Adverse reactions : תופעות לוואי

4.8     Undesirable effects

Summary of the safety profile

The most commonly reported adverse reactions during treatment with sacubitril/valsartan were
hypotension (17.6%), hyperkalaemia (11.6%) and renal impairment (10.1%) (see section 4.4).
Angioedema was reported in patients treated with sacubitril/valsartan (0.5%) (see description of
selected adverse reactions).


Tabulated list of adverse reactions

Adverse reactions are ranked by System organ class and then by frequency with the most frequent
first, 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). Within each frequency
grouping, adverse reactions are ranked in order of decreasing seriousness.

Table 1        List of adverse reactions

System organ class                        Preferred term               Frequency category
Blood and lymphatic system
Anaemia                      Common
disorders
Immune system disorders                   Hypersensitivity             Uncommon
Metabolism and nutrition                  Hyperkalaemia*               Very common
disorders                                 Hypokalaemia                 Common
Hypoglycaemia                Common
Nervous system disorders                  Dizziness                    Common
Headache                     Common
Syncope                      Common
Dizziness postural           Uncommon
Ear and labyrinth disorders               Vertigo                      Common
Vascular disorders                        Hypotension*                 Very common
Orthostatic hypotension      Common
Respiratory, thoracic and
Cough                        Common
mediastinal disorders
Gastrointestinal disorders             Diarrhoea                       Common
Nausea                          Common
Gastritis                       Common
Skin and subcutaneous tissue           Pruritus                        Uncommon
disorders                              Rash                            Uncommon
Angioedema*                     Uncommon
Renal and urinary disorders            Renal impairment*               Very common
Renal failure (renal failure,
Common
acute renal failure)
General disorders and                  Fatigue                         Common
administration site conditions         Asthenia                        Common
Psychiatric disorders                  Hallucinations**                Rare
Sleep disorders                 Rare
Paranoia                        Very rare
*See description of selected adverse reactions.
**Including auditory and visual hallucinations




ENT API JUL21 V2                                                              EU SmPC 05.2021
Description of selected adverse reactions

Angioedema
Angioedema has been reported in patients treated with sacubitril/valsartan. In PARADIGM-HF,
angioedema was reported in 0.5% of patients treated with sacubitril/valsartan, compared with 0.2% of
patients treated with enalapril. A higher incidence of angioedema was observed in Black patients
treated with sacubitril/valsartan (2.4%) and enalapril (0.5%) (see section 4.4).

Hyperkalaemia and serum potassium
In PARADIGM-HF, hyperkalaemia and serum potassium concentrations >5.4 mmol/l were reported in
11.6% and 19.7% of sacubitril/valsartan -treated patients and 14.0% and 21.1% of enalapril-treated
patients, respectively.

Blood pressure
In PARADIGM-HF, hypotension and clinically relevant low systolic blood pressure (<90 mmHg and
decrease from baseline of >20 mmHg) were reported in 17.6% and 4.76% of sacubitril/valsartan -
treated patients compared with 11.9% and 2.67% of enalapril-treated patients, respectively.

Renal impairment
In PARADIGM-HF, renal impairment was reported in 10.1% of sacubitril/valsartan -treated patients
and 11.5% of enalapril-treated patients.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorization 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/