Justeen Pharmaceauticals Limited

ATERL^? INJECTION

Artemether Injection 80mg/ml

• Composition

  Each m1 contains:
  Artemether: 80mg/ml

• DESCRIPTION

  Artemether is a lipid soluble methylether of dihydroartemisinin. Artemisinin is a novel sesquiterpene lactone, extracted from the leaves of the shrub Artemesia annua and possesses an endoperoxide bridge which is a rare feature in natural products. The endoperoxide bridge is essential for its antimalarial activity. Its chemical formula. is 3R, 5aS, 6R, 8aS, 9R, IDS, 12R, 12aR - Decahydro-l0-methoxy-3, 6, 9-trimethyl-3, 12- epoxy-12H-pyrano (4,3)-1,2-benzodioxepin. Its molecular formula is C16H29O5 and its molecular weight is 298.4.

• PHARMACOLOGY

  Artemether is active against all Plasmodia including those which may be resistant to other antimalarials.

  Artemether has very rapid schizontocidal activity. The schizontocidal activity of artemether is mainly due to destruction of the asexual erythrocytic forms of P. falciparum and P. vivax. There is inhibition of protein synthesis during growth of trophozoites.

  There is no cross resistance with chloroquine. It is not hypnozoiticidal but it reduces gametocyte carriage. There is no rationale at present for using artemether for chemoprophylaxis.

• PHARMACOKINETICS

  Artemether is hydrolyzed after administration to a biological active metabolite, dihydroarternisinin. Total protein binding is 95.4%. The drug is rapidly and extensively metabolized in the liver.

  The plasma concentrations of artemether are similar in healthy subjects and those with acute uncomplicated malaria. Plasma antimalarial activity is significantly greater with intramuscular administration than with oral use because the first-pass biotransformation is bypassed. Bioavailability of artemether following intramuscular administration was increased and clearance reduced in patients with acute renal failure.

  Artemether has been reported to clear fever in severe falciparum malaria within 30-84 hours.

• INDICATIONS

  ARTERL injection is indicated for:
  Treatment of severe and complicated malaria caused by P. falciparum both in adults and children in areas where there is multidrug resistance.

• CONTRAINDICATIONS

  Artemether is contraindicated in patients with hypersensitivity to artemether or other artemisinin compounds. Artemether is not recommended in the first trimester of pregnancy because of limited date.

• PRECAUTIONS

  1. Do not exceed the prescribed dose. In case of over dosage, urgent symptomatic treatment in a specialized unit is required.
  2. Caution is required in patients with
  3. Cardiovascular disease
  4. Hepatic impairment
  5. Renal insufficiency

  Usage in pregnancy

  As per information available from World Health Organisation, little experience has been gained with the use of this drug in pregnancy but it should not be withheld if it is considered life-saving to the mother. Artemether and its derivatives can be used for treatment of uncomplicated malaria during the second and third trimester of pregnancy in areas of multidrug resistance. Owing to lack of date, use in the first trimester of pregnancy is not recommended.

  Artemether and its derivatives have not been measured in the milk of nursing mothers. It is very likely that these are present in milk and nursing mothers should not be given artemisinin if they are suffefing from uncomplicated malaria either in multidrug resistance or drug sensitive situations. If the nursing mother is suffering from complicated and serious malaria induced by multidrug-resistant P. falciparum and artemisinin is indicated, breast feeding should be stopped.

• SIDE EFFECTS

  At the therapeutic dose, there are virtually no side effects. There are reports on laboratory abnormalities i.e. a decrease in reticulocytes count, an increase in transaminase and ECG changes (Sinus Bradycardia). However these are transient. At high dose, transient abdominal pain, diarrhoea and tinnitus occur.

• Drug interactions

  Since electrocardiographic QT prolongation has been reported in some patients treated with artemether, it is recommended to avoid prescription of medications known to produce a prolongation of QT interval or patients receiving such medications: erythromycin, terfenadine, astemizole, probucol, Class 1a anti-arrhythmic agents (quindine, procainarnide, disopyramide). Class III anti-arrhythmic agents (amiodarone, bretylium), bepridil, sotalol, tricyclic antidepressants, some neuroleptics and phenothiazines are to be monitored closely.

• ADVERSE DRUG REACTIONS

  Artemether has been remarkably well-tolerated, and appears less toxic than quinine or chloroquine, adverse effects include bradycardia, electracardiogram abnormalities, dizziness, injection site pain, skin reactions, and fever. Transient decreases in neutrophils and reticulocytes have been reported in some patients treated with artemether.

  Drug induced fever has been observed with artemether. Mild reactions were seen in patients to whom artemether had been administered intramuscularly. These include nausea, hypotension, dizziness and tinnitus. These side effects were also reported: dark urine, sweating, somnolence and jaundice.

  There were no deaths or any other side effects. No irreversible side effects were seen. Slight rise of SGOT and SGIT may occur in individual cases. Neurological side effects have not yet been observed in clinical use but clinical trials suggest that coma may be prolonged in patients treated with artemether and there was an increased incidence of convulsions in one trial in cerebral malaria.

  Transient first degree heart block has been documented in three patients receiving artemether. Neurotoxicity has been observed in animal studies but not in humans.

  Cardio toxicity has been observed following administration of high doses of Artemether.

• OVERDOSAGE

  There is no experience with overdosage with artemether. There is no specific antidote known for the artemisinin derivatives. However, experimental toxicological results obtained with large doses of artemisinin on the cardiovascular system and the CNS should be considered.

  Overdosage could bring on cardiac irregularities. An ECG should be taken before initiating treatment in cardiac patients. Irregularities in the pulse should be looked for and cardiac monitoring carried out if necessary.

  The animal results on the CNS suggest that overdose could result in changes in brain stem function, Clinicians testing cases of overdosage should Iook for changes in gait, loss of balance, or changes in ocular movements and reflexes.

• DOSAGE AND ADMINISTRATION

  When used as monotherapy, a minimum of 6 days course is required to prevent recrudescence. If regimens of less than 6 days are employed, combination therapy with oral lumefantrine or mefloquine or another effective blood schizontocide should be employed.

  Artemether injection is for intramuscular use only. The daily dose can: be given as a single injection. Severe malaria and complicated malaria including cerebral malaria:

  Adults: 1 ampoule (80mg) b.i.d. on first day, then followed by 1 ampoule (80mg) daily for the subsequent 5 days.

  Children: 1.6mg/kg body weight b.i.d. on first day, then followed by 1.6mg/kg body weight daily for the subsequent 5 days.

  In children, the use of tuberculin syringe is advisable since the injection volume will be small. 3.2mg/kg by the intramuscular route as a loading dose on the first day, following by 1-6mg/kg daily for a minimum 3 days or until the patient can take oral therapy to complete a 7-day course.

  The daily dose can be given as a single injection. In children, the use of a tuberculin syringe is advisable since the injection volume will be small.

  Or as directed by the Physician.

• PRESENTATION

  ATERL injection: Ampoule of 80mg/ml

• STORAGE

  Keep in a cool place away from light.
  KEEP All MEDICINES OUT OFREACHOF CHILDREN.