPT during post-marketing experience.
**Additional adverse reactions have been seen with ophthalmic beta-blockers and may potentially occur with COSOPT.

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