From the Guidelines
Inclisiran is generally well-tolerated, with the most common side effects being mild injection site reactions, including pain, redness, and swelling, occurring in approximately 5% of patients, as reported in a pooled patient-level analysis of 3,660 patients in phase 3 trials 1. The side effects of inclisiran are typically mild and transient, with the majority of patients experiencing no significant adverse effects.
Common Side Effects
- Injection site reactions (pain, redness, swelling) in about 5% of patients
- Joint pain
- Urinary tract infections
- Diarrhea
- Bronchitis
- Mild allergic reactions
Serious Side Effects
- Severe allergic reactions (rare) The mechanism of action of inclisiran, which uses RNA interference to reduce PCSK9 protein production in the liver, resulting in increased LDL receptor availability and lower LDL cholesterol levels, may contribute to its favorable side effect profile, as noted in a recent study published in 2024 1. It is essential for patients to report any persistent or concerning symptoms to their healthcare provider, although most side effects are transient and resolve without intervention.
Administration and Tolerability
Inclisiran is administered as a subcutaneous injection twice yearly after initial dosing, which may contribute to its generally good tolerability compared to daily oral medications. Recent data from the ORION 3 study and other trials have confirmed the excellent safety profile of inclisiran, with treatment-emergent adverse events occurring at a comparable rate between inclisiran and placebo groups 1.
From the FDA Drug Label
ADVERSE REACTIONS Common adverse reactions in clinical trials (≥ 3%): injection site reaction, arthralgia, and bronchitis (6) The side effects of Inclisiran (PCSK9 inhibitor) include:
- Injection site reaction
- Arthralgia
- Bronchitis 2
From the Research
Side Effects of Inclisiran
The side effects of Inclisiran, a PCSK9 inhibitor, have been studied in several clinical trials. The most commonly reported side effect is:
- Injection site reaction 3
Safety and Tolerability
Inclisiran has been shown to be generally safe and well tolerated in patients with hypercholesterolemia. Studies have reported that:
- Inclisiran was generally safe and well tolerated in patients with mild or moderate hepatic impairment 4
- All adverse events were mild or moderate in severity, and no discontinuations due to adverse events were reported 5
- Inclisiran was well tolerated and safe, without severe adverse events 6
- Inclisiran has a highly favourable side effect profile similar to placebo 7
Pharmacokinetics and Pharmacodynamics
The pharmacokinetics and pharmacodynamics of Inclisiran have been studied in several clinical trials. The results show that:
- Inclisiran has a relative short elimination half-life (T1/2,6.5 hours) 5
- Inclisiran exposure was 1.24-fold higher in the mild hepatic impairment group and 2.03-fold higher in the moderate hepatic impairment group compared to the normal hepatic function group 4
- LDL-C and PCSK9 plasma levels decreased from baseline up to the last assessment on Day 60 in all groups 4