Serious Adverse Reactions The following serious and otherwise important adverse reactions are discussed in greater detail in other sections of labeling:
- Hypersensitivity Reactions [see CONTRAINDICATIONS and Postmarketing Experience].
Clinical Studies Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rate observed in practice. The data described below reflect exposure to a 6-dose regimen of Coartem Tablets in 1,979 patients including 647 adults (older than 16 years) and 1,332 children (16 years and younger). For the 6-dose regimen, Coartem Tablets was studied in active-controlled (366 patients) and non-controlled, open-label trials (1,613 patients). The 6-dose Coartem Tablets population was patients with malaria between ages 2 months and 71 years: 67% (1,332) were 16 years and younger and 33% (647) were older than 16 years. Males represented 73% and 53% of the adult and pediatric populations, respectively. The majority of adult patients were enrolled in studies in Thailand, while the majority of pediatric patients were enrolled in Africa. Tables 1 and 2 show the most frequently reported adverse reactions ( ≥ 3%) in adults and children respectively who received the 6-dose regimen of Coartem Tablets. Adverse reactions collected in clinical trials included signs and symptoms at baseline but only treatment emergent adverse events, defined as events that appeared or worsened after the start of treatment, are presented below. In adults, the most frequently reported adverse reactions were headache, anorexia, dizziness, and asthenia. In children, the adverse reactions were pyrexia, cough, vomiting, anorexia, and headache. Most adverse reactions were mild, did not lead to discontinuation of study medication, and resolved. In limited comparative studies, the adverse reaction profile of Coartem Tablets appeared similar to that of another antimalarial regimen. Discontinuation of Coartem Tablets due to adverse drug reactions occurred in 1.1% of patients treated with the 6-dose regimen overall: 0.2% (1/647) in adults and 1.6% (21/1,332) in children. Table 1: Adverse Reactions Occurring in 3% or More of Adult Patients Treated in Clinical Trials with the 6-dose Regimen of Coartem Tablets
System Organ Class Preferred Term Adults*
N=647 (%) Nervous system disorders Headache 360 (56) Dizziness 253 (39) Metabolism and nutrition disorders Anorexia 260 (40) General disorders and administration site conditions Asthenia 243 (38) Pyrexia 159 (25) Chills 147 (23) Fatigue 111 (17) Malaise 20 (3) Musculoskeletal and connective tissue disorders Arthralgia 219 (34) Myalgia 206 (32) Gastrointestinal disorders Nausea 169 (26) Vomiting 113 (17) Abdominal pain 112 (17) Diarrhea 46 (7) Psychiatric disorders Sleep disorder 144 (22) Insomnia 32(5) Cardiac disorders Palpitations 115 (18) Hepatobiliary disorders Hepatomegaly 59 (9) Blood and lymphatic system disorders Splenomegaly 57(9) Anemia 23 (4) Respiratory, thoracic and mediastinal disorders Cough 37 (6) Skin and subcutaneous tissue disorders Pruritus 24 (4) Rash 21(3) Ear and labyrinth disorders Vertigo 21 (3) Infections and infestations Malaria 18(3) Nasopharyngitis 17(3) * Adult patients defined as > 16 years of age Table 2: Adverse Reactions Occurring in 3% or More of Pediatric Patients Treated in Clinical Trials with the 6-dose Regimen of Coartem Tablets
System Organ Class Preferred Term Children*
N=1,332 (%) General disorders and administration site conditions Pyrexia 381 (29) Chills 72 (5) Asthenia 63 (5) Fatigue 46 (3) Respiratory, thoracic and mediastinal disorders Cough 302 (23) Gastrointestinal disorders Vomiting 242(18) Abdominal pain 112 (8) Diarrhea 100 (8) Nausea 61 (5) Infections and infestations Plasmodium falciparum infection 224 (17) Rhinitis 51 (4) Metabolism and nutrition disorders Anorexia 175 (13) Nervous system disorders Headache 168 (13) Dizziness 56(4) Blood and lymphatic system disorders Splenomegaly 124 (9) Anemia 115(9) Hepatobiliary disorders Hepatomegaly 75 (6) Investigations Aspartate aminotransferase increased 51 (4) Musculoskeletal and connective tissue disorders Arthralgia 39(3) Myalgia 39(3) Skin and subcutaneous tissue disorders Rash 38 (3) * Children defined as patients ≤ 16 years of age Clinically significant adverse reactions reported in adults and/or children treated with the 6-dose regimen of Coartem Tablets which occurred in clinical studies at < 3% regardless of causality are listed below: Blood and lymphatic system disorders: eosinophilia Ear and labyrinth disorders: tinnitus Eye disorders: conjunctivitis Gastrointestinal disorders: constipation, dyspepsia, dysphagia, peptic ulcer General disorders: gait disturbance Infections and infestations: abscess, acrodermatitis, bronchitis, ear infection, gastroenteritis, helminthic infection, hookworm infection, impetigo, influenza, lower respiratory tract infection, malaria, nasopharyngitis, oral herpes, pneumonia, respiratory tract infection, subcutaneous abscess, upper respiratory tract infection, urinary tract infection Investigations: alanine aminotransferase increased, aspartate aminotransferase increased, hematocrit decreased, lymphocyte morphology abnormal, platelet count decreased, platelet count increased, white blood cell count decreased, white blood cell count increased Metabolism and nutrition disorders: hypokalemia Musculoskeletal and connective tissue disorders: back pain Nervous system disorders: ataxia, clonus, fine motor delay, hyperreflexia, hypoaesthesia, nystagmus, tremor Psychiatric disorders: agitation, mood swings Renal and urinary disorders: hematuria, proteinuria Respiratory, thoracic and mediastinal disorders: asthma, pharyngo-laryngeal pain Skin and subcutaneous tissue disorders: urticaria Postmarketing Experience The following adverse reactions have been identified during post-approval use of Coartem Tablets. Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
- Hypersensitivity reactions including urticaria and angioedema. Serious skin reactions (bullous eruption) have been rarely reported.
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