Uperio Adverse Reactions

Summary of the safety profile: The most commonly reported adverse reactions during treatment with UPERIO were hypotension, hyperkalaemia and renal impairment (see Precautions). Angioedema was reported in patients treated with UPERIO (see description of selected adverse reactions as follows).
The safety of UPERIO in patients with chronic heart failure was evaluated in the pivotal phase 3 study PARADIGM-HF, which compared patients treated twice daily with UPERIO 200 mg (n=4203) or enalapril 10 mg (n= 4229). Patients randomized to UPERIO 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 UPERIO 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 UPERIO in heart failure patients was comparable to enalapril. The pattern of the ADRs is consistent with the pharmacology of UPERIO 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 2.)


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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 UPERIO 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 3.)


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Description of selected adverse reactions: Angioedema: Angioedema has been reported in patients treated with UPERIO. In PARADIGM-HF, angioedema was reported in 0.5% of patients treated with UPERIO, compared with 0.2% of patients treated with enalapril. A higher incidence of angioedema was observed in Black patients treated with UPERIO (2.4%) and enalapril (0.5%).
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 Uperio-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 Uperio-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 UPERIO-treated patients and 11.5% of enalapril-treated patients.
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.