Entresto Adverse Reactions

Heart Failure: Summary of the safety profile: 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.
PARADIGM-HF: The safety of Entresto in patients with chronic heart failure with LVEF ≤40% (reduced ejection fraction) was evaluated in the pivotal phase 3 study PARADIGM-HF, which compared patients treated twice daily with Entresto 200 mg (n=4203) or enalapril 10 mg (n=4229). Patients randomized to Entresto received treatment for up to 4.3 years, with a median duration of exposure of 24 months; 3271 patients were treated for more than one year.
Discontinuation of therapy due to an AE in the double-blind period of the PARADIGM-HF trial occurred in 450 (10.71%) of Entresto treated patients and 516 (12.20%) of patients receiving enalapril. The events most commonly associated with dosage adjustment or treatment interruption were hypotension, hyperkalemia and renal impairment.
The overall incidence of adverse drug reactions (ADRs) of Entresto in heart failure patients was comparable to enalapril. The pattern of the ADRs is consistent with the pharmacology of Entresto and the patients underlying conditions.
The overall frequency of adverse reactions was not related to gender, age, or race.
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 3.)

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PARAGON-HF: The safety of Entresto in patients with chronic heart failure and LVEF ≥45% (preserved ejection fraction) was evaluated in the pivotal phase 3 study PARAGON-HF, which compared patients treated twice daily with Entresto 200 mg (n=2,419) or valsartan 160 mg (n=2,402). The safety profile of Entresto was consistent with the safety profile in patients with heart failure with reduced ejection fraction.
Essential 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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Adverse drug reactions from spontaneous reports and literature cases (frequency not known): The following adverse drug reactions have been derived from post-marketing experience with Entresto via spontaneous case reports and literature cases. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency, which is therefore categorized as not known. Adverse drug reactions are listed according to system organ classes in MedDRA. (See Table 5.)

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