Adverse reactions : תופעות לוואי

4.8 Undesirable effects

Summary of safety profile
The safety profile of ramipril includes persistent dry cough and reactions due to hypotension. Serious adverse reactions include angioedema, hyperkalaemia, renal or hepatic impairment, pancreatitis, severe skin reactions and neutropenia/agranulocytosis.

Tabulated list of adverse reactions

Adverse reactions frequency 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 (cannot be estimated from the available data).
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.


Common         Uncommon        Rare                    Very rare     Not known 

Blood and lymphatic                  Eosinophilia    White blood cell                      Bone marrow failure, system disorders                                     count decreased                       pancytopenia, (including                            haemolytic anaemia neutropenia or agranulocytosis), red blood cell count decreased,
hemoglobin decreased, platelet count decreased

Immune system                                                                              Anaphylactic or disorders                                                                                  anaphylactoid reactions, antinuclear antibody increased



Endocrine disorders                                                                  Syndrome of inappropriate antidiuretic hormone secretion (SIADH)



Metabolism and        Blood potassium       Anorexia,                                Blood sodium nutrition disorders   increased             decreased                                decreased appetite,



Psychiatric                                 Depressed mood, Confusional state        Disturbance in disorders                                   anxiety,                                 attention nervousness,
restlessness, sleep disorder including somnolence


Nervous system        Headache,             Vertigo,            Tremor, balance      Cerebral ischaemia disorders             dizziness             paraesthesia,       disorder             including ischaemic ageusia,                                 stroke and transient dysgeusia,                               ischaemic attack,
psychomotor skills impaired, burning sensation, parosmia

Eye disorders                               Visual            Conjunctivitis disturbance including blurred vision
Ear and labyrinth                                               Hearing impaired, disorders                                                       tinnitus 

Cardiac disorders                           Myocardial ischaemia including angina pectoris or myocardial infarction,
tachycardia,
arrhythmia,
palpitations,
oedema peripheral
Vascular disorders    Hypotension,        Flushing              Vascular stenosis,   Raynaud's orthostatic blood                         hypoperfusion,       phenomenon pressure decreased,                       vasculitis syncope


Respiratory,          Non-productive        Bronchospasm thoracic and          tickling cough,       including asthma mediastinal           bronchitis,           aggravated, nasal disorders             sinusitis, dyspnoea   congestion



Gastrointestinal       Gastrointestinal     Pancreatitis         Glossitis                                 Aphtous stomatitis disorders              inflammation,        (cases of fatal digestive            outcome have disturbances,        been very abdominal            exceptionally discomfort,          reported with dyspepsia,           ACE inhibitors),
diarrhoea, nausea,   pancreatic vomiting             enzymes increased, small bowel angioedema,
abdominal pain upper including gastritis,
constipation, dry mouth

Hepatobiliary                               Hepatic enzymes Jaundice cholestatic,                          Acute hepatic failure, disorders                                   and/or bilirubin hepatocellular                                cholestatic or conjugated       damage                                        cytolytic hepatitis increased,                                                     (fatal outcome has been very exceptional).



Skin and               Rash in particular   Angioedema;        Exfoliative              Photosensitivity   Toxic epidermal subcutaneous tissue    maculo-papular       very               dermatitis, urticaria,   reaction           necrolysis, Stevens- disorders                                   exceptionally, the onycholysis,                                Johnson syndrome, airway                                                         erythema multiforme, obstruction                                                    pemphigus, psoriasis resulting from                                                 aggravated, angioedema may                                                 dermatitis have a fatal                                                   psoriasiform, outcome;                                                       pemphigoid or pruritus,                                                      lichenoid exanthema hyperhidrosis                                                  or enanthema, alopecia
Musculoskeletal and Muscle spasms,          Arthralgia connective tissue   myalgia disorders


Renal and urinary                           Renal impairment disorders                                   including renal failure acute,
urine output increased,
worsening of a pre-existing proteinuria, blood urea increased,
blood creatinine increased


Reproductive system                         Transient erectile                                             Gynecomastia and breast disorders                        impotence, libido


decreased


General disorders    Chest pain, fatigue Pyrexia      Asthenia and administration site conditions



Paediatric population

The safety of ramipril was monitored in 325 children and adolescents, aged 2-16 years old, during 2 clinical trials. Whilst the nature and severity of the adverse events are similar to that of the adults, the frequency of the following is higher in the children:

Tachycardia, nasal congestion and rhinitis, “common” (i.e. ≥ 1/100 to < 1/10) in paediatric, and “uncommon” (i.e. ≥ 1/1,000 to < 1/100) in adult population.


Conjunctivitis “common” (i.e. ≥ 1/100 to < 1/10) in paediatric and “rare” (i.e. ≥ 1/10,000 to < 1/1,000) in adult population.

Tremor and urticaria “uncommon” (i.e. ≥ 1/1,000 to < 1/100) in paediatric population and “rare” (i.e. ≥ 1/10,000 to < 1/1,000) in adult population.

The overall safety profile for ramipril in paediatric patients does not differ significantly from the safety profile in adults.


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 http://sideeffects.health.gov.il