The most frequent adverse drug reactions (ADRs) during treatment with pretomanid in combination with bedaquiline and linezolid were nausea, vomiting and transaminases increased. Patients experienced peripheral neuropathy and anaemia, which are known adverse reactions to linezolid, respectively.
Nausea, vomiting and transaminases increased are possible adverse reactions to all three medicinal products in the regimen. The most frequent ADRs during treatment with pretomanid in combination with bedaquiline, linezolid and moxifloxacin were transaminases increased and QTc prolongation.
Refer to the Summary of Product Characteristics of bedaquiline, linezolid and moxifloxacin for more information on adverse reactions caused by these medicinal products. Tabulated list of pretomanid adverse reactions The table below displays ADRs, by system organ class and frequency, which are considered at least possibly related to the treatment regimens BPaL and BPaLM (Bedaquiline, Pretomanid, Linezolid and Moxifloxacin) and have been observed during the following clinical trials: • Nix-TB: 109 patients treated with pretomanid in combination with bedaquiline and linezolid (1 200 mg daily) for 26 weeks • ZeNix: 45 patients treated with pretomanid in combination with bedaquiline and linezolid (1 200 mg daily) for 26 weeks and 45 patients treated with pretomanid in combination with bedaquiline and linezolid (600 mg daily) • TB-PRACTECAL: 273 patients treated with pretomanid in combination with bedaquiline, linezolid (600 mg) with or without moxifloxacin (400 mg) for 24 weeks (N=151 patients in BPaLM arm + N=122 patients in BPaL arm) The ADR list below reflects in part the safety profile of the study regimens as it is hard to separate causality of one drug from another.
An overall population of 472 patients receiving BPaL regimen with or without moxifloxacin has been included. ADRs considered attributed to linezolid are marked with Δ. 8 ADRs attributed to moxifloxacin are marked with §.
Table 1:
Adverse Drug Reactions from Clinical Studies System Organ Class Very Common ≥1/10 Common ≥1/100 to <1/10 Uncommon ≥1/1,000 to <1/100 Infections and infestations Vulvovaginal candidiasis§, oral candidiasis* Blood and lymphatic system disorders Leukopenia* ∆, anaemia* ∆, lymphopenia ∆ Neutropenia* ∆, eosinophilia, thrombocytopenia* ∆ Pancytopenia ∆ Metabolism and nutrition disorders Hyponatraemia Δ, hypernatraemia Δ, hypocalcaemia, hypoalbuminaemia Δ, hyperkalaemia § Δ, hypokalaemia Δ, decreased appetite, hyperglycaemia § Δ, hypoglycaemia, lactic acidosis* ∆, hypomagnesaemia Dehydration, hypovolaemia, Psychiatric disorders Depression, insomnia Anxiety Nervous system disorders Headache, peripheral neuropathy* ∆, Dysgeusia, dizziness, tremor § Eye disorders Visual impairment* Lens disorder, eye pruritis, eye swelling, papilloedema, presbyopia, eye irritation, eye pain*, optic neuropathy*∆, cataract Ear and labyrinth disorders Deafness* Cardiac disorders Palpitations Sinus bradycardia, sinus tachycardia Vascular disorders Hypertension* Hypotension Respiratory, thoracic and mediastinal disorders Haemoptysis, epistaxis Cough* Gastrointestinal disorders Nausea, vomiting, Gastritis*, diarrhoea, constipation, pancreatitis, abdominal pain*, dyspepsia Gastrooesophageal reflux disease, abdominal distension, glossodynia, haematemesis, eructation 9 System Organ Class Very Common ≥1/10 Common ≥1/100 to <1/10 Uncommon ≥1/1,000 to <1/100 Hepatobiliary disorders Transaminase increased* Hyperbilirubinaemia Hepatomegaly, jaundice Immune system disorders Hypersensitivity Skin and subcutaneous tissue disorders Rash* Acne*, dry skin, , pruritus*, urticaria Alopecia, dermatitis allergic, erythema, skin hyperpigmentation, angioedema Musculoskeletal and connective tissue disorders Musculoskeletal pain* Muscle spasms* Polyarthritis* General disorders and administration site conditions Chest pain*, fatigue* Investigations Electrocardiogram QT prolonged Gamma- glutamyltransferase increased, , blood alkaline phosphatase increased, blood urea increased, lipase increased*, amylase increased*, blood creatinine increased § Δ, creatinine renal clearance decreased Blood creatine phosphokinase increased, albumin urine present, blood creatine phosphokinase MB increased, blood uric acid increased, *Selected terms are collapsed as follows: leukopenia (leukopenia, white blood cell count decreased); lymphopenia (lymphopenia, lymphocyte count decreased); peripheral neuropathy (burning sensation, hypoesthesia, hyporeflexia, neuropathy peripheral, paraesthesia, peripheral motor neuropathy, peripheral sensory neuropathy, polyneuropathy); gastritis (gastritis, chronic gastritis); acne (acne, dermatitis acneiform); musculoskeletal pain (arthralgia, back pain, costochondritis, myalgia, pain in extremity, musculoskeletal pain, muscle strain); transaminases increased (alanine aminotransferase (ALT) increased, aspartate aminotransferase (AST) increased, drug-induced liver injury, hepatic enzyme increased, hepatic function abnormal, liver function test increased, transaminases increased); rash (rash, rash erythematous, rash maculo-papular, rash papular, rash vesicular, rash pustular, nodular rash); pruritus (pruritus, pruritus generalized, rash pruritic); abdominal pain (abdominal pain, abdominal pain lower, abdominal pain upper, abdominal discomfort); visual impairment (vision blurred, visual acuity reduced, visual impairment); amylase increased (amylase increased, hyperamylasaemia); lipase increased (hyperlipasaemia, lipase increased); optic neuropathy (optic neuropathy, optic neuritis); pancreatitis (pancreatitis, haemorrhagic pancreatitis); anaemia (anaemia, haemoglobin decreased); thrombocytopenia (thrombocytopenia, platelet count decreased); neutropenia (neutropenia, neutrophil count decreased); hyperbilirubinemia (hyperbilirubinemia, blood bilirubin increased); lactic acidosis (lactic acidosis, acidosis, blood lactic acid increased, blood lactate increased); muscle […]