OXLUMO Solution for injection Ref.[10953] Active ingredients: Lumasiran

Severe or end-stage renal impairment

Treatment with lumasiran increases plasma glycolate levels, which may increase the risk of metabolic acidosis or worsening of pre-existing metabolic acidosis in patients with severe or end-stage renal disease. These patients should therefore be monitored for signs and symptoms of metabolic acidosis.

Moderate or severe hepatic impairment

In patients with moderate or severe hepatic impairment there is a potential for decreased efficacy. Therefore, efficacy should be monitored in these patients (see section 5.2).

Excipient (sodium content)

This medicinal product contains less than 1 mmol sodium (23 mg) per mL, that is to say essentially ‘sodium-free’.

No clinical drug interaction studies have been performed (see section 5.2).

Concomitant use with pyridoxine

Concomitant use of pyridoxine did not meaningfully influence the pharmacodynamics or pharmacokinetics of lumasiran.

Pregnancy

There are no data from the use of lumasiran in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3). The use of this medicinal product could be considered during pregnancy taking into account the expected health benefit for the woman and potential risks to the foetus.

Breast-feeding

It is unknown whether lumasiran is excreted in human milk. A risk to the newborns/infants cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Oxlumo therapy, taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Fertility

There are no data on the effects of lumasiran on human fertility. No impact on male or female fertility was detected in animal studies (see section 5.3).

Oxlumo has no or negligible influence on the ability to drive and use machines.

Summary of the safety profile

The most common adverse reaction reported was injection site reaction (32%).

Tabulated list of adverse reactions

Adverse reactions associated with lumasiran obtained from clinical studies are tabulated below. The adverse reactions are coded to preferred terms (PTs) under the MedDRA system organ class (SOC) and are presented by frequency. The frequency of the adverse reactions is expressed according to the following categories: 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).

Table 2. Adverse reactions:

^a Includes abdominal pain, abdominal pain upper, abdominal pain lower, abdominal discomfort, and abdominal tenderness.
^b Includes injection site reaction, injection site erythema, injection site pain, injection site pruritus, injection site swelling, injection site discomfort, injection site discolouration, injection site mass, injection site induration, injection site rash, injection site bruising, injection site haematoma and injection site exfoliation.

Description of selected adverse reactions

Injection site reactions

In placebo-controlled and open-label clinical studies, injection site reactions were reported in 26 of 81 patients (32.1%), occurring in 10% of injections. The most commonly reported symptoms were erythema, pain, pruritus, and swelling. The majority of injection site reactions started on the day of administration, with 7 of the patients having injection site reactions that started 5 or more days after administration (occurred in 1.6% of injections). Injection site reactions were generally mild, resolved within two days, and did not result in interruption or discontinuation of treatment.

Abdominal pain

In the placebo-controlled study, abdominal pain was reported in 1 of 13 (7.7%) placebo-treated patients and 4 of 26 (15.4%) lumasiran-treated patients. In the placebo-controlled and open-label clinical studies, 17 of 81 patients (21.0%) reported abdominal pain, including upper or lower abdominal pain, abdominal discomfort, or abdominal tenderness. Most of the events have been mild, transient and resolved without treatment. None have resulted in discontinuation of treatment.

Immunogenicity

In patients with PH1 and healthy volunteers dosed with Oxlumo, 6 of 100 (6.0%) individuals tested positive for anti-drug-antibodies (ADA). ADA titres were low and generally transient, with no impact on the efficacy, safety, pharmacokinetic, or pharmacodynamic profiles of the medicinal product.

Paediatric population

The safety profile of lumasiran was similar in paediatric (aged 4 months to 17 years) and adult patients with PH1.

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. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.