Eculizumab interacts in the following cases:
Concomitant use of eculizumab with neonatal Fc receptor (FcRn) blockers may lower systemic exposures and reduce effectiveness of eculizumab. Closely monitor for reduced effectiveness of eculizumab.
Concomitant use of eculizumab with intravenous immunoglobulin (IVIg) may reduce effectiveness of eculizumab. Closely monitor for reduced effectiveness of eculizumab.
No interaction studies have been performed. Based on the potential inhibitory effect of eculizumab on complement-dependent cytotoxicity of rituximab, eculizumab may reduce the expected pharmacodynamic effects of rituximab.
Due to its mechanism of action, eculizumab therapy should be administered with caution to patients with active systemic infections. Patients may have increased susceptibility to infections, especially with Neisseria and encapsulated bacteria. Serious infections with Neisseria species (other than Neisseria meningitidis), including disseminated gonococcal infections, have been reported. Patients should be provided with information from the Package Leaflet to increase their awareness of potential serious infections and the signs and symptoms of them. Physicians should advise patients about gonorrhoea prevention.
The use of adequate contraception to prevent pregnancy and for at least 5 months after the last dose of treatment with eculizumab should be considered for women of childbearing potential.
There are no well-controlled studies in pregnant women treated with eculizumab. Data on a limited number of pregnancies exposed to eculizumab (less than 300 pregnancy outcomes) indicate there is no increased risk of foetal malformation or foetal-neonatal toxicity. However, due to the lack of well-controlled studies, uncertainties remain. Therefore, an individual risk benefit analysis is recommended before starting and during treatment with eculizumab in pregnant women. Should such a treatment be considered necessary during pregnancy, a close maternal and foetal monitoring according to local guidelines is recommended.
Animal reproduction studies have not been conducted with eculizumab.
Human IgG are known to cross the human placental barrier, and thus eculizumab may potentially cause terminal complement inhibition in the foetal circulation. Therefore, eculizumab should be given to a pregnant woman only if clearly needed.
No effects on the breastfed newborn/infant are anticipated as limited data available suggest that eculizumab is not excreted in human breast milk. However, due to the limitations of the available data, the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for eculizumab and any potential adverse effects on the breastfed child from eculizumab or from the underlying maternal condition.
No specific study of eculizumab on fertility has been conducted.
Eculizumab has no or negligible influence on the ability to drive and use machines.
Supportive safety data were obtained from 33 clinical studies that included 1,555 patients exposed to eculizumab in complement-mediated disease populations, including PNH, aHUS, refractory gMG and NMOSD. The most common adverse reaction was headache, (occurred mostly in the initial phase of dosing), and the most serious adverse reaction was meningococcal infection.
The following table gives the adverse reactions observed from spontaneous reporting and in eculizumab completed clinical trials, including PNH, aHUS, refractory gMG and NMOSD studies. Adverse reactions reported at a very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1 000 to <1/100) or rare (≥1/10 000 to <1/1 000) frequency with eculizumab, are listed by system organ class and preferred term. Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
Adverse Reactions reported in eculizumab clinical trials, including patients with PNH, aHUS, refractory gMG and NMOSD as well as from postmarketing experience:
| MedDRA System Organ Class | Very Common (≥1/10) | Common (≥1/100 to <1/10) | Uncommon (≥1/1 000 to <1/100) | Rare (≥1/10000 to <1/1000) |
|---|---|---|---|---|
| Infection and infestations | Pneumonia, Upper respiratory tract infection, Bronchitis, Nasopharyngitis, Urinary tract infection, Oral Herpes | Meningococcal infectionb, Sepsis, Septic shock, Peritonitis, Lower respiratory tract infection, Fungal infection, Viral infection, Abscessa, Cellulitis, Influenza, Gastrointestinal infection, Cystitis, Infection, Sinusitis, Gingivitis | Aspergillus infectionc, Arthritis bacterialc, Genitourinary tract gonococcal infection, Haemophilus influenzae infection, Impetigo | |
| Neoplasms benign, malignant and unspecified (including cysts and polyps) | Malignant melanoma, Myelodysplastic syndrome | |||
| Blood and lymphatic system disorders | Leukopenia, Anaemia | Thrombocytopenia, Lymphopenia | Haemolysis*, Abnormal clotting factor, Red blood cell agglutination, Coagulopathy | |
| Immune system disorders | Anaphylactic reaction, Hypersensitivity | |||
| Endocrine disorders | Basedow’s disease | |||
| Metabolism and nutrition disorders | Decreased appetite | |||
| Psychiatric disorders | Insomnia | Depression, Anxiety, Mood swings, Sleep disorder | Abnormal dreams | |
| Nervous system disorders | Headache | Dizziness | Paraesthesia, Tremor, Dysgeusia, Syncope | |
| Eye disorders | Vision blurred | Conjunctival irritation | ||
| Ear and labyrinth disorders | Tinnitus, Vertigo | |||
| Cardiac disorders | Palpitation | |||
| Vascular disorders | Hypertension | Accelerated hypertension, Hypotension, Hot flush, Vein disorder | Haematoma | |
| Respiratory, thoracic and mediastinal disorders | Cough, Oropharyngeal pain | Dyspnoea, Epistaxis, Throat irritation, Nasal congestion, Rhinorrhoea | ||
| Gastrointestinal disorders | Diarrhoea, Vomiting, Nausea, Abdominal pain | Constipation, Dyspepsia, Abdominal distension | Gastroesophageal reflux disease, Gingival pain | |
| Hepatobiliary disorders | Jaundice | |||
| Skin and subcutaneous tissue disorders | Rash, Pruritus, Alopecia | Urticaria, Erythema, Petechiae, Hyperhidrosis, Dry skin, Dermatitis | Skin depigmentation | |
| Musculoskeletal and connective tissue disorders | Arthralgia, Myalgia, Pain in extremity | Muscle spasms, Bone pain, Back pain, Neck pain | Trismus, Joint swelling | |
| Renal and urinary disorders | Renal impairment, Dysuria, Haematuria | |||
| Reproductive system and breast disorders | Spontaneous penile erection | Menstrual disorder | ||
| General disorders and administration site conditions | Pyrexia, Fatigue, Influenza like illness | Edema, Chest discomfort, Asthenia, Chest pain, Infusion site pain, Chills | Extravasation, Infusion site paraesthesia, Feeling hot | |
| Investigations | Alanine aminotransferase increased, Aspartate aminotransferase increased, Gamma- glutamyltransferase increased, Haematocrit decreased, Haemoglobin decreased | Coombs test positivec | ||
| Injury, poisoning and procedural complication | Infusion-related reaction |
Included Studies: Asthma (C07-002), aHUS(C08-002, C08-003, C10-003, C10-004), Dermatomyositis (C99-006), refractory gMG (C08-001, ECU-MG-301, ECU-MG-302, ECU-MG-303), Neuromyelitis Optica Spectrum Disorder (ECU-NMO-301, ECU-NMO-302), IMG (C99-004, E99-004), PNH (C02-001, C04-001, C04-002, C06-002, C07-001, E02-001, E05-001, E07-001, M07-005, X03-001, X03-001A), Psoriasis (C99-007), RA (C01-004, C97-001, C99-001, E01-004, E99-001), STEC-HUS (C11-001), SLE (C97-002). MedDRA version 24.1.
* See paragraph Description of selected adverse reactions.
a Abscess includes the following group of PTs: Abscess limb, Colonic abscess, Renal abscess, Subcutaneous abscess, Tooth abscess, Hepatosplenic abscess, Perirectal abscess, Rectal abscess.
b Meningococcal infection includes the following group of PTs: Meningococcal infection, Meningococcal sepsis, Meningitis meningococcal, Neisseria infection.
c ADRs identified in postmarketing reports.
In all clinical studies, the most serious adverse reaction was meningococcal sepsis which is a common presentation of meningococcal infections in patients treated with eculizumab.
Other cases of Neisseria species have been reported including sepsis with Neisseria gonorrhoeae, Neisseria sicca/subflava, Neisseria spp unspecified.
Antibodies to eculizumab were detected in 2% of patients with PNH using an ELISA assay, 3% of patients with aHUS and 2% of patients with NMOSD using the ECL bridging format assay. In refractory gMG placebo-controlled studies, no antidrug antibodies were observed. As with all proteins there is a potential for immunogenicity.
Cases of haemolysis have been reported in the setting of missed or delayed eculizumab dose in PNH clinical trials.
Cases of thrombotic microangiopathy complication have been reported in the setting of missed or delayed eculizumab dose in aHUS clinical trials.
In children and adolescent PNH patients (aged 11 years to less than 18 years) included in the paediatric PNH Study M07-005, the safety profile appeared similar to that observed in adult PNH patients. The most common adverse reaction reported in paediatric patients was headache.
In paediatric aHUS patients (aged 2 months to less than 18 years) included in the aHUS studies C08-002, C08-003, C09-001r and C10-003, the safety profile appeared similar to that observed in adult aHUS patients. The safety profiles in the different paediatric subsets of age appear similar.
In paediatric patients with refractory gMG (aged 12 to less than 18 years) included in Study ECU-MG-303, the safety profile appeared similar to that observed in adult patients with refractory gMG. Eculizumab has not been studied in paediatric patients with NMOSD.
No overall differences in safety were reported between elderly (≥65 years) and younger refractory gMG patients (<65 years).
Supportive safety data were obtained in 12 completed clinical studies that included 934 patients exposed to eculizumab in other disease populations other than PNH, aHUS, refractory gMG or NMOSD. There was an un-vaccinated patient diagnosed with idiopathic membranous glomerulonephropathy who experienced meningococcal meningitis. Adverse reactions reported in patients with disease other than PNH, aHUS, refractory gMG or NMOSD were similar to those reported in patients with PNH, aHUS, refractory gMG or NMOSD (see the table above). No specific adverse reactions have emerged from these clinical studies.
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