Adverse reactions : תופעות לוואי

4.8   Undesirable effects

Summary of the safety profile
The most commonly reported adverse reactions were hypokalaemia (4.1%) and oedema related events (5.7%).

In 2 clinical trials with open label exposure of Lokelma up to 1 year in 874 subjects, the following events were reported as related by investigators: gastrointestinal events [constipation (2.9%), nausea (1.6%), diarrhoea (0.9%), abdominal pain/distension (0.5%) and vomiting (0.5%)]; and hypersensitivity reactions [rash (0.3%) and pruritus (0.1%)]. These events were mild to moderate in nature, none were reported as serious and were generally resolved while the patient continued treatment. Due to the open label study design, a causal relationship between these events and Lokelma cannot be established.

In clinical studies conducted in countries with a predominantly Asian population, constipation with an estimated frequency of 8.9% occurred in non-dialysis patients receiving Lokelma; and was resolved with dose adjustment or treatment discontinuation.

Tabulated list of adverse reactions
The safety profile of Lokelma was evaluated in clinical trials involving 1,760 patients with 507 patients exposed for one year.

The adverse reactions identified from controlled trials and post-marketing reports are shown in Table 1.
Adverse reactions listed below are classified according to frequency and system organ class (SOC).
The following convention was used for frequency of adverse reactions: 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).

Table 1. List of adverse reactions in clinical trials and post-marketing reports System Organ class                                     Common
Metabolism and nutrition disorders                     Hypokalaemia
Gastrointestinal disorders                             Constipation
General disorders and administration site              Oedema related events conditions


Description of selected adverse reactions
Hypokalaemia
In clinical trials, 4.1% of Lokelma patients developed hypokalaemia with a serum potassium value less than 3.5 mmol/L, which was resolved with dose adjustment or discontinuation of Lokelma.

Oedema related events
Oedema related events, including, fluid retention, generalised oedema, hypervolaemia, localised oedema, oedema, oedema peripheral and peripheral swelling, were reported by 5.7% of Lokelma patients. The events were observed in the maintenance phase only and were more commonly seen in patients treated with 15 g. Up to 53% were managed by initiating a diuretic or adjusting a diuretic dose; the remainder did not require treatment.

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: https://sideeffects.health.gov.il