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.
As a precautionary measure, it is preferable to avoid the use of obiltoxaximab during pregnancy.
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-feeding, only if clinically needed.
Fertility studies have not been conducted with obiltoxaximab.
Obiltoxaximab may have a minor influence on the ability to drive and use machines since headache, dizziness, fatigue and vomiting may occur following administration.
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%).
The table below 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.
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 | |
| 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 |
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.
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.
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