Arthemether causes QT prolongation in some patients

Concomittant use of erythromycin , tefanadine, procainamide, quinidine, bretylium, bepridil, solatol, astemizole, tricyclic antidepressants , phenothizines my be avoided

At high doses high neurotoxicity is the common side effect.

Neurotoxicity manifests itself as gait disturbances,

Loss of spinal responses incordination,

Respiratory depression,

Convulsions and respiratory arrest.

Other side effects are nausea, dizziness, and depressed GIT activity.

Clinical neurological, electrocardiographic and biochemical abnormality was seen.

Hypersensitivity

Pregnancy and lactation

Avoid concomittant use of drugs known to prolong QT interval or monitor such patients

Indication-

Falciparium malaria

Dosage-

Adult- 80mg daily to be taken withlumefantrine 480mg daily doses to be taken at diagnosis and repeated after 8, 24, and 36, 48 and 60 hrs

Total dose is 6

Children-  daily dose based on body weight. 5-14 kg- 20mg with lumefantrine 120mg

15-24 kg - 40mg with lumefantrine 240mg  25-34kg - 60mg with lumefantrine 360mg

> 34 kg- 80mg with luefantrine 480mg

and repeated after 8, 24, 36, 48hrs and 60hrs

Total dose is 6

Coartem (artemether/lumefantrine) Tablets

 PATIENT COUNSELING INFORMATION

See FDA-Approved Patient Labeling 

1 Information for Safe Use

• Instruct patients to take Coartem Tablets with food. Patients who do not have an adequate intake of food are at risk for recrudescence of malaria.

• Patients hypersensitive to artemether, lumefantrine, or to any of the excipients should not receive Coartem Tablets.

• Instruct patients to inform their physician of any personal or family history of QT prolongation or proarrhythmic conditions such as hypokalemia, bradycardia, or recent myocardial ischemia.

• Instruct patients to inform their physician if they are taking any other medications that prolong the QT interval, such as class IA (quinidine, procainamide, disopyramide), or class III (amiodarone, sotalol) antiarrhythmic agents; antipsychotics (pimozide, ziprasidone); antidepressants; certain antibiotics (macrolide antibiotics, fluoroquinolone antibiotics, imidazole, and triazole antifungal agents); certain nonsedating antihistamines (terfenadine, astemizole), or cisapride.

• Instruct patients to notify their physicians if they have any symptoms of prolongation of the QT interval, including prolonged heart palpitations or a loss of consciousness.

• Instruct patients to avoid medications that are metabolized by the cytochrome enzyme CYP2D6 while receiving Coartem Tablets since these drugs also have cardiac effects (e.g., flecainide, imipramine, amitriptyline, clomipramine).

• Inform patients that based on animal data, Coartem Tablets administered during pregnancy may result in fetal loss. Fetal defects have been reported when artemisinins are administered to animals.

• Halofantrine and Coartem Tablets should not be administered within one month of each other due to potential additive effects on the QT interval.

• Antimalarials should not be given concomitantly with Coartem Tablets, unless there is no other treatment option, due to limited safety data.

• QT prolonging drugs, including quinine and quinidine, should be used cautiously following Coartem Tablets due to the long elimination half-life of lumefantrine and the potential for additive effects on the QT interval.

• Closely monitor food intake in patients who received mefloquine immediately prior to treatment with Coartem Tablets.

• Use Coartem Tablets cautiously in patients receiving other drugs that are substrates, inhibitors or inducers of CYP3A4, including grapefruit juice, especially those that prolong the QT interval or are anti-retroviral drugs.

• Coartem Tablets may reduce the effectiveness of hormonal contraceptives. Therefore, patients using oral, transdermal patch, or other systemic hormonal contraceptives should be advised to use an additional nonhormonal method of birth control.

• Inform patients that Coartem Tablets can cause hypersensitivity reactions. Instruct patients to discontinue the drug at the first sign of a skin rash, hives or other skin reactions, a rapid heartbeat, difficulty in swallowing or breathing, any swelling suggesting angioedema (e.g., swelling of the lips, tongue, face, tightness of the throat, hoarseness), or other symptoms of an allergic reaction.

FDA-APPROVED PATIENT LABELING Patient Information Coartem® (co-AR-tem) (artemether and lumefantrine) Tablets Read this patient information before you start taking Coartem. There may be new information. 

Distributed by: Novartis Pharmaceuticals Corporation East Hanover, New Jersey 07936

Pharmacology:

Artermisinin derivativse are the potent and rapidly acting blood schizonides. The mechanism of action is novel and structure- activity relationship suggests that the endoperoxide bridge is essential for antimalarial activity. The schizonicidal activity of artemether is due the destruction of the asexual erythrocytic forms of P.falciparum and P.Vivax.

Pharmacokinetics:

Available data on pharmacokinetics indicate that following IM use of artemether, there is prolonged plasma drug concentration. Half-life is about 7 hrs at the theapeutic dose.

Take with food

Pregnancy

Since no clinical data is avialble for the use of arteether during pregnancy it should be used in pregnanct women if potential benefits justifies the potential risk to the fetus.

Lactation

It is not known whether arteether is excreted in human milk, caution should be excercised while using artemether.