Obiltoxaximab SFL

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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 
 
Obiltoxaximab SFL 100 mg/mL concentrate for solution for infusion 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each mL of concentrate contains 100 mg of obiltoxaximab.  
One vial of 6 mL contains 600 mg obiltoxaximab. 
 
Obiltoxaximab is produced in murine GS-NS0 myeloma cells by recombinant DNA technology. 
 
Excipient with known effect 
 
Each mL of concentrate contains 36 mg sorbitol. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM  
 
Concentrate for solution for infusion (sterile concentrate).   
Obiltoxaximab SFL is a clear to opalescent, colourless to pale yellow to pale brownish-yellow solution 
that may contain few translucent-to-white proteinaceous particulates (which will be removed by in-
line filtration) with a pH of 5.5 and an osmolality of 277 – 308 mOsm/kg. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Obiltoxaximab SFL is indicated in combination with appropriate antibacterial drugs in all age groups 
for treatment of inhalational anthrax due to Bacillus anthracis (see section 5.1). 
 
Obiltoxaximab SFL is indicated in all age groups for post-exposure prophylaxis of inhalational 
anthrax when alternative therapies are not appropriate or are not available (see section 5.1). 
 
4.2 Posology and method of administration 
 
Obiltoxaximab SFL should be given as soon as it is clinically indicated. 
 
Appropriate medical treatment and supervision should always be readily available in case of an 
anaphylactic event following the administration of Obiltoxaximab SFL.  
 
Posology 
 
The recommended dosage of Obiltoxaximab SFL in adult patients weighing at least 40 kg is a single 
intravenous infusion of 16 mg/kg body weight (bw). The recommended dosage of Obiltoxaximab SFL 
in adult patients weighing less than 40 kg is a single intravenous infusion of 24 mg/kg bw.  
 
Premedication with an antihistamine is recommended before administration of Obiltoxaximab SFL 
(see sections 4.4 and 4.8).  



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For dose modifications in case of infusion-related reactions (IRR) see table 1. 
 
Table 1: Obiltoxaximab dose modifications for infusion-related reactions 
Severity of IRR  Dose modification 

Grade 1–3 
Infusion-related 
reaction 

Obiltoxaximab infusion should be interrupted and supportive treatment should 
be given. 

For the first instance of Grade 3 wheezing, bronchospasm, or generalized 
urticaria, obiltoxaximab should be permanently discontinued. 

For recurrent Grade 2 wheezing or urticaria, or for recurrence of any Grade 3 
symptoms, obiltoxaximab should be permanently discontinued.   

Otherwise, upon complete resolution of symptoms, infusion may be resumed at 
50% of the rate achieved prior to interruption. In the absence of infusion-related 
symptoms, the rate of infusion is described in table 3.  

Premedication should be administered. 

Grade 4 
Infusion-related 
reaction 

Obiltoxaximab infusion should be stopped immediately. 
Supportive treatment should be given. 
Obiltoxaximab should be permanently discontinued.   

 
Special populations 
 
Elderly 
 
No dosage adjustment is needed for patients ≥ 65 years of age (see section 5.2). 
 
Paediatric population 
 
The recommended dose for paediatric patients is based on weight as shown in table 2 below. 
 
Table 2: Recommended paediatric dose of obiltoxaximab (weight-based dosing) 

Body weight [kg] Dose [mg/kg bw] 
> 40 16 

> 15 to 40 24 
15 or less 32 

 
Method of administration  
 
Obiltoxaximab must be administered via intravenous infusion over 90 minutes. 
 
Precautions to be taken before handling or administering the medicinal product 
 
The vial should not be shaken. Obiltoxaximab must be diluted in sodium chloride 9 mg/mL (0.9%) 
solution for injection prior to administration as an intravenous infusion (see section 6.6).  
 
The diluted obiltoxaximab intravenous infusion must be infused over 90 minutes with the infusion rate 
described in table 3, using an infusion bag or syringe for infusion and a 0.22 micron inline filter.  
 
Patients need to be monitored closely for signs and symptoms of hypersensitivity throughout the 
infusion and for at least one hour after administration (see section 4.4). Infusion related reactions 
should be managed as outlined in table 1. 
 
The line is to be flushed with sodium chloride 9 mg/mL (0.9%) solution for injection at the end of the 
intravenous infusion. 



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Table 3: Obiltoxaximab dose, total infusion volume and infusion rate by body weight 

Body weight [kg] 
(weight-based dosing) 

 

Total infusion volume 
[mL] 

[infusion bag or 
syringe]* 

Infusion rate 
[mL/h] 

> 40 kg or adult (16 mg/kg bw) 
> 40 250 167 

> 15 kg to 40 kg (24 mg/kg bw) 
31 to 40 250 167 
16 to 30 100 67 

15 kg or less (32 mg/kg bw) 
11 to 15 100 67 
5 to 10 50 33.3 

3.1 to 4.9 25 17 
2.1 to 3 20 13.3 
1.1 to 2 15 10 
1 or less 7 4.7 

* For instructions on dilution of the medicinal product and use of infusion bag or syringe before 
administration, see section 6.6. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
Traceability 
 
In order to improve the traceability of biological medicinal products, the name and the batch number 
of the administered product should be clearly recorded. 
 
Infusion-related reactions, hypersensitivity and anaphylaxis 
 
Infusion-related/hypersensitivity reactions were commonly observed during clinical trials with 
obiltoxaximab in healthy subjects. Due to the risk of severe reactions or anaphylaxis, obiltoxaximab 
should be administered in monitored settings by personnel trained and equipped to manage 
anaphylaxis. Patients should be monitored closely throughout the infusion period and for at least one 
hour after administration.  
 
Since the clinical trials were conducted in healthy volunteers, obiltoxaximab infusions were stopped at 
the onset of any reaction. Based on experience with other monoclonal antibodies used in the treatment 
of serious medical conditions, infusions can generally be completed if managed appropriately. 
Infusion-related reactions should be managed as outlined in table 1.  
 
Premedication with an antihistamine, e.g. diphenhydramine, is recommended prior to administration 
of obiltoxaximab (see section 4.2). Diphenhydramine was administered 30 minutes prior to treatment 
with obiltoxaximab in clinical trials conducted with obiltoxaximab. Premedication with an 
antihistamine does not prevent anaphylaxis and may mask or delay onset of symptoms of 
hypersensitivity. 
 
Anthrax meningitis 
 
Obiltoxaximab does not cross the blood-brain barrier and does not prevent or treat anthrax meningitis.  
 



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Paediatric population 
 
There have been no studies of safety or PK of obiltoxaximab in the paediatric population (see section 
5.2). 
 
Laboratory test interactions 
 
Exposure to Obiltoxaximab SFL may interfere with serological tests for anthrax. 
 
Sorbitol 
 
Each mL of Obiltoxaximab SFL contains 36 mg of sorbitol (see sections 2 and 6.1).  
Medicinal products containing sorbitol may be fatal if given intravenously to subjects with hereditary 
fructose intolerance (HFI). Obiltotoxaximab should not be used in subjects with HFI unless there is an 
overwhelming clinical need and no alternatives are available. A detailed history with regard to HFI 
symptoms should be taken from each patient prior to being given this medicinal product. 
 
Infants and toddlers (below 2 years of age) are at particular risk since the may not yet be diagnosed 
with HFI.  
 
Sodium 
 
This medicine contains less than 1 mmol sodium (23 mg) per each 6 mL vial, that is to say essentially 
‘sodium-free’. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Ciprofloxacin 
 
In an interaction study, a single dose of obiltoxaximab was given alone or co-administered with 
ciprofloxacin in 40 subjects. Twenty subjects received obiltoxaximab alone and 20 subjects received 
obiltoxaximab plus ciprofloxacin for 9 days. The administration of 16 mg/kg obiltoxaximab 
intravenous infusion prior to ciprofloxacin intravenous infusion or ciprofloxacin twice daily oral tablet 
ingestion did not alter the pharmacokinetics of obiltoxaximab. Likewise, obiltoxaximab did not alter 
the pharmacokinetics of ciprofloxacin administered orally or intravenously. 
 
No other interaction studies have been performed. Since obiltoxaximab is a monoclonal antibody, the 
risk of interaction is low. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
There are no data from the use of obiltoxaximab in pregnant women, however, human IgG is known to 
cross the placental barrier. 
Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity 
(see section 5.3). 
As a precautionary measure, it is preferable to avoid the use of Obiltoxaximab SFL during pregnancy. 
 
Breast-feeding 
 
It is unknown whether obiltoxaximab is excreted in human milk. Human IgG is known to be excreted 
in breast milk during the first days after birth and is decreasing to low concentrations soon afterwards. 
Consequently, a risk to breast-fed infants cannot be excluded during this short period. Afterwards, use 
of obiltoxaximab could be considered during breast-feading, only if clinically needed. 
 



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Fertility 
 
Fertility studies have not been conducted with obiltoxaximab. 
 
4.7 Effects on ability to drive and use machines 
 
Obiltoxaximab may have a minor influence on the ability to drive and use machines since headache, 
dizziness, fatigue and vomiting may occur following administration of Obiltoxaximab SFL (see 
section 4.8). 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
The safety of obiltoxaximab has been studied only in healthy adult subjects. 
 
The safety of obiltoxaximab was evaluated in 320 healthy subjects (aged 18 to 79 years old) treated 
with one or two 16 mg/kg intravenous doses in three clinical studies.  
 
Overall 250 of the 320 subjects received a single dose of 16 mg/kg obiltoxaximab. Hypersensitivity 
related adverse reactions (including rash) occurred in 9% (22/250) of these subjects, with one case of 
anaphylaxis that occurred during the infusion. The infusion was discontinued in 3% (8/250) due to 
hypersensitivity or anaphylaxis.  
 
The most frequently reported adverse reactions were headache (4%, 9/250), pruritus (4%, 9/250), and 
urticaria (2%, 6/250). 
 
Most commonly observed adverse reactions within the first three hours after start of infusion were 
pruritus (n=7; 2.8%), urticaria (n=6; 2.4%), headache (n=4; 1.6%), rash (n=3; 1.2%), cough (n=3; 
1.2%), dizziness (n=3; 1.2%) (includes dizziness and dizziness postural).  
The following severe adverse reactions occurred within the first three hours following the infusion: 
urticaria (n=1, 0.4%), pruritus (n=1, 0.4%) and back pain (n=1, 0.4%). 
The most commonly observed adverse reaction within 3 to 24 hours after start of infusion was 
headache (n=3; 1.2%). 
 
Tabulated list of adverse reactions 
 
Table 4 presents adverse reactions observed with obiltoxaximab in the 250 healthy human subjects 
that received a single intravenous dose of 16 mg/kg obiltoxaximab, by System Organ Class and 
frequency. 
 
The frequency of adverse reactions is defined as follows: very common (≥1/10); common (≥1/100 to 
<1/10); and uncommon (≥1/1,000 to <1/100). Within each frequency grouping, adverse reactions are 
presented in the order of decreasing seriousness. 
 
Table 4: Adverse reactions reported in healthy adult subjects 
MedDRA System Organ Class Common  Uncommon 
Immune system disorders  Anaphylactic reaction  

Hypersensitivity 
Nervous system disorders Headache Dizziness 

Dizziness postural 
Hypoaesthesia 

Eye disorders  Photophobia 
Ear and labyrinth disorders  Ear discomfort 
Vascular disorders  Phlebitis 



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MedDRA System Organ Class Common  Uncommon 
Respiratory, thoracic, and 
mediastinal disorders 

Cough Throat irritation  
Dysphonia  
Sinus congestion  
Dyspnoea 

Gastrointestinal disorders  Lip pain 
Skin and subcutaneous tissue 
disorders 

Pruritus, urticaria, 
rash 

Dermatitis allergic  
Rash generalised  
Skin exfoliation 

Musculoskeletal and 
connective tissue disorders 

 Pain in extremity  
Muscle spasm  
Muscle twitching  
Pain in jaw  

General disorders and 
administration site conditions 

Infusion site pain Pain  
Chest discomfort  
Chills  
Fatigue  
Infusion site swelling  
Non-cardiac chest pain  
Tenderness  
Vessel puncture site pain 

 
Description of selected adverse reactions 
 
Hypersensitivity and anaphylaxis 
The adverse reactions reported in the 8 subjects in whom the obiltoxaximab infusion was discontinued 
for possible hypersensitivity included urticaria, rash, cough, pruritus, dizziness, throat irritation, 
dysphonia, dyspnoea and chest discomfort. The remaining subjects with hypersensitivity had 
predominantly skin-related symptoms such as pruritus and rash, and 6 subjects reported cough. The 
anaphylaxis event was characterised by a diffuse pruritic urticarial rash over most of the body, 
including neck, chest, back, abdomen, arms, and legs, shortness of breath, and coughing. 
 
There was no evidence that the hypersensitivity reactions and rashes have been triggered by cytokine 
release; no clinically significant changes in cytokines have been observed. 
 
Immunogenicity 
The development of anti-obiltoxaximab antibodies was evaluated in all subjects receiving single and 
double doses of obiltoxaximab in three clinical studies. Eight subjects (2.5% (8/320)) who received at 
least one intravenous dose of obiltoxaximab were positive for a treatment-emergent anti-therapeutic 
antibody (ATA) response. Quantitative titres were low ranging from 1:20 to 1:320. There was no 
evidence of altered pharmacokinetics or toxicity profile in subjects with an ATA response. 
 
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, patients should be monitored for any signs or symptoms of adverse effects. 
 
 

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


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5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Immune sera and immunoglobulins, specific immunoglobulins, ATC 
code: J06BB22 
 
Mechanism of action 
 
Obiltoxaximab is a monoclonal antibody that binds the protective antigen (PA) of B. anthracis. 
Obiltoxaximab inhibits the binding of PA to its cellular receptors, preventing the intracellular entry of 
the anthrax lethal factor and oedema factor, the enzymatic toxin components responsible for the 
pathogenic effects of anthrax toxin. 
 
Pharmacodynamic effects 
 
Obiltoxaximab binds free PA with an affinity equilibrium dissociation constant (Kd) of 0.33 nM.  
In vitro, obiltoxaximab binds to PA from the Ames, Vollum, and Sterne strains of B. anthracis. The 
epitope on PA to which obiltoxaximab binds is conserved across reported strains of B. anthracis. 
 
In vitro studies in a cell-based assay, using murine macrophages, suggest that obiltoxaximab 
neutralises the toxic effects of lethal toxin, a combination of PA + lethal factor.  
 
In vivo efficacy studies in New Zealand White (NZW) rabbits and cynomolgus macaques challenged 
with the spores of the Ames strain of B. anthracis by the inhalational route, showed a dose-dependent 
increase in survival following treatment with obiltoxaximab. Exposure to B. anthracis spores resulted 
in increasing concentrations of PA in the serum of NZW rabbits and cynomolgus macaques. After 
treatment with obiltoxaximab there was a decrease in PA concentrations in a majority of surviving 
animals. PA concentrations in placebo animals increased until they died. 
 
Efficacy  
 
Because it is not feasible or ethical to conduct controlled clinical trials in humans with inhalational 
anthrax, the efficacy of obiltoxaximab administered as monotherapy compared with placebo for the 
treatment of inhalational anthrax is based on efficacy studies in NZW rabbits and cynomolgus 
macaques.  
 
In these studies, the animals were challenged with aerosolised B. anthracis spores (Ames strain) at 
approximately 200xLD50 and thereafter treated with obiltoxaximab at different time points. In 
treatment studies of inhalational anthrax, animals were administered treatment after exhibiting clinical 
signs or symptoms of systemic anthrax. In post-exposure prophylaxis studies, animals were treated 
following exposure to B. anthracis but prior to the development of symptoms. Cynomolgus macaques 
were treated at the time of a positive serum electrochemiluminescence (ECL) assay for B. anthracis 
PA at a mean time of approximately 40 hours post-challenge with B. anthracis. In NZW rabbit 
treatment studies, animals were treated after a positive ECL assay for PA or sustained elevation of 
body temperature above baseline, at a mean time of approximately 30 hours post-challenge. Survival 
was assessed at 28 days post-challenge with B. anthracis in studies described below. 
 
The efficacy of a single intravenous dose of obiltoxaximab as monotherapy for the treatment of 
inhalational anthrax was evaluated in one study in NZW rabbit studies and three studies in 
cynomolgus macaques (AP202, AP204 and AP301); all studies were placebo-controlled, randomized, 
and GLP-compliant. Studies AR033, AP202 and AP301 were blinded; study AP204 was blinded to 
group.  
 



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Table 5: Survival rates in monotherapy efficacy studies with obiltoxaximab (16 mg/kg) 

 
Proportion of survival at end of study 
(% [survived/n]) p-value2 95% CI3 
Placebo Obiltoxaximab 16 mg/kg  

Treatment - NZW rabbits 
Study AR0331 0 (0/13) 61.5% (8/13) 0.0013* (0.290, 0.861) 
Treatment - Cynomolgus macaques 
Study AP2041 6% (1/16) 46.7% (7/15) 0.0068* (0.089, 0.681) 
Study AP2021 0 (0/17) 31.3% (5/16) 0.0085* (0.079, 0.587)  
Post-exposure prophylaxis – Cynomolgus macaques 

Study 
AP3014 

18 h 
after 
exposure 

0 (0/6) 100% (6/6) 0.0012* (0.471, 1.000) 

24 h 
after 
exposure 

-- 83% (5/6) 0.0042* (0.230, 0.996) 

36 h 
after 
exposure 

-- 50% (3/6) 0.0345 (-0.037, 0.882) 

CI: Confidence Interval 
1Survival assessed 28 days after spore challenge, all randomised animals positive for bacteraemia prior 
to treatment, treatment triggered by a significant increase in body temperature (study AR033) or by a 
positive result in the protective antigen-electrochemiluminescence assay (studies AP204 and AP202). 
2p-value is from 1-sided Boschloo Test (with Berger-Boos modification of gamma=0.001) compared 
to placebo 
3Exact 95% confidence interval of difference in survival rates 
4Survival assessed 28 days after spore challenge  
*Denotes statistical significance at the 0.025 level 
 
Paediatric population 
 
The European Medicines Agency has deferred the obligation to submit the results of studies with 
Obiltoxaximab SFL in one or more subsets of the paediatric population in the treatment of bacillary 
infection (see section 4.2 for information on paediatric use). 
 
This medicinal product has been authorised under ‘exceptional circumstances’. This means that due to 
the rarity of the disease and for ethical reasons it has not been possible to obtain complete information 
on this medicinal product. 
The European Medicines Agency will review any new information which may become available every 
year and this SmPC will be updated as necessary. 
 
5.2 Pharmacokinetic properties 
 
Absorption 
 
The pharmacokinetics of obiltoxaximab are linear over the dose range of 4 mg/kg (0.25 times the 
lowest recommended dose) to 16 mg/kg following single intravenous administration in healthy 
subjects. Following single intravenous administration of obiltoxaximab 16 mg/kg in healthy, male and 
female human subjects, the mean Cmax and AUCinf were 400 ± 91.2 mcg/mL and 
5170 ± 1360 mcg·day/mL, respectively. The half-life of obiltoxaximab was approximately 20 days 
(mean). 
 



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Distribution 
 
Mean obiltoxaximab steady-state volume of distribution was 79.7 ± 19.2 mL/kg and greater than 
plasma volume, suggesting some tissue distribution. 
 
Biotransformation 
 
No formal metabolism studies have been conducted with obiltoxaximab. 
However, the disposition of monoclonal antibodies generally involves distribution beyond the vascular 
space with potential uptake into tissues, and catabolism by proteases to small peptides and amino acids 
which are subsequently incorporated into the endogenous pool or excreted. 
 
Elimination 
 
Mean obiltoxaximab clearance values were 3.35 ± 0.932 mL/d/kg and much smaller than the 
glomerular filtration rate, indicating that there is virtually no renal clearance of obiltoxaximab. 
 
Special populations 
 
Effects of gender, age and race 
Obiltoxaximab PK were evaluated via a population PK analysis using serum samples from 370 healthy 
subjects who received a single intravenous dose across 4 clinical trials. Based on this analysis, gender 
(female versus male), race (non-Caucasian versus Caucasian), or age (elderly versus young) had no 
meaningful effects on the PK parameters for obiltoxaximab. However, clinical studies of 
obiltoxaximab did not include sufficient numbers of subjects aged 65 years and over to determine 
whether their PK differs from younger subjects. Of the 320 subjects in clinical studies of 
obiltoxaximab, 9.4% (30/320) were 65 years and over, while 2% (6/320) were 75 years and over. 
 
Body size- related effects 
Clearance at a high body weight (109 kg) was approximately 38% higher than in a reference 
population. Following weight-based dosing (16 mg/kg) this results in an increase in AUCinf of 12%, 
which is not clinically meaningful. 
 
Paediatric population 
Obiltoxaximab pharmacokinetics have not been evaluated in children. The dosing recommendations in 
Table 2 (section 4.2) are derived from simulations using a population PK approach designed to match 
the observed adult exposure to obiltoxaximab at a 16 mg/kg dose. 
 
5.3 Preclinical safety data 
 
Non-clinical data reveal no special hazard for humans based on conventional studies of safety 
pharmacology, repeated dose toxicity and toxicity to reproduction and development. 
 
Central nervous system (CNS) lesions (bacteria, inflammation, haemorrhage and occasionally 
necrosis) were seen in anthrax-infected non-surviving NZW rabbits and cynomolgus macaques 
administered intravenously obiltoxaximab (≥4 mg/kg) or control at the time of disease confirmation. 
Microscopic changes in the non-surviving animals that received obiltoxaximab were due to the 
presence of extravascular bacteria and not the effect of obiltoxaximab. No dose response relationship 
for brain histopathology was identified. No treatment-related brain lesions were shown in anthrax-
infected surviving NZW rabbits (at day 28) or cynomolgus macaques (up to day 56) after a single 
administration of obiltoxaximab at doses up to 16 mg/kg and up to 32 mg/kg/dose, respectively. No 
obiltoxaximab-related neurobehavioural effects were observed in surviving anthrax-infected 
cynomolgus macaques following treatment with obiltoxaximab. 
 
A single embryonic-fetal development study was conducted in pregnant, healthy NZW rabbits 
administered 4 intravenous doses of obiltoxaximab up to 32 mg/kg (2 times the human dose on a 
mg/kg basis) on gestation days 6, 10, 13, and 17. No evidence of harm to the pregnant dam or the 



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foetuses due to obiltoxaximab was observed. Cumulative exposures in NZW rabbits 
(10,000 mcg•day/mL) at the NOAEL of 32 mg/kg/dose (n=4 doses) based on AUC0-15 days were 
approximately two-fold the human male and female combined mean AUC at the clinical intravenous 
dose of 16 mg/kg. Cmax values following a 32 mg/kg/dose were 1180 mcg•day/mL. 
 
Carcinogenicity, genotoxicity, and fertility studies have not been conducted with obiltoxaximab. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Histidine 
Sorbitol (E420) 
Polysorbate 80 (E433) 
Hydrochloric acid (E507, for pH-adjustment) 
Sodium hydroxide (E524, for pH-adjustment) 
Water for injections 
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products except those mentioned in 
section 6.6. 
 
6.3 Shelf life 
 
Unopened vial 
 
6 years 
 
Diluted solution in infusion bag 
 
After dilution in infusion bag, chemical, physical and microbial in-use stability has been demonstrated 
for 8 hours at room temperature (20°C – 25°C) or in the refrigerator (2°C – 8°C). 
 
From a microbiological point of view, unless the method of opening/reconstituting/dilution precludes 
the risks of microbial contamination, the product should be used immediately. 
 
If not used immediately, in-use storage times and conditions are the responsibility of the user. 
 
Diluted solution in syringe for infusion  
 
Once a diluted solution of Obiltoxaximab SFL has been prepared, it should be administered 
immediately and not stored. Any unused product should be discarded. 
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2°C – 8°C). 
Do not freeze. 
Store in the original packaging in order to protect from light. 
 
For storage conditions after dilution of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 
600 mg/6 mL of concentrate in vial (type I glass) with rubber stopper and a polypropylene cap with 
aluminium seal. 



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Pack contains 1 vial. 
 
6.6 Special precautions for disposal and other handling 
 
Important preparation instructions 
 
• The concentrate for solution for injection should be inspected visually for particles and 

discoloration prior to administration. Obiltoxaximab SFL is a a clear to opalescent, colourless to 
pale yellow to pale brownish-yellow solution that may contain few translucent-to-white 
proteinaceous particulates (which will be removed by in-line filtration). 

• Discard the vial if the solution is discoloured or contains foreign particles (see section 3). 
• Do not shake the vial. 
 
Preparation and dilution in infusion bag  
 
1. Calculate the milligrams of obiltoxaximab needed by multiplying the recommended mg/kg dose 

in table 2 (see section 4.2) by the individual patient’s body weight in kilograms. 
2. Calculate the required volume in millilitres of obiltoxaximab concentrate for solution for 

infusion and number of vials needed for the dose by dividing the calculated dose in milligrams 
(step 1) by the concentration, 100 mg/mL. Each single vial allows delivery of 6 mL of 
obiltoxaximab concentrate for solution for infusion. 

3. Select an appropriate size infusion bag of sodium chloride 9 mg/mL (0.9%) solution for 
injection. Withdraw a volume of solution from the infusion bag equal to the calculated volume 
in millilitres of obiltoxaximab in step 2 above. Discard the solution that was withdrawn from the 
infusion bag. 

4. Withdraw the required volume of obiltoxaximab concentrate for solution for infusion 
(calculated from step 2) from the Obiltoxaximab SFL vial(s). Discard any unused portion 
remaining in the Obiltoxaximab SFL vial(s). 

5. Transfer the required volume of obiltoxaximab concentrate for solution for infusion to the 
selected infusion bag.  

6. Gently invert the infusion bag to mix the solution. Do not shake. 
7. The infusion must be administered over 90 minutes with the infusion rate described in table 3 

(see section 4.2), using a 0.22 micron inline filter.  
8. The prepared solution is stable for 8 hours stored at room temperature 20°C to 25°C or 8 hours 

stored in the refrigerator at 2°C to 8°C. 
 
Preparation and dilution in syringe for infusion 
 
1. Calculate the milligrams of obiltoxaximab needed by multiplying the recommended mg/kg dose 

in table 2 (see section 4.2) by the individual patient’s body weight in kilograms. 
2. Calculate the required volume in millilitres of obiltoxaximab concentrate for solution for 

infusion and number of vials needed for the dose by dividing the calculated dose in milligrams 
(step 1) by the concentration, 100 mg/mL. Each single vial allows delivery of 6 mL of 
Obiltoxaximab SFL concentrate for solution for infusion. 

3. Select an appropriate size syringe for the total volume of infusion to be administered. 
4. Using the selected syringe and a 0.22 micron inline filter, withdraw the required volume of 

obiltoxaximab concentrate for solution for infusion (calculated from step 2). Discard any unused 
portion remaining in the Obiltoxaximab SFL vial(s).  

5. Withdraw an appropriate amount of sodium chloride 9 mg/mL (0.9%) solution for injection to 
prepare the total infusion volume specified in table 2. 

6. Gently mix the solution. Do not shake. 
7. Once a diluted solution of obiltoxaximab has been prepared, administer immediately. Do not 

store solution in syringe. Discard unused product. 
 



 

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Disposal 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
SFL Pharmaceuticals Deutschland GmbH 
Marie-Curie-Strasse 8 
79539 Lörrach 
Germany 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/20/1485 
 
 
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/


14 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURER OF THE BIOLOGICAL ACTIVE 
SUBSTANCE AND 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 

 
E. SPECIFIC OBLIGATION TO COMPLETE POST-

AUTHORISATION MEASURES FOR THE MARKETING 
AUTHORISATION UNDER EXCEPTIONAL 
CIRCUMSTANCES 



15 

A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE SUBSTANCE(S) AND 
MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 

 
Name and address of the manufacturer(s) of the biological active substance(s) 
 
Lonza Biologics, Inc.  
101 International Drive 
Portsmouth, NH 03801  
USA 
 
Name and address of the manufacturer(s) responsible for batch release 
 
PharmaKorell GmbH 
Georges-Köhler-Strasse 2 
79539 Lörrach 
Germany  
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE  
 
Medicinal product subject to medical prescription . 
 
 
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 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 

E. SPECIFIC OBLIGATION TO COMPLETE POST-AUTHORISATION MEASURES 
FOR THE MARKETING AUTHORISATION UNDER EXCEPTIONAL 
CIRCUMSTANCES 

 
This being an approval under exceptional circumstances and pursuant to Article 14(8) of Regulation 
(EC) No 726/2004, the MAH shall conduct, within the stated timeframe, the following measures: 
 
Description Due date 
 
In order to validate the obiltoxaximab PK method (GCL-160) in 
human serum, the MAH should submit the results from the assay 
validation for the following aspects prior to use of the assay for 
sample analysis for clinical study AH501: interference by PA (63 and 
83), EF, LF and ADAs, and assay performance in haemolytic and 
lipemic serum. Parallelism should be performed with incurred 
samples from the planned open-label field study AH501. 
 
 
 
In order to evaluate the clinical response, safety and tolerability, 
including the course of illness and survival in subjects with 
suspected, probable, or confirmed cases of inhalational anthrax 
treated with obiltoxaximab, the MAH should conduct, according to 
an agreed protocol, and submit the results of the final report for the 
phase 4, open-label field study AH501 upon the occurrence of an 
anthrax outbreak in the countries where obiltoxaximab is authorised 
and available. 
 
 
 
 

 
To be submitted together 
with the final clinical report 
of study AH501 
 
 
 
 
 
 
 
Annual reports to be 
submitted  
 
Final report will be 
provided no later than 12 
months after the last 
administration of 
obiltoxaximab or last data 
collection in case of 
retrospective data collection 

 



17 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 



18 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



19 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Obiltoxaximab SFL 100 mg/mL sterile concentrate 
obiltoxaximab  
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 mL: 100 mg of obiltoxaximab. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: histidine, sorbitol, E433, hydrochloric acid, sodium hydroxide, water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Concentrate for solution for infusion 
600 mg/6 mL 
1 vial 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
IV after dilution. 
For single use only. 
Do not shake. 
 
QR code to be included + www.obiltoxaximab-sfl.eu 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator.  
Do not freeze.  



20 

Store in the original packaging in order 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 
 
SFL Pharmaceuticals Deutschland GmbH 
Marie-Curie-Strasse 8 
79539 Lörrach 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/20/1485 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted. 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC  
SN  
NN  



21 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Obiltoxaximab SFL 100 mg/mL sterile concentrate 
obiltoxaximab  
IV after dilution. 
 
 
2. METHOD OF ADMINISTRATION 
 
For single use only. 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
600 mg/6 mL 
 
 
6. OTHER 
 
 



22 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



23 

Package leaflet: Information for the patient 
 

Obiltoxaximab SFL 100 mg/mL concentrate for solution for infusion 
obiltoxaximab 

 
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 start using 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, pharmacist or nurse. 
- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
 
1. What Obiltoxaximab SFL is and what it is used for  
2. What you need to know before you receive Obiltoxaximab SFL 
3. How Obiltoxaximab SFL will be given 
4. Possible side effects  
5. How to store Obiltoxaximab SFL 
6. Contents of the pack and other information 
 
 
1. What Obiltoxaximab SFL is and what it is used for 
 
Obiltoxaximab SFL contains the active substance obiltoxaximab. Obiltoxaximab is a monoclonal 
antibody, a type of protein that attaches to and inactivates the toxins produced by the bacteria that 
causes anthrax. 
 
Obiltoxaximab SFL is used with antibiotic medicines to treat adults and children with anthrax caused 
by breathing in the bacteria (inhalational anthrax).  
 
Obiltoxaximab SFL may also be used if you could have come into contact with anthrax bacteria or 
spores but do not have any symptoms of the disease, and if there is no other treatment available and 
appropriate. 
 
 
2. What you need to know before you receive Obiltoxaximab SFL 
 
You should not be given Obiltoxaximab SFL 
- if you are allergic to obiltoxaximab or any of the other ingredients of this medicine (listed in 

section 6). 
 
Warnings and precautions  
Talk to your doctor, pharmacist or nurse before you are given Obiltoxaximab SFL: 
 
- if you (or your child) have hereditary fructose intolerance (HFI), a rare genetic disorder, or if 

your child can no longer take sweet foods or drinks because it feels sick, vomits or gets 
unpleasant effects such as bloating, stomach cramps or diarrhoea. 

 
Allergic reactions that may occur after treatment with Obiltoxaximab SFL can sometimes be severe. 
You may be given an antihistamine before you are given Obiltoxaximab SFL to reduce the risk of 
allergic reactions. 
 



24 

Other medicines and Obiltoxaximab SFL 
Tell your doctor or pharmacist if you are using, have recently used or might use any other medicines. 
You may be given antibiotics (e.g. ciprofloxacin) to help treat inhalational anthrax. 
 
Pregnancy and breast-feeding 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor for advice before this medicine is given to you. 
 
It is not known if Obiltoxaximab SFL can harm an unborn baby.  
 
It is not known if Obiltoxaximab SFL passes into breast milk. You and your doctor will decide if you 
should breast-feed after receiving Obiltoxaximab SFL. 
 
Driving and using machines 
Obiltoxaximab SFL may cause side effects such as headache, dizziness, fatigue and vomiting. This 
may affect your ability to drive or operate machinery. 
 
Obiltoxaximab SFL contains sorbitol (E420) 
Sorbitol is a source of fructose (a type of sugar). If you (or your child) have hereditary fructose 
intolerance (HFI), a rare genetic disorder, your doctor may decide that you (or your child) must not 
receive this medicine. Patients with HFI cannot break down fructose, which may cause serious side 
effects. 
You must tell your doctor before receiving this medicine if you (or your child) have HFI or if your 
child can no longer take sweet foods or drinks because they feel sick, vomit or get unpleasant effects 
such as bloating, stomach cramps or diarrhoea. 
 
Obiltoxaximab SFL contains sodium 
This medicine contains less than 1 mmol sodium (23 mg) per each 6 mL vial of Obiltoxaximab SFL, 
that is to say essentially ‘sodium-free’. 
 
 
3. How Obiltoxaximab SFL will be given 
 
Obiltoxaximab SFL will be given to you by a doctor or a nurse. Your doctor or nurse will calculate the 
dose based on your (or your child’s) weight.  
 
Your doctor, nurse or pharmacist will prepare the medicine for infusion.  
The Obiltoxaximab SFL solution will be given as an infusion (drip) over 90 minutes into a vein, 
usually in your arm. You will be monitored while you are given Obiltoxaximab SFL and also for at 
least one hour after the infusion.  
Before you are given Obiltoxaximab SFL, you will usually be given medicines to prevent or reduce 
allergic reactions.  
 
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Tell your doctor or the person giving you the infusion straight away if you notice any of the 
following side effects:  
 
Itching, rash, shortness of breath or wheezing – these may be signs of an allergic reaction 
(hypersensitivity). 
 



25 

Other side effects of Obiltoxaximab SFL include: 
 
Common (may affect up to 1 in 10 people) 
- Headache 
- Cough 
- Infusion site pain 
- Itching, skin rash, including an itchy raised rash (hives) 
 
Uncommon (may affect up to 1 in 100 people) 
- Allergic reactions 
- Dizziness 
- Numbness 
- Visual sensitivity to light (photophobia) 
- Ear discomfort 
- Throat irritation 
- Hoarse voice 
- Sinus congestion 
- Shortness of breath 
- Lip pain 
- Eczema, pealing skin 
- Muscle twitching, muscle spasms 
- Fatigue 
- Chills (feeling of coldness) 
- Chest discomfort  
- Pain in general, and pain affecting limbs, chest, jaw, muscles, ligaments, tendons, or bones  
- Infusion site swelling, pain, or phlebitis (inflamed veins) 
 
Reporting of side effects 
If you get any side effects, talk to your doctor,pharmacist 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 Obiltoxaximab SFL 
 
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 on the label after EXP. 
The expiry date refers to the last day of that month. 
 
Store in a refrigerator (2°C – 8°C).  
Do not freeze.  
Store in the original packaging in order to protect from light. 
 
After dilution in infusion bag, chemical, physical and microbial in-use stability has been demonstrated 
for 8 hours at room temperature (20°C – 25°C) or in the refrigerator (2°C – 8°C). 
 
After dilution of Obiltoxaximab SFL in a syringe for infusion, it should be administered immediately 
and not stored. Any unused product should be discarded. 
 
 

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


26 

6. Contents of the pack and other information 
 
What Obiltoxaximab SFL contains  
- The active substance is obiltoxaximab. Each mL of concentrate contains 100 mg of 

obiltoxaximab. One vial of 6 mL contains 600 mg of obiltoxaximab. 
- The other ingredients are histidine, sorbitol (E420), polysorbate 80 (E433), hydrochloric acid 

(E507) and sodium hydroxide (E524). See also section 2 “Obiltoxaximab SFL contains 
sorbitol”. 

 
What Obiltoxaximab SFL looks like and contents of the pack 
Obiltoxaximab SFL is a clear to opalescent, colourless to pale yellow to pale brownish-yellow 
concentrate for solution. 
Obiltoxaximab SFL is available in packs containing 1 vial. 
 
Marketing Authorisation Holder 
SFL Pharmaceuticals Deutschland GmbH 
Marie-Curie-Strasse 8 
79539 Lörrach 
Germany 
 
Manufacturer  
PharmaKorell GmbH 
Georges-Köhler-Strasse 2 
79539 Lörrach 
Germany 
 
This leaflet was last revised in  
 
This medicine has been authorised under ‘exceptional circumstances’. This means that because of the 
rarity of this disease and for ethical reasons it has been impossible to get complete information on this 
medicine. 
The European Medicines Agency will review any new information on this medicine every year and 
this leaflet will be updated as necessary. 
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. There are also links to other websites about rare diseases and treatments. 
 
This leaflet is available in all EU/EEA languages on the European Medicines Agency website. 
 
Further information: www.obiltoxaximab-sfl.eu QR code to be included  

http://www.obiltoxaximab-sfl.eu/


27 

 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX IV 

CONCLUSIONS ON THE GRANTING OF THE MARKETING AUTHORISATION 
UNDER EXCEPTIONAL CIRCUMSTANCES PRESENTED BY THE EUROPEAN 

MEDICINES AGENCY 

 

 



28 

Conclusions presented by the European Medicines Agency on: 
 
• Marketing authorisation under exceptional circumstances 
 
The CHMP having considered the application is of the opinion that the risk-benefit balance is 
favourable to recommend the granting of the marketing authorisation under exceptional circumstances 
as further explained in the European Public Assessment Report. 
 
 
 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE SUBSTANCE(S) AND MANUFACTURER(S) 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
	E. SPECIFIC OBLIGATION TO COMPLETE POST-AUTHORISATION MEASURES FOR THE MARKETING AUTHORISATION UNDER EXCEPTIONAL CIRCUMSTANCES
	A. LABELLING
	B. PACKAGE LEAFLET
	CONCLUSIONS ON THE GRANTING OF THE MARKETING AUTHORISATION UNDER EXCEPTIONAL CIRCUMSTANCES PRESENTED BY THE EUROPEAN MEDICINES AGENCY