Drutemal® -Plus Tablets and Oral Suspension
COMPOSITION
Each 5ml oral suspension of Drutemal®- Plus (after reconstitution) contains Artemether 20mg + Lumefantrine 120mg.
Each tablet of Drutemal®- Plus contains Artemether 40mg + Lumefantrine 240mg
Each tablet of Drutemal®- Plus (DS) contains Artemether 80mg + Lumefantrine 480mg.
ACTION
Artemether is a semisynthetic derivative of artemisinin while lumefantrine is a chlorobenzylidine derivative. The site of antiparasitic action of both components is the food vacuole of malaria parasite, where they interfere with the conversion of haem, a toxic intermediate produced during haemoglobin breakdown, to the nontoxic haemozin. Lumefantrine is thought to interfere with the polymerisation process, while artemether generates reactive metabolites as a result of the interaction between its peroxide bridge and haem iron. Both artemether and lumefantrine have a secondary action involving inhibition of nucleic acid and protein synthesis within the malaria parasite.
PHARMACOKINETICS
Peak plasma concentrations have been achieved in about 3 hours after oral administration of artemether. The bioavailability of lumefantrine after oral administration is variable; absorption begins after a lag-time of up to 2 hours and bioavailability is substantially increased by administration with food, particularly meals high in fat. Peak plasma concentrations occur after about 6 to 8 hours. Artemether and lumefantrine are both highly bound to human serum protein in vitro (95.4% and 99.7% respectively). Dihydroartemisinin an active metabolite of artemether is also bound to human serum proteins (47%-76%).
Lumefantrine is N-debutylated, mainly by CYP3A4, in human liver microsomes.
Artemether and dihydroartemsinin are rapidly cleared from plasma with an elimination half life of about 2 hours. Lumefantrine is eliminated very slowly with a terminal half-life of 2-3 days in healthy volunteers and 4-6 days in patients with falciparum malaria.
INDICATIONS
Drutemal®- Plus is indicated for the treatment of uncomplicated Plasmodium falciparum malaria including severe malaria caused by multiple drug resistant Strains of P. falciparum.
DOSAGE
The first dose of the Drutemal®- Plus Suspension (after reconstitution) and tablets should be given at the time of initial diagnosis, then should be followed by five further doses at 8,24,36,48 and 60 hours thereafter.
See Table below
Drutemal®- Plus Suspension (Artemether 20mg + Lumefantrine 120mg)
| Age/Weight
(kg) |
Total Quantity | Dosage Regimen | |||||
| Day 1 | Day 2 | Day 3 | |||||
| 0 Hour | 8 Hours | 24 Hours | 36 Hours | 48 Hours | 60 Hours | ||
| 6 mths-3yrs
(5-14)kg |
30ml | 5ml (one teaspoonful) | 5ml (one teaspoonful) | 5ml (one teaspoonful) | 5ml (one teaspoonful) | 5ml (one teaspoonful) | 5ml (one teaspoonful) |
| 4-8 years
(15-24)kg |
60ml | 10ml (two teaspoonful) | 10ml (two teaspoonful) | 10ml (two teaspoonful) | 10ml (two teaspoonful) | 10ml (two teaspoonful) | 10ml (two teaspoonful) |
Table for Oral administration
To increase absorption, tablets should be taken with food or a milky drink. If patients are unable to tolerate food, the tablets should be administered, but the systemic exposure may be reduced. Patients who vomit within 1 hour of taking the medication should repeat the dose.
Drutemal®- Plus Tablets (Artemether 40mg + Lumefantrine 240mg)
| Age/Weight
(kg) |
Total Quantity | Dosage Regimen | |||||
| Day 1 | Day 2 | Day 3 | |||||
| 0 Hour | 8 Hours | 24 Hours | 36 Hours | 48 Hours | 60 Hours | ||
| 6 mths-3yrs
(5-14)kg |
3 | ½ | ½ | ½ | ½ | ½ | ½ |
| 4-8 years
(15-24)kg |
6 | 1 | 1 | 1 | 1 | 1 | 1 |
| 9-14 years
(25-34)kg |
9 | ½ | ½ | ½ | ½ | ½ | ½ |
| Adult
35kg and above) |
12 | 2 | 2 | 2 | 2 | 2 | 2 |
Drutemal® – Plus (DS) Tablets (Artemether 80mg + Lumefantrine 480mg)
| Age/Weight
(kg) |
Total Quantity | Dosage Regimen | |||||
| Day 1 | Day 2 | Day 3 | |||||
| 0 Hour | 8 Hours | 24 Hours | 36 Hours | 48 Hours | 60 Hours | ||
| 6 mths-3yrs
(5-14)kg |
6 | 1 | 1 | 1 | 1 | 1 | 1 |
CONTRAINDICATIONS:
Artemether-lumefantrine is contraindicated in:
* Patients with known hypersensitivity to the active substances or to any of the excipients.
* Antiarrhythmics of classes lA and lll.
* Certain antibiotics including some agents of the following classes: macrolides, fluoroquinolones.
* Patients with a history of symptomatic cardiac arythmias or with clinically relevant bradycardia or with congestive cardiac failure accompanied by reduced left ventricle ejection fraction.
* Patients with disturbances of electrolyte balance e.g hypokalemia or hypomagnesemia.
ADVERSE EFFECTS:
Adverse effects associated with lumefantrine in combination with artemether commonly include headache, dizziness, sleep disturbance, palpitations, gastrointestinal disturbances, anorexia, pruritus, rash, cough, arthralgia, myalgia and fatigue.
DRUG INTERACTIONS:
In patients previously treated with halofantrine,Drutemal®- Plus should not be administered earlier than one month after the last halofantrine dose.
Due to limited data on safety and efficacy, Drutemal®- Plus should not be given concurrently with any other anti-malarial agent unless there is no other treatment option.
PREGNANCY AND LACTATION
The safety of this medicine for use during pregnancy has not been established. It should be avoided wherever possible during the first trimester. It should only be used during later stages of pregnancy if the expected benefits to the mother outweigh any risks to the foetus.
It is not known if this medicine passes into breast milk. Women who need to take this medicine should not breastfeed during treatment, and for at least a week following their last dose. Seek medical advice from your doctor.
WARNINGS/PRECAUTIONS
– The oral bioavailability of artemether may be increased by concomitant administration of grapefruit juice, it would be better not to drink grape fruit juice while taking Drutemal®- Plus
– The prescribed course of this medicine should be completed for effectiveness, unless otherwise directed by the doctor. Caution is advised when administering artemether -lumefantrine combination to patients with severe renal or hepatic problems. ln these patients, ECG and blood potassium monitoring is advised.
– Patients receiving artemether -lumefantrine should be warned that dizziness or fatigue may occur in which case they should not drive or use machines.
KEEP OUT OF THE REACH OF CHILDREN!
OVERDOSE
ln cases of suspected overdosage symptomatic and supportive therapy should be given as appropriate, which should include ECG and blood potassium monitoring.
STORAGE
Store in a cool, dry place below 30oC. Protect from light.
PRESENTATION
Drutemal®- Plus suspension is presented in 60ml oral suspension (after reconstitution) containing 20mg artemether and 120mg lumefantrine in 5ml suspension.
Drutemal®- Plus tablets is available as 40mg artemether + 240mg lumefantrine in a blister pack of 12’s and Drutemal®- Plus (DS) tablets as 80mg artemether + 480mg lumefantrine in a blister pack of 6’s.