Entresto Adverse Reactions

Heart failure: 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 Precautions). Angioedema was reported in patients treated with sacubitril/valsartan (0.5%) (see Description of selected adverse reactions as follows).
A total of 6,622 heart failure patients were treated with Entresto in the PARADIGM-HF (vs. enalapril) and PARAGON-HF (vs. valsartan) clinical trials. Of these, 5,085 were exposed for at least 1 year.
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. (See Table 3.)

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Hypertension: Summary of the safety profile: The safety of Entresto in patients with essential hypertension was evaluated in clinical trials involving more than 7,000 hypertensive patients (over 3.500 treated with Entresto).
In a pooled group of short-term, double-blind, controlled studies, 3,272 patients were exposed to Entresto with median duration of 8 weeks, dizziness occurred at a higher frequency in patients treated with Entresto than in patients treated with olmesartan (see Table 4).
Adverse drug 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), including isolated reports. Within each frequency grouping, adverse reactions are ranked in order of decreasing seriousness. (See Table 4.)

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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 Precautions).
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.
In PARAGON-HF, no new adverse reactions were identified.
Laboratory Abnormalities: Hemoglobin and Hematocrit: Decreases in hemoglobin/hematocrit of >20% were observed in approximately 5% of both Entresto- and enalapril-treated patients in the double-blind period in PARADIGM-HF. Decreases in hemoglobin/hematocrit of >20% were observed in approximately 7% of Entresto-treated patients and 9% of valsartan-treated patients in the double-blind period in PARAGON-HF.
Serum Creatinine: During the double-blind period in PARADIGM-HF, approximately 16% of both Entresto- and enalapril-treated patients had increases in serum creatinine of >50%. During the double-blind period in PARAGON-HF, approximately 17% of Entresto-treated patients and 21% of valsartan-treated patients had increases in serum creatinine of >50%.
Serum Potassium: During the double-blind period of PARADIGM-HF, approximately 16% of both Entresto- and enalapril-treated patients had potassium concentrations >5.5 mEq/L. During the double-blind period of PARAGON-HF, approximately 18% of Entresto-treated patients and 20% of valsartan-treated patients had potassium concentrations >5.5 mEq/L.