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*
|Nervous system disorders||Headache||360 (56)|
|Metabolism and nutrition disorders||Anorexia||260 (40)|
|General disorders and administration site conditions||Asthenia||243 (38)|
|Musculoskeletal and connective tissue disorders||Arthralgia||219 (34)|
|Gastrointestinal disorders||Nausea||169 (26)|
|Abdominal pain||112 (17)|
|Psychiatric disorders||Sleep disorder||144 (22)|
|Cardiac disorders||Palpitations||115 (18)|
|Hepatobiliary disorders||Hepatomegaly||59 (9)|
|Blood and lymphatic system disorders||Splenomegaly||57(9)|
|Respiratory, thoracic and mediastinal disorders||Cough||37 (6)|
|Skin and subcutaneous tissue disorders||Pruritus||24 (4)|
|Ear and labyrinth disorders||Vertigo||21 (3)|
|Infections and infestations||Malaria||18(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*
|General disorders and administration site conditions||Pyrexia||381 (29)|
|Respiratory, thoracic and mediastinal disorders||Cough||302 (23)|
|Abdominal pain||112 (8)|
|Infections and infestations||Plasmodium falciparum infection||224 (17)|
|Metabolism and nutrition disorders||Anorexia||175 (13)|
|Nervous system disorders||Headache||168 (13)|
|Blood and lymphatic system disorders||Splenomegaly||124 (9)|
|Hepatobiliary disorders||Hepatomegaly||75 (6)|
|Investigations||Aspartate aminotransferase increased||51 (4)|
|Musculoskeletal and connective tissue disorders||Arthralgia||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
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.