Pegcetacoplan interacts in the following cases:
There are no data available for the use of pegcetacoplan in patients with end-stage renal disease (ESRD) requiring haemodialysis.
There may be interference between silica reagents in coagulation panels and pegcetacoplan that results in artificially prolonged activated partial thromboplastin time (aPTT); therefore, the use of silica reagents in coagulation panels should be avoided.
There are no or limited amount of data from the use of pegcetacoplan in pregnant women. Studies in animals have shown reproductive toxicity.
Pegcetacoplan is not recommended during pregnancy and in women of childbearing potential not using contraception.
It is unknown whether pegcetacoplan is excreted in human milk. The potential for absorption and harm to the breastfed infant is unknown. Animal data suggest a low excretion (less than 1%, not pharmacologically significant) of pegcetacoplan in monkey milk. It is unlikely that a breastfed infant would have clinically relevant exposure.
It is recommended to discontinue breast-feeding during pegcetacoplan treatment.
It is recommended that women of childbearing potential use effective contraception methods to prevent pregnancy during treatment with pegcetacoplan and for at least 8 weeks after the last dose of pegcetacoplan. For women planning to become pregnant, the use of pegcetacoplan may be considered following an assessment of the risks and benefits.
No animal or human data on the effect of pegcetacoplan on fertility are available. In toxicity studies, there were no microscopic abnormalities in male or female reproductive organs in monkeys.
Pegcetacoplan has no or negligible influence on the ability to drive and use machines.
The most commonly reported adverse reactions in patients treated with pegcetacoplan were injection site reactions: injection site erythema, injection site pruritus, injection site swelling, injection site pain, injection site bruising. Other adverse reactions reported in more than 10% of patients during clinical studies were upper respiratory tract infection, diarrhoea, haemolysis, abdominal pain, headache, fatigue, pyrexia, cough, urinary tract infection, vaccination complication, pain in extremity, dizziness, arthralgia and back pain. The most commonly reported serious adverse reactions were haemolysis and sepsis.
The table below gives the adverse reactions observed from the clinical studies with pegcetacoplan in patients with PNH. Adverse reactions are listed by MedDRA system organ class (SOC) and frequency, using the following convention: 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), very rare (<1/10 000), and not known (cannot be estimated from available data).
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
Adverse reactions:
| MedDRA System Organ Class | Frequency | Adverse reaction |
|---|---|---|
| Infections and infestations | Very common | Upper respiratory tract infection Urinary tract infection |
| Common | Sepsis1 COVID-19 Gastrointestinal infection Fungal infection Skin infection Oral infection Ear infection Infection Respiratory tract infection Viral infection Bacterial infection Vaginal infection Eye infection | |
| Uncommon | Cervicitis Groin infection Pneumonia Nasal abscess Tuberculosis Oesophageal candidiasis COVID-19 pneumonia Anal abscess | |
| Blood and lymphatic system disorders | Very common | Haemolysis |
| Common | Thrombocytopenia Neutropenia | |
| Metabolism and nutrition disorders | Common | Hypokalaemia |
| Nervous system disorders | Very common | Headache Dizziness |
| Vascular disorders | Common | Hypertension |
| Respiratory, thoracic and mediastinal disorders | Very common | Cough |
| Common | Dyspnoea Epistaxis Oropharyngeal pain Nasal congestion | |
| Gastrointestinal disorders | Very common | Abdominal pain Diarrhoea |
| Common | Nausea | |
| Skin and subcutaneous tissue disorders | Common | Erythema Rash |
| Musculoskeletal and connective tissue disorders | Very common | Arthralgia Back pain Pain in extremity |
| Common | Myalgia Muscle spasms | |
| Renal and urinary disorders | Common | Acute kidney injury Chromaturia |
| General disorders and administration site conditions | Very common | Injection site erythema Injection site pruritus Injection site swelling Injection site bruising Fatigue Pyrexia Injection site pain |
| Common | Injection site reaction Injection site induration | |
| Investigations | Common | Alanine aminotransferase increased Bilirubin increased |
| Injury, poisoning and procedural complications | Very common | Vaccination complication2 |
The adverse reactions listed in the table are from clinical studies APL2-308, APL2-302, Study 202, Study 204, and Study CP0514 in PNH.
Medically similar terms are grouped, where appropriate, on the basis of similar medical concept.
1 Sepsis includes one case of septic shock.
2 Vaccination complications were related to the mandatory vaccinations.
Based on its mechanism of action, the use of pegcetacoplan may potentially increase the risk of infections, particularly infections caused by encapsulated bacteria including Streptococcus pneumoniae, Neisseria meningitidis types A, C, W, Y, and B, and Haemophilus influenzae. No serious infection caused by encapsulated bacteria was reported during Study APL2-302. Forty-eight patients experienced an infection during the study. The most frequent infections in patients treated with pegcetacoplan during Study APL2-302 were upper respiratory tract infection (28 cases, 35%). Most infections reported in patients treated with pegcetacoplan during study APL2-302 were non-serious, and predominantly mild in intensity. Ten patients developed infections reported as serious including one patient who died due to COVID-19. The most frequent serious infections were sepsis (3 cases) (leading to discontinuation of pegcetacoplan in one patient) and gastroenteritis (3 cases); all of which resolved. Eleven patients experienced an infection during study APL2-308. All but one infection were reported as mild or moderate in intensity. One patient who had an infection developed septic shock and died.
Nineteen patients reported haemolysis during Study APL2-302 in patients treated with pegcetacoplan. Seven cases were reported as serious, and 5 cases led to discontinuation of pegcetacoplan and the dose of pegcetacoplan was increased in 10 patients. There were 3 cases of haemolysis during study APL2-308 in patients treated with pegcetacoplan. None of these cases were reported as serious or led to discontinuation of pegcetacoplan. The dose of pegcetacoplan was increased in all 3 patients.
Anti-drug antibody (ADA) incidence (seroconverted ADA or boosted ADA from pre-existing level) were low, and when present, had no noticeable impact on the PK/PD, efficacy, or safety profile of pegcetacoplan. Throughout studies APL2-302 and APL2-308, 3 out of 126 patients who were exposed to pegcetacoplan had confirmed positive anti-pegcetacoplan peptide antibodies. All 3 patients also tested positive for neutralising antibody (NAb). NAb response had no apparent impact on PK or clinical efficacy. Eighteen out of 126 patients developed anti-PEG antibodies; 9 were seroconversions and 9 were treatment-boosted.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
