Oxlumo

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



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This medicinal product is subject to additional monitoring. This will allow quick identification of 
new safety information. Healthcare professionals are asked to report any suspected adverse reactions. 
See section 4.8 for how to report adverse reactions. 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Oxlumo 94.5 mg/0.5 mL solution for injection. 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each mL of solution contains lumasiran sodium equivalent to 189 mg lumasiran. 
 
Each vial contains 94.5 mg lumasiran in 0.5 mL. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Solution for injection. 
 
Clear, colourless to yellow solution (pH of approximately 7; osmolality 210 to 390 mOsm/kg). 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Oxlumo is indicated for the treatment of primary hyperoxaluria type 1 (PH1) in all age groups. 
 
4.2 Posology and method of administration 
 
Therapy should be initiated and supervised by a physician experienced in the management of 
hyperoxaluria. 
 
Posology  
 
Oxlumo is administered by subcutaneous injection. The recommended dose of Oxlumo consists of 
loading doses given once a month for 3 months, followed by maintenance doses, as shown in Table 1. 
Dosing is based on body weight. 
 
The patient dose (in mg) and volume (in mL) should be calculated as follows: 
 
Patient body weight (kg) × dose (mg/kg) = total amount (mg) of medicinal product to be administered. 
 
Total amount (mg) divided by concentration (189 mg/mL) = total volume of medicinal product (mL) 
to be injected. 
 



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Table 1: Oxlumo weight-based dosing regimen 

Body weight Loading dose Maintenance dose 

(the maintenance dose should begin 
one month after the last loading dose) 

less than 10 kg 6 mg/kg once monthly for 
3 months 

3 mg/kg once monthly 

10 kg to less than 20 kg 6 mg/kg once monthly for 
3 months 

6 mg/kg once every 3 months 
(quarterly) 

20 kg and above 3 mg/kg once monthly for 
3 months 

3 mg/kg once every 3 months 
(quarterly) 

 
Missed dose 
If a dose is delayed or missed, treatment should be administered as soon as possible. Prescribed 
monthly or quarterly dosing should be resumed from the most recently administered dose. 
 
Special populations  
 
Elderly 
No dose adjustment is necessary in patients ≥65 years of age (see section 5.2). 
 
Hepatic impairment 
Oxlumo has not been studied in patients with hepatic impairment. No dose adjustment is necessary in 
patients with transient elevation in total bilirubin (total bilirubin >1.0 to 1.5×ULN). Caution is 
required when treating patients with moderate or severe hepatic impairment (see sections 4.4 and 5.2). 
 
Renal impairment 
No dose adjustment is necessary in patients with mild (estimated glomerular filtration rate (eGFR) 
60 to <90 mL/min/1.73 m2) or moderate (eGFR 30 to <60 mL/min/1.73 m2) renal impairment (see 
section 5.2). Limited clinical data are available in patients with severe renal impairment 
(eGFR 15 to <30 mL/min/1.73 m2), end-stage renal disease (eGFR <15 mL/min/1.73 m2), or who are 
on dialysis. Safety monitoring is warranted when treating patients with severe or end-stage renal 
impairment (see sections 4.4 and 5.2). 
 
Paediatric population 
In patients under 1 year of age, limited data are available. Caution should be used when treating these 
patients (see section 5.2). 
 
Method of administration  
 
For subcutaneous use only. 
 
This medicinal product is provided as a ready-to-use solution in a single use vial. 

 
• The required volume of Oxlumo should be calculated based on the recommended weight-based 

dose as shown in Table 1. 
• If the dose is more than 0.5 mL (94.5 mg), more than one vial will be needed. 
• The maximum acceptable single injection volume is 1.5 mL. Doses requiring more than 1.5 mL 

should be administered as multiple injections (the total dose divided equally between syringes 
with each injection containing approximately the same volume) to minimise potential injection 
site discomfort due to injection volume. 



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• Having the medicinal product on the needle tip before the needle is in the subcutaneous space 
should be avoided. 

• This medicinal product should be injected subcutaneously into the abdomen, upper arms, or 
thighs. 

• For subsequent injections or doses, rotating the injection site is recommended. 
• This medicinal product should not be administered into scar tissue or areas that are reddened, 

inflamed, or swollen. 
 
Oxlumo should be administered by a healthcare professional. For instructions on the medicinal 
product before administration, see section 6.6. 
 
4.3 Contraindications 
 
Severe hypersensitivity to the active substance or any of the excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
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’. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
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. 
 
4.6 Fertility, pregnancy and lactation 
 
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. 



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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). 
 
4.7 Effects on ability to drive and use machines 
 
Oxlumo has no or negligible influence on the ability to drive and use machines. 
 
4.8 Undesirable effects 
 
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 

System organ class Adverse reaction Frequency 

Gastrointestinal disorders Abdominal paina Very common 

General disorders and administration 
site conditions 

Injection site reactionb Very common 

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. 
 



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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. 
 
4.9 Overdose 
 
In case of overdose, it is recommended that the patient be monitored as medically indicated for any 
signs or symptoms of adverse reactions and appropriate symptomatic treatment be instituted. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: not yet assigned, ATC code: not yet assigned. 
 
Mechanism of action  
 
Lumasiran is a double-stranded small interfering ribonucleic acid (siRNA) that reduces levels of 
glycolate oxidase (GO) enzyme by targeting the hydroxyacid oxidase 1 (HAO1) gene messenger 
ribonucleic acid (mRNA) in hepatocytes through RNA interference. Decreased GO enzyme levels 
reduce the amount of available glyoxylate, a substrate for oxalate production. This results in reduction 
of urinary and plasma oxalate levels, the underlying cause of disease manifestations in patients with 
PH1. As the GO enzyme is upstream of the deficient alanine: glyoxylate aminotransferase (AGT) 
enzyme that causes PH1, the mechanism of action of lumasiran is independent of the underlying 
AGXT gene mutation. 
 
Clinical efficacy  
 
The efficacy of lumasiran was studied in a randomised, double-blind, placebo-controlled clinical study 
in patients 6 years and older with PH1 (ILLUMINATE-A) and in a single-arm clinical study in 
patients less than 6 years of age with PH1 (ILLUMINATE-B).  
 
ILLUMINATE-A 
A total of 39 patients with PH1 were randomised 2:1 to receive subcutaneous doses of lumasiran or 
placebo during the 6-month double-blind, placebo-controlled period. Patients 6 years and older with 
an estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2 were enrolled, and received 
3 loading doses of 3 mg/kg lumasiran or placebo administered once monthly, followed by quarterly 
maintenance doses of 3 mg/kg lumasiran or placebo (see section 4.2). After the 6-month double-blind 
treatment period, patients, including those originally assigned to placebo, entered an extension period 
with administration of lumasiran. 
 
During the 6-month double-blind, placebo-controlled period, 26 patients received lumasiran, and 
13 received placebo. The median age of patients at first dose was 14.9 years (range 6.1 to 61.0 years), 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


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66.7% were male, and 76.9% were white. The median 24-hour urinary oxalate excretion corrected for 
body surface area (BSA) at baseline was 1.72 mmol/24 h/1.73 m2, the median spot urinary 
oxalate: creatinine ratio at baseline was 0.21 mmol/mmol, and the median plasma oxalate level at 
baseline was 13.1 µmol/L. Overall, 33.3% of patients had normal renal function (eGFR 
≥90 mL/min/1.73 m2), 48.7% had mild renal impairment (eGFR of 60 to <90 mL/min/1.73 m2), and 
18% had moderate renal impairment (eGFR of 30 to <60 mL/min/1.73 m2). Of the patients enrolled in 
the study, 84.6% reported a history of symptomatic renal stone events and 53.8% reported a history of 
nephrocalcinosis at baseline. The treatment arms were balanced at baseline with respect to age, urinary 
oxalate level, and eGFR. 
 
The primary endpoint was the percent reduction from baseline in 24-hour urinary oxalate excretion 
corrected for BSA averaged over months 3 through 6. Lumasiran was associated with a statistically 
significant reduction of 65.4% in 24-hour urinary oxalate corrected for BSA, as compared to 11.8% in 
the placebo group, representing a difference of 53.5% (95% CI: 44.8, 62.3; p<0.0001). Consistent with 
the primary endpoint, a reduction of 60.5% was observed at month 6 in spot urinary oxalate: creatinine 
ratio in the lumasiran arm compared to an 8.5% increase in the placebo arm. Furthermore, patients 
treated with lumasiran had a rapid and sustained decrease in 24-hour urinary oxalate corrected for 
BSA, as shown in Figure 1. 

Figure 1: ILLUMINATE-A: Percent change from baseline in 24-hour urinary oxalate 
corrected for BSA by month 

 
Abbreviations: BL = baseline; BSA = body surface area; M = month; SEM = standard error of mean. 
Results are plotted as mean (±SEM) of percent change from baseline. 
 
At month 6, a higher proportion of lumasiran-treated patients achieved normal or near-normal levels 
of 24-hour urinary oxalate corrected for BSA (≤1.5×ULN) compared to placebo-treated patients, as 
shown in Table 3. 
 

Table 3: ILLUMINATE-A: Secondary endpoint results over the 6-month double-blind, 
placebo-controlled period 

Endpoints Lumasiran 
(N=26)  

Placebo  
(N=13)  

Treatment difference  
(95% CI) 

p-value 

Proportion of patients with 
24-hour urinary oxalate 
levels at or below ULN‡ 

0.5 (0.3, 0.7)§ 0 (0, 0.2)§ 
 

0.5 (0.2, 0.7)¶ 0.001# 

Proportion of patients with 
24-hour urinary oxalate 

0.8 (0.6, 1.0)§ 0 (0, 0.2)§ 0.8 (0.5, 0.9)¶ <0.0001# 



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Endpoints Lumasiran 
(N=26)  

Placebo  
(N=13)  

Treatment difference  
(95% CI) 

p-value 

levels at or below 
1.5×ULN‡ 
Percent reduction in plasma 
oxalate from baseline*Þ 

39.8 (2.9)† 0.3 (4.3)† 39.5 (28.9, 50.1) <0.0001 

Abbreviations: ULN = upper limit of normal; SEM = Standard Error of Mean 
Results are based on liquid chromatography tandem mass spectrometry (LC-MS/MS) assay. 
*The estimate based on the average of the least square mean of percent reduction at Months 3, 4, 5, 
and 6 using a mixed model for repeated measures. 
†LS Mean (SEM). 
‡ULN=0.514 mmol/24 hr/1.73 m2 for 24-hour urinary oxalate corrected for BSA. 
§95% CI based on Clopper Pearson Exact confidence interval. 
¶Calculated using the Newcombe Method based on the Wilson Score. 
#p-value is based on Cochran–Mantel–Haenszel test stratified by baseline 24-hour urinary oxalate 
corrected for BSA (≤1.70 vs >1.70 mmol/24 hr/1.73 m2). 
ÞAnalysed in 23 lumasiran and 10 placebo patients who had baseline levels that allowed for reduction 
to occur. 
 
Reduction in 24-hour urinary oxalate corrected for BSA from baseline in patients with PH1 receiving 
lumasiran compared to placebo was similar across all pre-specified subgroups, including age, sex, 
race, renal impairment, baseline pyridoxine (vitamin B6) use, and history of symptomatic renal stone 
events (Figure 2). 

Figure 2: ILLUMINATE-A: Percent change from baseline in 24-hour urinary oxalate 
corrected for BSA, subgroup analysis 

 
 
Reduced oxalate levels observed in the double-blind period were maintained through 12 months 
during the extension period of study.    
 
eGFR and renal stone events (reported by events per 100 person-days) were assessed through the 
double-blind and extension periods for a total of 12 months. eGFR remained stable in patients 
administered lumasiran. In the lumasiran arm, the rate of renal stone events reported 12 months prior 
to consent was 0.87 (95% CI: 0.70, 1.08). The observed events during the double-blind period and the 
first 6 months of the extension period were 0.30 (95% CI: 0.17, 0.51) and 0.23 (95% CI: 0.13, 0.43), 
respectively. In the placebo arm, the rate of renal stone events reported 12 months prior to consent was 
0.15 (95% CI: 0.07, 0.31) and the observed events during the double-blind period were 
0.18 (95% CI: 0.07, 0.48).  During the first 6 months of lumasiran treatment in the extension period a 
rate of 0.05 (95% CI: 0.01, 0.32) events were observed in patients previously receiving placebo. For 



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nephrocalcinosis, data through the 6-month double-blind period are available. Of the 34 patients with 
baseline and month 6 renal ultrasounds, 3 of 22 in the lumasiran group showed improvement in 
nephrocalcinosis, and 1 of 12 in the placebo group showed worsening in nephrocalcinosis. None of the 
other lumasiran (n=19) or placebo-treated (n=11) patients exhibited a change in nephrocalcinosis. 
 
ILLUMINATE-B 
A total of 18 patients were enrolled and treated with lumasiran in an ongoing multi-center, single-arm 
study in patients with PH1 (ILLUMINATE-B). The study enrolled patients less than 6 years of age 
with an eGFR >45 mL/min/1.73 m2 in patients 12 months of age and older, and normal serum 
creatinine in patients less than 12 months of age. In the 6-month primary analysis, at first dose, 
3 patients were less than 10 kg, 12 were 10 kg to less than 20 kg, and 3 were 20 kg and above. The 
median age of patients at first dose was 51.4 months (range 4.0 to 74.0 months), 55.6% were female, 
and 88.9% were white. The median spot urinary oxalate: creatinine ratio at baseline was 
0.47 mmol/mmol.  
 
At month 6, patients treated with lumasiran achieved a reduction of 72.0% (95% CI: 66.4, 77.5) in 
spot urinary oxalate: creatinine ratio from baseline (averaged over months 3 through month 6), the 
primary endpoint. Lumasiran was associated with rapid, and sustained reductions in spot urinary 
oxalate: creatinine ratio (Figure 3), which were similar across all weight strata. The percent reduction 
in urinary oxalate excretion was consistent with data from ILLUMINATE-A. 

Figure 3: ILLUMINATE-B: Percent change in spot urinary oxalate: creatinine ratio from 
baseline by month 

 
 
Nine patients achieved near normalisation (≤1.5×ULN), including 1 patient who achieved 
normalisation (≤ULN), at month 6 in spot urinary oxalate: creatinine ratio. 
 
Furthermore, from baseline to month 6 (average of month 3 to month 6), a mean plasma oxalate 
reduction of 31.7% (95% CI: 23.9, 39.5) was observed. During the 6-month period, the eGFR 
remained stable, and 2 post-baseline renal stone events in 2 patients were reported, compared to 
4 renal stone events in 3 patients in the 12-month period prior to consent. Fourteen of 18 patients had 
baseline nephrocalcinosis. Renal ultrasound data at month 6 indicated improvement in 8 patients, 
including 3 with bilateral improvement. None of the 18 patients had new onset or worsening 
nephrocalcinosis. 
 
Paediatric population 
The European Medicines Agency has deferred the obligation to submit the results of studies with 
Oxlumo in one or more subsets of the paediatric population in hyperoxaluria (see section 4.2 for 
information on paediatric use). 
 



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5.2 Pharmacokinetic properties 
 
Absorption  
 
Following subcutaneous administration, lumasiran is rapidly absorbed with a median (range) time to 
reach maximum plasma concentration (tmax) of 4.0 (0.5 to 12.0) hours. In children and adults with PH1 
≥20 kg, the peak plasma concentration of lumasiran (Cmax) and area under the concentration curve 
from time zero to the last measurable concentration after dosing (AUC0-last) following the 
recommended lumasiran dose of 3 mg/kg were 529 (205 to 1130) ng/mL and 
7400 (2890 to 10700) ng·h/mL, respectively. In children less than 20 kg, Cmax and AUC0-last of 
lumasiran following the recommended lumasiran dose of 6 mg/kg were 912 (523 to 1760) and 
7960 (5920 to 13300). Lumasiran concentrations were measurable, up to 24 to 48 hours post-dose. 
 
Distribution  
 
In healthy adult plasma samples, the protein binding of lumasiran is moderate to high (77 to 85%) at 
clinically relevant concentrations. For an adult patient with PH1, the population estimate for the 
apparent central volume of distribution (Vd/F) for lumasiran is 4.9 L. Lumasiran primarily distributes to 
the liver after subcutaneous dosing. 
 
Biotransformation  
 
Lumasiran is metabolised by endo- and exonucleases to oligonucleotides of shorter lengths. In vitro 
studies indicate that lumasiran does not undergo metabolism by CYP450 enzymes. 
 
Elimination  
 
Lumasiran is primarily eliminated from plasma by hepatic uptake, with only 7 to 26% of the 
administered dose recovered in urine as lumasiran in the pooled data from healthy adult subjects and 
patients with PH1 >6 years of age. The mean (%CV) terminal plasma half-life of lumasiran is 
5.2 (47.0%) hours. The population estimate for apparent plasma clearance was 26.5 L/h for a typical 
70-kg adult. The mean renal clearance of lumasiran was minor and ranged from 2.0 to 3.4 L/h in 
paediatric and adult patients with PH1. 
 
Linearity/non-linearity  
 
Lumasiran exhibited linear to slightly nonlinear, time-independent pharmacokinetics in plasma 
following single subcutaneous doses ranging from 0.3 to 6 mg/kg and multiple doses of 1 and 3 mg/kg 
once monthly or 3 mg/kg quarterly. There was no accumulation of lumasiran in plasma after repeated 
once monthly or quarterly dosing. 
 
Pharmacokinetic/pharmacodynamic relationship(s)  
 
Plasma concentrations of lumasiran do not reflect the extent or duration of the pharmacodynamic 
activity of lumasiran. Rapid and targeted uptake of lumasiran by the liver results in rapid decline in 
plasma concentrations. In the liver, lumasiran exhibits a long half-life leading to maintenance of 
pharmacodynamic effect over the monthly or quarterly dosing interval. 
 
Interactions  
 
In vitro studies indicate that lumasiran is not a substrate or an inhibitor of cytochrome P450 (CYP) 
enzymes. Lumasiran is not expected to inhibit or induce CYP enzymes or modulate the activities of 
drug transporters. 
 



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Special populations  
 
Elderly 
No studies have been conducted in patients ≥65 years of age. Age was not a significant covariate in the 
pharmacokinetics of lumasiran. 
 
Gender and race 
In clinical studies, there was no difference in the plasma exposure or pharmacodynamics of lumasiran 
based on gender or race. 
 
Hepatic impairment 
No studies have been conducted in patients with hepatic impairment (see section 4.2). Limited 
pharmacokinetic data in patients with mild and transient elevations in total bilirubin (total 
bilirubin >1.0 to 1.5×ULN) showed comparable plasma exposure of lumasiran and similar 
pharmacodynamics as patients with normal hepatic function. Published literature show lower 
expression of the asialoglycoprotein receptors in the liver, i.e. the receptors responsible for lumasiran 
uptake, in patients with hepatic impairment. Nonclinical data suggest that this may not influence liver 
uptake or pharmacodynamics at therapeutic doses. The clinical relevance of these data is unknown. 
 
Renal impairment 
Patients with mild renal impairment (eGFR 60 to <90 mL/min/1.73 m2) had comparable plasma 
exposure of lumasiran and similar pharmacodynamics as patients with normal renal function (eGFR 
≥90 mL/min/1.73 m2). In patients with moderate renal impairment (eGFR 30 to <60 mL/min/1.73 m2) 
Cmax was similar to that in patients with normal renal function; AUC was 25% higher based on limited 
data. Limited clinical data are available in patients with severe renal impairment 
(eGFR 15 to <30 mL/min/1.73 m2), end-stage renal disease (eGFR <15 mL/min/1.73 m2), or who are 
on dialysis (see section 4.2). For ESRD patients on dialysis, within the same body weight category, a 
transient 3- to 7-fold higher Cmax and 2- to 3.5-fold AUC0-last increase was observed (see section 5.2 
Pharmacokinetic/pharmacodynamic relationship(s)). However, plasma concentrations decline below 
the level of detection within 24 to 48 hours, similar to patients without renal impairment. 
 
Paediatric population  
Data in children younger than 1 year of age are limited. In children <20 kg, lumasiran Cmax was 2-fold 
higher due to the nominally higher 6-mg/kg dose and faster absorption rate. The pharmacodynamics of 
lumasiran were comparable in paediatric patients (aged 4 months to 17 years) and in adults, despite the 
transiently higher plasma concentrations in children <20 kg, due to the rapid and predominant 
distribution of lumasiran to the liver. 
 
Body weight 
The recommended dosing regimens yielded up to 2-fold higher Cmax in children <20 kg while AUC 
was similar across the body weights studied (6.2 to 110 kg). 
 
5.3 Preclinical safety data 
 
Non-clinical data reveal no special hazard for humans based on conventional studies of safety 
pharmacology and genotoxicity. 
 
In rats, but not in monkeys, microscopic changes in the liver (e.g. hepatocellular vacuolation, mitosis 
and karyomegaly) were observed, accompanied by decrease in plasma fibrinogen levels and other 
laboratory changes. The reason for the apparent rodent-specificity is not understood and the relevance 
for humans is unclear. 
 
Lumasiran did not show any adverse effects on male and female fertility and pre- and post-natal 
development in rats. In embryo-foetal development studies in rats and rabbits, skeletal abnormalities 
were observed, but at high exposure multiples relative to human therapeutic exposures. The NOAELs 
were approximately 20- to 70-times higher (based on monthly exposures). 
 



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A dose-range finding toxicity study in neonate rats did not show increased sensitivity of the 
developing rat to either the toxicology or pharmacology of lumasiran at exposure multiples of 2 
compared to human therapeutic exposures (based on monthly exposures). 
 
Animal studies have not been conducted to evaluate the carcinogenic potential of lumasiran. 
 
 
 6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Sodium hydroxide (pH adjustment) 
Phosphoric acid (pH adjustment) 
Water for injections 
 
6.2 Incompatibilities 
 
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 
products. 
 
6.3 Shelf life 
 
3 years. 
 
Once the vial is opened, the medicinal product should be used immediately. 
 
6.4 Special precautions for storage 
 
Do not store above 30°C. 
 
Keep vial in the outer carton to protect from light. 
 
6.5 Nature and contents of container 
 
Glass vial with a fluoropolymer-coated rubber stopper and an aluminium overseal with a flip-off 
button. Each vial contains 0.5 mL solution for injection. 
 
Pack size of one vial. 
 
6.6 Special precautions for disposal and other handling 
 
This medicinal product is ready-to-use and for single use only. 
 
For subcutaneous use only 
 
• Before administration, materials not included in the pack that are needed for administration should 

be collected, which will include a sterile syringe (0.3 mL, 1 mL, or 3 mL), an 18-gauge (G) 
needle, and a 25 G to 31 G needle. 

• The required volume of Oxlumo should be calculated based on the recommended weight-based 
dose (see section 4.2). 

• An 18-gauge needle should be used to withdraw Oxlumo from the vial. The vial should be held 
upright or tilted at a slight angle, and the flat edge of the needle should be pointed downwards. 

• For volumes less than 0.3 mL, a sterile 0.3 mL syringe is recommended. 
• The medicinal product should be administered with a sterile 25- to 31-G needle with a 13 mm or 

16 mm needle length for subcutaneous injection. 
• Note: This medicinal product should not be pushed into the 25 G to 31 G needle. 
• Syringes, transfer needles, and injection needles should only be used once. 



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Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Alnylam Netherlands B.V. 
Antonio Vivaldistraat 150  
1083 HP Amsterdam  
Netherlands  
 
 
8. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/20/1496/001 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 
 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu  

http://www.ema.europa.eu/


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ANNEX II 
 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 

 



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A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer responsible for batch release  
 
Alnylam Netherlands B.V. 
Antonio Vivaldistraat 150  
1083 HP Amsterdam  
Netherlands  
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, section 4.2). 
 
 
C.  OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
• Periodic safety update reports (PSURs) 
 
The requirements for submission of PSURs for this medicinal product are set out in the list of 
Union reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC 
and any subsequent updates published on the European medicines web-portal. 
 
The marketing authorisation holder (MAH) shall submit the first PSUR for this medicinal product 
within 6 months following authorisation. 
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
• Risk management plan (RMP) 

 
The marketing authorisation holder (MAH) shall perform the required pharmacovigilance 
activities and interventions detailed in the agreed RMP presented in Module 1.8.2 of the 
marketing authorisation and any agreed subsequent updates of the RMP. 
 
An updated RMP should be submitted: 
• At the request of the European Medicines Agency; 
• Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached. 

 
 
  



16 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
  



17 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
  



18 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Oxlumo 94.5 mg/0.5 mL solution for injection 
lumasiran 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each mL of solution contains lumasiran sodium equivalent to 189 mg lumasiran. 
 
Each vial contains 94.5 mg lumasiran in 0.5 mL. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: 
Sodium hydroxide 
Phosphoric acid 
Water for injections 
See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
solution for injection 
94.5 mg/0.5 mL 
1 vial 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
For single use only. 
Read the package leaflet before use. 
Subcutaneous use 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 



19 

9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 30°C. 
Keep vial in the outer carton to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Alnylam Netherlands B.V. 
Antonio Vivaldistraat 150  
1083 HP Amsterdam  
Netherlands  
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/20/1496/001 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Oxlumo 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 
  



20 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Oxlumo 94.5 mg/0.5 mL solution for injection 
lumasiran 
 
 
2. METHOD OF ADMINISTRATION 
 
Subcutaneous use 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
94.5 mg/0.5 mL 
 
 
6. OTHER 
 
 
  



21 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



22 

Package leaflet: Information for the patient 
 

Oxlumo 94.5 mg/0.5 mL solution for injection 
lumasiran 

 
This medicine is subject to additional monitoring. This will allow quick identification of new 

safety information. You can help by reporting any side effects you may get. See the end of section 4 
for how to report side effects. 
 
Read all of this leaflet carefully before you are given this medicine because it contains important 
information for you. 
• Keep this leaflet. You may need to read it again. 
• If you have any further questions, ask your doctor or nurse. 
• If you get any side effects, talk to your doctor or nurse. This includes any possible side effects 

not listed in this leaflet. See section 4. 
 
What is in this leaflet: 
 
1. What Oxlumo is and what it is used for 
2. What you need to know before you are given Oxlumo 
3. How Oxlumo is given 
4. Possible side effects 
5. How to store Oxlumo 
6. Contents of the pack and other information 
 
 
1. What Oxlumo is and what it is used for 
 

What Oxlumo is 
Oxlumo contains the active substance lumasiran. 
 
What Oxlumo is used for 
Oxlumo is used to treat primary hyperoxaluria type 1 (PH1) in adults and children of all ages. 
 
What PH1 is 
PH1 is a rare illness in which the liver produces too much of a substance called oxalate. Your kidneys 
remove oxalate from the body and it is passed out in the urine. In people with PH1, the extra oxalate 
can build up in the kidneys and cause kidney stones, and can stop the kidney from working as well as 
they should. A build-up of oxalate can also damage other parts of the body such as eyes, heart, skin, 
and bone. This is called oxalosis. 
 
How Oxlumo works 
Lumasiran, the active substance in Oxlumo, reduces the amount of an enzyme called glycolate oxidase 
that the liver makes. Glycolate oxidase is one of the enzymes involved in producing oxalate. By 
lowering the amount of the enzyme, the liver produces less oxalate and the levels of oxalate in the 
urine and blood also fall. This can help to reduce the effects of the illness. 
 
 
2. What you need to know before you are given Oxlumo 
 

You must not be given Oxlumo: 
• if you are severely allergic to lumasiran, or any of the other ingredients of this medicine (listed 

in section 6).  
 



23 

Warnings and precautions 
Talk to your doctor before being given this medicine. 
 
Your doctor may monitor you for signs of metabolic acidosis (the build-up of acid in the body). 
 
Other medicines and Oxlumo 
Tell your doctor if you are using, have recently used, or might use any other medicines. 
 
Pregnancy 
If you are pregnant, think you may be pregnant, or are planning to have a baby, ask your doctor or 
nurse for advice before using this medicine. Your doctor will decide whether you should take Oxlumo 
after considering the expected health benefits for you as well as the risks to your unborn baby. 
 
Breast-feeding 
This medicine may pass into breast milk and it could have an effect on your baby. If you are 
breast-feeding, ask your doctor for advice before taking this medicine. Your doctor will help you 
decide whether to stop breast-feeding or to stop treatment.  
 
Driving and using machines 
This medicine is unlikely to have any effect on your ability to drive or use machines. 
 
Oxlumo contains sodium 
This medicine contains less than 1 mmol sodium (23 mg) per mL, that is to say essentially 
‘sodium-free’. 
 
 
3. How Oxlumo is given 
 
How much Oxlumo is given 
Your doctor will work out how much medicine to give you. The dose will depend on how much you 
weigh. Your doctor will adjust your dose as your weight changes. 
 
You will receive your first doses (loading doses) once a month for 3 months. You will then start 
maintenance dosing one month after the last loading dose. 
 

Body weight less than 10 kg  
• Loading doses: 6 mg for every kg of your weight, given once a month for 3 months. 
• Maintenance dosing: 3 mg for every kg of your weight, given once every month. 

 
Body weight from 10 kg to less than 20 kg  

• Loading doses: 6 mg for every kg of your weight, given once a month for 3 months. 
• Maintenance dosing: 6 mg for every kg of your weight, given once every 3 months. 

 
Body weight 20 kg or more  

• Loading doses: 3 mg for every kg of your weight, given once a month for 3 months. 
• Maintenance dosing: 3 mg for every kg of your weight, given once every 3 months. 

 
How Oxlumo is given 
This medicine will be given to you by a doctor or nurse. 
• It is given as an injection under the skin (subcutaneously) into your stomach area (abdomen), or 

in some cases, your upper arm or thigh. You will be given the injection in a different spot from 
one injection to the next. 

• Depending on your dose, more than one subcutaneous injection may need to be given. 
• Your doctor or nurse will not inject into skin areas that are scarred, reddened, inflamed, or 

swollen. 
 



24 

If you are given too much Oxlumo 
In the unlikely event that your doctor or nurse gives you too much (an overdose) they will check you 
for side effects. 
 
If you miss your dose of Oxlumo 
If you miss a dose of Oxlumo, talk to your doctor or nurse as soon as possible about when to get your 
next dose. 
 
If you have any further questions on the use of this medicine, ask your doctor or nurse. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
The following side effects may occur when taking Oxlumo: 
 
Very common: may affect more than 1 in 10 people 
• Redness, pain, itching, swelling, discomfort, colour changes, mass, induration, rash, bruising or 

exfoliation at the site of the injection (injection site reaction). 
• Stomach pain or discomfort (abdominal pain) 
 
Reporting of side effects 
If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not 
listed in this leaflet. You can also report side effects directly via the national reporting system listed in 
Appendix V. By reporting side effects you can help provide more information on the safety of this 
medicine. 
 
 
5. How to store Oxlumo 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date, which is stated on the carton and vial after EXP. The 
expiry date refers to the last day of that month. 
 
This medicine is for single use only. Once the vial is opened, use immediately. 
 
Do not store above 30°C. 
 
Keep vial in the outer carton to protect from light. 
 
Do not throw away any medicines via wastewater or household waste. Your doctor or nurse will throw 
away any medicines that are no longer being used. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Oxlumo contains 
• The active substance is lumasiran. 
• Each vial contains lumasiran sodium equivalent to 94.5 mg lumasiran. 
• The other ingredients are water for injections, sodium hydroxide, and phosphoric acid (see 

“Oxlumo contains sodium” in section 2). 
 
What Oxlumo looks like and contents of the pack 
This medicine is a clear, colourless-to-yellow solution for subcutaneous injection. 
 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


25 

Each pack contains one single use vial containing 0.5 mL solution. 
 
Marketing Authorisation Holder and Manufacturer 
Alnylam Netherlands B.V. 
Antonio Vivaldistraat 150  
1083 HP Amsterdam  
Netherlands 
   

For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
  
België/Belgique/Belgien 
Alnylam Netherlands B.V. 
Tél/Tel: 0800 81 443 (+32 234 208 71) 
medinfo@alnylam.com 
 

Malta 
Genesis Pharma (Cyprus) Ltd 
Tel: +357 22769946 
medinfo@genesispharmagroup.com 
 

България 
Genesis Pharma Bulgaria EOOD 
Teл.: +359 2 969 3227 
medinfo@genesispharmagroup.com 
 

Nederland 
Alnylam Netherlands B.V. 
Tel: 08002820025 (+31 203697861) 
medinfo@alnylam.com 
 

Česká republika 
Alnylam Czech s.r.o. 
Tel: 800 050 450 (+420 234 092 195) 
medinfo@alnylam.com 
 

Norge 
Alnylam Sweden AB 
Tlf: 800 544 00 (+472 1405 657) 
medinfo@alnylam.com 
 

Danmark 
Alnylam Sweden AB 
Tlf: 433 105 15 (+45 787 453 01) 
medinfo@alnylam.com 
 

Österreich 
Alnylam Austria GmbH 
Tel: 0800070339 (+43 720 778 072) 
medinfo@alnylam.com 
 

Deutschland 
Alnylam Germany GmbH 
Tel: 08002569526 (+49 8920190112) 
medinfo@alnylam.com 
 

Portugal 
Alnylam Portugal 
Tel: 707201512 (+351 707502642) 
medinfo@alnylam.com 
 

Ελλάδα 
ΓΕΝΕΣΙΣ ΦΑΡΜΑ Α.Ε 
Τηλ: +30 210 87 71 500 
medinfo@genesispharmagroup.com 
 

România 
Genesis Biopharma Romania SRL 
Tel: +40 21 403 4074 
medinfo@genesispharmagroup.com 
 

España 
Alnylam Pharmaceuticals Spain SL 
Tel: 900810212 (+34 910603753) 
medinfo@alnylam.com 
 

Slovenija 
Genesis Pharma Adriatic d.o.o 
Tel: +385 1 5813 652 
medinfo@genesispharmagroup.com 
 

France 
Alnylam France SAS 
Tél: 0805542656 (+33 187650921) 
medinfo@alnylam.com 
 

Suomi/Finland 
Alnylam Sweden AB 
Puh/Tel: 0800 417 452 (+358 942 727 020) 
medinfo@alnylam.com 
 

Hrvatska 
Genesis Pharma Adriatic d.o.o 
Tel: +385 1 5813 652 
medinfo@genesispharmagroup.com 
 

Sverige 
Alnylam Sweden AB 
Tel: 020109162 (+46 842002641) 
medinfo@alnylam.com 
 



26 

Italia 
Alnylam Italy S.r.l. 
Tel: 800 90 25 37 (+39 02 89 73 22 91) 
medinfo@alnylam.com 
 

United Kingdom 
Alnylam UK Ltd. 
Tel: 08001412569 (+44 1628 878592) 
medinfo@alnylam.com 
 

Ireland 
Alnylam Netherlands B.V. 
Tel: 1800 924260 (+353 7 667 05596) 
medinfo@alnylam.com 
 

Eesti, Ísland, Latvija, Lietuva, Magyarország, 
Polska, Slovenská republika 
Alnylam Netherlands B.V. 
Tel/Sími: +31 20 369 7861 
medinfo@alnylam.com 
 

Κύπρος 
Genesis Pharma (Cyprus) Ltd 
Τηλ: +357 22769946 
medinfo@genesispharmagroup.com 
 

 

Luxembourg/Luxemburg 
Alnylam Netherlands B.V. 
Tél/Tel: 80085235 (+352 203 014 48) 
medinfo@alnylam.com 
 

 

  
This leaflet was last revised in MM/YYYY. 
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu.. 
 
 
<------------------------------------------------------------------------------------------------------------------------> 
 
The following information is intended for healthcare professionals only: 
 
Instructions for use  
 
For subcutaneous use only. 
 
• Collect materials not included in the pack that are needed for administration which will include a 

sterile syringe (0.3 mL, 1 mL, or 3 mL), an 18-gauge (G) needle, and a 25-G to 31-G needle. 
• Calculate the required volume of Oxlumo based on the recommended weight-based dose. If the 

dose is more than 0.5 mL, you will need to use more than one vial. The maximum acceptable 
single injection volume to be administered is 1.5 mL. If more than 1.5 mL is needed, you may 
need to give more than one subcutaneous injection. 

• To withdraw Oxlumo, hold the vial upright or tilt at a slight angle and ensure the flat edge of the 
needle is pointed downwards. 

• Point the needle and syringe straight up and tap the syringe to move any bubbles to the top. Once 
the bubbles are at the top, gently push the plunger to force the bubbles out of the syringe. Check to 
ensure the correct amount of medicine is in the syringe. 

• Administer the medicine with a sterile 25- to 31-G needle with a 13-mm or 16-mm needle length 
for subcutaneous injection. For volumes less than 0.3 mL, a sterile 0.3-mL syringe is 
recommended. 

• Note: Do not push this medicine into the 25-G to 31-G needle. When using 0.3 mL (insulin) 
syringes, do not force the bubble from syringe. 

• Injection can be into the abdomen, upper arms, or thighs. Consider rotating injection sites. Do not 
administer into scar tissue or areas that are reddened, inflamed, or swollen. 

http://www.ema.europa.eu./


27 

• Note: When administering subcutaneous injections into the abdomen, avoid a 2.0-cm diameter 
circle around the navel. 

• Clean the area of planned injection with an alcohol swab and wait for the area to dry completely. 
• Ensure proper injection technique. Do not inject into a vein or muscle. 
• Insert the needle at a right angle (90 degrees) to deliver the injection just below the skin. In 

patients with little subcutaneous tissue, the needle should be inserted at a 45-degree angle. 
• Do not press down on the plunger while piercing the skin. Once the needle is inserted through the 

skin, release the pinched skin and administer the dose in a slow and steady manner. Once the 
medicine has been administered count for at least 5 seconds before withdrawing the needle from 
the skin. Lightly press gauze or cotton ball on the injection site as needed. Do not put the needle 
cap back on. 

• Note: Do not aspirate after inserting the needle to prevent tissue damage, haematoma, and 
bruising. 

• If more than one injection is needed for a single dose of Oxlumo, the injection sites should be at 
least 2 cm apart. 

• Only use the vial once. After administering the dose, dispose of any unused medicine in the vial 
according to local regulations. 

• Use the syringes, transfer needles, and injection needles only once. Dispose of any used syringes 
and needles in accordance with local regulations. 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C.  OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET

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