Administration of Coartem Tablets with drugs that are metabolized by CYP2D6 may significantly increase plasma concentrations of the coadministered drug and increase the risk of adverse effects. Many of the drugs metabolized by CYP2D6 can prolong the QT interval and should not be administered with Coartem Tablets due to the potential additive effect on the QT interval (e.g., flecainide, imipramine, amitriptyline, clomipramine) [see Warnings and Precautions (5.1), Drug Interactions (7.6), and Clinical Pharmacology (12.3)].
Food enhances absorption of artemether and lumefantrine following administration of Coartem Tablets. Patients who remain averse to food during treatment should be closely monitored as the risk of recrudescence may be greater [see Dosage and Administration (2.1)].
In the event of recrudescent P. falciparum infection after treatment with Coartem Tablets, patients should be treated with a different antimalarial drug.
Coartem Tablets have not been studied for efficacy and safety in patients with severe hepatic and/or renal impairment [see Dosage and Administration (2.4)].
Coartem Tablets have been shown in limited data (43 patients) to be effective in treating the erythrocytic stage of P. vivax infection. However, relapsing malaria caused by P. vivax requires additional treatment with other antimalarial agents to achieve radical cure i.e., eradicate any hypnozoites forms that may remain dormant in the liver.
The following serious and otherwise important adverse reactions are discussed in greater detail in other sections of labeling:
- Hypersensitivity Reactions [see Contraindications (4)]
- Prolongation of the QT Interval [see Warnings and Precautions (5.1)]
- Use of QT Prolonging Drugs and Other Antimalarials [see Warnings and Precautions (5.2)]
- Drug Interactions with CYP3A4 [see Warnings and Precautions (5.3)]
- Drug Interactions with CYP2D6 [see Warnings and Precautions (5.4)]
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 1979 patients including 647 adults (older than 16 years) and 1332 children (16 years and younger). For the 6-dose regimen, Coartem Tablets was studied in active-controlled (366 patients) and noncontrolled, open-label trials (1613 patients). The 6-dose Coartem Tablets population was patients with malaria between ages 2 months and 71 years: 67% (1332) 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 (greater than or equal to 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% (21/1332) in children.
|*Adult patients defined as greater than 16 years of age.|
|System Organ Class||Preferred Term||Adults* N = 647 (%)|
|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)|
|*Children defined as patients less than or equal to 16 years of age.|
|System Organ Class||Preferred Term||Children* N = 1332 (%)|
|General disorders and administration site conditions||Pyrexia||381 (29)|
|Respiratory, thoracic and mediastinal disorders||Cough||302 (23)|
|Gastrointestinal disorders||Vomiting||242 (18)|
|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)|
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 less than 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, hook-worm 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, hypoesthesia, 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
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